Jump to:

RJ Reynolds

Phyllis Small and Denise Fubini, Individually, and on Behalf of Others Similarly Situated Vs. Lorillard Tobacco Company, Inc., Et Al. Videotaped Deposition of Thomas A. Perfetti, Ph.D. Volume I Pages 1-291 Exhibits 1-14. Volume II Pages 292-494 Exhibits 15-38.

Date: 19980120;19980121
Length: 800 pages
517701148-517701947
Jump To Images
snapshot_rjr 517701148-517701947

User-Contributed Notes

  1. Module 4 activité 2 - référence 2 témoignage d'un expert chez Reynolds qui explique pourquoi les recherches sur les taux de nicotine-goudron ont été arrêtées: goût désagréable des cigarettes.

Fields

Type
DEPOSITION
Date Loaded
07 Jan 1999
Copied
Turbiner
F Jenny
F Carol
Box
Rjr4311
Characteristic
Marginalia
Site
Law
Request
Agreement
California
by
Ohioironworkers
Bluecrossblueshield
UCSF Legacy ID
raj82d00

Document Images

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size:

Page 1: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPERIOR COURT OF THE STATE OF CALIFORNIA FOR THE CITY AND COUNTY OF SAN FRANCISCO CASE NO•.: 980864 x THE PEOPLE OF THE STATE OF CALIFORNIA, et al., Plaintiffs, VS. PHILIP MORRIS, INC., et al., Defendants. Videotaped Deposition of THOMAS A. PERFETTI, Ph.D (Taken by Plaintiffs) Winston-Salem, North Carolina January 20, 1998 Reported by: Geralyn M. LaGrange Registered Professional Reporter Notary Public 3 HUSEBY & ASSOCIATES (800) 333-2082
Page 2: raj82d00
4 1 3 4 5 6 7 8 9 10 .11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPERIOR COURT OF WASHINGTON FOR KING COUNTY CASE NO. : 96-2-,150'56-8 SEA STATE OF WASHINGTON, Plaintiff, VS. AMERICAN TOBACCO COMPANY, INC., et al., Defendants. x x Videotaped Deposition of THOMAS A. PERFETTI, Ph.D (Taken by Plaintiff) Winston-Salem, North Carolina January 20, 1998 Reported by: Geralyn M. LaGrange Registered Professional Reporter Notary Public HUSEBY & ASSOCIATES (800 333-2082
Page 3: raj82d00
6 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Videotaped Deposition of THOMAS A. PERFETTI, Ph.D., taken by the Plaintiffs at Womble Carlyle Sandridge & Rice, 200 West Second Street, Winston-Salem, North Carolina, on Tuesday, the 20th day of January, 1998, at 9:40 a.m., before Geralyn. M. LaGrange, Registered Professional Reporter and Notary Public. HUSEBY & ASSOCIATES (800) 333-2082
Page 4: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Q• What group is that? Research and Development. Do you have any children? 10 A. Yes. Q. How many? A. We have two. Q. What are their ages? A. Eleven and fourteen. Q. Were you ever in the military? A. No. Q. Where did you attend high school? A. I attended high school at Greensburg Central Catholic High School in Greensburg, Pennsylvania. •Q. And what year did you graduate? A. I graduated in -1970. Q. And where did you attend college? A. I attended college at Indiana University of Pennsylvania, Indiana -- in Indiana, Pennsylvania. Q. What years? A. 1970 to 1974. Q. And what degree did you obtain? A. A BS in chemistry. Q. Any college education after that? I HUSEBY & ASSOCIATES (800) 333-2082
Page 5: raj82d00
1 2 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I live at 2116 Newcastle Drive, Winston-Salem, North Carolina 27103. Q. And how long have you resided there? A. About 18 years. Q. Any plans to move in the near future? A. No. Q. Are you married? A. Yes. Q. How long have you been married? A. Twenty-two years. Q. And your wife's name? A. Patricia Finley Perfetti. Q. Has she ever worked for Reynolds? A. Yes. Q. In what capacity? A. Patricia is a research chemist for Reynolds. Q. And for how long has she worked at Reynolds? A. She's worked there at Reynolds for 17 years. Q. Is she in the same department or group as you are? A. She is not in the same department. She's in the same group. 9 ~ m I HUSEBY & ASSOCIATES (800) 333-2082
Page 6: raj82d00
8 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 P R O C E E D I N G S Whereupon, THOMAS..A. PERFETTI, Ph.D., having been duly sworn, was examined and testified as follows: EXAMINATION BY COUNSEL FOR PLAINTIFFS BY MR. MAISTROS: Q. Good morning. It's Dr. Perfetti? A. Yes. Q. Would you prefer I call you Doctor? A. Yes. Q. My name is Jack Maistros. I'm going to ask you a series of questions today. If at any time you want to take a break, let your counsel- know. If you don't understand your -- a question I ask you, let your counsel know; or if you just want to confer with your counsel, let me know. Okay? A. Okay. Q. Could you please state and spell your full name? A. My name is Thomas Albert Perfetti, T-H-O-M-A-S A-L-B-E-R-T P-E-R-F-E-T-T-I. Q A. And your date of birth? 3-22-52. What's your current home address? HUSEBY & ASSOCIATES (800) 333-2082
Page 7: raj82d00
7 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CONTENTS The Witness: Thomas A..--Perfetti, Ph.D Examination By Mr. Maistros 8 INDEX OF THE EXHIBITS For the Plaintiffs Page 1 Memo Dated December 14, 1977 161 2 Quarterly Section Research Report 169 3 1978 Program Project 1250 4 Memo Dated January 9, 1978 5 Memo Dated January 4, 1978 6 Memo Dated January 5, 1978 177 191 197 198 7 Handwritten Notes - January.28, 1978 219 8 Notebook Pages - January 30, 1978 227 9 Memo Dated February 9, 1978 249 10 Memo Dated February 14, 1978 258 11 Memo Dated February 17, 1978 264 12_ Notebook Pages - February 24, 1978 271 13 Memo Dated March 2, 1978 274 14 Memo Dated April 13, 1978 280 HUSEBY & ASSOCIATES (800) 333-2082
Page 8: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes. Q. Where? A. At Virginia Polytechnic Institute and State University. Q. Where's that located? A. Blacksburg, Virginia. Q. And what degree did you obtain? A. I attained my Ph.D. degree there. Q. What year? A. 1977. Q. What did you do after that? A. I came to work at Reynolds. Q. In 1977? A. Yes. Q. at Reynolds? campus. Q. How did you hear about the position Reynolds had a recruiter visit the Was there -- I'm sorry. A. Any -- the -- the recruiter visited our department. Q. And were they looking for a specific position to fill? A. I'm not sure. I assumed it was for a research chemist position. 11 i HUSEBY & ASSOCIATES (800) 333-2082
Page 9: raj82d00
2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPREME COURT OF THE STATE OF NEW YORK COUNTY OF NEW'YORK SHARLENE HOBERMAN and AUDREY HULSE, as Executrix, on behalf the Estate of Lewis Hulse, individually, and•on behalf of others similarly situated, X of : Plaintiffs, . VS. . BROWN & WILLIAMSON TOBACCO CORPORATION, B.A.T., et al., Defendants. -------------------------------- X Index No. 110953/96 ROSE FROSINA, ELIZABETH COLAVITO : and ANILDA ROSS, individually, . and on behalf of others similarly: situated, . Plaintiffs, : : Index No. 110950/96 VS. . PHILIP MORRIS, INC., et al., . Defendants. . -------------------------------- X CATHERINE ZITO, PETER HOBERMAN, and GEORGE ELISSEOU, individually,,and on behalf of others similarly situated, Plaintiffs, : : ndex No. 110952/96 VS. THE AMERICAN TOBACCO COMPANY, INC., et al., Ln ~ ~ ~ Defendants. X m ~ ~ ~ LD j HUSEBY & ASSOCIATES (800) 333-2082
Page 10: raj82d00
I 1 2 3 4 6 7 8 9 . 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 APPEARANCES: For the Plaintiffs (State of -New York): JACK D. MAISTROS, Esq. KATE M. McNAMARA, Esq. Climaco, Climaco, Lefkowitz & Garofoli, L.P.A. The Halle Building - Ninth Floor Cleveland, Ohio 44115 (216) 6 2 1 - 8 4 8 4 For the Plaintiffs (State of California): MICHAEL SOBOL, Esq. Lieff, Cabraser, Heimann & Bernstein, L.L.P. 275 Battery Street - 28th Floor San Francisco, California 94111 (415) 956-1000 For the Plaintiff (State of Washington): CHRISTOPHER A. O'HARA, Esq. Hagens Berman & Mitchell, P.L.L.C. Suite 620 2425 East Camelback Road Phoenix, Arizona 85016 (602) 840-5900 For the Defendant R.J. Reynolds Tobacco Co.: DENISE A. FEE, Esq. Jones, Day, Reavis & Pogue 1450 0 Street, Northwest Washington, D.C. 20005-2088 (202) 879-3939 Also Present: Brent Troublefield, Videographer 5 HUSEBY & ASSOCIATES (800) 3,33-2082
Page 11: raj82d00
13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. No. 25 1 Q. Have you ever tried to quit smoking? f Q. Had you, prior to 1977, done any research with respect ta•any health issues related to tobacco? A. No. Q. Had you done any research with respect to nicotine? A. No. Q. How about -- how about any other chemical compounds that are in tobacco or tobacco smoke? A. No. Had you smoked prior to 1977? A. Yes, I had. Q. When did you begin smoking? A. I-- I guess I began smoking when I was in college. Q. In the '70s? A. I guess it was in the '70s, yes. Q. And how long did you smoke? A. I still smoke today. Q. Does your wife smoke? A. No. Do either of your children smoke? HUSEBY & ASSOCIATES (800) 333-2082
Page 12: raj82d00
19 1 2 3 4 5. 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Reynolds, yes. Q . What type._.of courses? A. These -- the courses that I've I've taught at Reynolds are -- are -- they're multi -- multiday courses and there are a number of speakers that normally talk. It was on the Tobacco Technology Training Course, I believe, is what it is known as. There was another course that I also partake in with some other scientists on, and it is called the Designer Cigarette Course. Q. Is either Townsend or Norman involved in that design of cigarette course? A. Yes. Q. Do you use the Townsend/Norman Cigarette Design Manual? A. No, I do not. Q. Are you familiar with that manual? A. Yes. Q. Do you consider yourself to be well-versed in cigarette design? A. Yes, I have a -- I think I have some knowledge in that area, yes. Q. What do you consider your design or your specialty to be? MS. FEE: Specialty generally or in Ln ~ m N ~ m m HUSEBY & ASSOCIATES (800).333-2082
Page 13: raj82d00
20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarette design? MR. MAISTROS: Generally, tobacco. THE WITNESS: I guess the -- I-- I've done a lot of research in terms of in two years. One is in menthol and the design of mentholated cigarettes and the -- the second area is in tobacco, nicotine, and blends. BY MR. MAISTROS: Q. Do you consider yourself a blend -- blend expert? A. No, I do not. Q. Do you consider yourself a nicotine expert? .A. Only in the facet of -- that I've done research. Q. Was the majority of your work since '77 been related to nicotine in some fashion? A. No, I wouldn't think the majority of it. Q. What percentage do you think is related to nicotine? A. I would imagine maybe 40 percent of the work. Q. Did you ever assist Reynolds or their HUSEBY & ASSOCIATES (800 333-2082
Page 14: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Have you ever appeared before any governmental body, such__as the FTC, to provide testimony? A. No. Q. Have you ever submitted any sworn statements to any.governmental body, such as the FTC? before on any A. Q. A. A. No. Q. Have you ever been interviewed by the No. Or the FDA? No. Did you ever consult with Reynolds litigation they were involved in? FBI? for a A. Yes. Q. When? A. In 19 -- no. I guess it was in 1977. Q. Did that.have to do with tobacco? A. No. A friend of mine was applying position with the FBI. Q A. Q. That was the only occasion? Yes. Ever interviewed by anyone from the Justice Department? 15 ~ m N I HUSEBY & ASSOCIATES (800) 333-2082
Page 15: raj82d00
12 1 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• Q. In any specific,group? I don't t•Yrink -it was for any specific Who did you interview with at The recruiter's name was Dr. Piehl, I What was his or her first name? Donald. Did you interview with anyone else? A. Not when -- yes, I did. When I was at Virginia Tech, I interviewed -- I interviewed with several other firms, too, and I -- I can't think of their names right now. Q. Did you interview with anyone else at Reynolds before accepting the position? A. Yes. I was invited to come down to -- to Reynolds to talk to the -- some of the staff who were there. Q. Were you advised what your duties would be? A. No, not at the time. Q. Had you had any prior experience or contact with tobacco companies? A. No. HUSEBY & ASSOCIATES (800) 333-2082
Page 16: raj82d00
1 ~ A. I have quit smoking before, yes. 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• A. Q. Did you uae any_aids or therapy or No. - medical devices to quit smoking? A. No. I just stopped when I had to. Q. When did you have to? A. Well, it was my -- it was my -- I voluntarily, I just -- I just didn't want to smoke anymore for -- there were -- there were certain periods where I just didn't feel like smoking. Q. Why did you start again? A. Because I -- I felt like smoking again, I guess. Q. Did you ever smoke any of the Eclipse cigarettes? A. I have tried the Eclipse cigarettes before, yes. Q. Did you ever smoke them for any length of time? A. Q• Q. No, I did not. Have you been deposed before? No. Have you ever testified in any litigation before? A. No. 14 Ln HUSEBY & ASSOCIATES (800).333-2082
Page 17: raj82d00
21 1 2 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 counsel in putting together information that was provided to either the FDA or the FTC relating to nicotine? A. Yes, I have. On what occasions? A. I worked with our -- our law and legal department when requested to resource some -- some documents, some literature, open literature on the areas that were mentioned in the FDA -- FDA documents. Q. Did you ever participate - participate in the process of gathering documents to provide to the FDA? A. No. Q. Were you aware if the FDA ever requested of.Reynoldg a list or a production of all nicotine-related research Reynolds had ever undertaken? A. I -- could you repeat that, please? Q. Were you aware of any occasion whereby the FDA requested of Reynolds a list or a-- a -- requested Reynolds to supply the actual documents of FDA -- I'm sorry -- of ~ ~ ~ ~ ~ - ~ nicotine-related research undertaken by Reynolds? o co 25 1 A. I've -- I've only heard that -- that. HUSEBY & ASSOCIATES (800) 333-2082
Page 18: raj82d00
23 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. Have you talked.to them about their depositions? A. No. Q. Do you know anyone who's been deposed? A. Yes. Q. Who? A. Dr. John Robinson, Dr. Dave Townsend, Dr. Alan Norman? Q. Have you read any of their depositions? A. No. Q. What did you do -- what did you do to prepare for today's deposition? A. I worried a lot. Q. No need to worry. You're much brighter than anyone sitting at this table. A. My counsel, Attorney Fee, have -- we've -- we've sat down and talked. Q. Okay. On how many occasions? A. On three occasions. Q. How many hours or minutes each occasion? A. I -- I was -- in total, about six HUSEBY & ASSOCIATES (800) 333-2082
Page 19: raj82d00
SUPREME COURT OF THE STATE OF NEW YORK COUNTY OF NEW•YORK - - - - - = - - - - - X PHYLLIS SMALL and DENISE FUBINI, individually, and on behalf of . others similarly situated, Plaintiffs, : Index No. VS. : 110949/96 LORILLARD TOBACCO COMPANY, INC., : et al., . Defendants. . ---------------------------------X VOLUME I MARY ANN HOSKINS, Executrix of . the Estate of Edwin Paul Hoskins,: PAGES 1- 291 WALTINA BROWN and DANTE AUBAIN, . individually, and on behalf of . others similarly situated, . Plaintiffs, : Index No. . 110951/96 VS. R.J. REYNOLDS TOBACCO COMPANY, : et a1., Defendants. . X Videotaped Deposition of THOMAS A. PERFETTI, Ph.D (Taken by Plaintiffs) Winston-Salem, North Carolina January 20, 1998 C2ro l -orl- 0S19g HU~EBY & ASSOCIAT~cS al Servicea Com pn A° ~'~/tn Le p y g + R e p o r t e d b y: G e r a 1 yn M. L a G r a n g e The 0ak House : 1316 Harding Place Registered Professional Reporter Chariotte,NC2g2o4 -9889 N o t a r y P u b 1 i c Fax R4)372-4593 http://www.huseby.com : email rpr(a3husoby.com Atlanta, GA / Gainesville, GA / Asheville, NC / Greensboro, NC / Raleigh, NC / Winston-Salem, NC / Columbia, SC / Greenville, SC / Florence, SC / Chattanooga, TN
Page 20: raj82d00
22 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 there is -- that they have requested documents nicotine-related research. on Q. Have you ever been asked to provide a list of nicotine-related research undertaken by you? A. No. Q. Do you have a list or a catalog of. all the nicotine-related research you've done at Reynolds since '77? A. I have a -- a curriculum vitae that I have that lists all of my publications and internal documents that I've -- reports that I've -- that I've written over the years. Q. It would enlist -- it would list both published to what, the outside world, when you say published documents? A. Yes. Q. And it would list also internal documents? A. Yes. Q. Have you spoken to anyone that's been deposed in any of this tobacco litigation? MS. FEE: Object to the form. THE WITNESS: I -- I -- I talk to scientists at Reynolds all the time. HUSEBY & ASSOCIATES (800) 333-2082
Page 21: raj82d00
1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. No. Q. The FTC? _. A. No. Q. The FDA? A. No. Q. Congress? A. No. Q. Agriculture Department? A. No. Q. The -media? , A. No. Q. Ever been -- never been quoted in any newspaper articles? A. Yes. Q. Which ones? A. I -- I-- I believe it was the Los Angeles Times. Q. And what was the subject? A. The subject was over a memoranda that I had written. Q. What was the memorandum? A. It was a memorandum in 1977 on a research proposal that I had written. Q. What was the research proposal? A. The research proposal was on 16 ! HUSEBY & ASSOCIATES {800) 333-2082
Page 22: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 me. Q. were you always_required to get approval before you would commence a -- a specific project? A. Yes. Q. And was there ever occasion where you could be working on a project without your supervisor knowing about it? A. I guess there could have been the time, but I normally never kept anything from my supervisors. Q. And the supervisors you listed, would they be considered management? A. Either -- either pure management or there was -- there's another area where I was like -- like scientific advisor. 'Some of them were pure managers, other were -- others held the dual role of technical leader/manager. Q. Did you ever w'ork under Dr. Rodgman? A. Yes. Q. What years? A. When I was hired at Reynolds,in '77, Dr. Rodgman was, you know, the director of R&D until he -- well -- and held a similar-type position until he retired, basically. You know, 27 HUSEBY & ASSOCIATES (800) 333-2082
Page 23: raj82d00
17 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1'7 . 18 19 20 21 22 23 24 investigating some -- the relationship between nicotine and materials known as enkephalins. .Q. And what are those -- what are enkephalins? A. At the time, when I wrote these, it was really unknown what enkephalins were. They were either believed to be neurotransmitters or. receptor sites. Q. That research have to do with similarities between the interaction of those receptors with nicotine and cocaine? A. No, it did not. MS. FEE: Object to the form. BY MR. MAISTROS: Q. Was there -- cocaine related in any fashion to that research? A. N Q. And what quest -- type of questions were you asked by the Los Angeles Times? A. I was not asked questions. They referred to a quote that I had in that memorandum in a --in the news article. Q. And do you remember the quote? A. No, I do not. 25 And do you remember what you said HUSEBY & ASSOCIATES (800) 333-2082
Page 24: raj82d00
25 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Do you know who it was addressed to? A. I think I_.-- I wrote the document to Mary Stowe. Q. What have your -- if you could, just briefly tell me your different titles and the years that they applied,from '77 to the present. A. In'1977, I was hired as a research chemist, and then the -- the next position that I -- I held was senior research chemist, and then I was promoted to senior staff scientist, and then I was promoted to master scientist, and most recently to principal scientist. Q. Okay. Do you recall what years you were a research chemist? •A. I believe I was a research chemist for -- from 1977 to about 1980, and then senior research chemist from about somewhere in 1980 to '82 or '83, and then a senior staff chemist from '83 to '85, master scientist from '85 to '91, and then been a principal scientist from '91 to present. Q. Is there anything above a principal scientist? A. Yes, sir. Q. What's that? HUSEBY & ASSOCIATES (800) 333-2082 a
Page 25: raj82d00
1 2 3 5 6 7 9 10 11 12 13 14 15 16 17 18 19. 20 21 22 23 24 25 senior principal scientist. I. believe. A. It's -- it's -- the title is called Q. Have your supervisors changed over the years? A. Yes, sir. Q. Who have been your primary supervisors? A. Let's see. Dr. Walt Henley, Dr. Mary Stowe, Dr. Robert Lloyd, Doctor -- oh, I'm sorry. No. Mrs. Margarette Savoca, Mrs. Brenda Hodge, Dr. John Reynolds, Dr. Brad Ingebrethsen. Q. And this has always been in Research and Development? A. Yes. Q. Although you were in Research and Development, did you work on any products or areas outside of Research and Development? A. All of the projects that I've ever been involved with have been originated -- almost all of them have been originated, I guess, in -- in Research and Development, to my knowledge. Q. And how is it or over the years how was it that you were assigned projects? . I either conceived the projects or there was a need that my supervisor presented to 26 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 26: raj82d00
29 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I -- I know him as a author of scientific papers. Q. Did you know a Mr. Willard? A. Could you be more specific? I know a -- a number of Willards. It's a common name. Q. At Reynolds. Do you know a Willard at Reynolds? A. Yes, I do. Q. Which ones? A. I know a -- a Ron Willard. Q. And what does he do? A. Ron is a -- I think Ron is now a vice president of Product Division. Technology and Development Q. Did you ever work with Dr. Hayes, Wallace Hayes? A. No, I did not. Q. Did you ever work on Premier? A. I worked only as a consultant. Q. What capacity? A. When there were difficulties or issues that they had, we would be -- a number of scientists might have been called into a room and we were asked for our opinion on how -- how one might be able to solve this issue. And I -- I took HUSEBY & ASSOCIATES (800) 333-2082
Page 27: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 there were people sometimes above him. Q. Did you euer work with Dr. Senkus? .A. Dr. Senkus was at Research and Development when I was -- when I was hired there, yes. Q. Did you ever get to know Dr. Senkus? A. Yes, I did. Q. Did you develop an opinion with respect to Dr. Senkus' scientific work? A. No, I did not develop an opinion. Q. Did you develop an opinion with respect to Dr. Senkus' credibility? A. No, I did not. Q. Do you have an opinion with respect to Dr. Senkus' credibility? A. Do I have an opinion, sir? Q. Yes. A. No. Q. Did you ever work with Dr. Teague? A. Dr. Teague I've -- I was not in -- in Research and Development when I got there, I don't -- don't believe in 1977. Q. Did you ever work with Gary Huber? A. No, I did not. Q. Did you know him? 28 i HUSEBY & ASSOCIATES (800) 333-2082
Page 28: raj82d00
18 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 about the quote? A. Again, I Was not interviewed by anyone,out of Los Angeles. This just appeared in the newspaper. Q. So, you never spoke to a reporter? A. No. Q. Was that the only occasion you were interviewed by the media, or not interviewed, but appeared in the media? A. I think that is the only kind -- time that I was mentioned. Q. Have you given presentations either at Reynolds or outside of Reynolds with respect to the work you do? A. Yes. Q. What type of presentations? A. We have -- the tobacco industry chemists have a conference every year, and I have made some presentations at a CORE, which is known as the Tobacco Research Chemist Conference, occasionally over the years. Q. Have you taught courses? A. I'm sorry, sir? - Q. Have you taught courses? A. I have taught some courses at HUSEBY & ASSOCIATES (800) 333-2082
Page 29: raj82d00
30 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 part in a number of those types of discussions. Q respect to the Premier? A. Q• cigarette was A. Q. transferred A. a principal fuel source Did you work in any fashion with issue of the nicotine content of Could you be more specific, please? Do you understand how the Premier designed? Yes, I know how it was designed. And how was it that nicotine would be from the cigarette to the smoker? The Premier cigarette worked on a -- of conduction of -- of heat from a -- a that would warm the -- warm the tobacco and release flavorants into the smoke. .Q. In the cigarette itself, where was the nicotine contained, in the Premier cigarette? A. it was contained in the -- the flavor section and in the tobacco roll section, near the mouth end. Q. In the flavor section, are you referring to the -- the -- the beads, the beads, little round beads? MR. MAISTROS: Bless you. THE WITNESS: Those are -- those round beads were a support for the flavors m 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 30: raj82d00
35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. The plant was in shambles. It had -- it was literally rusting.apart. Excuse me. Q. Is it shut down now? A. Yes, it is no longer operational. Q. When was it shut down? A. I believe it was shut down about three years ago, maybe four years ago. Q. And what did Reynolds or where did Reynolds use its denicotinized tobacco? A. Reynolds used it -- it in -- in our -- as a part of the -- the lamina that went into our blends. There was a very small quantity of it, about maybe 4 percent in the blend. Q. And what has Reynolds used since the plant was shut down three years ago? A. We use undenicotinized tobacco, just normal tobacco. Q. What was the purpose of using a denicotinized tobacco? A. There were some sensory -- unique sensory properties that some -- some scientists thoughts were real good with denicotinized KDN tobacco, but the -- over the years, we had used -- kept on using less and less and less of this material in our blends. And it was very hard to m HUSEBY & ASSOCIATES (800) 333-2082
Page 31: raj82d00
38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 to the current seed lots we use today. Q. What did Reynol-ds do with the nicotine it removed from its tobacco in the KDN process? A. It was burned. Q. Is that the case from '60 to when the plant shut down three years ago? A. Almost all the time it was burned, there were -- I imagine there were some times when it wasn't. But as far as I can remember, we -- we used to burn the material in this large -- large incinerator that was -- incinerator that was located beside it. Q. That incinerator had a permit, I assume? A. Yes. Q. What years was that permit in existence? A. I'm -- I'm not certain, sir. Q. Was any of the nicotine or tobacco flavorants that was removed in the KDN process ever used in any cigarettes Reynolds commercially A. No. Q. It was never used in Premier? A. Not that I know of. sold? HUSEBY & ASSOCIATES (800) 333-2082
Page 32: raj82d00
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 hours, I think. Q. And were y.ou provided any documents to review? A. No. Q. Did you meet with anyone other than Ms. Fee? A. I -- yes, I did. I'm sorry. I can't think of the -- the lady's name. I should know this. Marilyn Forbes? A. A. Yes, sir. She's everywhere. That was included in the six hours? I -- no. That was an additional one hour, I believe. Q. And you have -- did you review any of your own internal reports in preparing for your deposition? A. I -- I did look over the -- the one document that was cited in the -- in the Los Angeles newspaper article I had mentioned earlier. Q. Do you remember the title of that document? A. No, I don't. I'm sorry. 24 Ln N HUSEBY & ASSOCIATES (800) 333-2082
Page 33: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MS. FEE: Same objection. BY MR. MA_LSTROS: Q. Is the filter different? A. It is constructed differently than our normal filters, yes. Q. What's the most significant difference? A. It has a -- it is a -- it has a two-piece filter, but that's -- and -- and the - the materials used in one of the sections has -- carbon paper. Q. Is that also known as Winston Select? 40 A. They -- they may have used that particular filter on Winston Select. I'm not really•sure. I'm not sure. Q. What group at Reynolds has been in charge of determining the health risk consequences, et cetera, of cigarettes that are produced by Reynolds? MS. FEE: Object to the form. BY MR. MAISTROS: Q. I mean, I assume there's some group at Reynolds that tests the cigarettes to make sure they're safe for human consumption. Is there such a group? HUSEBY & ASSOCIATES (800) 333-2082
Page 34: raj82d00
I 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 flavorants were applied onto those beads. Q. And inclucled in the flavorants was nicotine? A. As part of the flavor system that was from the tobacco, there was nicotine in there, yes. Q. Where did the nicotine come,from? A. The nicotine came from the tobacco. Q. What tobacco? A. The -- the tobacco that was used for preparation -- preparing the flavors, the tobacco flavors. Q. Are you familiar with the KDN process? A. Yes, sir. Q. And what is the KDN process? A. The KDN process is a -- is a means for denicotinizing tobacco. Q. And has Reynolds employed that process in its commercially sold cigarettes? A.. Yes, it has. Q. For how long? A. The plant had been operational, I imagine, from about -- I think about in the '60s early in the '90s. Q. And what happened in the '90s? to 34 1 HUSEBY & ASSOCIATES (80.0) 333-2082
Page 35: raj82d00
43 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 remember the acronym, Product Stewardship -- PSTA is their acronym and I-- and I can't think of the other -- Product Stewardship something Assessment. And -- and those people are -- are the individuals that, if I wanted to test a prototype, I would submit information to them on what -- on the -- on the prototype, how it was constructed, what types of tobaccos I had in it, and I would submit some smoke chemistry and some tobacco chemistry information to them for their evaluation. And there -- those people are trained toxicologists and that -- would look at the information and tell the researcher if he was -- if he or she had a problem. Q. Okay. You're aware, are you not, that various groups over the years have alleged that cigarettes are the cause of certain diseases? A. I'm aware of those allegations. Q. You're aware that over the years certain.groups have alleged that there are certain constituents in the cigarette smoke that are harmful to humans? A. I've heard those allegations. Q. What group at Reynolds has been HUSEBY & ASSOCIATES (800) 333-2082
Page 36: raj82d00
I 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 conducting investigations to determine if those allegations are correct?, A. I mentioned a-- a couple of -- of things. I think that there was a-- another -- another group of -- of people that -- that are in a -- in a department, I think, called Smoking and Health. I think that's the name of that group. Q. And do they do research to determine if the allegations about cigarette smoke are true? A. I -- some of the stuff that I think that they do is look at, like, epidemiological studies and that. I'm not -- it's out of my -- my scientific background. So, I'm really not sure exactly what they do, sir. Q. Okay. Which diseases do you believe are appropriately linked to cigarette smoking, if any? A. I don't know if any of them are, sir. Q. Do you believe there's a causal connection between cigarette smoking and lung cancer? A. No. Could I get a glass of water? Q. Sure. THE VIDEOGRAPHER: Do you want to go 44 HUSEBY & ASSOCIATES (800) 333-2082
Page 37: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 off record? MR. MAISTRaOS: .•We' 11 just keep going. THE VIDEOGRAPHER: Okay. THE WITNESS: Thank you. MS. FEE: Thank you, Chris. MR.•0'HARA: Sure. BY MR. MAISTROS: Q. Rather than run through the list, would it be your testimony you do not believe there's any causal connection between smoking and any disease? A. I think that would be true. Q. Do you believe there's any adverse health risks related to smoking? .A. Yes, I think there can be some risks associated with smoking. Q. What risks? A. You know, people can have irritation in their throat and -- and respiratory tract. I think there's a -- that's one thing I think can happen. Q. Anything else? A. I think people can be allergic to smoke. I think that can be a irritation. Q. So, irritation in the throat and 45 , HUSEBY & ASSOCIATES (800) 333-2082
Page 38: raj82d00
32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. A. I'm sorry, sir? A minute Ago,.did you not say the flavor,section of the Premier cigarette had nicotine contained in it? A. I don't believe I said. Q. Okay. The nicotine in Premier was both on the tobacco and on these beads, correct?. A. What was applied there was tobacco flavorants. Q. Okay. Included among the tobacco flavorants was nicotine; was it not? A. There was -- there was no nicotine added to the tobacco flavorants. Q. Are you saying that the only nicotine that was in Premier was actually in the tobacco itself? A. Yes. Q. So, you'd have no knowledge of a nicotine compound being sprayed to those beads in the Premier cigarette? A. My only understanding of that was there were tobacco flavorants that were applied to those beads. That was my understanding. Q. Okay. And among those tobacco flavorants, are you saying that there would or HUSEBY & ASSOCIATES (800) 333-2082
Page 39: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. They're -- they're more than willing to tell me that, because,that_'s what they've been taught at school. Q. You wouldn't tell them that, because you don't believe it? A. That's -- that's correct. Q. Anyone -- anyone you know ever died from cancer? I A. Yes. Q. Do you know if the cancer was related to smoking? A. No, I do not know that. Q. Who is the most knowledgeable person at Reynolds with respect to the issue of smoking and health? A. Gees. I would imagine Dr. Simmons is. Q. Did you ever participate in any fashion in critiquing or synthesizing any of the ek,. Surgeon General reports on smoking? No, sir. Have you read them? I've read parts of -- of some of the Q. This is related to your work at 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 40: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 allergies. Is there -- are there any other risks that you believe are related to smoking? A. I'm not a medical person. So, I mean, I-- I don't know. I mean, perhaps -- perhaps -- I mean -- there's other things that people have alleged that are -- that'are associated with that risk, but I'd really be speaking out of my area. Q. Would you be concerned if either of your -- your eleven- or fourteen-year-old children started smoking today? A. Yes. Q. Why? A. I just don't think it's appropriate for someone at their age to even think about smoking. Q. Okay. How about when they turn eight,een? Is it okay if they start smoking? A. Well, by that time they have to start making some of their own judgments, sir. Q. Would you care if they started smoking when they turned eighteen? A. I'd probably ask them why. Q. Would you try to discourage them from 46 I HUSEBY & ASSOCIATES (800) 333-2082
Page 41: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 would not be nicotine? A. I think that within the tobacco flavorants, one of the hundreds of compounds that were in that would have been nicotine. Q. Do you consider nicotine to be a tobacco flavorants? A. Yes. Nicotine in itself is a -- is not a -- a tremendously good flavorant, but it -- tobacco nicotine, when it is heated up, it does produce a large number of flavorants in and of itself. And as a result, it is -- it can be the source of tobacco flavors. Q. Where did Reynolds get the nicotine that it applied to the beads in Premier? MS. FEE: Object to the form. It mischaracterizes his testimony.. BY MR. MAISTROS: Q. Are you gonna -- are you testifying that nicotine was not applied to those beads? A. Yes, I am. Q. All right. Then tell me again how it was part of the flavorants that was'applied to the beads. A. There were tobacco flavorants that 25 1 were produced from tobacco, and those tobacco 33 . HUSEBY & ASSOCIATES (800) 333-2082
Page 42: raj82d00
31 1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that were -- were part of the Premier flavor system, yes. BY MR. MAISTROS: Q. And did you work in any fashion with respect to those beads and those flavor supports? A. Not directly, no. Q. How about indirectly? A. Again, I was involved in some of the discussions in terms of the flavor elements of that. At the time I was working in the Flavor Division for Reynolds. Q. How long were you in the Flavor Division? A. I believe I was in the Flavor Division for about 11 months, maybe 12 months. Q. And what nicotine work did the Flavor Division do? MS. FEE: Object to the form. THE WITNESS: The -- the -- the Flavor Division never really did any work on nicotine. BY MR. MAISTROS: Q. You referred to this -- the flavor section of the Premier as having -- also containing nicotine, did you not, just a minute ago? HUSEBY & ASSOCIATES (800) 333-2082
Page 43: raj82d00
49 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Reynolds? A. Some of it.was-- is personal interest. I read a lot of scientific information. I'm not much on novels. I usually read textbooks. Q. You believe the Surgeon General's report was a novel.? A. No. I don't read novels. Q. Do you believe the Surgeon General's report was a novel? A. No. Q. What specific reports did you review? A. I can't remember all the dates. I think I've read the -- I think there was one in '75, there was one in '79. I read the more recent one. I forget exactly when it was. In the '80s, late '80s. Q. Did you read -- did you read the one that posited the position that nicotine was addictive? A. Yes, I've read over some of that. Didn't read it cover to cover, but I have read sections of that one. Q. Have you ever done any research to determine if nicotine was habit forming or addictive? HUSEBY & ASSOCIATES (800) 333-2082
Page 44: raj82d00
Do you know if Philip Morris had a 1 Q• 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 similar process? A. I don't believe that they have a similar process, no. Q. Did you participate at all in any portion of the Premier monograph? A. No, I did not. 4. Have you participated at all in this 39 new cigarette, Winston No Bull? A. No, I have not. Q. Did you participate in EW? A. Just as sometimes where there was comments or consulting. Only in that aspect. Q. Any specific issues you can recall? A. Some of the members of -- that had worked on that over the number of years we worked on it have been in groups that I've been in my work group. And so, we would discuss issues associated with the filter that's used on that. Q. How is that filter different than a typical Reynolds filter? MS. FEE: Object to the form. THE WITNESS: I'm sorry. BY MR. MAISTROS: Q. How is that filter different? I HUSEBY & ASSOCIATES (800) 333-2082
Page 45: raj82d00
36 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 substantiate whether it had any -- any -- any real taste benefit or not. So, when -- when it come time to - to either build a new plant or get rid of it, we decided that we should just, you know, get rid of the plant and not -- not -- and not the incur the cost of building a brand new one. Q• .The cigarettes that contained the 3 or 4 percent denicotinized tobacco, what do they have now, 3 or 4 percent regular tobacco instead? A. Yeah. It's just a replacement for the normal tobacco that was here. Q. Did you find that your nicotine and tar levels were altered, once you started using -- or started using undenicotinized tobacco? A. No, we did not. Q. So, the use of the denicotinized tobacco didn't affect tar and nicotine levels? A. Not at the levels we were using, no. Q. So, the use of denic tobacco was solely a sensory issue? A. To a large extent, yes, it was. This cn is at the end. At the very beginning, the reason J ~ 24 25 we -- we -- we even started the plant was to -- N there are many times there's crop years or a number 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 46: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of crop years where it's dry outside and that generally leads to a higher.total nicotine content in the,tobacco when you have dry seasons. And -- and it originally was built to try to even out the amount of -- of -- of -- of nicotine in the crops from year to year so we could produce a consistent product. Over the years, with a -- the greater variety of tobaccos that we could buy, there wasn't any real need to -- you didn't see the wide shifts in nicotine content in -- in our cigarettes. And -- and so, the -- the need for it kept on dwindling. I mean, there was a less and less of a need for it as the years went on. Q. Was that solely a by-product of being able to buy different blends or did it also have to do with improvements in infiltration and ventilation? A. I guess it was'partly due to -- to both the cigarette design aspect and in terms of the availability of -- of the tobaccos we could buy and the agronomics had changed over the years. People didn't use as much fertilizer and the like as they had had early on and the varieties of tobaccos have changed dramatically from about 1950s 37 I HUSEBY & ASSOCIATES (800) 333-2082
Page 47: raj82d00
42 1 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Well, how does Reynolds know that the cigarettes itself are safe for human consumption? .A. We -- we -- we do analyze certain smoke components that'have been alleged to be I harmful to smokers. Q. And what group? A. NCI, I think, had some -- a list of -- of -- of -- of components that we routinely would -- would check. And certainly.we -- we would certainly check smoke components that are -- have levels that you don't have to use very sophisticated techniques to -- to -- to monitor, like, tar and nicotine, CO, C02. We have methodologies to -- to look at a number of -- types of constituents in the microgram per cigarette level. Q. Is there a -- a group or -- set aside or a person set aside that looks at each cigarette marketed by Reynolds to make'certain that the constituents, such as you just referred to, are or are not at certain levels? I mean, is it monitored on a regular basis? -j i-1 Ln A. I -- not really. We -- we do have ~ m a -- we do have a group of people in the -- let's ~ see. They used to be -- let's see. If I can co tD l HUSEBY & ASSOCIATES (800) 333-2082
Page 48: raj82d00
50 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. No. Q. So, you c_o.uld.not offer an opinion on whether nicotine was habit-forming or addictive? A. No. Q. Have you heard anyone at Reynolds ever express the belief that nicotine was habit-forming or addictive? A. No, I have -- I don't think anyone believes that it is habit-forming and addictive. Q. Anyone at Reynolds, right? A. Yes. And I think there are other people in the -- in the scientific community believe the same thing. Q. Who would that be? A. There are -- boy, I wish I could remember these guys' names. I'm sorry. I can't remember their names. There's a -- there's a British -- a couple of British scientists that -- that I'm familiar with and I -- I can't remember their name right now. I'm sorry about that. Q. Do you know of any scientist that isn't employed or paid by a tobacco company that believes that nicotine is not addictive? A. Could you repeat that again, sir? 25 1 Q. Can you give me the name of any HUSEBY & ASSOCIATES (800) 333-2082
Page 49: raj82d00
41 1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. There is -- there is a group. We have a Human Research Review~Committee at -- at Reynolds. And, you know, if -- if we want to -- to -- to have anybody smoke a cigarette, we -- the prototype that we -- we put together, we -- we need to -- to go to that committee and let them review the data that we have collected on it. Q. Is that Human Research Review Committee, do they test all the cigarettes that are commercially sold by Reynolds to determine at what, levels certain toxins are released? A. No, that's -- that's -- that's not the purpose of that committee. Q. Is there a group that actually tests the cigarettes so determinations are made as to what levels, if any, toxins are released when cigarettes are smoked? A. I'm not sure that there's any particular group that has that charge at Reynolds. Q. Well, what -- what person or group at Reynolds makes certain that the cigarettes they sell are safe for human consumption? A. I -- I don't think there is any group that -- that does that. We do collect data on cigarettes. Ln ~ J J m HUSEBY & ASSOCIATES (800) 333-2082
Page 50: raj82d00
51 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 scientist in the world that believes that nicotine is not addictive? Start.there. A. Dr. John Reynolds -- John Robinson. Q. Okay. He's employed by Reynolds; is he not? A. Yes, sir. Q. Is there anyone that you can give .me the name of that believes that nicotine is not addictive that is either not employed or not paid by a tobacco company? A. Again, I -- I just can't remember their names. I've -- I've read papers by these individuals, but I cannot remember the name right now. Oh, I do know. How about Dr. Domino. Q. Who's Dr. Domino? A. He is a world renowned psychopharmacologist that has done a lot of work on a host of -- of compounds to determine if they're addictive. I've -- I've heard him speak at a number of conferences. We read some of his work. I. think he would agree with that statement. Q. Who is he connected with, a university or a private foundation or what? A. He's associated with a university, but I can't think of -- I'm not sure where -- where Ln ~ ~ ~ m ~ ~ ~ 00 J HUSEBY & ASSOCIATES (800) 333-2082
Page 51: raj82d00
52 1 2 3 4 that is. Do you know if he's ever received any grants.from any tobacco companies? A. No, I don't know that. And what conference did he speak at? 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I've heard him talk at two separate nicotine conferences. Q. Which ones? A. I think -- I think it was the second international conference on nicotine. I believe that one was in Uppsala, Sweden. And I think the third one where I heard him was at the conference -- it's the third international conference on it, and I think that one was in Hamburg, Germany. Q. What literature have you published outside of Reynolds relating to nicotine? A. I had a-- a paper that in, I believe, 19 -- 1980 that was published in Beitraae. It was on nicotine salt confirmational analysis. Q. Were you the sole author? A. Yes. Q. What was the hypothesis or conclusion you reached in that paper? A. That pure nicotine salts come in a HUSEBY & ASSOCIATES (800) 333-2082
Page 52: raj82d00
54 1 2 3 4 5 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. That -- that wasn't their -- their - their charge. There wexe -- there was a bunch of tobacco chemists here that -- that looked at -- at, you know, tobacco, how it was grown. And 'one of the things that they did look at was -- was nicotine levulinate. That was a good indicator of -- of the types of tobaccos that were used. The first group that I was in was in the tobacco chemistry section in '77. And, of course, we've always looked at FTC nicotine in smoke. Q. What is the FTC nicotine in the smoke? A. That is the -- the mainstream smoke nicotine that gets collected on a Cambridge pad at a particular puffing regime. Q. Did you ever study smokers to determine how the FTC testing method related to actual smoking conditions? A. No, I've never done that. Q. Did you ever see any literature where somebody else had done that? Ln ~ ~ A. Yes. There's just loads of it -- a ~ m N large number of articles that have been written on N m N that subject in the -- in the -- in the literature I HUSEBY & ASSOCIATES (800) 333-2082
Page 53: raj82d00
47 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 smoking when they turned eighteen? A. I really.don't -think I'm going to have to. They've been -- they've been exposed to a number of programs at school on that, on the dangers of -- of smoking. And there's a DARE program down here. I can't think exactly what DARE stands for now. It's another acronym. And they don't particularly like me smoking. So, I don't think I'm going to have to have much.of a conversation with them on that subject, whether they really want to or not. Q. If they ask you about the health risk related to smoking, the only two things you would tell them is it can irritate your throat and it could cause allergies? A. They've never asked*me, sir. Q. If they asked you, those are the only two things you'd tell your children? A. I think that I''d tell them that there are other -- other diseases that -- that people have said that -- that cause -- that, you know, they've been linked with -- with smoking. Ln . ~ ~ Q. But you wouldn't tell them that m smoking is related to heart disease or cancer or ~ ~ emphysema? I HUSEBY & ASSOCIATES (800) 333-2082
Page 54: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. In tobacco, nicotine is an alkaloid, correct? _ A. Yes, sir. Q. And is it the largest alkaloid in tobacco? A. In the types of tobacco that we -- we used for cigarettes, yes. But it's not -- I mean -- there are -- there are other tobacco types where it's not the -- the major alkaloid. Q. Do you know the -- generally what the nicotine content differences are between burley, flue-cured, oriental tobacco? A. Generally, yes. Q. Which generally has the highest nicotine content? A. Generally, it's -- it's burley, but it's very, very close to, in -- in level, to -- to flue-cured. Q. And then oriental? A. Then oriental, yes. Q. Now, when you did this literature review, is that something you decided to do on your own or somebody asked you to do? A. You know, I can't remember. That's been 20 years ago, but I think that there was -- I 56 I HUSEBY & ASSOCIATES (800) 333-2082
Page 55: raj82d00
57 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 think they thoughty my boss, who was Walt Henley at the time, he thought thgLt would be a good thing for me to do to get my feet wet. Q. What would be the goal or purpose of conducting that literature review? A. Originally, I -- I only spent a -- a few weeks looking at things. And -- and I -- I remember going back to Walt and saying, you know, "Walt, there isn't a whole lot of stuff here. I think I-- I better do a full -- I'd like to do a full review, a much broader review, because I only looked at about ten years." And -- and he said, "Yeah. Go ahead. See what you can learn." And this ended up to be 170 year -- I looked at 170 years of -- of literature. Q. So, in 1977, you conducted a literature research which examined the entire history of nicotine for the last 170 years? A. That's about right, yes, sir. Q. And you did a list of this literature review? A. No, I didn't -- I didn't -- the library did that. They helped me on getting the - the, you know, the articles and that. And we went to the normal sources that one would go to, like, HUSEBY & ASSOCIATES (800) 333-2082
Page 56: raj82d00
53 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 variety of -- of forms configurationally, and the -- the arrangement of the.-- of the acids that that -- that can be bonded, I guess, to -- to a nicotine molecule varyd and that it depends mostly on the -- the acid form on what type of salt ratio you will get. Q. Any other papers? A. That have to do with nicotine, sir? Q. Yes. A. No. Q. What work have you done in the area of nicotine since 1977? A. In 1977, one of the first things I did was a -- a large review of the literature on -- on nicotine and tobacco nicotine, anything that had to do with nicotine. Q. Is this internal or ext•ernal or both? A. The majority of it was external work. Q. Did you ever%look at the internal research Reynolds had done on nicotine? A. Well, the problem was, there wasn't a whole lot there. Q. Was there a group or a set of individuals that worked on nicotine at Reynolds when you joined Reynolds? HUSEBY & ASSOCIATES (800) 333-2082
Page 57: raj82d00
59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 about whether or not nicotine was addictive or habit-forming? A. I'm not sure. There -- there might -- I mean, certainly there was probably some in this -- in this collection that I reviewed. Q. Did.you review articles that discussed any health consequences of nicotine? A. Again, I'm sure there were articles in there, sir, that I reviewed, but I wasn't -- I'm -- I'm not -- I wasn't a -- a medical person. I didn't have training in that area. So, I didn't concentrate on those. Q. What actual research did you then undertake with respect to nicotine? •A. As I mentioned, after that, I -- I started -- I thought it would be important to look at some of the nicotine salts, because there was - they said that -- there was -- there was a number of references in the literature that nicotine existed in the salt form in tobacco. And so, I found out what are the normal acids that are in tobacco and I -- and I thought, well, let's see if any of these -- if I can make any of these nicotine salts. Q. And why were you trying to make HUSEBY & ASSOCIATES (800) 333-2082
Page 58: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Could you repeat that again, Q. Had you read any articles or by Reynolds people that stated or suggested sir? research that nicotine was the reason people smoked? A. No, I can't remember reading any -- any of that. Q. Did you read any articles or research papers by Reynolds employees that stated that cigarettes were merely nicotine delivery devices? A. Not during that -- this is -- this is in the 1970s. I can't remember reading any of that. Q. Have you ever read it? A. Only what has been in the newspaper in the more recent time. Q. Did you ever work on any projects trying to develop nicotine analogs? A. Yes. There's -- there was a project that, again, I was -- I was -involved in the early stages that -- that had to do with looking at nicotine analogs. Q analogs? Why were you looking at nicotine . There was a -- a fairly good size 61 body of -- of information, of literature out -- out I HUSEBY & ASSOCIATES (800) 333-2082
Page 59: raj82d00
1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in the -- you know -- public literature where people have been looking.at.nicotine, nicotine isomers, nicotine enantiomers, compounds that had different substituents associated, attached to nicotine at different positions. And in terms of their effect on -- on -- as a insecticide, there was a -- and also in -- in -- there was also some -- some -- some studies done in Europe on the toxicology and mild -- some type of -- of -- of -- I guess it's called -- they're called physiological studies on some of the -- on some nicotine analogs. And it was kind of intriguing, since we weren't involved in that, to -- to think about, you know, maybe we should get into some of this also and understand more about nicotine and nicotine-like compounds, because we hadn't ever done anything on that, as far as I knew. Q. What was Reynolds trying to learn or discover about nicotine? A. Part of it was just some knowledge. There was very little -- we didn't, as I mentioned back then, we didn't really have much of a understanding of -- of different, what I'm calling, analogs of nicotine, other -- other nicotine-like 62 I HUSEBY & ASSOCIATES (800) 333-2082
Page 60: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 compounds that might have been.in the tobacco or the smoke. We just didn!t ever look for those things.and we didn't know what effect they had. And I think a -- a lot of this was in terms of just our general understanding. There was also at the time some -- some work in the literature on the effect of nicotine related -- nicotine light compounds in terms of reduction to platelet aggregation. And, again, please -- I don't know what that means, but it has to do something with the blood in terms of atherosclerosis, I think, or clogging of the arteries, but there was some -- there was some articles on platelet aggregation, I remember, and the effect of -- of nicotine and nicotine-related compounds on that. We didn't really have a good understanding of that. So, I thought -- I thought it would be interesting to get into this. Other people at Reynolds also thought it might be good to do some preliminary work in terms of nicotine analogs. Q. Was ever -- was any of Reynolds nicotine research ever undertaken for the specific purpose of maintaining or increasing the sale of its cigarettes? 63 I HUSEBY & ASSOCIATES (800) 333-2082
Page 61: raj82d00
1 A. No. Q. So, is it_,faiz,to say, to your 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 knowledge, that none of the research Reynolds ever undertook with respect to nicotine had anything to do with its desire to sell more cigarettes? A. I don't believe that that was ever the -- the reason to -- to do the kind of work that we did on nicotine analog work. Q. I'm not limiting it to nicotine analog. I want to open it up to your knowledge of- the entire nicotine research ever undertaken by Reynolds that you're familiar with. Okay? was any of that nicotine research ever undertaken for the specific purpose of maintaining or increasing Reynolds' sale of cigarettes? A. We -- we did do work in an area called reduced tar nicotine cigarettes. There had been a lot of work published domestically and internationally on -- on giving some direction, particularly in the Froggatt Commission, some direction to the tobacco industry in terms of -- of -- of preparing cigarettes that had a reduced tar-to-nicotine ratio. And we did do quite a bit of work 64 , HUSEBY & ASSOCIATES (800) 333-2082
Page 62: raj82d00
1 2 3 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 on -- on preparing low tar-to-nicotine ratio cigarettes. And, of course,. some of the work that we had.done in terms of our basic understanding of nicotine salts was used in that area to prepare these reduced tar-to-nicotine cigarettes. Q. Well, was the work that you were doing in reducing the tar-to-nicotine ratios to make a"safer-" cigarette or to increase the sale of your cigarettes? A. We were -- we were trying to -- to -- to see how far we could go in terms of producing a -- a -- a cigarette that had a reduced tar-to-nicotine ratio, first of all, because it's not something that's done all the time. And -- and it's very difficult to make a cigarette that has a reduced tar-to-nicotine ratio that has any -- that's palatable to the smoker. So, I mean, that was -- that was -- a lot of the work we -- we were doing was to -- to see if it could be -- if we could produce a-- a low tar-to-nicotine cigarette and, secondly, if it would be palatable to -- to smokers. Q. Well, was -- was one of the goals of -- of producing a low tar-to-nicotine ratio cigarette to increase the sale of Reynolds' 65 i HUSEBY & ASSOCIATES (800) 333-2082
Page 63: raj82d00
67 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 mentioned, in -- in Great Britain had recommended that we produce low -- that.the industry worldwide produce cigarettes that are low -- low T-to-N ratio. They had done a number of studies in Europe in terms of these, what they called, medium nicotine cigarettes. And there was difficulties associated with that, even before we got into it, in that it was difficult to produce them, first, you know, secondly, they were not real palatable. So, we knew all that going into what we were -- we were trying to do in terms of could we overcome these hurdles. Q. Does Reynolds produce low tar-to-nicotine ratio cigarettes? A. • No, not really at this point. There are a certain number of our cigarettes, just by their design, have a lower tar-to-nicotine ratio, but that's only because they're highly diluted and -- and low tar to begin with. Q. What is the range of -- of tar and nicotine cigarettes that Reynolds produces? A. Our tar range, I think, right now runs between 15 and less than 1, I think, is how they categorize it. And I imagine a nicotine -- HUSEBY & ASSOCIATES (800) 333-2082
Page 64: raj82d00
1 2 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 smoke nicotine delivery level of about 1.1 or 1.2 milligrams per cigarette,down to less than .05 I think is the -- Q. Has Reynolds undertaken any tests to determine if the levels of toxins or compounds of concern, if you will, of the cigarettes with the lower nicotine and tar are any different than the cigarettes with the higher nicotine and tar? A. Can you repeat that again, sir, please? Q. You don't -- I want to avoid asking you if you believe that the lower tar, lower nicotine cigarettes are any safer than the higher tar, higher nicotine cigarettes, because you don't believe there's any safety concerns about smoking. So, I'll put it in terms of -- of the toxics or the compounds of concern, if you will, that are in tobacco smoke. Do you know if Reynolds had undertaken any research to determine if there are less compounds of concern in the lower tar, lower nicotine cigarettes than in the higher tar, higher nicotine cigarettes? A. we -- we do have information that -- that there is less of the controversial-type 68 HUSEBY & ASSOCIATES (800) 333-2082
Page 65: raj82d00
1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 out there, in the scientific literature. And there were some individuals at,.Reynolds that had also done some work along those lines. Q. But you did not participate in that? A. No. Q. Why did you do a literature review of nicotine in 1977? A. When I was hired at Reynolds, I -- I didn't even know what a tobacco plant was. I was a -- a northern boy and city boy and I -- I didn't. even know what a tobacco plant was. So, I thought it would be important for me to understand what the industry was about, what tobacco was, what are the major constituents associated with tobacco. And one of the ones -- one -- the major -- one of the major positions that I was interested in was nicotine. Q. How did you select nicotine as opposed to tar, stems, or roots or farm machinery? A. I'm an organic chemist and -- and there was a-- a compound in tobacco. There's a fairly high -- high concentration easily extractable, something that we monitored routinely. So, I thought it would be something we -- a good one to look at. I mean - 55 I HUSEBY & ASSOCIATES (800) 333-2082
Page 66: raj82d00
1 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 chem abstracts, biological abstracts, Beitrage, a lot of'the old German type of_Beilstein. Q. And what did review? you do once you did your A. I wrote a small summary, because I -- I went back -- it took me about five or six months to -- to go through this. The library had cataloged most of these articles, and I asked -- I asked at the time, "What would you like me to do?" And he said, "Well, write up a small summary on it." I said -- I was needed to do some other work. And I felt like I had a good -- good grounding on what -- what the literature was at the time. And I said -- they asked me if I felt comfortable. I said, "Yeah." Said -- so, I wrote up a small summary of the articles, the major classifications of the articles that.I reviewed. And I think it was only a couple page memo. And I went on to do some additional work where they needed me. Q. You classified the articles.into what type of categories? A. Biochemistry, chemistry, physiology, number of -- I think there was 12 or 14 categories. Q. Did you review articles that talked 58 HUSEBY & ASSOCIATES (800) 333-2082
Page 67: raj82d00
74 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. The vice president of R&D probably would be -- generally, that'.s_-- that's the last person,who sees it or a director. Q Are you familiar with the concept of free versus bound nicotine? A. Yes.. Q. What is your understanding of that? A. Bound nicotine is a -- an ionized form of nicotine and free nicotine is form of nicotine. an un-ionized Q. Is there such a thing as free nicotine in cigarette smoke? A. Yes. It~exists at a very small level, less than -- normally, about 1 percent. Q. So, 99 percent of nicotine is in a bound form? A. Yes. Q. What makes it unbound? A. It is -- when it's in an un-ionized form, sir. Q. And how does it get in the un-ionized form? Ln N -j A. It could be one of a number of ways. m ~ Once nicotine hits a certain temperature, generally N ~ the -- a bound form of nicotine releases an acid i HUSEBY & ASSOCIATES (800) 333-2082
Page 68: raj82d00
70 1 2 . 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you have to take into account. Q. And this Winston No Bull cigarette that's,being marketed now, is it your understanding there's no additives in that cigarette? A. That is my understanding. Q. And is it your understanding that there are more compounds of concern in that cigarette than the regular Winston cigarette? A. I-- I -- I've not looked at any of that data, sir. Q. Well, do any of the additives that Reynolds has used over the years reduce the compounds of concern? A. 'Yes. Q. So, as a general proposition, if there are no additives in Winston No Bull, it will have more compounds of concern than a regular Winston? A. I can't -- I can't give you a -- a - an answer on that, because I -- I just haven't looked at any of that information, sir. Q. Okay. MS. FEE: He'd like to take a break. THE WITNESS: Could I take a break, sir? HUSEBY & ASSOCIATES (800) 333-2082
Page 69: raj82d00
1 2 3 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes, sir. Q. For what.purpos.e? A. Just to determine what types of how different types of tobacco transfer their how they -- how they transfer their nicotine into mainstream smoke. It turns out that certain types of tobacco do not transfer nicotine very well into the mainstream smoke and others do it relatively well. I mean, at a 10 percent level. Q. In other words, in burley, for example, it contains more nicotine, but has a lower transfer efficiency rate? A. Burley has a lower transfer efficiency rate than perhaps flue-cured, for example. Q. And when did Reynolds first understand the process of nicotine transfer efficiency? A. I guess we -- we -- we did work on that in the '80s, early '80s, and it was based on prior work that was done in Germany and -- and Japan where they had reported this in -- in some of the scientific literature. Q. Why is nicotine transfer efficiency important to understanding the smoking process? 76 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 70: raj82d00
79 1 I the transfer efficiency of nicotine when it designs 2 4 6 7 8 9 10 11 12. 13 14 15 16 17 18 19 20 21 22 23 24 25 its cigarettes? A. No. Q. Does Reynolds analyze today the nicotine transfer efficiency of cigarettes? A. I don't think we've done that for a -- a number of years, to my knowledge, sir. Q. Did Reynolds ever explore ways to increase nicotine transfer efficiency rates? A. Yes. Q. Did Reynolds ever commercially employ those methods? A. No. Q. Did Reynolds determine ways to increase the nicotine transfer efficiencies of its cigarettes? A. I'm -- I'm -- I'm sorry, sir. Could you repeat that? Q. Reynolds research how to increase nicotine transfer efficiency of its cigarettes? A. We did research on nicotine transfer efficiency. Q. And did Reynolds ever determine a method to increase nicotine transfer efficiencies? A. We -- we -- we did try to -- to see HUSEBY & ASSOCIATES (800) 333-2082
Page 71: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Does Reynolds take into consideration 78 i smoking conditions, the -- the.work that we -= we did. . Q. If you take two tobacco rods with the same nicotine content in terms of levels in the tobacco rod and one is burley and one is flue-cured, won't the smoker of the burley tobacco rod actually take in more nicotine, everything else being equal? A. Again, it would -- it depends on how that smoker is smoking the cigarette, sir. Q. If you take two cigarettes, each with the same nicotine content, one burley, one flue-cured, and you put them in an FTC smoking machine -- A. Yes. Q. -- you'll end up with more nicotine on the pad of the burley cigarette than the flue-cured; will you not? A. No, I believe it's just the opposite. You'll get slightly more nicotine under FTC conditions with the flue-cured rod than with a burley rod, if they were both at exactly the same nicotine content. They're very, very close, burley and flue-cured, in terms of our understanding. HUSEBY & ASSOCIATES (800) 333-2082
Page 72: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarettes? A. Well, I'm not"s.ure if that's -- that was the end goal. I mean, we are -- we -- we do - we're in the -- we're in a for profit company. I mean, we -- and --. I mean, I -- I think that you're not going to try to spend a lot of money on something you don't think is of any value to the. bottom line, but you have to test these things somehow, you know: You're not going to -- you're not going to be able to put out a cigarette if -- if people don't -- don't like it. So, there had to be a lot of product research done before we get into anything like product development and product introduction. Q. Was one of the goals of reducing tar-to-nicotine ratios to create a "safer" cigarette? A. Those -- that terminology, I think, was used in the Froggatt Commission quite -- quite a lot and also by people in the United States, like, the NCI. They had done research and we had cooperated with the,NCI to -- to do a lot of that -- those studies that dealt with some cigarettes that had low tar-to-nicotine ratio. The Froggatt Commission, as I 66 i HUSEBY & ASSOCIATES (800) 333-2082
Page 73: raj82d00
71 MR. MAISTROS: Sure. THE VIDEOGRAPHER: Off record at 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 11:12 a.m. (Recess 11:12 a.m. to 11:20 a.m.) THE VIDEOGRAPHER: Back on record at 11:20 a.m. BY MR. MAISTROS: Q. You're reviewed on an annual basis; are you not, Doctor? A. Yes, I am. Q. Have you ever applied for any positions you were not given? A. No. .. Q. Have yo.u ever been demoted? A. No, sir. Q. Ever been disciplined in any fashion? A. No. Ever been the subject of any internal investigations? A. No; no, sir. Q. Do you have a written employment agreement with Reynolds? A. I think every -- I think every -- I did sign just a standard type of agreement, you know, when I came to work here that everyone does. HUSEBY & ASSOCIATES (800) 333-2082
Page 74: raj82d00
81 1 2 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 we didn't go out and actually find it by some real neat scienti.fic method. It was by -- by accident actually that we came across a method or a means to increase transfer efficiency. BY MR. MAISTROS: Did it have anything to do with reverse engineering on Philip Morris's Marlboro cigarette? A. No, it didn't. Q. , How did you discover it by accident? A. During the last -- I guess about 1990, we were trying to produce a real low cost cigarette. And we're always trying to reduce -- to make -- make our products more -- more efficient in terms of our costs. And tobacco Is an important cost obviously in -- in making cigarettes. So, a gentleman named Jack White and I placed a -- a very, very skinny cigarette rod in an insulator jacket. And we found out that, to our surprise, that it actually would smolder during the -- you know -- between puffs, because we thought that it would just go out. I mean, normal -- logic would say it would go out, but we thought we'd try it anyway. And to our surprise it , U1 ~ ~ ~ m N N co I HUSEBY & ASSOCIATES (800) 333-2082
Page 75: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nicotine salts? A. Well, no.one re.ally knew a whole lot about nicotine salts, only that that was the form that they were in tobacco and they were nonvolatile form, but they didn't know ahy of the physicall properties of -- of nicotine salts in tobacco. And so, I thought, well, I can at least find something about what -- how their -- how -- how -- why these things are stable or how stable they are and how they're -- how they're configured, because that was not known at the time. Q. This literature review, did you go back and read any of Senkus or Teague's work on nicotine? A. No, I didn't, that I can remember. I mean, I may have looked at them, but I remember them particularly. can't Q. Well, do you know if Senkus or Teague looked at the issue of -- of the properties of nicotine and whether or not it was addictive and habit-forming? A. I'm not sure. Q. Had you read any research done by Reynolds that stated or suggested that nicotine was a reason people smoked? 60 i HUSEBY & ASSOCIATES (800) 333-2082
Page 76: raj82d00
72 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17. 18 19 20 21 22 23 24 25 Q You haven't announced any intention to retire in the near future?. A. No, sir. Q. Do you know anyone at Reynolds who has been interviewed by the FBI? A. No. Q. Do you know anyone at Reynolds who's testified in front of a grand jury? A. I don't -- I guess -- I don't know them personally, no. Q. Do you know of anyone who has, whether you know them personally or not? A. I -- I'm -- I'm not -- I'm not sure whether John Reynolds -- he was -- he was on a Grand Jury. I don't know if that means the same thing, sir. Q. Did you help in any fashion preparing anyone who appeared before Congress to provide testimony on tobacco or nicotine? A. No, I didn't -- I didn't get into that. Q. Were you familiar with James Johnston's testimony before Congress in 1994? A. I did see that on the television. You did not participate in preparing HUSEBY & ASSOCIATES (800) 333-2082
Page 77: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 .17 18 19 20 21 22 23 24 25 him for his testimony? A. No, I didn!t. Q. Did you ever see the written report or statements submitted by Reynolds to Congress in 1994? Q. A. No, I didn't. Have you ever advised Mr. Johnston what you know about nicotine? Q• . No. Have you ever provided any written memorandums to Mr. Johnston with respect to nicotine? A. No. That's -- that would have been out of -- out of place, I think. I -- normally they don't -- don't do anything like that. Q. How was management kept apprised of 73 what people, such as yourself, were doing in the research department? A. I write reports on all of the research that I've ever done, and then there's a signature -- there's a sign-off sheet for my supervisor and the next manager and then the next manager up. Usually three signatures. Q. What would be the highest person that would sign your sheets? 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 78: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 and it goes into a -- an un-ionized form; or just in terms of decomposition of a nicotine salt, because they are not all inherently unstable -- they're not -- they're not all inherently stable, then you can -- you would have a dissociation of the acid from the nicotine that could be in the -- the non- or the un-ionized form. Q. Do you know what the concept of transfer efficiency is with respect to nicotine? A. Yes; I -- I do understand that. Q. What is your understanding of that? A. Nicotine -- percent nicotine transfer is what I understand is a -- a -- a ratio of the amount of nicotine that gets transferred to mainstream smoke. There's a ratio of the amount of nicotine in the -- trapped on a Cambridge pad versus the -- I mean -- over the amount of nicotine in a portion of the smokable rod. Of course, times a hundred. Q. And what role does nicotine transfer efficiency play in the smoking process? A. I'm not really sure exactly what you're getting at, sir. Q. Have you ever studied nicotine transfer efficiency? 75 I HUSEBY & ASSOCIATES (800) 333-2082
Page 79: raj82d00
1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that.we looked at also. And we filed for a invention disclosure and,we were granted a U.S. patent on this. Q. And is Reynolds currently attempting to develop that cigarette to sell commercially? A. No, we're not. Q. Is that the only means Reynolds has determined to alter or increase the nicotine transfer efficiency? A. It's the only one that I'm ever that I was aware of. Q. Has Reynolds undertaken any research to determine if other tobacco companies have figured out a way to increase nicotine transfer efficiency? A. I'm -- I'm not aware of any program that we ever had to -- to -- at -- with that purpose, to find out if other tobacco companies are increasing their nicotine transfer efficiency. Q. Are you familiar with how nicotine is metabolized by the body? A. I'm -- I'm not. That really isn't my area of expertise, sir. I know it's metabolized, but I'm not sure exactly what the end products are. Q. Are you familiar with the manner in HUSEBY & ASSOCIATES (800 333-2082 83 .
Page 80: raj82d00
85 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 is a slight reduction in stress that I've experienced when,I've smQked, and those are -- those are some of the -- the pharmacological actions that are normally associated with -- with cigarettes. Q. Have you read any research undertaken by Reynolds that looked at the level'of pharmacological activity that nicotine induced? A. 0 because I really haven't been involved in that, that -- that -- that area of -- of nicotine research that we've been doing. Q. Have you looked at the research to determine if Reynolds conducted research to look at the issue of whether or not there was a minimum level of nicotine necessary to make a cigarette successful? A. Again, I'm not -- I wasn't familiar with a lot of that work that was being done. Q. Is there a range of nicotine that Reynolds knows makes a cigarette acceptable? A. I'm -- I'm not sure if Reynolds knows what that level is or if there is a level. Q. Are there flavorants that can be used to substitute for the flavor of nicotine? 25 A. As I had mentioned before, nicotine, HUSEBY & ASSOCIATES (800) 333-2082
Page 81: raj82d00
1 2 3 4 5 6 7 8 9 . 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 compounds, the alleged controversial compounds in -- in -- in the ultra.low tar version versus those cigarettes which are the fuller flavor type. Q. Do you believe that the lower tar, lower nicotine cigarette pose less of a health risk to the smoker than the higher tar, higher nicotine cigarettes? A. No, I -- not -- not really. It -- it -- it's not -- I mean -- it's -- it's -- it's -- it's not just the cigarette itself. I mean, it's -- it's how -- how any smoker would smoke a cigarette. There's a lot of other things involved, a lot of other things that determine, I guess, what the risk level that an individual's willing to live with or -- or presents himself with in -- in doing -- normal life. Sometimes, depending on how they would smoke a cigarette, how much of the cigarette they smoke, all their -- all the -- all the -- all these things, the rituals that they go through, coLild determine a lot of this. So, I don't know if you could say unequivocally that, you know, an ultra low tar product presents less risk than a full flavor, because there's lots of other circumstances that 69 I HUSEBY & ASSOCIATES (800) 333-2082
Page 82: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. It would be interesting to find out -- we felt it would_.be interesting to find out how different tobacco types in a blend could they transfer their -- their nicotine to the mainstream smoke. And the -- would -- would . - - how would, for example, the question came up, would, for example, G7, our reconstituted tobacco sheet, transfer nicotine better or worse than flue-cured? Because we -- we looked at the data that was out there and it looked like they were not consistent.. There were -- there were -- there was a wide range in -- in these nicotine transfer numbers that were published in the literature. And as a result, we wanted to go back and research that to make sure that -- where we stood on -- on those issues. Q. Does the nicotine transfer efficiency affect the amount of nicotine the smoker actually takes into his system? A. Well, nicotine transfer ratio really is-all about smoking and FTC conditions. You know, if you -- if you smoke at other conditions, like, human smoking conditions that are other than FTC, we haven't really done a lot of work in that that I know of. Whereas, this was all under standard 77 , HUSEBY & ASSOCIATES (800) 333-2082
Page 83: raj82d00
1 2 3 4 6 7 8 10 11 12 13 14 15 16 1'7 18 19 20 21 22 23 24 25 a lot of it, gets degraded during the smoking process and it may gene.rate.a. lot of other flavor,ants. There are pyradines and pyrazines and the like. And, as a starting point, they do generate some of these compounds and they can - they do have tobacco character, tobacco smoke character associated with them. Q. Are there flavorants that Reynolds could employ to replace the tast,e of.nicotine? A. I imagine there are some. I don't know if it would be -- if we'd be able to totally replace it or not,"sir. Q. Does Reynolds use flavorants to mask the taste of nicotine? A. I don't think there's -- there isn't direct work along it. I mean, we -- we do try to apply our flavorants to reduce irritation, sometimes to increase the irritation, but it's ever directed towards nicotine itself. It's - not it's like this total experience you get. The smoke has a certain characteristic. It's either astringent or maybe it's harsh, too sweet, not sweet enough. And we do add flavorants to try to augment that. Q. Does -- does Reynolds design its 86 Ln ~ N W W 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 84: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 -13 14 15 16 17 18 19 20 21 22 23 24 25 Okay? A. Yes. Q. What's that called? Do you know what that's called? A. I think it's Doral full flavor, sir. Q. And on Monday morning, the factory calls over and says, "Give me the recipe for Doral full flavor,".right? Let's assume this hypothetically. A. Right. Q. The factory knows that when that cigarette comes out, it has to have 11 milligrams of tar and .8 milligrams of nicotine, correct? A. Yes. Q. And is it your testimony that none of the manufacturing processor design specs are drafted or undertaken with the goal of achieving those .8 milligrams of nicotine that's by chance? A. No, that -- there are specs. Q. Okay. A. And those specs are based on paper, weight of the blend going in, filter type, filter dilution, number of holes in -- in those filters, length of the filter, length of the rod and, of course, the blend composition. HUSEBY & ASSOCIATES (800) 333-2082
Page 85: raj82d00
88 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 brands, styles called Doral. Q. There is a,Doral, is there not, that has a-- and give me the -- an example of a tar and nicotine content of a typical Doral. A. Probably somewhere around 11 milligrams of tar and 8/10s of a milligram of nicotine. Q. And is it your testimony that at the beginning of manufacturing process, Reynolds is not concerned with whether or not those Dorals come out of the factory with 8 milligrams of nicotine in them or .8 milligrams of nicotine in them? Yes, we are -- we are concerned about the tar at the level of -- of -- of Doral that hits -- that hits specifications that we say on our package. Yes, we try to hit those. Q. In fact, before the first cigarette is manufactured, that Doral cigarette is designed to come out of the factory with .8 milligrams of nicotine in it or thereabouts, isn't it? A. We -- we try to make a cigarette that's consumer acceptable. And, normally, whatever that turns out to be -- when we first came out with Doral, it wasn't exactly at 11 and .8 milligrams of tar and nicotine respectively.. HUSEBY & ASSOCIATES (800) 333-2082
Page 86: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. And all those different things will affect the nicotine content.of the cigarette? ,A. Yes, yes. Q. And some of those things affect the nicotine yield of the cigarette; do they not? A. These -- the smoke nicotine - Q. Yes. A. -- in the mainstream? Q. Yes. A. Yes. Each of those -- THE VIDEOGRAPHER: We have five minutes left on the videotape. THE WITNESS: All right. Each -- each of those -- each of those things that I mentioned, which were specified in terms of its configuration, interact because a cigarette is a system. If you change one of those, other things will -- will change. BY MR. MAISTROS: Q. All right. In fact, you could -- of that cigarette, let's assume that you put that same tobacco in. We'll call it the Reynolds number one cigarette. If you put that same tobacco in the Reynolds number one cigarette and altered either the paper, the filter, the dilution, the holes, the 91 i HUSEBY & ASSOCIATES (800) 333-2082
Page 87: raj82d00
1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 if we could increase the transfer rate of -- I mean -- if there was any,means of doing that, to -- to try.to increase nicotine transfer -- yes, we did try to -- to do some research along those lines. Q. Why? A. Well, part of it was a curiosity, because it turns out that not only does nicotine transfer at about, on average, 10 percent plus, but almost every -- every other flavorant that you've ever applied to tobacco. This number of about 10 percent is good for menthol, anethole, a lot of the tobacco flavorants that we put on. And it's kind of curious that we can't ever get a -- out -- outside this range. And so, we -- we decided to -- to look and find out if we could increase that rate, not only for nicotine, for some of the other flavorants we have, because they're relatively expensive in terms of what we pay for, you know, tobacco flavorants to put on our cigarettes. Q. And how did Reynolds determine they could increase the nicotine transfer efficiency? MS. FEE: Object to the form. THE WITNESS: Again, the -- the -- this was a curiosity that we had and we - 80 i HUSEBY & ASSOCIATES (800) 333-2082
Page 88: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 prepare that cigarette. BY MR. MA;STROS: Q. Okay. We have to switch tapes. Okay? A. I'm sorry. THE VIDEOGRAPHER: This concludes tape number one of the deposition of Dr. Thomas Perfetti. The time is 11:49 a.m. (Off-the-record discussion.) THE VIDEOGRAPHER: This is tape number two of the deposition of Dr. Thomas Perfetti. The time is 11:51 a.m. BY MR. MAISTROS: Q. Let's take this hypothetical Doral full flavor. The 11 milligrams of tar, .8 milligrams of nicotine is by the FTC test method, correct? A. Yes, sir. Q. So, at the beginning of the day when you're manufacturing these cigarettes, it's the goal of Reynolds to have a cigarette that when it's smoked by the FTC test method that will reach those (n ~ ~ levels or was pretty close to those levels, ~ m N N correct? IV~ A. Yes. I HUSEBY & ASSOCIATES (800 333-2082
Page 89: raj82d00
94 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. And that's all a function of those factors you listed, including the blend, right? A. Yes. Q. If you change one or more of those factors, you can change the tar and nicotine yields of that cigarette; can you not? A. Yes. Q. And you can change them to the point where you can have a totally different brand of cigarette or a level of cigarette? In other words, you could have a cigarette of up to 1.1 milligrams_ of nicotine or up to 14 milligrams of tar; could you not? A. Yes, you could. Q. Hypothetically, depending how you change these factors. And my question is, again, in determining what paper you use, what weight of the blend, what filter type you use, is any consideration at all given to the goal of achieving a specific nicotine yield by the FTC test method? A. No. That is normally directed by the consumer, because -- by the consumer ratings that we get on these. Because before we went out, and we do test prototypes out -- out there that have HUSEBY & ASSOCIATES (800) 333-2082
Page 90: raj82d00
84 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 which nicotine interacts with the central nervous system? A. Again, I-- it's not my area of expertise. Q. You could not, then, offer testimony or opinions on nicotinic receptors or transmitters or anything else? A. At one -- at one time I thought I knew a little bit about this came out of graduate school, when I was a -- when I but I don't think I I'm a -- I would -- I could offer an opinion now. It's been just too -- too many years. Q. Could you offer an opinion on what role nicotine plays in the, smoking process? .A. It gets delivered, it's part of the flavor package or flavor -- flavor of the cigarette smoke. There's enjoyable elements of that that the smoker experiences. Mild pharmacological action of the nicotine is there. That's -- that's about all I could speak to maybe. Q. What is pharmacological action? A. You know, that there is -- there are certain -- there are several pharmacological aspects of -- of nicotine that I've read about. Some of them are increased cognitive ability, there HUSEBY & ASSOCIATES (800) 333-2082
Page 91: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 17 18 19 20 21 22 23 24 25 Q. What the filter was? A. Yes. Q. What the paper was? A. Yes. Q. What the location of the filter holes were? A. Yes. Q. How big they were, how the filter was crimped? A. Yes, all those things. Q. The compression factor, you knew all that, and you duplicated it in every Doral you made after that date, correct? So, on some date certain there is a specific intent to design a cigarette that had a certain tar and a certain nicotine delivery; was there not? I'm not saying you repeated it every time you made the cigarette, but you knew going in what those various factors were and how they affected the tar and nicotine deliveries; did you not? A. Yes. Q. And you know that today? A. Yes. Q. I mean, if I picked up the phone, I could call somebody over who writes these specs and 97 I HUSEBY & ASSOCIATES (800) 333-2082
Page 92: raj82d00
1 2 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 different tar and nicotine yields, and we come we -- when we look at the dat.a when it comes back, if it says that the one that really did best that had 11 and -- 11 milligrams of tar, is one .8 milligrams of nicotine, that's what we're going to be making. Q. I understand that. My question is, at the beginning of that process, isn't your goal to arrive at a cigarette that has .8 milligrams of nicotine yield? MS. FEE: Objection, asked and answered. BY MR. MAISTROS: Q. I know you know it's going to end up that way based upon the combination of factors you've listed. A. Yes. Q. But the point is, you specifically employ.certain methods to arrive at that end result; do you not? It's not by chance that you use a filter with 16 holes -- A. Oh. Q. -- versus 8 holes? A. That is true. We -- you can use - for Doral, let's put it this way, for Doral we 95 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 93: raj82d00
87 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarettes to have a specific nicotine level in them? .A. No, that's not one of the design criteria that we try to match. Q. So,.Reynolds is not concerned with the nicotine content of its cigarettes? A. Oh, yes, we are concerned about that, but in terms of designing cigarettes are not normally the types of things that we -- we try to key on. We normally look at filtration efficiency,, cigarette -- cigarette filters, cigarette papers, the weight of tobacco that's put into the product, the blend composition, but not normally do -- do we set out, then target a certain -- not that I ever know of -- target a -- a certain nicotine. Q. Well, what's -- what's your best selling cigarette? A. I think today it's probably Camel Light. No. I take it back. Probably Doral, I imagine. I think Doral. It used to be Camel Light. Doral or Camel Light, one of those two, I imagine. Q. And there's different types of Dorals? A. Yeah, there's quite a few different m W $P HUSEBY & ASSOCIATES (800) 333-2082
Page 94: raj82d00
! 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 say, "Give me the specs for Doral full flavor," and they'll list how many d&fferent specs? A. . That's -- that's correct. There's - there's Q. How many will they list? A. Hundreds of specs -- Q. Hundreds of specs. And you know -- A. In terms of our bill of inventory, what we use in there. Q. Right. And it's how much reconstituted tobacco, how much expanded tobacco, the type of filter, the compression of the filter, the length of the filter, et cetera? A. Yes. Q. And they know going in.what the nicotine delivery of that end product will be; do they not? A. It is a resultant thing. This is not a design variable. There's a difference between designing something and --,and being a result of these things. And these are results of, or responses, not -- not a design variable. Q. Give me an example of a design 98 HUSEBY & ASSOCIATES (800) 333-2082
Page 95: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Whatever it was, I -- I think it was a little bit higher than that. When it originally came out, I think it was 12 and .9. And that was an -- consumer acceptable product and we knew what that blend was. It was a relatively low cost blend and we try to maintain that'same level of -- of tar and nicotine until the consumers tell us differently that they're having problems with -- with irritation or it's too bitter or it's -- whatever the complaint was, and then we'll adjust the blend to -- to try, to get that back in the line. And the way we normally do that is - is with configurational parameters; filter, air dilution, and things like that. Q. But you're not suggesting, are you, that it's not the goal of Reynolds to come out with Doral cigarettes all in the range of .8 milligrams of nicotine? A. No, because we make Doral cigarettes a number of different brand styles. Some of them are full flavor, some of them full flavor, low tar, some are hundreds. Q. Let's -- let's take the Doral that's 11 milligrams of tar and .8 of -- of nicotine. 89 i HUSEBY & ASSOCIATES (800) 333-2082
Page 96: raj82d00
1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 wanted to use -- it's a -- it's a -- it's a brand of generic. We wanted to, u'see those inventory items that were at the reasonable cost, at low -- a low cost as we could get the manufacturers to produce them for us. So, we did have a limited range of tar and nicotine with a combination of these design parameters that could give us a range of tar and nicotine. And what we did was actually go out there with as lowest cost blend that we tested in terms of, internally, did it taste like cigarette smoke, did it taste reasonable with these combinations of -- of our papers and filters from our suppliers. And it was -- it was just like I told you, we went out with a range of tar and nicotine levels and we asked consumers which one they wanted -- Q. I know. A. -- best. Q. And when they said -- when they came back and said, "We like the 11 milligrams of tar, .8 milligrams of nicotine," you knew what the blend was? A. Yes, sir. w 1P. HUSEBY & ASSOCIATES (800) 333-2082
Page 97: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 variable. A. The porosi,ty of.the cigarette paper, the su,rface area of the filter used in a product, those are things that you can control. They're controllable features in the construction of something. A response is something that is afforded from the -- the use of -- of something; for example, the CO yield, the nicotine yield, the tar yield. Q. Would you agree as a general proposition, if you change the porosity of the cigarette paper, you're going to change the tar and nicotine yields? A. Yes. .Q. Would you agree, as a general proposition, that the changes in the tar and nicotine yields will not be equal? A. It -- that depends on the changes you made in terms of the configuration, sir. Q. Everything else being equal, if you increase the porosity of the cigarette paper, will you decrease the tar at a greater level than you'll decrease the nicotine? A. Not for that parameter, no. Not within measurable differences. 99 ~ ~ ~ m N a, , HUSEBY & ASSOCIATES (800) 333-2082
Page 98: raj82d00
1 2 3 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 filter length, you could come out with a cigarette with vastly different tar and.nicotine deliveries; could you not? MS. FEE: I object to the form. I'm not sure it's clear. You may answer if you can. THE WITNESS: There -- there is -- there is a -- a -- only a certain range of -- of tar and nicotine that is possible in the production of cigarettes. That universe is bound by the -- the variation in the components that we -- that we use in the industry. For example, we do not have manufacture -- our paper manufacturers cannot produce for us a very high efficiency, low pressure drop filter. So, we are bound by the materials used in that -- in -- in the -- in the cigarette industry in terms of how wide a range of tar and nicotine are possible. So, it's not like there's an infinite quantity of -- of -- of nicotine or tar that can be generated with X quantity of tobacco with conventionally available materials to 92 ! HUSEBY & ASSOCIATES (800) 333-2082
Page 99: raj82d00
101 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17' 18 19 20 21 22 23 24 25 Q. And has Reynolds undertaken research to determine what effect.ventIlation plays on nicotine yields versus tar yields? A. we have looked at tar and nicotine as responses to changes in design variables affecting ventilation of the filter, yes, sir. Q. And what conclusions has Reynolds reached with respect to how ventilation affects nicotine yields as opposed to tar yields? A. In terms of ventilation, the -- I'm trying to remember how this goes. The, as you increase the ventilation, the -- the tar-to-nicotine ratio decreases. So, as you go to lower and lower yield products, your tar-to-nicotine ratio will-decrease. Q. Another way of saying that is that the increased ventilation reduces the tar content at a greater level than the nicotine? A. Yes, sir, that's another way of saying that. Q. So, one of the design parameters that you use in making your cigarettes; that is, ventilation, is known by Reynolds to decrease tar without decreasing nicotine? A. No, that is not correct. 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 100: raj82d00
107 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. No. Q. Did you e_v.er see any research to determine if the gaseous ammonia caused any biological activity that was not caused by the DAP or ammonia? A. I-- I have not looked at any of those reports. Did Reynolds do tests to determine if -- do you know what an Ames number is? A. Yes. Q. What's an Ames number? A. An Ames number is a result of an Ames test developed -- it's a test developed by Bruce Ames in California, where it looks at a -- there are certain strains of a bacteria that are put onto a plate and it looks for changes in those -- in the -- in the growths along those plates when they're exposed to either something called S9. And what they're looking for is increased -- increased growths of -- of unusual bacteria on those plates with time and as concentration of the material is increased. You get a -- a plot basically of concentration versus amount or numbers of colonies mutated. Q. So, as a general proposition, an HUSEBY & ASSOCIATES (800) 333-2082 L"
Page 101: raj82d00
82 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 remained lit and we had filed -- we filed for an invention disclosure on_,that,-- on that particular cigarette. And when we -- we normally did our -- our -- our normal FTC analysis on that cigarette and we found out, gee, you know, this is kind of interesting that -- that it -- that it only -- it did increase -- it doubled the nicotine transfer efficiency. And the reason it does is because in a normal cigarette when you smoke it, we only burn up about 25 percent of the tobacco that's delivered to the mainstream smoke. If you don't, the rest of the nicotine and flavorants go off into the sidestream and -- or it is decomposed. And this cigarette, since it doesn't have any sidestream smoke at all, it's all contained in this insulator jacket, transferred more material to the -- to mainstream smoke than -- more nicotine to the mainstream smoke than we anticipated. Also, it delivered -- it transferred more flavorants when we added it to it, because we -- we looked at a menthol version of this. So, it held for two -- two things that we normally would -- would monitor, nicotine and we had analysis for menthol that we would -- HUSEBY & ASSOCIATES (800) 333-2082
Page 102: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 increased or higher Ames number will mean you should be more concerned,about that compound? A. It's one indicator. It is one indicator of biological activity. Q. And Reynolds has used the Ames test over the years to determine biological activity; have they not? A. Yes, we have. Q. And that Reynolds relies on the Ames -- Ames test in its research; does it not? A. As one indicator, yes. Q. And what Ames test did Reynolds do on either gaseous ammonia or DAP before they used it? A. I'm not -- I'm not sure, sir. Q. What was the primary motivating factor in switching from gaseous ammonia to DAP? A. When we took out the -- the KDN unit where the -- the tanks of gaseous ammonia were -- were in close proximity, it is a fairly large - it's a fairly long distance from there to the -- our facility that uses G7, where we make our G7. And they thought it would be closer to -- to move those -- those -- those either -- either to move the gaseous ammonia to the G7 plant or to just buy different tanks and use aqueous ammonia. The price 10E HUSEBY & ASSOCIATES (800) 333-2082
Page 103: raj82d00
102 1 2 Q And why is it incorrect? .creases nicotine. It is It also de 4 5 6 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 just the ratio that changes. Q. Okay. I'm sorry. The ventilation decreases the -- both, but it decreases the tar at a greater level? A. That is true. Q. Has Reynolds employed any compounds or additive for the specific purpose of increasing the nicotine yield of its cigarettes? A. Not that I know of. Q. And your testimony is, they haven't employed any compounds to increase the nicotine transfer efficiency? A. That's correct, yes. Q. Why does -- why has Reynolds in the past employed ammonium or diammonium phosphate in its cigarette manufacturing process? ' A. Ammonia and diammonium phosphate have -- have been used in our reconstituted sheet operation as processing aids. The use of diammonium phosphate and ammonia produces a much stronger sheet in terms of making the product than we're able to otherwise. And that's one of the reasons why we have used that. HUSEBY & ASSOCIATES (800) 333-2082
Page 104: raj82d00
111 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 low efficiency compared to other tobacco types. Q• And the pgimar.y_use of gaseous ammonia -- I'm sorry --.aqueous ammonia in the G7 process now is to add flavors to the G7 sheet? A. There are -- there's -- there's two -- two reasons. Q. And the sheet strength. I'm sorry.. A. Sheet -- sheet strength, and then it does do something for the tobacco taste. Q. Is it -- does it have your test panels shown that the people prefer the taste of ammoniated recon as opposed to nonammoniated recon? A. Only in certain products. Not all products, and that's probably why we're only using -- only about a quarter of our products have it in it. Different smokers have'different aspect -- expectations, I guess, and not every brand has it in it. Q. Were you at the company when they first started using gaseous ammonia? A. No. They were -- they had done that before I got here. Q. Do you know if Reynolds' decision to use gaseous ammonia had anything to do with Philip Morris' use of ammonia in its products? I HUSEBY-& ASSOCIATES (800) 333-2082
Page 105: raj82d00
113 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 . 22 23 24 25 expanded material, because we use di -- we use this dry ice expanded tobacco,. It's a C02 process for expansion and there isn't any ammonia that's used in there. Q. Well, if ammonia helps the flavor of recon tobacco, hasn't Reynolds looked at using it in all their tobacco? MS. FEE: Asked and answered. said some people like it, some people don't. THE WITNESS: We -- this is not -- I mean -- our use of -- of flavorants and -- DAP doesn't really fall into the area of a flavorant. It really is a processing aid. There have been -- I mean -- diammonium phosphate is a burn retardant. So, I mean, I'd be at fault if I didn't tell you this. We have, looked at experiments when we had to reduce burn rate and,-- because chemists, in general, know that diammonium phosphate is a burn retardant. And if we wanted to have increased puff count, you will find reports that -- where we've tried to increase the puff count by using DAP. BY MR. MAISTROS: ! HUSEBY & ASSOCIATES (800) 333-2082
Page 106: raj82d00
100 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. They aren't -= that's correct, they 25 are not all the same. Q• Would you distinguish between the porosity and the ventilation,of the paper? ,A. Porosity or permeability of the paper is the amount of air that is --that -- air that is able to pass through the paper at a particular air flow for particular size diameter that you're passing that air through. Q .And how's that measured? In CORESTA units. Ventilation of the paper, you only talk.about that when the paper is electrostatically perforated, where they have very huge holes of where they're put into the paper by an electrostatic perforator. The total surface area of the hole, for example, is -- is much greater in terms of yields of permeability than it is for ventilation or ESP. And that affects the smoke-chemistry in very different ways. Q. There's different specifications for ventilation of particular filters, correct? A. There are specifications for ventilation of filters, that's correct, yes. Q. They're not all the same; are they not? HUSEBY & ASSOCIATES (800) 333-2082
Page 107: raj82d00
112 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. The story that I heard was -- I mean -- it's -- it's basically -- and it was an engineering decision, because it's -- it was for - at that time it was much easier to pump this material, and we were using it on -- in the process. It would have been better to have gaseous, because we were using a countercurrent steam coming in one end of this tunnel and gaseous ammonia was coming into the other. Otherwise, you would have had to heat up the -- heat up the aqueous ammonia to get into a gaseous form. So, it was -- engineeringwise, it was much -- much more efficient to use gaseous ammonia in this countercurrent denicotinization process. It was called KDN. Q. Did it have anything to do with Philip Morris' use of ammonia? A. It -- it might have. I'm not sure. This is before I got here. Q. So, Reynolds_does not employ ammonia in any fashion in its nonreconstituted tobacco or its expanded tobacco? A. I-- I mentioned that -- that they may be using it in the -- in this CRES material. I'm -- I'm not sure. And certainly not in our I HUSEBY & ASSOCIATES (800 333-2082
Page 108: raj82d00
114 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Are you familiar with the annual reports that are submitted to_Health and Human Services with respect to the constituents of tobacco? A. I'm -- I'm aware that -- that Reynolds and other tobacco companies have to submit those. Q. Is diammonium phosphate or was gaseous ammonia listed as a processing aid, a flavorant, or what? A. I believe they were listed as processing aids. That's how we were using them, but I'm -- I can't be certain for that. That's not -- not my area at the division I work in or anything. Q. And it's your testimony, to your knowledge, that Reynolds has never employed either gaseous ammonia or diammonium phosphate for the specific purpose of affecting nicotine yields or transfer efficiencies of nicotine? A. Correct. MR. MAISTROS: Okay. Can we take a break for lunch? MS. FEE: Sure. MR. MAISTROS: How about one o'clock? HUSEBY & ASSOCIATES (800) 333-2082
Page 109: raj82d00
105 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 phosphate ammonia sheet. Q. Okay. Let!s back up. A. Yes. Q. Are you distinguishing between the use of gaseous ammonia and diammonium phosphate? A. Originally, everything -- when G7A was done, on gaseous ammonia. Q. And then it switched to diammonium phosphate? A. Yes. And that was a combination of diammonium phosphate and ammonia. Q. And how long did Reynolds use diammonium phosphate? A. Well, we're -- we're currently using it right now. Q. So, once Reynolds began using ammonia in some form, they've used it to this day? A. I can't think of any time when we haven't used any ammonia. It's always been around some place. Now, yet, you need to remember that this is not being slathered across all of our products inadvertently and not all of our G7 reconstituted sheet is ammoniated. Some of it is not. In fact, there's only about maybe 25 percent HUSEBY & ASSOCIATES (800) 333-2082
Page 110: raj82d00
103 1 I Q. What was the original reason that 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Reynolds first began using ammonia or diammonium phosphate in its manufacturing process? A. In -- I guess this was late '60s, we needed to have a-- a milder smoke. Our products were relatively irritating. And one of our scientists thought that if you would add ammonia to the -- to the G7, that it might do two things; make the product milder and make the -- make the product milder and have a little bit better flavor associated with it. And so, a-- a -- an ammoniated reconstituted sheet was -- was developed and used for a number of years. There were -- there was varying opinions on how useful this actually was. Q. That's known as G7A? A. Yes. Q. And how long was G7A used? A. years, maybe Q• Oh, boy! It was used for probably 15 more. Maybe 15, maybe 20 years. When did it stop being used? A. Gees, it had to have been probably 8 years ago. Q. Why was it stopped being used? A. Well, there'was enough research that HUSEBY & ASSOCIATES (800) 333-2082
Page 111: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of it that has any ammonia in it at all. Q. And is the.only use of ammonia or diammonium phosphate in the recon process? A. As far as I know,.t.hat's -- that's - that's where it's used. It may be used in one other place. We've done some experimentation on something called CRES -- CRESA, which is a Cut Rolled Expanded Stem process that we -- that we -- we use in -- in some of our brands. And -- and I know we have done some experimentation in looking at using diammonium phosphate on that material. Whether we're -- whether we're using that or not, I'm not sure, but -- Q. Did the switch from gaseous -- is the switch from gaseous ammonia the one you referred to about eight years ago? A. Actually, I think it was less than that. There was a time -- I think we -- we've just gone to looking at liquid ammonia or ammonium hydroxide, aqueous ammonia, in the last four years; maybe three, four years. Q. Did the switch from gaseous ammonia to DAP have anything to do with the fact that the G7 -- I'm sorry -- the gaseous ammonia produced greater mutagenicity results in testing? 106 HUSEBY &_ASSOCIATES (800) 333-2082
Page 112: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 1, 7 18 19 20 21 22 23 24 25 MS. FEE: Object to the form. THE WITNE.%S: Generally, as I mentioned before, we -- pH is not a variable that you can change. It's a response to something that you've changed in the cigarette design or in the tobacco blend. So, it's a -- it's something -- it's a response factor that you -- that you -- that you monitor. BY MR. MAISTROS: Q. Does the smoke pH affect nicotine delivery? A. No. Q. Is there any correlation between smoke pH and nicotine delivery or nicotine of cigarettes? A. Not to my knowledge. yields Q. Does smoke pH affect nicotine transfer efficiency? A. No, it does not. Q. Does smoke pH affect the rate at which nicotine is metabolized by the body? A. I-- I -- I don't think so, but that's only my opinion. Q. Does smoke pH affect the amount of 117 HUSEBY & ASSOCIATES (800) 333-2082
Page 113: raj82d00
116 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nothing else, it is an indicator of some - something has gorle on and that there are differences. (Mr. Sobol enters the proceedings.) BY MR. MAISTROS: Q. Do you know if there's a range of acceptable pH levels that Reynolds is aware of? A. They're generally in the tobacco. If we're considering tobacco pH, there is tobacco -- pH of tobacco will probably go somewhere between about four and a half in terms of some acidic types of flue-cured tobacco to maybe as high as six and a half in terms of some -- some basic tobaccos. And those would be -- burley is basic, flue-cured is acidic. In the smoke, there's a relatively narrow range of -- of smoke pH that has been observed for cigarettes that are on the market, running somewhere between about five six to maybe six two, give or take just a tad on either side, I guess. There isn't a real broad range, is what I'm getting at. Q. Are you aware of any research Reynolds has undertaken to determine how they can affect the smoke pH? HUSEBY & ASSOCIATES (800) 333-2082
Page 114: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. What is levulinic acid? A. Let's see.., It's a -- it's a delta keto butyric acid, I believe, is what it is. It's a -- it's a flavorant. It's used in lots of cosmetics and other commercially -- commercial F products as a smoothing agent. Q. Does Reynolds employ it? A. I know that at one time we did have it as a -- a s a component of some of our top dress in gs. Whether they're still doing that or not, I' m n ot sure, because I -- I haven't been in l that d i vis io n in a ong time. Q. And what was the purpose in Reynolds f l l i i a id? use o ev u n c c A. It was a -- it was used as a -- as part o f a mixture of other compounds in the top dressi n g. Often it was used to take off any sharp nose that might occur. If something was a little irritating, you might want to put some of that in. But there is lots of other different acids that are available, and normally we use very, very low levels of materials and -- as -- for top dressings. And, again, it would only be one part of a -- of a series of materials that would constitute the top dressing. HUSEBY & ASSOCIATES (800) 333-2082
Page 115: raj82d00
1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Did its use have anything to do with attempting to alter the_.nicot•ine yields or transfer efficiencies of cigarettes? A. No, not -- not in -- in -- in the use that we had it in terms of our top dressings. Q. Did the use of levulinic acid have anything to do with nicotine? A. Not in our products, no. Q. Did Reynolds explore the use of levulinic acid for the purpose of affecting nicotine deliveries? A. I -- I would have to say, no, not -- not in that respect, no. Q. What was project XGT? A. XGT was a research program where we were trying to develop some low tar-to-nicotine cigarettes. Q. How did you try to do that? A. There was a -- a number of ways that we were experimenting with. One of the -- one of the ways was to -- to adjust the tobacco nicotine in a blend by using higher -- higher nicotine, levels of burleys and flue-cures that had higher nicotine levels. That can only get you so far, because, I mean, you have to -- to really look into 120 , HUSEBY & ASSOCIATES (800) 333-2082
Page 116: raj82d00
122 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 its research at least to attempt to increase the nicotine levels in its cigarettes? ,A. Yes. And, I remember, our entire purpose of this was to produce a low tar-to-nicotine ratio cigarette. We were doing -- all this was in our experimental research along those lines. Excuse me. There were -- there were several -- several projects at that time trying to determine how to produce a low tar-to-nicotine cigarette. Q. Well, instead of increasing the nicotine, did you look at ways to reduce the tar to arrive at the same result? A. I wasn't involved in -- in any of that research. I'm not sure that that is actually a feasible way to do this; because, as.you mentioned earlier, both tar and nicotine, when you smoke them, there's a certain relative ratio of tar-to-nicotine that goes into the smoke. And unless you're burning a lot more material that had low nicotine in it, I don't know how you would adjust -- how you'd be able to, because, again, that's a response variable, not something that you can control. Q. The tar levels of cigarette -- or 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 117: raj82d00
121 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17" 18 19 20 21 22 23 24 25 the inventory to find tobaccos we had bought over the years that were high. in .nicotine. And then other ways were, that they explored, were use of nicotine levulinate as a - as an additive to -- to the reconstituted tobacco sheet, I Q. A. You can prepare nicotine levulinate in that manner. You can take nicotine and titrate or add levulinic acid to it until you have a have A. That is what we call a nicotine salt. believe. Was is nicotine levulinate? Like nicotine in its,pure form? ratio of either one, two, three levulinic -- levulinic acid molecules per -- per molecule of nicotine. Q. 0 Reynolds did look at the use of levulinic acid as a means of controlling the nicotine levels in its cigarettes? A. We used it as a-- as a -- as a means to increase the level of nicotine in reconstituted sheet and we blended that with our other tobaccos. Q. So - A. I don't know if we were controlling anything. Q. Reynolds did use levulinic acid in HUSEBY & ASSOCIATES (800) 333-2082
Page 118: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tobaccos varies, doesn't it, from tobacco to tobacco? A. I'm sorry, sir? Q. Does the tar level of different tobaccos vary? A. Only to a small extent. It does not -- not over -- it is not over a large range. It's probably less than a milligram change between the different tobacco types. Q. And were -- were these efforts to lower the tar-to-nicotine ratios all related to this Froggatt Commission's findings? A. That and the earlier commission. I can't remember the name of it. It was a -- it was a prelude to the Froggatt Commission and also to the work that was.done in the United States. NCI did a lot of work on that and -- and C3ori voiced his opinions in the United States on this, as well as guys like Russell even said, this would be a good thing to do, and, again, Wynder said that. Q. When did one of these groups of people first come out with the idea that it would be a good thing to do to lower tar-to-nicotine ratios? I think that was in the early '80s, 123 HUSEBY & ASSOCIATES (800) 333-2082
Page 119: raj82d00
1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in time those in charge still believed it had flavor benefits? A. Yes, yes. Q. Did the use of either gaseous ammonia or aqueous ammonia have anything at all to do with the nicotine or the nicotine content of the tobacco? A. Yes. Q. And what was that? A. The -- when you prepare G7 now, and there's a number of different kinds of G7. There -- there was probably a dozen kinds, those that used diammonium phosphate or ammonia or both, the -- the final sheet that comes out is lower in nicotine than the -- the -- the sheet -- the sheets that are prepared without either of those materials. Q. How's the nicotine transfer efficiency compare of those sheets with those that do not use those materials? A. In my experience, they're about the same, sir. They're low already. The nicotine transfer efficiency for reconstituted sheet is normally in the range of 6 percent, give or take a little bit. And so, you're already at a relatively i HUSEBY & ASSOCIATES (800) 333-2082
Page 120: raj82d00
109 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 differential was basically the same. And so, we.decided to use gravity to feed this material rather than pressure pump to pump the -- the gaseous ammonia into the thing. It was an engineering decision. Q. And.the aqueous ammonia is used only in the recon process? A. I think that's correct.. That's the only place where we used them. Q. Has that always been the case? A. Using liquid ammonia -- using aqueous ammonia in the recon? Q. Yes. A. No, we've only gone to aqueous ammonia on the recon since about four -- four years ago, I guess. Q. I know, but it's only been used on the recon. There's no other use Reynolds employs aqueous ammonia? A. There -- I-- I really think that was the only place where we ever had any commercial production for -- for tobacco treatment. I think that was the only place we ever used it. Q. And when they switched from gaseous ammonia to aqueous ammonia, I assume at that point ~ ~ -j m ~ N (li Ql I HUSEBY & ASSOCIATES (800) 333-2082
Page 121: raj82d00
125 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 commissions came out and also said that of the two different things, tar varsus~nicotine, that it would be most beneficial for -- to have reduced tar at -- at a nominal nicotine, there was additional work being done then. It would have been good work to be done. Q. Why was -- A. -Advantageous. I'm sorry. Why was nominal nicotine thought to be required? A. There.was a belief that -- that if you were -- if you reduce the -- the smoke nicotine, that people might not accept those products. And there's a lot of good evidence that -- that bears this out. I mean, one -- one example is -- that comes to mind is the -- the Philip Morris product, No Nic, I guess, or a Next. It was very difficult to produce the same type of smoke flavor that you had in a conventional cigarette when you had lower levels of -- of nicotine in there, mainly because, you know, putting a-- a flavor together that is from bottles off a shelf is not the same as producing a complex 25 flavor from the combustion pyrolysis of tobacco HUSEBY & ASSOCIATES (800) 333-2082 ~ ~ ~ ~ m
Page 122: raj82d00
127 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 produce some type of smoke flavor. None of those.panned out well in terms of producing a - a good smoke flavor. They were always lacking in -- in some of their -- the notes associated with it. Q. Did you work on the Eclipse project? A. Again, just -- just when they had an issue, they would pull some of our scientists in and we would give them our opinions. I never did any real active work on it, no. Q. Did you -- have you done any work on any special new products that Reynolds is attempting to develop? A. Yes, I -- I've worked on exploratory products over the years. Q. What are some examples? A. We worked on a -- prototypes that -- that had low sidestream smoke, which are now -- we've -- we've introduced some of those things - have low visible sidestream. Q. Is one of those being marketed in Japan? A. Yes, some of that technology, sir. Q. And what's the name of that cigarette? HUSEBY & ASSOCIATES {800) 333-2082
Page 123: raj82d00
124 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 early to mid-',80s, somewhere in there, but I could be wrong. It would have,been earlier than that. Q. Are you aware of any published reports where anyone suggested lowering tar-to-nicotine ratios before 1980? A. I can't remember right now, sir. Q. And would it be your testimony that any research I showed you from the '70s with respect to looking at lowering tar-to-nicotine ratios would or would not have anything to do with the suggestions of Froggatt, NCI, and others? MS. FEE: Object to the form. THE WITNESS: I missed the first part of your question. I'm sorry. BY MR. MAISTROS: Q. I take it your testimony is that any document I show you with respect to how Reynolds was spending money trying to reduce tar-t,o-nicotine ratios was all in an effort to incorporate the suggestions of Froggatt, NCI, or others to reduce tar-to-nicotine ratios? A. I think there was a lot to do -- yes, I-- I-- I think that a lot of the work was directed at trying to further reduce the tar and nicotine. And then when the -- when the -- these Ln HUSEBY & ASSOCIATES (800) 333-2082
Page 124: raj82d00
1 2 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was done that showed that, you know, this wasn't the greatest thing that__ever was. And there was some people that really loved this that were in -- in positions in the company that sustained its use, that would -- that it's continued to be used. And eventually we did.some more work on that area and thought that, you know, maybe it really wasn't that important to have this in there and it was additional process stuff. After -- after the materials was made -- were made, it had to be passed through this same KDN unit that was deteriorating. And we thought, well, maybe this isn't the best thing in our use of our time and --.and energy. And we tested•products that had G7 that had ammonia and -- ammonia in them in other -- other ways. And one of the things that we had done during the time was looking at trying to make a stronger sheet. And one way to make a -- a much stronger reconstituted tobacco sheet is to use ammonia and diammonium phosphate as a processing agent. And that was -- since they both contained some ammonia, we thought, well, maybe we don't need to be using this G7A. Maybe we'd get the same benefit in terms of flavor with this diammonium 104 ,HUSEBY & ASSOCIATES (800) 333-2082
Page 125: raj82d00
115 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Is that okay? MS. FEE:.Uh-huh. THE VIDEOGRAPHER: Off record at 12:17 p.m. (Recess 12:17 p.m. to 1:14 p.m.) THE VIDEOGRAPHER: Back on record at 1:14 p.m. •BY MR. MAISTROS: Q. Doctor, what if any of your work involved looking at pH and its role in the smoking,_ process? A. Over the years, I -- I can't remember any particular work objective that had to deal directly with work pH -- work pH -- with smoke pH or tobacco pH, but it was used as an indicator in a number of different studies that we did. We -- we analyzed materials for pH. Q. Do you know what role pH plays in the smoking process? MS. FEE: Object to the form. THE WITNESS: Well,,the -- the whole concept of smoke pH is -- is not a well-understood subject. There's lots of common -- there's lots of opinions on -- on what -- what it really is, but if -- if, for HUSEBY & ASSOCIATES (800) 333-2082
Page 126: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I believe the name of that in Japan is Pianissimo. Q. And what does Pianissimo mean in Japanese? A. I don't think it means anything. I think it means little in Italian, if I'm not mistaken. Q. Has Reynolds introduced this low sidestream smoke cigarette in America? A. Yes. Q. As what brand? A. Excel. I think it was introduced as Vantage How did it do? A. It didn't do very well at all. Q. And,did you find out why from your consumer test? A. Well, one of the things is, it didn't taste very good and the ash -- the ash was very bad, a bad ash. It would -- the ash would fall off and then get on your clothes and -- very annoying. Subsequent to that, before the introduction of Pianissimo, some of those problems were -- were reduced. Q. What other projects did you work on? HUSEBY & ASSOCIATES (800) 333-2082 128 1 I
Page 127: raj82d00
118 1 2 3 4 5 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 free nicotine in tobacco smoke? A. Theoretically';.yes . Q. In what way? A. You know, if -- if there was a -- a large -- a large amount of a -- of a- f a high pH substance in the smoke, you would drive the amount of -- of ionized nicotine to a -- a un-ionized nicotine to -- for your base. That normally does not occur, though. I mean, normally cigarettes would be very, very unpalatable at that high a pH. Q. Have you seen Reynolds' consumer studies which analyze pH levels to determine consumer acceptance of certain brands of cigarettes or styles of cigarettes? A. It's normally not one of the things that we analyze. We -- we do analyze for a series of, like, FTC tar, you know, in nicotine CO, C02 for menthol, smoke menthol, but that's normally not one of the things that we analyze before going out for a consumer test. So, there would -- I -- I don't think there would be any data on that. Q. And, again, smoke pH is not a design parameter of your cigarettes? A. That is correct, it is not. HUSEBY & ASSOCIATES (800) 333-2082
Page 128: raj82d00
129 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Of course I -- I worked on XB, XGT, GT. Those were the low,tar-to-nicotine prototype developments. Q. Now, as I understand from your testimony, Reynolds has been unsuccessful in developing a low tar/nicbtine ratio cigarette or is that incorrect? A. No, that -- that is correct. Q. And what year did they start working on that after the Froggatt Commission came out? A. Well, my -- my recollection was, I think it was in the mid-'85 -- I mean -- '85, somewhere in that range, when we started working on it. I've worked on a lot of projects over the- years and I usually don't -- I don't keep up with the year dates. I'm sorry. Q. That's okay. In any event, the work that you began in the mid-'80s on low tar-to-nicotine ratio cigarettes has not resulted in a commercially suCcessful cigarette, correct? A. That is correct. Q. Is that research still going.on today? ~ m A. No, it isn't; no, it isn't. 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 129: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17' 18 19 20 21 22 23 24 25 made, I guess, during those '80s. Early in '80 there was something called the Gori cigarette, and there was some unique blends and cigarette construction parameters that were put together to try to produce this -- this -- these levels of smoke components that Gori said were -- I think he had a paper called -- "Prescription For a Safe Cigarette." And he had listed some -- some smoke component levels that -- that would be optimal to reach. And we went and tried to prepare some prototypes that might approach that. Q. were any of those commercially sold? A. No. Q. So, has Reynolds produced and sold commercially a cigarette which Reynolds specifically designed for the purpose of being a "safe" cigar,ette? ' A. Not that I know of, no. Q. I know that Reynolds does tests -- Ames tests, for example,.on new prot,otypes to compare it to a traditional cigarette. Do you know if Reynolds ever did Ames tests on just their ordinary everyday cigarettes that they sold, as opposed to comparing it to a test product? 131 HUSEBY & ASSOCIATES (800) 333-2082
Page 130: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 doing versus somebody else. It would make sense. Have you aver.worked on any projects to specifically reduce any compounds in cigarettes -- A. Yes. Q. -- or smoke? A. Yes, I have. Q. Which compounds? A. Generally, compounds like some of the controversial compounds is what we call them. And they're like ACN, ammonia, NO. Q. Ammonia what? A. NO, and then ammonia, carbonyl compounds, and hydroxybenzene compounds. Q. These efforts to reduce the ammonia NO, is that similar to ammonium -- diammonium phosphate? MS. FEE: Objection. I think you misunderstood his answer. MR. MAISTROS: Yeah. BY MR. MAISTROS: Q. Tell me again what are compounds of concern you've worked on? A. I. -- I believe the question was, have I worked on research to try to reduce certain 133 J HUSEBY & ASSOCIATES (800) 333-2082
Page 131: raj82d00
126 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that contains nicotine. Q. These nic¢tine-analogs you talked about earlier, do they mimic the taste of nicotine? A. Excuse me. Only -- only certain ones that contain nicotine. Certainly, the nicotine salts with nicotine as a component would produce similar -- excuse me -- similar -- similar pyrolysis products. Other nicotine analogs that had a change perhaps in the substituents on the rings, I have no idea how they would turn out, but_ I wouldn't -- I wouldn't think that they would have the same type of flavor profile that -- that tobacco nicotine would give. Q. Has Reynolds produced flavorants in an effort to duplicate the taste of nicotine? A. There were efforts at one time to produce a -- a "no nicotine" cigarette. Some of the prototypes, it started out with looking at some of the older work from the Riussiane where they'd use things, like, pyrolysis of complex, natural products like, leaves, and things like that to -- to see if they could produce any of the -- a base flavor that would have similar to tobacco smoke. And, then, on top of that, we applied normal conventional top dressing to see if we could HUSEBY & ASSOCIATES (800) 333-2082
Page 132: raj82d00
132 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes. A number of times, if you have a -- a new flavor, for axample, that you want to use on.-- on a Camel Light, you will test, like, the reference, the Kentucky reference, because that's always a part of the Ames test and then the current Camel and then the Camel with the adjusted top dressing. And you will -- so, it is -- I mean -- you -- you will find data and we have done on -- on some of our commercial cigarettes out there. Q. That's comparing a new product or a -- a product that contains a new flavorant to an existing cigarette, correct? A. Sure. Q. But does. Reynolds know, for example, what the Ames numbers would be on all the cigarettes it sells? A. I'm -- I'm not sure. They -- they may. And they may have done those tests. I'm not sure. Q. Does Reynolds do Ames tests on competitors' cigarettes? A. I'm not sure about that, but I would -- I would assume that they do, yes. For the same reason where you'd like to know how you're HUSEBY & ASSOCIATES (800) 333-2082
Page 133: raj82d00
135, 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 believe there would be more ammonia in the tobacco that is pulled out of the ground and burnt or the tobacco that is processed with.the use of ammonia and burned? A. I would have to say that that would depend on the type of tobacco that you're burning. Q. Okay. Let's take two specific tobacco leaves off the same plant that have the same ammonia content. One of them goes through the process and has ammonia added during the processing and one doesn't. And you burn both leaves. Which one do you think would have more ammonia in the smoke? A. Again, it depends on the type of tobacco. If this was burley tobacco, there would be probably more ammonia in the smoke on a process burley; but if it was flue-cured, there would be less in the smoke. Q. I know that there would be less in the flue-cured, as opposed to the burley, but if you took a burley with the exact same ammonia content in it and added ammonia in the process, don't you think you'd see more ammonia in the smoke once that tobacco was burned? A. It really depends on how much ammonia HUSEBY & ASSOCIATES (800) 333-2082
Page 134: raj82d00
140 1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes, it can. Q. As does the type of plug wrap? ,A. Only when the cigarette is -- uses a perforated tipping. Q. Okay. And the manner in which a person smokes can affect nicotine yields? A. Correct. Q. Now, all those factors Reynolds has studied over the years, is it your testimony that none of those have been analyzed with specific design criteria in mind to affect the ultimate nicotine delivery of a cigarette? They're just known? MS. FEE: Object to the form, that Reynolds has researched all of those things. BY MR. MAISTROS: Q. Assuming that Reynolds has researched and knows the effect those factors have on nicotine yields,,is it.your testimony that none of that knowledge has been incorporated in a commercially sold cigarette? A. Well, we do -- when -- when we have consumer results that tell us that we have a problem with our -- the amount of strength of our. cigarette or we are trying to produce a cigarette HUSEBY & ASSOCIATES (800) 333-2082
Page 135: raj82d00
based on consumer wants that would have a lower tar 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 yield, we will use some_.of those technologies that you have talked about there, some of those ways to bring the -- the tar and nicotine yield of a cigarette back into line. Now, in terms of our research efforts in terms of the XGT and GT programs, XB, we were. aware of different ways that we could try to reduce tar-to-nicotine ratio. And some of those things that you mentioned there were.attempted in our research prototypes. Q. With the hope of eventually incorporating them in a commercially successful cigarette, I would assume? .A. That is normally the aim of what we were trying to do, yes. Q. Because your company makes more money if it sells more cigarettes, correct? A. And it was -- it was -- it was a -- it was a -- something that the scientific community and the medical community thought would be the right thing to do in terms of producing a low tar-to-nicotine cigarette. And certainly in keeping with our -- the work that we've been doing since 1954 in terms of reducing the tar and 141 Ln ~ J J m I HUSEBY & ASSOCIATES (800) 333-2082
Page 136: raj82d00
143 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 throughout its research memorandum to nicotine satisfaction. Have you heard that term used? MS. FEE: Object to the form. Do you have a specific document you're talking about? MR. MAISTROS: Oh, we will get to it. BY MR. MAISTROS: Q. But do you know -- have you ever used -- heard the phrase "nicotine satisfaction"? A. Yes. Q. And what does that mean to you? A. I -- I'd hate to -- it's used -- it's used all of the time. Unfortunately there's no real strong definition of it. I must have asked the same question hundreds of times. It's generally a -- a-- a cigarette, what. I -- my understanding, it's generally a cigarette that would-°.'.be consumer acceptable at a particular tar and nicotine level. Q. Well, does the satisfaction relate to a sensory notion of taste or does it relate to a chemical notion or neither or both? A. I think that it has to do with a number of factors: One of -- there's a sensory HUSEBY & ASSOCIATES (800) 333-2082
Page 137: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 We now know, flavorants we add to our -- our cigarettes at a higher rcate,.-to -- to use less of them. But we never found a way to -- to do that and really don't know what's causing that. Q. And it's your testimony that Reynolds was looking at ways to transfer all of its flavorants as well as nicotine? A. .0h, yes. Q. What research were you involved in that looked at any flavorant -- transfer rate of any flavorant other than nicotine? A. I have -- I've done a lot of work in terms of menthol, looking at some of the same factors in terms of cigarette design, moisture, and casing levels, lots of different things that we thought might be useful in terms of transferring more menthol to the smoke so we could use less of it, and nothing seemed to work out. We could not find a good way to do that. Q. So, Reynolds has not figured out how to-transfer -- increase the transfer efficiency of any flavorants? Ln - ~ A. That is correct, except for the -- o ~ k you now -- I did mention this morning, if you ~ w remember, the -- that one invention disclosure that HUSEBY & ASSOCIATES (800) 333-2082
Page 138: raj82d00
1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nicotine yields of our products. Q. And when did Reynolds first attempt to begin reducing the tar and nicotine yields of its products? A. We started that work in about 1954. Q. Was that voluntarily or in response to the concerns of the medical and scientific community? MS. FEE: Object to the form. THE WITNESS: Early in the -- in that early part of -- of -- it was a competitive thing that we were doing, since we found that there were other filtered cigarettes being -- you know -- that were already on the market in Europe and were being produced in the United States. And there was a,, certainly, a-- a need for reduction based on the consumer appeal of -- of Kent and some of those European brands that were being smoked. o, there was an appeal there and it was important for us to get into that market. BY MR. MAISTROS: Now, you refer or Reynolds refers 142 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 139: raj82d00
144 1 3 4 5 6 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 factor obviously associated with it. There's a - a ritual associated wit1l,it and there's a, you know, some mild pharmacology -- pharmacological effect associated with the cigarette smoke. And although those things together, which we were never really able to put our handle on, comprised what was, in my -- in my, you know, reading and talking with people associated with this, what nicotine satisfaction was. It was also called consumer satisfaction. Q. The satisfaction, is that something that could be defined objectively or is it subjective? A. This was always -- that's part of the problem, because there's no way -- there was always a subjective rating and it wasn't something that you could turn a knob on a machine and -- so, it was very difficult to get a handle on. First, to know::,what it was and then how to attack the problem. Q. What does nicotine transfer efficiency have to do with nicotine satisfaction? MS. FEE: Object to the form. It assumes it has anything to do with it. THE WITNESS: Well, I'm not really HUSEBY & ASSOCIATES (800) 333-2082
Page 140: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 you're processing with, sir. Q. Why is amn1onia,a compound of concern? A. I'm not sure. Q. You don't know of any adverse health effects related to ammonia in the smoke? A. Not in the manner that we're using ammonia. Q. In your 20-some years at Reynolds, are you aware of any additive process or technique that was commercially employed to affect nicotine yields of the tobacco? MR. MAISTROS: Bless you. THE WITNESS: Bless you. MS. FEE: Thank you, thank you. THE WITNESS: Yes, I do. BY MR. MAISTROS: Q. And what are those? A. The KDN process that was used to to take out the nicotine. Q. Any others? A. No. I think that was the only process that -- that I can remember that we actually, you know, wanted to do something with the ammonia in terms of nicotine. 25 1 Q. And so, we're including everything -- 136 , 333-2082 HUSEBY & ASSOCIATES (800
Page 141: raj82d00
1 sure exactly if it has anything to do with -- with -- with.t~he whole concept of 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of consumer satisfaction or nicotine satisfaction. BY MR. MAISTROS: Q. Was there ever a concern at Reynolds that if you had developed this cigarette that had reduced tar-to-nicotine ratios, that you would need to increase the nicotine transfer efficiency in order to have a consumerly acceptable cigarette? A. No, because since we didn't know how to do it, it wasn't even -- it wasn't -- wasn't a concern. I mean, we didn't know how to do it. So, it really never raised its head as a concern. Q. And you didn't try to learn how to do it? A. There were -- there were, you know, experiments that were run to try to increase transfer rate, but we never knew how to do it. Q. But why were you looking to do it? A. Just as our -- as I mentioned earlier in the day was, you know, most -- most flavorants transfer at a rate of about 10 percent. Why that happens, I have no idea. It would be nice to be able to transfer flavorants -- tobacco flavorants. i N j HUSEBY & ASSOCIATES (800) 333-2082
Page 142: raj82d00
134 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 compounds in the smoke, and the answer was, yes. The compounds that -- tYlat I was telling you there are some of the ones that we try to reduce, which are ammonia, hydrogen cyanide, NO, carbonyl compounds, hydroxybenzenes. MS..FEE: There was ammonia, NO. BY MR. MAISTROS: Q. Okay. Ammonia is a standalone compound, correct? A. Yes, air. Q. Couldn't you reduce the ammonia in the smoke by not adding ammonia to your a7? A. No, not necessarily, because ammonia is a naturally occurring smoke component and there are lots of other factors that -- that can account for decreases in ammonia. Q. Okay. Ammonia appears in tobacco when you pull it out of the ground, right, before it gets to your plant? There is ammonia naturally occurring in the leafj is there not? A. Yes. Q. And then there's ammonia that Reynolds adds in the.tobacco process, correct? A. In some of our processing, yes. Q. Everything else being equal, do you HUSEBY & ASSOCIATES (800) 333-2082
Page 143: raj82d00
150 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 And -- and -- and then after that, because, again, we had.hit the point of state of the art in terms of technology in terms of identifying smoke components, we -- we focused a lot more effort on -- on nicotine. I think it's probably equal --•equal amounts there, over the -- the last 30 years. Q. How many different compounds are there in tobacco? A. At last count, I think there -- they had analyzed about 1,900, 2,000 in the tobacco. Q. Out of those 1,900 to 2,000 compounds, which compound has received the most research at Reynolds? In the tobacco, I would say nicotine, probably. Q. And how many compounds are in their tobacco smoke? A. I would say over 4,000, way over 4,000. Maybe 4,500, 5,000, somewhere in there. lot -- lots of compounds. Q. And which compound has Reynolds researched the most in the tobacco smoke? A A. I -- I'd say there have to be a class of compounds. Probably the ones that they've put HUSEBY & ASSOCIATES (800) 333-2082
Page 144: raj82d00
137 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 are you also including in there that there are no blending techniques that,have been employed to that have the purpose or effect of affecting the nicotine yield of cigarettes? MS. FEE: Object to the form. THE WITNESS: The -- you can always adjust nicotine by the inherent amount of nicotine in tobacco that you would use in a blend. That's a-- that's a simple way of doing it. BY MR. MAISTROS: Q. I've seen over the last couple months various documents where Reynolds was researching factors that affected nicotine yields of deliveries. A. Uh-huh. Q. Do you know what I mean by that? There's research,.we'll get to them. There's papere-in here where Reynolds was looking at how moisture affected nicotine yields, how fertilizers affected nicotine yields, how packaging affected nicotine yields, how filters.affected nicotine yields. Are you aware of that research? MS. FEE: Object to the form, HUSEBY & ASSOCIATES (800) 333-2082
Page 145: raj82d00
1 2 3 4 6 -8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 factors, such as fertilizers, the moisture content, the construction paramet.ers,..the burn rate. Does that affect nicotine yield? , A. In some respects, yes. Q. And the porosity and the ventilation affects nicotine yields? A. Yes. Q. And the type or length of filter affects nicotine yields? A. Yes. Q. And the compression of the filter affects nicotine yields? A. I'm not certain what you meant by the compression, sir. .Q. Okay. Are you aware of the the -- what's the fiber in a filter called? A. Cellulose acetate. Q. Are you aware that the fibers in those filters are compressed to different levels? A.~ Oh, I -- I understand what you're taking -- yes, I do know that. Q. And the compression level of those filters, I'm not sure that's the technical term, the compression ratio of those filters can affect nicotine delivery; can it not? 139 m HUSEBY & ASSOCIATES (800) 333-2082
Page 146: raj82d00
149 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 it. As I mentioned before, I think there's a - there's a sensory aspec.t• of . i-t . I -- I think that there is a -- a ritual aspect of it and I think there's a mild pharmacological action to the tobacco smoke that has to do with this whole consumer satisfaction, nicotine satisfaction thing. Q. You will agree, will you not, that Reynolds explored the role that nicotine played in the smoking process from the time you joined them till the present? A. There have been research efforts, you know, on -- on tobacco nicotine, smoke nicotine, lot of aspects of nicotine ever since I've come to the company, yes. And I think it's important that we understand our products and the materials that we use in our products. Q. You think there's been•more research on nicotine or tar? A. I think in the early days there was more research done on tar, and that's probably like from 1954, '53-'54, whenever the research thing got started, through about the late '60s, early '70s, much more on tar than there was on -- on nicotine. And in that -- a lot of that work was to the identification of the smoke components. I HUSEBY & ASSOCIATES (800) 333-2082
Page 147: raj82d00
138 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15. 16 17 18 19 20 21 22 23 24 25 compound. BY MR. MAZSTROS: Q. Are you aware of any of that research? A. There's a -- there's a lot of research in terms of how, for example, in the agriculture area, how you can adjust the amount of nicotine that's in the plant by adjusting the fertilization rate. That's -- that's well-known in the literature. There are -- it's well-known in the literature that moisture levels in tobacco affect the smoke delivery rates of nicotine in the smoke. That's -- that's been known for years. And on the other aspects that you mentioned in terms of cigarette construction paramet'ers, yes, there's been work done on that and it's been documented very well in the.literature over the years how those factors can affect smoke nicotine yield. Q. I -- I guess I'm going to get to this eventually. There seems to be an awful lot of research on different factors that affect nicotine yield, and I can go through the list if you want and ask you if you're familiar with them. You've mentioned agricultural HUSEBY & ASSOCIATES (800) 333-2082
Page 148: raj82d00
151 1 most of their effort in has been in terms of these 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 controversial compounda... We~have spent just a tremendous amount of -- of effort in terms of looking at those. And, you know, obviously nicotine was one, but it's -- it's -- it's so simple to measure, that we have not spent a lot of research time in terms of analyzing that. Those ones are much-more difficult to -- to get at and we spent a lot more time trying to ferret that out. Q. What is:the Nicotine Analog Research,, Committee? A. I don't -- I don't know if there was a committee actually called that. There was a -- it was -- there was several committees that had nicotine in them. One of the committees was called Committee on Nicotine Analog Research and the other committee was Nicotine Review Committee, I think. Q. What were the purposes of those two committees? A. They were different in terms of their -- what we were doing. The CONAR Committee was -- looked at -- it -- nicotine analogs. Ln - ~ Initially what we were trying to do.is find out how ~ many nicotine analogs were -- I mean -- it was a research thing, going back in the literature and 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 149: raj82d00
1 2 3 4 7 8 9 10 11 12 13 18 19 20 21 22 23 24 25 smoke A. Primarily nontobacco material,e material. .Q. Does this alternate filler material -- it's filler, right, not filter? A. Filler, yes. Q. Does this alternate filler material contain nicotine? A. It contains tobacco. A portion of it contains tobacco. Q. And what else is in it? A. Calbium carbonate, rice flour, diammonium phosphate, potassium nitrate, potassium carbonate. Q. What is the goal of this project? A. The goal is to produce a low biologically active cigarette. Q. Low compared to what? A. Kentucky iR4F, referenced earlier. Q. Is this going to be a burned material or a heated material? A. Burned material. Q. What's the, if it's been determined, the nicotine yield of this product? A. When smoked by itself, it is about one-tenth of a milligram per cigarette. 154 HUSEBY & ASSOCIATES (800).333-2082
Page 150: raj82d00
130 Q. When did it stop or when was it 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 abandoned? .A. I guess it was about '89: We -- we were never really able to get a low T/N -- a low tar/nicotine ratio product that was -- that had enough tobacco taste associated with it. There wa.s always an artificial note associated with it. .The people -- we had -- there was a lot of artificial flavor in it and then it was -- it was either -- and there wasn't enough tobacco taste. And I -- I -- I really, I mean even today, I really don't know how we could have fixed that. I think we -- we exhausted the -- the technology base at the time and -- and, you know, chances are, we might try to do this again, as soon as we can get some new -- newer technologies developed to see if we can improve the deficiencies we had in that, which were tobacco taste and reduction of artificial taste. Q. Are you aware of any specific cigarette projects that were undertaken for the purpose of developing what would be considered a safer cigarette? A. There -- there -- there was some research -- some prototypes -- research prototypes HUSEBY & ASSOCIATES (800) 333-2082
Page 151: raj82d00
156 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Well, since these are research prototypes and nobody really has ever smoked these outside myself, I -- I mean, I don't know. I Q. Why is Reynolds attempting to develop a low biologically active cigarette? A. This -- well, we believe this is the responsible thing to do. We have --'we have an Eclipse prototype or we have Eclipse cigarettes out there. It -- it's a nonburned back cigarette. You missed.some of the rituals associated with smoking with that and it did have some deficiencies in terms of its lightability and its taste. And it would be -- might -- you know -- there's -- there is a-- there's a place out there, they believe, for people that would like to have a cigarette that was -- had -reduced biological activity, but had a burn down that was -- that -- that you could burn and you could treat like your normal.cigarettes. Q. Have any marketing plans been developed for this cigarette? A. I'm not sure, sir. Q. Do you know.if it's going to be advertised as a less biological activity cigarette? A. I do not know. I HUSEBY & ASSOCIATES (800) 333-2082
Page 152: raj82d00
147 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 we put out, and that does appear to increase the rate of materials, smoke generated. because there's no sidestream Q. Did you ever work with Michael Shannon? A. No, I never did. A. Oh, yes. Did you know of him? And what was his position at Michael was hired right -- right after I was hired. And he worked at a number of positions in R&D and in manufacturing. And - - and then he came back to -- to R&D after his couple years of manufacturing. None of those times did I have any direct relation -- any direct relationships with him. working Q. So, you have no knowledge of his either his credibility or the nature of his work? him? A. Not really. Q. How about Tony Colucci? Do you know A. No. I've only heard of the name. Q. And where did you hear of the name? A. There was -- you know -- both in HUSEBY & ASSOCIATES (800) 333-2082
Page 153: raj82d00
157 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1'7 18 19 20 21 22 23 24 25 Q. Do you know if Reynolds has ever advertised a less or reduced biological activity cigarette as such? A. No. I -- I-- no, we have none. Q. Do you believe that a cigarette that has less biological activity is a safer cigarette? A. I -- I'm not sure. I mean, certainly, I think there's -- they would have less risk. You know, everything being equal on an FTC tar bases, but it really depends on how the consumer uses the product. Q. Do your ultra low products have less biological activities than your full flavor products? A. Not that I know of, no. Q. What is the health benefit of an ultra low product as opposed to a full flavor product? MS. FEE: Object to the form. THE WITNESS: I'm sorry. BY MR. MAISTROS: Q. What's the health benefit, if any, of Ln ~ an ultra low product compared to a full flavor m product? A. I don't -- I don't know if there is HUSEBY & ASSOCIATES (800) 333-2082
Page 154: raj82d00
1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 a -- a -- you know -- that they were produced, because there were, you_.know,~..some health benefit. We certainly didn't advertise it as such. There are people that do like and will only smoke ultra low tar prototypes. So, there is a consumer desire for something that had less flavor and less taste associated with it. Q. Have your consumer.test results told you whether or not the people who smoke ultra low cigarettes believe they are "safer".? I'm not privy to a lot of those marketing information that might have been gathered, sir. Q. But you -- you say there is research out there that indicates people wanted a cigarette with less flavor? A. We have been -- you know -- when we produced the NOW cigarette, there was a trend to producing lower and lower tar cigarettes, and that's why we did that. There was obviously a need for that. And it -- and it sells out there. So, we -- we have been producing cigarettes that have lower tar and nicotine yields and we had a technologist to do that. It was -- it was the right thing to do. 158 HUSEBY & ASSOCIATES (800) 333-2082
Page 155: raj82d00
159 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. But you don't know if there are any ..cigarettes? health benefits to those A. I'm -- I'm not -- I'm not -- I have no medical expertise in terms of this kind of thing. Q. But you do know there is or you don't believe there's any less biological activity related to those cigarettes? A. I don't think there -- there would be. Again, it -- it truly depends on how you're measuring biological activity. Q. Ames test, would there be higher or lower Ames numbers for an ultra low cigarette versus a full flavor? A. I think there have been literature in the -- scientific literature that would say that the Ames activity is higher for the ultra low tar cigarettes compared to normal full flavor cigarettes. Then, again, I've seen just the opposite also where there's no difference. Q. Have you seen any research which indicates that there is lower Ames activity for the Ln ~ ~ 'i ultra low than a full flavor? m ~ w A No I have not seen that . , . m rn Q. So, all the research indicates it's I HUSEBY & ASSOCIATES (800) 333-2082
Page 156: raj82d00
148 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 conversations that I had with Sam Simmons. I think Sam must know him. And_.thenthere was things in the newspaper about Mr. Colucci. Q. How about Mr. Baumgarner? Do you know him? A. Do you -,- do you have -- do you have a first name on that, sir? Q. I will after we take a break. It doesn't ring a bell? A. Well, there's -- there's a Baumgarner. It's a manufacturing company that we use a lot. Q. Joseph. A. Joe Baumgarner? Q. Yes. A. No. There is a manufacturer called Baumgarner that we use, though, that makes filters. Were you ever advised to use the word "nicotine satisfaction" to substitute for the habit-forming or addictive qualities of nicotine? A. No. Q. Does nicotine satisfaction have anything to do with the pharmacological effects of nicotine? I -- I think it must have a piece of I HUSEBY & ASSOCIATES (800) 333-2082
Page 157: raj82d00
162 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I worked, I think, in the -- it's very difficult to say, laecause I think I got transferred somewhere close to this time period, but I believe I worked in the Tobacco Division and Mary was in charge of the Smoke Division. Q. And what was the difference? A. In the Tobacco Division, a lot of. research was done on tobaccos; and the Smoke Division, a lot of work was done on,cigarette smoke, cigarette smoke condensates. Q. All right. And this third paragraph refers to a literature review you conducted. Is that in reference to the literature review you previously testified about? A. Yes, as -- that's -- that's the literature review that they're talking about here. Q. On the fourth sentence into that paragraph is Doctor -- it begins with Dr. Perfetti. Could you read that out loud? A. "Dr. Perfetti has ordered a pyrolysis-gas chromatograph combined with a Varian which we used in the study of factors influencing nicotine delivery efficiencies." Q. And when did you start at Reynolds? A. In October of 1977. HUSEBY & ASSOCIATES (800) 333-2082
Page 158: raj82d00
1 I Q. So, you anticipate adding regular 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tobacco to this product?- .A. Yes, we do add regular tobacco to this prototype. Q. And what's the total nicotine yield? A. Smoke nicotine yield on the -- on the 10 milligram prototypes that we've made, for example, is about .45 milligrams of nicotine per cigarette. Q. Where does that fall in the range of. RJR cigarettes? Well, in terms of tar -- tar, it's -- it's in a full flavor low tar range. Q. How about nicotine? .A. In terms of nicotine, it falls into a -- the ultra low tar range. Q. How did you arrive at the .45 milligrams of nicotine per cigarette? Is that by chance or design? A. That's a result of the -- of the the cigarette that was developed. That's all, you know. Q. There's no number by -- by which Reynolds would say, "That's too low, it will never sell"? 155 m I HUSEBY & ASSOCIATES (800) 333-2082
Page 159: raj82d00
I 1 2 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 aspect of it, and what factors were important in terms of cigarette design could be modified to give a better impression of the smoke in terms of our acceptance. Q. Was this particular work mentioned in this memo in the third paragraph related to the taste properties of nicotine or the pharmacological properties of nicotine? A. Neither. It was to deal with the physical properties of nicotine. Q. Could you read the last sentence of the third paragraph out loud? Out loud. A. Yes. "Differences in pharmacological properties of D- and L-nicotine and their salts has suggested that the release of -- the release and delivery of both isomers should be examined in studies of means to control tar-to-nicotine ratios and to increase nicotine impact." Yes. Q. And what does that sentence mean in lay terms? A. It means that there have been work done in -- in the literature on d- and 1-nicotine. Those are the two`isomers of nicotine. D-nicotine 164 i HUSEBY & ASSOCIATES (800) 333-2082
Page 160: raj82d00
1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 mainstream smoke. Q. What was meant-by the reference to increasing nicotine impact? A. I believe at that time that was a - nicotine impact was the -- you know this throat sensation that we are -- that's what we were calling it, it was a throat sensation term, I guess. And it -- it's hard to believe that there were some times when even Winston wasn't strong enough for our smokers and they wanted to have more of that, I believe, or we wanted to find out how.it varied with different -- different -- that it varied if you had more nicotine, L-nicotine or inherent nicotine or nicotine salts, would that affect this impact that you're getting in terms of your throat impact. Q. Well, wasn't a portion of this project relating to attempting'to determine the optimum transfer -- the optimum nicotine transfer to mainstream smoke? A. Part of Project 1250, I think, was -- was dealing with that, but that was being done in another division. Q. What division? A. In -- in Walt Henley's division, 166 I HUSEBY & ASSOCIATES (800) 333-2082
Page 161: raj82d00
165 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was less irritating on certain animals than 1-nicotine. And the sa;.ts ofL-nicotine were less irritating than L-nicotine itself. o, that's where this -- and they -- they did this, this irritation thing, based on pharmacology. And this was done on a number of different animal species where there -- where they would put material -- the neat material on -- on the eyes of rabbits -- let's see. What are some of the other things? They would inject them subcutaneously under their skin and look for reactions. There was a number of different ways that they would treat animals of different species to see if -- if there was more of a irritation associated with the 1- or the d-nicotine, and that's where that statement was coming from. It was known previously also in some other work that the salts were less irritating than the freebase L-nicotine. In the last statement, it says here, "Their salts have suggested that the release and delivery of both isomers should be examined.° There were studies out there that say that the L-nicotine and L-nicotine salts both delivered nicotine at the same rate into the HUSEBY & ASSOCIATES (800) 333-2082
Page 162: raj82d00
169 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 share for Winston. o, I thirnk I.worked in this area for about two years. And during that time I -- I-- I used this new equipment that we were about to purchase. Q. Did you determine any means to increase nicotine impact? A. No, I wasn't successful in doing that. (PLAINTIFFS' EXHIBIT NUMBER 2 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. If you'd take a look at this document. I'm not going to ask you about the entire document, but while I'm gathering the other copies, if you just might familiarize yourself with it. While you're looking at it, let me ask you, first of all, in the period of January lst of 1978 to March 31st of 1978, were you in the Chemical Research Department? A. Chemical Research Department? Where do you see that, sir? Q. It's on the very first page underneath the recipient's name. HUSEBY & ASSOCIATES (800) 333-2082
Page 163: raj82d00
161 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I would say taste really .reof distinguishes a lack the .Q. Do you mind if we take a-little break? A. Yes. Thank you. THE VIDEOGRAPHER: Off record at 2:17 p.m. (Recess 2:17 p.m. to 2:26 p.m.) (PLAINTIFFS' EXHIBIT NUMBER 1 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: Back on record at 2:26 p.m. BY MR. MAISTROS: Q. 'I'm showing you what I've marked as Perfetti Exhibit Number 1., ask you, first of all, you are copied on this document, correct? A. Oh, yes. Q. In 1977 you were employed by Reynolds? A. Correct. Q. And who was J.D. Fredrickson? A. He was a research scientist that worked in Mary Stowe's group. Q. What group did you work in in this period of time? HUSEBY & ASSOCIATES (800) 333-2082
Page 164: raj82d00
160 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 either the same or higher Ames activity for the ultra low product? _ MS. FEE: Object to the form. THE WITNESS: We need to remember that -- that Ames activity is only one indicator of -- of -- with just one biological indicator. There's loads of other ones that -- that need to be looked at in terms -- in -- in unison to get a full picture of the biological activity of -- of a material, whether it be cigarette smoke or any other product. BY MR. MAISTROS: Q. ~ Have you seen any research that determine that the biological activity, regardless of the method used to measure it, was lower for ultra low cigarettes than full flavor? A. I'm trying to think back. I-- I can't remember reviewing a lot of other biological tests except Ames for -- in the category of ultra low tar. So, I -- I really don't know at that point. I really don't know right now. Q. If you had to identify one thing to distinguish ultra low cigarettes.from full flavor cigarettes, would it be their taste? 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 165: raj82d00
152 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 finding what was done on nicotine analogs; how many there were, what they l,ooked-like. , And then there was an aspect of it where we found out how many were commercially available. And, then, what we were going to do is to look at some structure activity relationships associated with these nicotine analogs. Q. For what purpose? A. As -- ae I mentioned earlier, we were interested in, first of all, just a general understanding of how nicotine was working in the body and in how it transferred into smoke and how nicotine analogs changed. And, then, secondly, there was some aspects -- there were some of the -- some of the people on the committee had some toxicological background and they were aware of literature on some of the positive aspects of smoking in terms reduced or reduced platelet aggregation, some cognitive, you know, improvements in -- in our - our cognitive ability. of There were some benefits in terms of reduction in dementia diseases. And they -- it might have been -- you know -- we thought that if we knew something about the basic structure of some I HUSEBY & ASSOCIATES (800) 333-2082
Page 166: raj82d00
168 1 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of -- of tar and nicotine in the response were most acceptable. There was - a lot of this work was done by Dr. Cal Neumann. And what he was finding, that there were some optimum prototypes of acceptance in the range of about, I think it was like -- a ratio of -- a T/N ratio of about 15. And he was calling those optimal -- optimal nicotine transfer or optimal cigarettes, optimal T/N ratio prototypes, a number of things that he called them. And it turns out that Winston was pretty close to that already. So, the other prototypes that he made at higher TIN ratio were too weak. Once he went at -- lower TIN ratios were too much, too strong. Q. How long did you work at or research relating to means to control tar/nicotine ratios and to increase nicotine impact, as suggested in this memo? A. Not very long, because subsequently after this, there was a program developed where we were trying to -- our -- our share of Winston -- our -- our -- our market share was dropping rapidly and there was a program developed for us to get into trying to find means-to improve our market I HUSEBY & ASSOCIATES (800) 333-2082
Page 167: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes, I do. Q. And who first.came up with the idea to alter sugar levels as a means of altering nicotine transfer? . What was known at the time was that, as we increased the casing load on burley tobacco that had got smoother, and we wondered whether this was affecting the nicotine transfer rate. So, what we did was case some Winston cigarettes at different levels and had those smoked and looked at the amount of nicotine that was trapped on the Cambridge pad. Q. Why were you attempting to alter nicotine transfer through the use of sugar? A. Because it -- it had to do with -- with this nicotine impact and the'irritation associated with it. If you could -- if you could apply nicotine -- if you could apply nicotine -- if you could apply sugar to the -- as a casing material, you might be able to influence the amount of'irritation associated with it, which we thought had something to do with the amount of nicotine. Q. And you say in this paragraph that you obtained your cigarettes from a Michael Shannon. Ln N J J m 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 168: raj82d00
163 1 2 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• o, at least three months into your employment you were looking.at factors influencing nicotine delivery efficiencies? A. . That's -- that's true, yes. Q. And do you recall, as you read this document or without reading this document what Project 1250 was? A. Project 1250, I think, was called nicotine satisfaction. I think there was another project also called 1245 that was called the same thing. How did they differ? A. I'm not sure. Q. And how was nicotine satisfaction used in the context of Projects 1245 and 1250? A. It was generally in what I had discussed earlier, that there was -- there were - there must be factors that influence smokers to smoke certain brands. And one of the things we were trying to"determine was, I think, not me, but that division, and there was many aspects of it, what -- what -- what things were most important, how much -- was the flavor more important, was -- was there work that we could do in terms of the ritual m N w N m ! HUSEBY & ASSOCIATES (800) 333-2082
Page 169: raj82d00
1 2 3 4 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes. I was working with Larry Hayes at the time or Lawrence.Hayes at the time. Larry was my.mentor. He was -- he had been here many, many, many years and was trying to..get my feet wet on a number of different pieces of research that was being done by Harris.who had a number of years under his belt, trying to get me associated with certain thing.s that people use and instrumentation, different methodologies for collecting smoke. He was -- so, I worked a lot with Larry. I was in the same laboratory as he was. We were lab mates. Q. Okay. So, from the time you started in October until at least the end of March of '78, your work focused on reviewing literature on nicotine, analyzing nicotine transfer efficiencies, and looking at the pH of cigarettes or of extracts of cigarette filters? A. Yes, except one thing, that I had not totally prepared -- I did not -- I had not done the pyrolysis work yet, because I hadn't prepared all of-the nicotine salts. Q. Okay. But you began that work. Is that -- I mean -- but does that fairly catch 95 percent -- A. Yes. 176 I HUSEBY & ASSOCIATES (800) 333-2082
Page 170: raj82d00
167 1 3 4 5 7 8 9 10 il 12 13 14 15 16 17 18 19 20 21 22 23 24 25 which was the tobacco side. in? Q. Q. Well, what-divi-sion was Dr. Harris A. Dr. Harris was in the smoke side. And wasn't he looking at ways to determine the optimum nicotine transfer to -- to mainstream smoke? A. What I -- what he -- it says up here, "Prototypes which have optimum" -- y.eah, he was looking at prototypes in terms of trying to measure what this was. These -- these prototypes were being developed, I think, under another project. Q. Why was he looking at the optimum nicotine transfer to mainstream smoke? A. They were calling -- there was -- there was a belief out there that there was some optimal level of tar and nicotine out there that smokers wanted. There was a belief that there was something out there like that. And there was research being done in -- in terms of the response surface methodologies. And this is just a way to design a study where we would vary tar -- actually, we would vary nicotine in, for example, moisture in the pack, cigarette moisture, and determine which of the prototypes that -- that had varied levels HUSEBY & ASSOCIATES (800) 333-2082
Page 171: raj82d00
170 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Oh, yes, yes. Q. And Mary S_towe-was your supervisor? A. Yes. Q. And she is the author of this document? A. I take it, yes. Q. Do you recall seeing this document before? A. Yes, I -- I-- I think I do remember this. Q. And when was the last time you would have seen this 1978 document? A. About 1978. Q. Okay. In here on the page that's with big numbers on the lower right-hand corner, it says 16444 -- A. Yes, sir. Q. -- see there's a heading that's underneath "satisfaction"? A. Uh-huh. Q. Projects 1250 and 1245 and underneath A, it's "how nicotine is bound in tobacco." Do you see that? A. Yes. Q. And, then, B, "Factors affecting I HUSEBY & ASSOCIATES (800) 333-2082
Page 172: raj82d00
153 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of these nicotine analogs, that similar structures could be looked at in tarms.off a structure activity -- in terms of structure activity relationship studies might be able to explore that Q. What -- what have you been doing primarily since the '80s to the present? A. In terms of what, sir? Q. You. What have you been doing? What's your typical day been like from the '80s to the present? MS. FEE: Object to the form. That's so broad. BY MR. MAISTROS: Q. I mean, do you manage people, do you attend management meetings, do you do bench-level research? A. I -- I have been a manager, I have been a research scientist, and, you know, depending on what the need of the company was at the time, I was one of those two different things. Q. Well, what are you working on now? What are you doing now? A. I am in the middle of producing alternate filler material. Q. Alternate in terms of nontobacco? m HUSEBY & ASSOCIATES (800) 333-2082
Page 173: raj82d00
171 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nicotine transfer efficiency," and your name is listed? A. Yes. Q. Do you know what this document is summarizing, at least this portion? MS. FEE: Object to the form. THE WITNESS: What we were attempting c to do -was prepare nicotine salts of known origin and then to pyrolyze those salts in a specially designed pyrolysis unit that would fit -- that would be married to this Varian 3700 gas chromatogram to find out what effluents -- what effluents there were from the pyrolysis. We were going to try to determine what they -- how -- how the salts pyrolyzed. Did they just split and give nicotine in the acid or -- or did the nicotine decompose or some combination of that. BY MR. MAISTROS: Q. And the next page is -- reference to "means to alter nicotine is a transfer by variations of the sugar levels in the tobacco blend." Do you see that? HUSEBY & ASSOCIATES (800) 333-2082
Page 174: raj82d00
175 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Well, there wasn't very months - there wasn't very many months involved here. I mean, from October till December, March, there wasn't a whole lot of time there actually. There was only about three months. We had to -- a lot of that, as I mentioned, was a -- a study on literature study, which was a good three months worth of work. And then coming to then work with Mary, I guess, early in -- early in 1978 and then, you know, developing some -- some feel for the types of material that I was dealing with. I had -- you have to remember at this point, you know, I-- I still didn't know how -- how cigarettes were made very well. I didn't know how we,raised andi-- how tobacco was raised, how it was cured, how it was -- there was a lot of things that I didn't know here, but this was very, very early in my career and Q. Does this memo accurately describe the work you were doing in this time period? A. Yes, sir. Q. Again, if you can go to the large number, page 6-- 16449, this page describes work at the bottom you.were doing with respect to smoke pH? I HUSEBY & ASSOCIATES (800) 333-2082
Page 175: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 undertakings to accomplish that objective, correct? A. Correct. .Q. And among those undertakings was to investigate the form of nicotine as found in various tobaccos and that was being done by Fredrickson, correct? A. Yes. Q. And do you know if that was ever achieved, that undertaking? A. Part of it, I-- I -- I think -- I remember part of it was achieved where -- what he tried to do is determine how -- how long did it take to totally extract all the nicotine out of tobacco using a variety of solvents that were from totally apolar to totally polar. And that was one way he was trying to figure out how -- how difficult it is for the -- were all nicotine salts the same or how were they bound and positioned in the tobacco, how difficult were they to get out. Q. And he also looked at, did he not, how smoke pH effected nicotine delivery? A. I'm not sure about that. But even though -- I mean, I didn't work with -- with Jim all the time on this. Normally I worked with Larry Hayes. So, I didn't -- I wasn't -- I don't think I HUSEBY & ASSOCIATES (800) 333-2082
Page 176: raj82d00
178 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. So, there's no relation between tar and nicotine control and• smoktng satisfaction? A. Well, there wasn't in this -- in what we were doing. Q. What is the objective -- stated objective of Project 1250? What is -- if you can read it or tell me - A. Yes. Q. -- what was the stated objective of Project 1250? A. It looked like there were three aspects of that. The first aspect was to develop or -- some new techniques and methods for -- "will lead to new techniques and methods for altering, controlling nicotine control rate -- nicotine-to-tar ratios." Second aspect is "will define important factors related to smoker's satisfaction in -- in both minimum and optimum nicotine levels and thus permit design of more precise experiments concerned with nicotine delivery, nicotine -- smoker satisfaction in a consumer environment," and the third aspect will be "which will ultimately meet company needs for low tar cigarettes with high smoker satisfaction." Q. Okay. And then listed are 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 177: raj82d00
worked on that part of it. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• Whether ynu worked on it or not, are --,are you aware that Fredrickson was working on determining how smoke pH affected nicotine delivery? A. I'm.not sure, sir. Q. What does the first paragraph of this document say under specific undertakings? A. "Investigate the form of nicotine" MS. FEE: Hang on, Tom. If you want to read that into the record, you certainly can, Jack, but he's not going to sit here and read all these documents into the record. record. MR. MAISTROS: I'11 read it into the BY MR. MAISTROS: Q. "Investigate the form of nicotine as found in various tobaccos (how bound) and the properties of various nicotine salts that elevated temperatures and the influence of these factors and smoke pH on nicotine delivery, satisfaction, throat harshness." Does that tell you one way or the other whether he was looking at how smoke pH 180 i HUSEBY & ASSOCIATES (800) 333-2082
Page 178: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yes. Q. Do you know if Mr.,Michael Shannon knew why he was giving you those different cigarettes in 1978? A. Oh, I'm sure -- I always -- I mean, I discussed with Michael, you know, what we were doing. Q. And you told him you were looking at the nicotine impact on the throat? A. Well, that wasn't what I was actually looking at. I was looking at how much w,as on -- first of all, you have to know if there's anything different in terms of the -- what we're collecting on a Cambridge pad first. If I didn't see any difference there, I wasn't going to be smoking these things or spend a lot of time trying to smoke them. Q. Did you tell Mr. Shannon why you were requesting that he provide you with these different cigarettes and what the test was going to involve? A. I'm sure I must have. I can't remember, you know, exact conversation with that, but - Q. And what did these tests show you? A. That there really wasn't a -- a large 173 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 179: raj82d00
183 1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you don't know what this document is referring to when it cites to profile,in.tobaccos treated to alter smoke pH or free nicotine? MS. FEE: I don't see anything about profiling. MR. MAISTROS: Okay. Let's read the whole paragraph. BY MR. MAISTROS: Q. "Determine nicotine transfer efficiency and temperature nicotine release profile for various tobaccos such as," and it lists -- do you see the types of tobaccos? A. Yes. Q. Now, these are tobaccos that Reynolds was employing? A. Some of these tobaccos.. Q. Okay. Which ones was Reynolds employing? A. Certainly flue-cured, burley, 07, KDN, and aged and unaged tobaccos. I was not aware of-any special high nicotine tobaccos. We may have been discussing some high nicotine burleys that we were purchasing at the time that they ran through . m the KDN process. w w ~ Q. And you were not aware of tobaccos 1 HUSEBY & ASSOCIATES (800) -333-2082
Page 180: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 change in terms of the smoke nicotine trapped on the Cambridge pad per unit of_material burned. There was a wide range of -- of change in the sugar and not a very wide range in terms of the smoke nicotine. Q. How many different people were -- what was -- all of projects -- I'm sorry. Back up. At this point in time, how many people were in this Chemical Research Department? A. I'm -- I'm -- I'm not exactly sure. There -- there may have been 10 or 12 people. Q. How many were looking at the issue of nicotine transfer efficiency? A. I think it may have only been Jim Fredrickson and Hayes and myself. Q. So, three of you? A. I think that might have been all there was. I'm not sure. Certainly what was described here, this was all we were doing. I mean, if Mary had not -- that's how Mary identified who was working on what'by the names beside, you know, beside the -- the titles here. Q. Had you generally been doing the same type of work from the time you joined till this point in time? 174 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 181: raj82d00
of what you were doing in this 1 Q. 2 A. Yes, I-- .Z thi-nk so. Q. -- first six months of your 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 employment? A. I think so, yes. (PLAINTIFFS' EXHIBIT NUMBER 3 WAS MARKED FOR IDENTIFICATION) THE WITNESS: That's the last one. BY MR. MAISTROS: Q. Yeah, we'll have to get them -- A. Oh, you want them back. Q. -- stapled. MS. FEE: That goes with that.. THE WITNESS: Oh, yeah. I'm sorry. BY MR. MAISTROS: Q. Exhibit Number 3 is' entitled, just at the top, "1978 Program." A. Uh-huh. Q. You see underneath "project," it says, "1250 Smoking Satisfaction and Tar and Nicotine Control"? A. Yes. Q. and the same? Are those two separate items or one They're two different things. 177 1 m HUSEBY & ASSOCIATES (800) 333-2082
Page 182: raj82d00
185 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Reynolds- has not, but there are seed lots that -- that will Sonerate high -- high nicotine levels, high nicotine level in -- in the -- in the leaf. They're produced by -- they were generated-by the USDA and they're available to anybody that wants to go and get those seeds and plant them. Q. Are these like the -- the Y-1 seeds that Philip Morris exported? A. I don't know if they're the Y-1 seeds, but they're certainly seed types that were produced down at the Oxford Research Safe Station by Dr. Chaplin, I believe. Those were done at a project under the auspices of USDA to evaluate different cultivars that have low disease resistance. And one way of doing that is to -- to -- he thought one way to do that was to either have very, very high nicotine or very, very low nicotine varieties and he produced those seed lots. Q. Okay. It doesn't list a person who was doing Number 4. Do you know who that was? A. Normally, if there wasn't a person directly, it was something that was up for grabs. And if you wanted to do some of this work, you HUSEBY & ASSOCIATES (800) 333-2082
Page 183: raj82d00
186 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 could do it. That's how Mary usually ran it. Q. The fifth_.undertaking was to develop a nicotine impact measurement or index which would be useful in evaluating smoker satisfaction. Was that ever accomplished? A. Yes. I mean, to some extent, it was. What -- what Calvin looked at was --*was that there appeared to be some level of T/N ratio for Winston smokers that gave higher ratings than others. Calvin went out with a series of prototypes to consumers that had varying levels of tar and nicotine in a design fashion. And he found out that there were certain levels of or -- or certain ratios -- certain TIN ratios that -- that gave higher ratings than others. Q. But how did he measure those? A. By looking at the 70-plus rating there, the acceptance rating. Q. But what was the index or impact measurement used?? It says, "Develop a nicotine impact measurement or index." I aesume that means there wasn't one in existence? A. That's right. It was -- and this index was the tar-to-nicotine ratio. HUSEBY & ASSOCIATES (800) 333-2082
Page 184: raj82d00
187 1 2 3 4 5 6 7 8 9 10 11 12 1'7 18 19 20 21 22 23 24 25 How do you measure whether or not I mean -- it looks to ma•, if you read this, "Develop a nicotine impact measurement or index which would be useful in evaluating smoker's satisfaction," I mean that's not a-- a test or a questionnaire to develop a means of evaluating smoker satisfaction? That's an end result, tar-to-nicotine ratio? A. That was a -- it was a.-- it was a measurement that we could measure in the lab, an objective measure that we could compare to a subjective measurement from consumers. Q. And what were you attempting to develop, the objective measure or the subjective measure? A. The subjective measure. Q. And what was the subjective measure that was developed? A. There was an acceptance rating of the product. Q. What -- what kind of questions did you ask to figure out what the acceptance rating was? A. Aht Okay. The scale ran from zero w ~ to 100 with zero being something, like, terrible, HUSEBY & ASSOCIATES (800) 333-2082
Page 185: raj82d00
1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Were they asked, for example, "Does this cigarette relax you!'? A. No. They were asked things like tobacco taste, harshness, strength, smoothness, mildness. I think they were also asked how fast you burn. There were a couple other ones that were also in there. And then aftertaste, aftertaste. They were asked about that. Q. Does this test have a name today at Reynolds? A. It was -- it was just a -- an NFO ballot, I guess. It was a National Family Organization that had a standard ballot that we used - - Q. Is it still in use today? A. -- marketing used.. I don't think that they, use NFO any longer. I think they've gone to some other firms over the years. Q. Now, the end, it says, "This project effort is expected to remain at approximately the current level through 1980." A. Did that occur? It may have. I'm not sure. And at least in 1978 three people HUSEBY & ASSOCIATES (800 333-2082 189 I i
Page 186: raj82d00
181 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 affected nicotine delivery? A. I think that was the objective of what.he was trying to do. Whether he accomplished that, I don't know. Q. Okay. Number two, "Determine the minimum tar/nicotine levels for smoker satisfaction through panel and consumer testing."' Was that accomplished? A. I'm not sure. Q. Number 3, "Identify factors influencing nicotine delivery efficiency and determine means to control tar/nicotine ratio and to increase nicotine impact." That's you 100 percent. I assume that's your time, correct? A. Yes. Q. Or is that how much the project is done? Is that your time? A. No, no, that was how much time I was being -- I was going to be committed to doing this project. Q. Okay. And did you accomplish that? A. I accomplished some of that objective, but not very much. Q. Number 4, "Determine nicotine m ~ w N co HUSEBY & ASSOCIATES (800) 333-2082
Page 187: raj82d00
1 2 3 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 were spending a hundred percent of their time looking at this issue and four people were spending 20 to 90 percent of their time looking at this issue? A. Uh-huh. Correct. Q. And,that's out of the 11 people in this group? A. I guess I was right. I mean, I-- I-- if you say there's 11 people, there's 11. I'm not quite sure. I didn't count them up. Q. No. You -- I -- you said that. I-- A. Yeah. I mean, that's -- somewhere around a dozen people, but I -- I could count and we could find out, if you'd like. Q. But at least seven of the people in the group were spending their time looking at . smoker satisfaction and tar-to-nicotine control? A. Yes. Q. Was this a -- this chemistry group, was this the entire chemistry group at Reynolds? A. This was at the -- on the tobacco side, yes, but there was another whole group of chemistry. Almost -- almost everybody there was a chemist. Q. But there was actually a group called 190 I HUSEBY & ASSOCIATES (800) 333-2082
Page 188: raj82d00
195 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 years. THE WITNESS: .I don't think we have a total understanding or an adequate understanding of that, no. BY MR. MAISTROS: Q. Up above the conclusions, it talks about nicotine pharmacology and says that, "In fact, some researchers are actively working on , nicotine and its role in brain chemistry in an attempt to identify how it works. This research work could.provide breakthroughs in understanding nicotine satisfaction and we will at least try to keep up-to-date with the literature." Do you know if that was done? A. Yes. Q. Were there breakthroughss in understanding nicotine satisfaction through the nicotine pharmacology? MS. FEE: Well, wait. Object -- THE WITNESS: No. MS. FEE: Hang on. Object. Was what done? Was the -- the reviewing of the -- keeping up-to-date with the.literature or research? BY MR. MAISTROS: HUSEBY & ASSOCIATES (800) 333-2082
Page 189: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 doing fairly well in terms of that division. Q. Do you s.ee,. --. could you go to the page that says "conclusions"? A. Yes. Page 4889? Q. Right. It says that "we have yet to adequately understand smoking satisfaction. Obviously, nicotine is important, but just how important has not been defined." And then it goes on. It concludes, "Nicotine taste and satisfaction may be totally independent responses." Was that ever confirmed? A. No, not that I know of. Over the years, we have had several programs like this and we've never really'resolved this question. Q. So, as of -- as you sit here today in 1988, Reynolds doesn't know what contributes to nicotine satisfaction? MS. FEE: 1998, I assume you meant to say? MR. MAISTROS: What did I say? MS. FEE: '88. MR. MAISTROS: Did I? MS. FEE: Uh-huh. MR.. MAISTROS: I meant '98. Lost ten 194 I HUSEBY & ASSOCIATES (800) 333-2082
Page 190: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Well, how did you answer it when you said "yes"? .A. We did keep up with the literature. Q. Okay. And you have not had any breakthroughs in understanding nicotine satisfaction through the pharmacology? A. No, that link has not been -- I don think we -- I don't think we've been able to make any,link in that area. Q. So, Lippiello has reached no conclusions on the connection, if any, between nicotine satisfaction and pharmacology? A. Not in terms of relation to cigarettes, no, not that I know of. Q. Nor has Pritchard? A. He has -- you know -- what -- what I understand from Dr. Pritchard's work is that he has, again, looked at some objective measures from EEG and he can tell when some person has smoked and, you know, and -- and activity in -- in the t brain and how that affects some of the cognitive properties when someone smokes or if they don't smoke. But how this is -- how this relates to this nebulous smoking satisfaction, I don't think he has pinpointed that at all. 196 HUSEBY & ASSOCIATES (800) 333-2082
Page 191: raj82d00
I'll show what you I'll mark as 1 Q• 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Exhibit 5. (PLAINTIFFS' EXHIBIT NUMBER 5 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. It is -- appears to be another version of Exhibit 4 with the handwritten changes. You can tell me if you think that's a fair characterization or not, but at the end, though, you'll note the-last page it lists the people that participated in the work that led to this subject, and you're listed on the last page. Do you see that? A. Yes, sir. Q. If you could look through this Exhibit 5 and just tell me if you believe it appears to be a complete and accurate version of the January 4th, 1978 memo. MS. FEE: I'm sorry. What's the question? BY MR. MAISTROS: Q. Does it appear to be an accurate and complete version of the memo? I mean, do all the pages appear to be present, et cetera? A. I believe that this memoranda has HUSEBY & ASSOCIATES (800) 333-2082 197
Page 192: raj82d00
1 2 3 4 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 summarized the prior memorandum, yes. Q. Okay.. And, at+ least by this memorandum, it appears as though, including the author, that there were ten people at Reynolds working on nicotine and smoker satisfaction in January of 1978 in one fashion or the other? A. That -- that's what it would appear, although they- they don't have the -- the same - they don't have -- happen to have the same people on them altogether. Q. But the Exhibit 5 lists, including. the author, ten people that contributed to the study -- A. Yeah. Q. -- entitled "Nicotine and Smoker Satisfaction," correct? A. Yes. (PLAINTIFFS' EXHIBIT NUMBER 6 WAS MARKED FOR IDENTIFICATION) Q. Exhibit 6 is a January 5th, 1978 menmorandum authored by you. MR. O'HARA: Thank you. BY MR. MAISTROS: Q. Do you recall authoring this memorandum? l HUSEBY & ASSOCIATES (800) 333-2082
Page 193: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 treated to alter smoke pH or free nicotine? A. No. That.may , have -- that may have been alluding to the fact that cased -- heavily cased tobacco. Q. Heavily cased tobacco will increase the smoke .-- will -- A. Will -- will alter. Q. -- affect smoke pH and free nicotine? A. I mean, that was the assumption. Remember, these -- these are just -- these are < things that we thought we could undertake. These are -- this is not something that we finished, not something we did. This was a -- a -- a -- an objective, some -- some work plan that we were putting together early in the year at -- to lead us along some path, give us some direction. Q. Okay. Up to this point in time, to your knowledge, had Reynolds developed a high nicotine tobacco? A. No, we had -- no. Q. Had Reynolds made efforts to develop a high nicotine tobacco? A. Not that I know of, no. Q. To this day, has Reynolds attempted to develop,a high nicotine tobacco? 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 194: raj82d00
188 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 with a hundred being would definitely buy and smoke ..that•. Some -- some very products, something like high acceptance of the product with 70 being at -- at a scale of 70, I think it would be most -- most probably buy and smoke the product or something like that. But it was an acceptable rating. It was a -- some -- it was a rating that marketing came up with at this 70 percent rating that gave them indication that this was -- that this was someone that would like the product,. would probably buy it. Q. Was there a series of questions that people answered to get to that rating or was it just, tell us on a scale of zero to a hundred whether you'd buy this product? A. It was just a thermometer scale with -- with the -- with each of the -- every ten -- ten points there was a -- a rating -- I mean'-- there was some verbiage of what each of the ratings were. Q. Okay. Were they asked, "What do you think about the taste of this cigarette"? A. Yes, they were also asked affective measurements, but that was after they were rate the overall product. asked to HUSEBY & ASSOCIATES (800) 333-2082
Page 195: raj82d00
Do you recognize any of the 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 handwriting on this document7_ A. No, I don't. Q. Having - - A . Yes. Q. Having reviewed this document, do you recall if you contributed to the -- any portion.of this document? A. Yes, to -- to some -- to some portions of it. Q. Which portions? A. On page 4885, I-- I made some straight grade cigarettes of individual.blend cigarettes made from individual blend components and was determined that blending alone can greatly alter the T/N ratio while other techniques to date, such as adding nicotine and other additives, are less effective. No breakthroughs -- no breakthroughs in substantially increasing nicotine transfer efficiency were achieved. Work in 1978 is aimed at determining how nicotine is bound in the tobacco and transferred to smoke that specific means for increasing transfer efficiency might be developed. I mean, I can remember Mary -- Mary, 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 196: raj82d00
202 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 they're binding to those receptor sites and how this mode of action trarlsmits.it to the brain and how it,'s turning on and turning off certain, you know, brain functions. Q. What's an opiate? A. Oh,.opiates, those are -- those can be any of a-- a large variety of types of compounds that have actions similar to opium. Q. Okay. And wasn't Goldstein looking at the interaction of opium with receptors in the brain of the central nervous system? A. You know, he -- he might have been. I'm not sure, but he might have been doing that. Q. And you list in paragraphs 1-- numbered 1, 2, and 3 the similarities between opiates and nicotine; do you not? A. No, not -- not -- not nicotine, but nicotinic agents, nicotinic receptors, things that are nicotinic in action, not necessarily nicotine. Q. What -- what is the only compound that interacts with a nicotinic receptor? A. There are hundreds of compounds that react with the nicotinic receptor. Some of them look like nicotine, some of them have no -- no structure anywhere near what the shape of nicotine I HUSEBY & ASSOCIATES (800) 333-2082
Page 197: raj82d00
191 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. I'm not sure. I have to -- I would 25 have to read it. Chemistry; was there not? A. There was.a group called Tobacco Chemistry and one called Smoke Chemistry, if I'm not mistaken. And they worked under the Chemical Division from -- with Don Piehl, I guess, was the -- the head guy. And then there was an Analytical Chemistry Division that Don also had as part of his responsibilities. Q. What was the Blood Chemistry Group? A. I didn't know there was one. (PLAINTIFFS' EXHIBIT NUMBER 4 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. This document is dated -- well, it says in top in handwriting "Draft 1-3-78," and you're listed as being on it on the right. Do you see your name there? A. Yes. It's entitled "Nicotine and Smoker Satisfiction"? A. Uh-huh. Q. Did you participate in the drafting of this document? HUSEBY & ASSOCIATES (800) 333-2082
Page 198: raj82d00
204 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 generalization we now use to determine satisfaction"? A. Well, the thought there was, if you knew enough about nicotine receptor chemistry and you knew how -- how compounds interact with that to -- to give some type of signal to the brain -- we're talking about knowing a whole lot of stuff. here -- then you might be able to get a -- a good handle, numerical, something that you could quantify objectively without going and asking people, you know, through lots -- lots and lots of consumer evaluation, how -- how -- how they would appreciate a cigarette or -- how satisfying a cigarette might be. This is a real wish list here, really stretching it, I thought, even-back in 1978. Q. Did Reynolds subsequently approximately three and a half years later develop an entire program related to-this wish list? A. There was work that was started after this, yes. Q. Didn't that work continue till at least when Dr. Lippiello testified this summer? A. Well, as far as I know, a lot of that work is still going on. HUSEBY & ASSOCIATES (800) 333-2082 I
Page 199: raj82d00
1 2 3 Q. And as to -- A. I mean, it, may.have -- it may have been terminated. I don't know. Q. , As to determine the chemical 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 reactions of nicotine on the body as opposed to some subjective reactions? A. Well, you know, I -- I got away -- I don't know exactly what -- what Dr. Lippiello's been doing for a long time, because our paths separated a long time ago. He was more biochemically oriented than I was and I did most of my work on cigarette design aspects. Q. Okay. In the next page, what did you mean by "I have Ao doubt that the work will be done and relatively soon, since nicotine is the next naturally occurring alkaloid used in a.ppreciable amounts which has been implicated as an addictive drug"? A. Well, what I thought was -- well, I -- I guess I wasn't being very -- I-- I thought that this was such a great idea that someone else would pick it up, because it was something that wasn't so -- so abstract. And actually else did this work. Q. Who was that? someone 205 I HUSEBY & ASSOCIATES (800) 333-2082
Page 200: raj82d00
207 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Let's see now. Where is - Q. The second.paragraph. A. Okay. Well, there -- there had always been -- you know -- people have always been saying, you know, that nicotine is addictive. And so, I'm just -- Russell has said this kind of thing, all -- and a lot of his stuff have been published. So, I was kind of parodying what I already read in the literature. Q. Well, what -- when you said, "I can't stress this fact enough, since its results could be devastating to the tobacco industry as a whole," what is that in reference to? -A. Well, I'm not really sure what I meant by that. It seemed like I was kind of operatic at the time, you know, looking at this now. I don't know why -- why I was -- I don't know why I said that. Q. Well, I'm trying to figure out, not why you said it, but what is it in relating -- is it in relation to attempting to find out this chemical satisfaction notion or what's it -- what are you referring to? What could be devastating to the tobacco industry? HUSEBY & ASSOCIATES (800) 333-2082 Ln ~ ~ ~ I
Page 201: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 transfer efficiency and temperature nicotine release profile for various.t.obaccos, such as flue-cured, burley, G7, KDN tobacco, special high nicotine tobaccos, tobaccos treated to alter smoke pH or free nicotine, and aged and unaged tobaccos." Did you look at that issue? A. I looked at some of those tobaccos and looked at determining what the nicotine transfer efficiency were for some of.those tobaccos. Q. Did you -- were you familiar with tobaccos treated to alter smoke pH? A. No. Q. Do you know what -- MR. MAISTROS: We have to change the tapes. I'm sorry. THE VIDEOGRAPHER: This concludes tape number two of the deposition of Dr. Thomas Perfetti. The time is 2:57 p.m. (Off-the-record discussion.) THE VIDEOGRAPHER: This is tape number three of the deposition of Dr. Thomas Perfetti. The time is 2:58 p.m. BY MR. MAISTROS: Q. Do you -- is it your testimony, then, HUSEBY & ASSOCIATES (800) 333-2082
Page 202: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 sir. Q. When was the last time you saw this memo? . A. Well, I -- I mentioned I did look at this. You know, I've had this at my desk for a while, since they -- Los Angeles -- since, I think, some -- one -- I think it was this -- in fact, it was this statement here. I think it was the statement on the second paragraph that it -- that was in that -- in that article in the Los Angeles Times. So, I've had this memo at my desk for -- in a pile of stuff that I have around my desk for quite a while. Q. Well, the Los Angeles Times you believe quoted the portion of the memo that talked about the -- devastating to the tobacco industry as a whole? A. I think it -- it took the entire paragraph, sir. Q. The entire second paragraph? A. Yes. Q. And when they quoted your entire second paragraph, did they quote it in context or did they take it out of context? A. It -- it didn't look good. I mean, 210 I HUSEBY & ASSOCIATES (800) 333-2082
Page 203: raj82d00
I 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that's all they had. I mean, they didn't explain what the memorandum was_.about-_or anything. -So, I guess ,it's -- it was -- Q. What were they -- A. -- out of context. Q. -- suggesting? What were they suggesting you meant by that or did they? A. I think this was in relationship to some other memorandum that was by Dr. Teague on young adult smokers. Q. The manner in which they quoted your paragraph out of this memo, you say it was not -- I'm sorry. What was the word you used? A. I'm sorry. I can't remember what I said. Q. Was not good? A. Yeah, it wasn't good, yeah. Q. Did you write them and tell them that they had either taken you out of context or it was not good? A. No, I didn't. Q. Have you ever done any research on young smokers? A. No, I haven't. 211 i HUSEBY & ASSOCIATES (800) 333-2082
Page 204: raj82d00
212 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Were you aware that Reynolds was targeting young smokers.3• MS. FEE: Object to the form, assumes a fact not in evidence. MR. MAISTROS: Well, it's on the Internet. MS. FEE: That doesn't make it evidence. THE WITNESS: I attended a number of, you.know, little seminars and the like on, you know, the young adult smoker. There was a, actually, a program called -- it was just called that. And there -- there was never any indication there that we were going to •do anything that we had never done before. We'd always only -- only go out and get smokers, you know, recruit smokers that are eighteen to twenty-one, is the youngest crowd that we ever -- we ever -- we ever get. And they're very difficult to get, because they were never around. I mean, most of them were always, you know, working late and they were hard -- hard to get them to come to the sessions and they weren't very reliable smokers. HUSEBY & ASSOCIATES (800) 333-2082
Page 205: raj82d00
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Uh-huh. Q. And what Was your purpose in drafting this memorandum? A. This was my attempt at putting together a research proposal based on what I thought was some exciting work that was done -- being done by Dr. Goldstein on enkephalins. Q. Okay. And that was -- was one of the end goals of this work to attempt to,place objective standards,on the subjective notion of nicotine satisfaction? A. I don't know. I don't know if it could have been used for that or not. Q. Well, what -- what do you -- A. I wasn't that far advanced in my thinking at that time. Q. What was the -- your goal then? This idea to start a project, was it? A. Yeah. There was -- I had been reading some very interesting stuff. It was very hot in the -- in the scientific literature at that time, the -- the work on discovering these things called enkephalins and endorphins. And at the time one of the major researchers in the area was this Dr. Avram 199 i HUSESY & ASSOCIATES (800) 333-2082
Page 206: raj82d00
1 I So, I've never -- you know -- I've 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 I've done some consumer paneling and I've never seen anything done on younger smokers than that. And I don't know where they.came up with this material that we were trying to solicit younger smokers. BY MR. MAISTROS: Q. -You know Frank Colby? A. I've heard of Frank Colby. Q. Ever'see any memos he's authored on soliciting younger smokers? MS. FEE: Object to the form, assumes a fact not in evidence. THE WITNESS: No. BY MR. MAISTROS: Q. To your knowledge, has Reynolds ever marketed to nonsmokers? A. I don't think so. I'm not sure who they're marketing these cigarettes called Flog to, but I'm not sure. I don't -- I don't think so, though. Q. So, Reynolds' potential cigarette smokers that they market to are current smokers over the age of eighteen? A. That's my general understanding, yes. , HUSEBY & ASSOCIATES (800) 333-2082
Page 207: raj82d00
203 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 is. Q. Are there_.specific nicotinic receptors in the brain? A. At -- at the time of this writing, they didn't know. Q. Today, do you know? Well, I mean, I've read that there are. I mean,,there are other people at Reynolds r that know more about this than I do. It's not my field, but there has been reported nicotine receptors, yes. Many different kinds, in fact. Q. Okay. Well, what did you mean in the second paragraph, "Opiates, like nicotine, have receptor sites throughout the body, primarily mediating their pharmacological effects in the smooth muscles"? A. Oh, all I meant, that these receptor sites generally for nicotine are found all over the body in smooth muscles. I mean, like, in your hands, on your lungs, in your brain. Any type of epithelial tissue is a smooth-type tissue, muscle tissue. Q. What did you mean by "this could relate directly to the chemistry of satisfaction w Ln m and relief us.of the gross subjective l HUSEBY & ASSOCIATES (800) 333-2082
Page 208: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Goldstein, I guess, Goldstein, and -- and there was very little -- little kgown,about these kind of .things., but -- and they didn't know whether they were like neurotransmitters or whether they were actually receptor sites. But the effect -- they were -- they were -- they did have an idea what the -- what the effect was of these things. And they would -- there was more of these things in your body when you were under stress. As soon as you were.in -- in a -- in a situation where you -- you had a lot of pain, the body seemed to give off these endorphins or enkephalins. And so, they were really unique type of -- of compounds that had similar properties to these -- these keto -- I could -- I could never pronounce this before -- ketobemidones.. And -- and the thought here was, I think, or -- or the question was, "Could these relate to any -- the chemistry of satisfaction"? Not necessarily nicotine satisfaction with the cigarette, but just general satisfaction, because most of these types of endorphin compounds had similar properties to, you know, some of the -- the -- the positive aspects of -- of nicotine. There were increased cognitive properties to reduce 200 I HUSEBY & ASSOCIATES (800) 333-2082
Page 209: raj82d00
214 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• Did any of the research you undertook from '78 to the present_.have,.as either a stated or unstated goal, increasing the sale of cigarettes? A. No, not -- not -- not in R&D. I don't see how that possibly could be in the realm of Research and Development. Q. So, understanding nicotine transfer efficiencies is not related to increasing the sale of cigarettes? MS. FEE: Objection, asked and answered. THE WITNESS: You know, it's -- it's very difficult to market anything if you don't know what it is or how to describe it. I mean, I think we have a-- we have a duty and a -- to the company to understand what it is that we're trying to sell or what we're marketing. So, I think there is reason enough to pay researchers, you know, a number of researchers to do this kind of work, you know, to try to increase our knowledge base on what it is that we produce here at Reynolds and, you know, what is in -- what is in the -- in the smoke of -- what is in J HUSEBY & ASSOCIATES (800) 333-2082
Page 210: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 I assume, wrote this. I'm -- I'm not sure. It was from input from us. .Q. Did you write the portion on "flue-cured tobacco most important nicotine contributor"? A. I don't know if I wrote this, but -- but certainly this is some of the work that I did, I think. I think this is some of the work that I did in terms of looking at nicotine transfer efficiency. Q. Any other portions you recall specifically you participated in?. A. I think I participated in the transfer experiments with freebase nicotine versus nicotine maleate. Q. On what page? A. Oh, I'm sorry. it's on page 4886, first burger dot up there. Does this memorandum actually set fortha:the'=work accurately -- accurately set forth the work you were doing in 1978? A. it -- it covers a lot of ground. I mean, I think -- I think it summarizes -- this probably was going to management or something to that effect, and I think it summarized what we were HUSEBY & ASSOCIATES (800) 333-2082 I
Page 211: raj82d00
206 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Dr. Leo Abood did some work on.seeing if there was any relatioush'ip_between nicotine and enkephalins in terms of -- I think it was -- I think he -- his -- the end point that he was dealing with was binding -- membrane binding studies. And -- and that, I guess, that's something like the first step in this thing, if something doesn't bind to it, it probably's not going to elicit a further reaction. So, you do a nicotine or you do a binding study. And what he found out, there wasn't any real relationship between nicotine and enkephalins. But that was done in 1997, I guess, reported in 1997 at a NIDA meeting. Yeah, I think that's right, a NIDA meeting. And then Dr. Goldstein in 1980 published something along this line also. So, it kind of was -- well, maybe -- maybe it wasn't so crazy, I guess. So, it was kind of neat that someone did actually do something with this after, you know, after -- after it ideally didn't,go anywhere at Reynolds. Q. Well, what were you referring to in -- in January of '78'that implicated nicotine as an addictive drug? 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 212: raj82d00
201 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 stress, but in a very different way, I guess.. I mean, to the degree. Q. Well, wasn't one of the stated goals that you had in -- in proposing this -- following up on this research was to determine if there could be a chemical explanation for nicotine satisfaction, as'opposed to just a subjective explanation? A. Did I write that down, sir? Q. Yeah, the second page at the top. What did you mean by "Goldstein's approach will determine if nicotine satisfaction has its basis in chemistry"? A. Oh, the -- the thought was that -- you know -- at the -- at the time they had just come up with some of the structures associated with what these enkephalins were. And the.y were -- they were multi and they're amino acids in link, two and three amino acids in a -- in a chain. And, you know, Goldstein's approach was, yeah, if we know something about the -- the chemistry of these things and the structure of it, maybe we'll be able to determine something about the -- how these fit and how -- what the receptor sites look like, and then go on and find out how . HUSEBY &sASSOCIATES (800) 333-2082
Page 213: raj82d00
209 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 has mild pharmacological effects. I have no-doubt in that, and I'm not going to, you know, argue with some of these great people like Burger and the like who has written about some of the properties of nicotine, but I don't know if that's the way it is in -- in the smoke or in -- or in the tobacco plant. Q. Well, when you said that neither tobacco nor smoke nicotine is addictive, that's your personal opinion, as opposed to based upon any scientific basis since you're not qualified -- A. That's true; that's true. Q. You have not undertaken any specific scientific research to determine if smoke nicotine is addictive, have you? A. No. Q. That's what we're concerned about presently in this litigation. A. Oh, okay. Q. Again, I'll go back to my question. Was there any possibility when you were referring to devastating to the tobacco industry as a whole, you were referring to the addictive issue? A. I can't tell you why I wrote that, Ln N V V H w Ln m 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 214: raj82d00
208 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I really don't know, sir. I don't know what I was -- I don•'t know what I was getting at at •this point. Q. Well, let's assume that these tests would prove one way or the other whether nicotine was -- had a chemical satisfaction notion attached to it. 'Would that be devastating.to the tobacco industry? A. I don't think so. Q. What if this research could prove or disprove whether or not nicotine was addictive. Could that be devastating to the tobacco industry? A. I don't know. I don't know. Q. Well, if it was'proven that nicotine was addictive, would that be devastating to the tobacco industry? A. Well, the -- the point of fact is that', you know, tobacco nicotine and smoke nicotine, they are not addictive. I mean, nicotine in the pure state is -- you can read that in any chemical -- any biochemistry book. It's a -- you know -- deal with this. They were always calling the freebase nicotine addictive. You know, this l HUSEBY & ASSOCIATES (800) 333-2082
Page 215: raj82d00
1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 study and we don't have very many -- we don't have anybody here really to -;- to,coordinate it who understands what's going on. And Don didn't understand and, really, I guess maybe didn't appreciate what it was we were doing and it really didn't go anywhere, as far as I know. I think, though, at a little later time,Don did ask me to try to brush this up as a research proposal. Q. And did you? A. Yeah, I think I did. I think it was somewhere a couple months aft,er this. And -- and subsequently to that, we wrote a -- I asked Don if we could not -- we had had -- we had had a number of -- of new hires about ten or -- ten of us came in and I was trying to use this as a place to jump off to -- as a -- as sort of like a seminar session. Q. And was that research undertaken? A. What research was that? Q. When you subsequently redid this -- A. Oh, no, no. A. -- different format. No, no. Have you ever been questioned about HUSEBY & ASSOCIATES (800) 333-2082
Page 216: raj82d00
217 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 this memo, other than by me? A . Meaning?` • Q. A. memo? A. Anyone. I'm sorry. Anyone ever question you about this Yes. Q. Who? A. When -- when -- when it came out in the -- you know -- as I mentioned in the -- that Los Angeles Timgs thing, Mark Holton and Attorney Crist, they -- they asked me about, did I know about a memo like this and that -- and I said, yeah, you know. And we talked a little bit about it. Q. Did you remember then what you meant by "devastating to the tobacco industry as a whole"? A. No, sir. Q. Does this memo appear to be accurate? A. Well, looking here, there's a-- there's several -- there's several typos in it, but I can remember that the lady that -- that used to type, she could never understand my handwriting. There's some typos, but other than that -- HUSEBY & ASSOCIATES (800) 333-2082
Page 217: raj82d00
1 1 Q. But it's -- it's a complete copy of a 2 3 5 6 7 . 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 memo you authored . A. Q. Yes, sir. January 5th, 1978? A. Yes, sir. Q. Kept in the regular and ordinary course of business by you -- .MS. FEE: Object to -- BY MR. MAISTROS: Q. -- while employed at Reynolds? BY MR. MAISTROS: Did you keep this while you were Reynolds? I'm sorry? Did you keep this memo while you were Reynolds? Well, not always at my desk. I -- I put it in record retention. Q. But it was kept in the ordinary course of your employment at Reynolds? MS. FEE: Same objection to the extent you're asking him to make a legal conclusion. MS. FEE: Object to the extent you're asking him to make a legal determination. 218 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 218: raj82d00
219 1 2 3 4 5 6 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 THE WITNESS: I don't know what that means. What -- what .- - what is it you're asking me, sir? BY MR. MAISTROS: Q. Did you draft this while you were employed at Reynolds? A. Yes, sir. Q. And you kept it in your Reynolds' records? A. I kept it, yeah, yes. Q. And it was a two-page memo and that's your signature on the second page? A. Yes, it is. Q. And it appears to be a accurate copy of some original memo? A. Yes, it does appeare to be a - (PLAINTIFFS' EXHIBIT NUMBER 7 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Number 7 is a handwritten memo dated 1-28-78 at the top. yes. Is this your handwriting? . It does appear to be my handwriting, Oh! Q. Is that "yes"? m ti w rn m HUSEBY & ASSOCIATES (800) 333-2082
Page 219: raj82d00
220 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q A. Yes; yes, sir. What' is this,.not this specific memo, but what is this memo, in the context of your employment back in 1978, what was the purpose of drafting a memo like this? A. We would incorporate things into our research notebooks. This is -- this is out of a research notebook. And this was not unheard of to -- to do that, to keep records of proposals for work to do. I think t-hat's what this is. I'd have to read it. Q. Okay. What's the title of this specific proposal? A. It says, "A novel method for the introduction of flavorants into smoke with increased nicotine transfer." Q. What type of flavorants? A. Well, let me read the memoranda, if you would, then I can -- I think I can answer that better. Okay. Q. Okay. This is a-- a four-page document? A. Yes. Q. It's a complete copy of your original HUSEBY & ASSOCIATES (800) 333-2082 1i I
Page 220: raj82d00
223 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 as a flavorant and also be able to increase nicotine transfer. Q. And is it your testimony that prior to January 28th of 1978, Reynolds had not experimented with flavorants to increase nicotine transfer? Q . Not in this method, I don't think. Forget the method. Did Reynolds employ flavorants to - in an effort to increase nicotine transfer? A. Not that I know of. Q. So, you were the first person that ever came up with the idea of using flavorants as a means of increasing nicotine transfer? A. This is what this is about, yes. That would be what this would be happened. This is what this is proposing to do. Q. Okay. Did you carry out this research? A. Yes, Q. And did you come up with flavorants that increased nicotine transfer? A. No. Q. How long did you conduct such research? HUSEBY & ASSOCIATES (800) 333-2082
Page 221: raj82d00
225 1 Q Yeah. Forget the method, again. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Did Reynolds after 1978 look at using flavorants as a means of increasing nicotine transfer efficiency? A. Not to my knowledge. Q. When I say "flavorants," that includes the universe of additives, processing aids, et cetera. Is your answer still the same? A. What was the question again? Q. Let's -- let's start over. You were looking at a means to increase nicotine transfer, correct, with this research? A. Yes. Q. And other than flavorants, did Reynolds explore any other means post-'78 to look at means of increasing nicotine transfer efficiency? A. Yes, we did. Q. Okay. What means were those? A. We were -- I looked at -- at applying Ln - N potassium carbonate to the blend, see if that would ~ m do it. We looked at some other strong bases and we w ~ N looked at strong acids, weak and strong acids and 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 222: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 efficiency. MS. FEE :..--Jack,'-_before we start the •next document, can we take a break? MR. MAISTROS: Yeah. MS. FEE: It's been about an hour and 45, I think. THE VIDEOGRAPHER: Off record at 4:02 p.m. (Recess 4:02 p.m. to 4:11 p.m.) (PLAINTIFFS' EXHIBIT NUMBER 8 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: Back on record at 4:11 p.m. BY MR. MAISTROS: Q. Doctor, I've handed you Exhibit 8. It's a January 30th, '78 memo authored by you and a Lawrence Hayes. Have you seen this document before today? A. Really, when -- when I wrote it. Not for a lot of years. Q. Okay. It's stamped "RJR Secret Number 13 by blank." Who was Number 13? A. I have -- have no idea, sir. HUSEBY & ASSOCIATES (800) 333-2082
Page 223: raj82d00
215 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarette smoke and then try to help in terms of our -- our br.ands -- brands area in terms of trying to make the best product we possibly can for consumers. BY MR. MAISTROS: Q. was this -- this was a request to begin research, was it not, or suggestion? A. This was a suggestion. Q. What did Dr. Piehl say in response to your suggestion? A. I think what -- what Dr. Piehl did, if I can remember, I -- I think that he -- I think he may have sent this to a colleague of his and to ask for some -- what his advice was. Q. Who was that? A. I -- I think -- I think it was Don Roberts, but I'm not sure. Q. And where did Don Roberts work? A. At -- at -- at Research and Development. Q. And what response did you get back? A. What -- what -- what it was, what my understanding was that, you know, is that we're probably not going to do this, because it takes - it's going to take a long time to do this kind of HUSEBY & ASSOCIATES (800) 333-2082
Page 224: raj82d00
228 1 Did you have an,RJR secret stamp? A. No. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 •Q. Do you know what criteria RJR uses to determine which documents are secret and which aren't? A. No, I don' Q. What's the title of this document? A. 'This invention disclosure.is titled "Improved Ammoniated Reconstituted Sheet." Q. In 1978 Reynolds was using what form of ammonia in its tobacco processing, January of '78? A. I believe we were only using gaseous ammonia in the treatment of formed 07 sheet. Q. 07 as reconstituted? A. Yes. Q. And how was this different than that process? MS. FEE: Object to the form. THE WITNESS: What we're -- what we were attempting here is, we -- this is like a cast sheet almost we're proposing to make here. This is not something that we did, but this is something that we're proposing to do. It -- it's like an invention. You I HUSEBY & ASSOCIATES (800) 333-2082
Page 225: raj82d00
231 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. No test results.were done to see if this worked? - •A. Not that I know of. I didn't do them. Q. In January of 1978, were you pretty familiar with the manner in which Philip Morris made its reconstituted sheet? A. I'm not sure if I knew at that time, but I certainly knew a little bit after that, little -- you know -- maybe a -- within this time -- within this three or four period -- three- or four-year period,. I -- I had a feel -- I had a greater feel for how they were making their sheet, because I did. I reviewed the patent literature and there were other people that were knowledgeable in that area. And we'd have discussions, talk about it. Q. The overall goal of this particular idea, though, was to, first, was to increase nicotine transfer, correct? the A. I don't know if that was the ultimate goal of this. I mean, like, it was to -- it was a;a ~ way to -- this improved ammoniated reconstituted m w sheet would have put ammonia,into the product in a ~ much more stable form than -- than the gaseous HUSEBY & ASSOCIATES . (80.0),:333-2082
Page 226: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 ammonia. Part of the problem..with G7A is that the ammonia never stood --••Btayed-.there. So, it was would migrate around and you'd have -- if you -- if you would pick the -- the -- the reconstituted sheet out of the blend after two or three weeks, that reconstituted sheet never had any ammonia in it. Q. But Philip Morris' did? It retained -- A. Yes. Q. -- its ammonia? A. Yes. Q. Did you ever figure out why that was? A. Well, we thought that they were perhape in their cast operation making this ammonium pectinate, but we -- we weren't sure. And there's no way to really tell; because once you've cast something, it's -- it's done. I mean, the chemical reaction is finished up and you never know really how they go -- how they went about doing that, except what we -- what we could glean from the -- from the patent literature. Q. Now, the- - you say that the method used by Reynolds, the ammonia, would disappear after two or three weeks? 232 ~ w ~ kD I HUSEBY & ASSOCIATES (800) 333-2082
Page 227: raj82d00
A. I prepared nicotine salts for about 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nine months and then py,xolyzed those salts to determ.ine their thermal stability. And none of them appeared to be useful in terms of -- of doing the dual role of increasing flavorants and transferring nicotine -- increasing nicotine transfer into mainstream smoke. Q. And what salts -- where did you get the salts you used? A. I prepared them. Aesthetically prepared them. Q. You didn't get any from the KDN process? A. No. Q. After this work in, what, the end of '78 when you ceased doing it, was there ever any additional work looking at flavorants as increasing nicotine transfer? A. Not to my knowledge. Q. So, there should be no documents or research indicating that Reynolds was looking at flavorants as a means of increasing nicotine transfer after 1978? A. There may be, but not -- not in terms of what I was doing here. 224 I HUSEBY & ASSOCIATES (800) 333-2082
Page 228: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 flavorants and increase nicotine transfer." Q. And that.was true before you came up with this novel idea, right, or is that the novel idea? A. This -- this is basically the novel idea, yeah. Q. There were not in existence before January 28th, 1978 known flavorants that increased nicotine transfer? A. Right. Q. which -- A. That's correct. Q. -- flavorants did you come up with? A. Well, I was planning to do a series of things, as -- as stated in here, to try to prepare some nicotine salts that were more thermally stable than the ones that had been tried before, because they were -- they did not increase nicotine transfer. And that the -- the thought was, if you could produce -- you could make these nicotine , salts with -- with acid groups that -- that were beneficially beneficial to the taste of the cigarette smoke, that you might do two things at one time, add the -- add the acids into the smoke 222 HUSEBY & ASSOCIATES (800) 333-2082
Page 229: raj82d00
234 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 different levels of ammonia? A. sheet?. A. Q• On the G.--- on 'the reconstituted Right. Yes, yes. And it would disappear 100 percent? A. Well, it went somewhere else. Q. Okay. So -- A. I don't know where it -went to. I mean, it's not like it vanishes. I mean -- Q. It's not in the tobacco? A. It went somewhere else. Most likely it went to other tobaccos. That's what Lawrence Hayes found out, that when you had ammdniated 07 at -- at a -- at a nicotine level of about 1 percent, that's what it normally was, if you put that in contact with other tobaccos like a high nicotine burley, the ammonia would migrate to the burley*tobacco and nicotine would start migrating onto the G7. Q. Would the end nicotine yields of the cigarettes actually change over time? A. We didn't see a big change in the -- in that, but that was a question that we were interested in. 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 230: raj82d00
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 weak and strong -- just a number of different kinds of acids and bases to sae what -- if it had any effect.in terms of changing nicotine transfer. I'm trying to think if there was anything else there. Q. And neither ammonia or diammonium phosphate is related to those issues? A. Yes, both of those are related to that issue. They're both weak acids -- weak bases. Q. And was either ammonia or diammonium phosphate one of the compounds you looked at for increasing nicotine transfer efficiency? A. I believe that was looked at in -- as a particular action item, but we've also looked at it on -- as a result of -- of applying it for burn rate control, see if it had any effect in terms of change in the nicotine transfer. Q. So, Reynolds has researched whether or not the use of diammonium phosphate or ammonia increases nicotine transfer efficiency? A. Yes. Q. And you found it did not? A. That's true, it did not. Q. ' It did not or it did not appreciably? A. It did not change it and -- and in some cases it reduced the nicotine transfer 226 HUSEBY & ASSOCIATES (800) 333-2082
Page 231: raj82d00
237 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 make cigarettes you sell commercially? A. No. It's--much too small. •Q. And you're saying that you can't add ammonia in any form to the G7 process that you currently employ, other than the gaseous ammonia? A. No., The current -- the current G7 that we -- some of the different current G7s that we've -- that we make for incorporation in our cigarettes have diammonium phosphate and ammonia in them. As I mentioned earlier, there's about 25 percent of the total number of sheets that we prepare. Different types of reconstituted sheet have ammonia and -- and diammonium phosphate in them. 'Q. I -- I still don't understand why you couldn't apply ammonia in the form of pectate to your reconstituted sheet. A. Oh, remember, what we were planning on doing here, it was where I was putting it in. I was -- I said that we were going to add this and -- to break down the pectin in tobacco. And where we wanted to do this was in the pulping process. This is where it's done in the cast sheet operation. You take the entire tobacco and you pulp it up and you add diammonium phosphate and it u, ~ ~ _j m w ~ ~ HUSEBY & ASSOCIATES (800) 333-2082
Page 232: raj82d00
221 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 handwritten notes? A. It -- it J.s. This does appear to be a complete copy of the whole thing. Q. Wrote while you were employed at Reynolds? A. Yes, sir. Q. And kept in your records while you were employed at Reynolds? A. Yes, this came out of research notebooks. Q. Okay. What is the novel method for the introduction of flavorants into smoke which increased nicotine transfer? A. Okay. This is an invention disclosure. I wrote this up before we did any of the work. So, this is my thoughts on -- on a way, on a novel method for the introduction of flavor into -- for flavorants into smoke with increased nicotine transfer. It does not say that it actually happened. Q. I understand that. And in the -- what does the first L, N ~ sentence underneath "summary" say? m N A. "There are compounds available that W Ch co when pyrolyzed in the smoking process may introduce HUSEBY & ASSOCIATES (800) 333-2082
Page 233: raj82d00
i 230 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 In this case here, you'd be using ammonium monoammonium o.r-diammonium phosphate as a -- as a processing aid to incorporate -- to make the ammonium pectinate. Q. Would it still go through the application of the gaseous ammonia? A. No, that would.not -- you know -- you wouldn't need -- you wouldn't do that in this case. Q. All right. Was there research done subsequent to this memo to carry out this process? Was this the beginning? A. This was -- in fact, this was the beginning. One -- one thing that we did do, I did make some nicotine pectinate, and that was reported in -- that was reported in the -- in the literature in a article along with about, you know, 15 or 20 other nicotine salts on the thermal pyrolysis of that, but we never actually got about to -- to making these reconstituted sheets. Q. What do you mean you never got about -- We never made any of these sheets. Q• stage? This idea never got beyond the memo 25 I A. That's correct. I HUSEBY & ASSOCIATES (800) 333-2082
Page 234: raj82d00
247 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 percent water or volatile, that particular extract is then not reapplied 100 percent to the tobacco, is it?. It's reduced to -- A. It's reduced, yes -- Q. Right. A. -- at that point, sir. Q. How is it reduced? A. To something that.'s 80 percent. Q. All right. How is it reduced? A. Okay. That is -- that goes through a-- a -- it goes into this big pot, basically, with a condenser up above under reduced pressure and it's heated. And it's heated at 80 -- 80 degrees centigrade under reduced pressure and that boils off some of the water. And that water is retained in this entire loop of the system. Q. The water that's boiled off? A. Yes. Q. But in the kettle when you're done, you have something that is more of a solid than it is a liquid? A. Well, there's still only 20 percent solids in this stuff. Q. And how is that reapplied to the sheet? HUSEBY & ASSOCIATES (800) 333-2082
Page 235: raj82d00
246 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 keep saying "reduced to 20 percent solids." A. Yes, sir..--• •Q. What does that mean? A. After you've -- after you've initially extracted the -- the stems and the -- and the -- and the tobacco and the dust, there is this very dilute extract that -- that's at about 10 percent solids. That's all there is. If you --g meaning that if you evaporated 90 percent water, 90 percent water. Q. Okay. A. If you -- and the reason I'm saying it's 90 percent, it's 90 percent volatiles -- let's put it this way, 90 percent volatiles. They will take a -- a sample of this and put it on a watch glass and then heat that watch glass up in a steam bath and they will take off anything•that's volatile off of that. Q. Okay. So -- that's what I -- A. Anything that's left is soluble. Q. -- that's what I was getting to. When you put the water through the tobacco and the -- the water and the -- whatever comes with the water is laying in the bottom of the bin, okay, in some form you're saying that's 90 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 236: raj82d00
243 1 2 3 4 5 6 7 . 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 percent water. So, there is a lot of water that you're putting into thi,s•flue-cured and burley stems and scrap and dust. So, there is stuff -- said -- Q. Okay. Eighty percent of what? You A. Okay. Like,if you had a hundred pounds of stuff that you're extracting, 80 pounds of it would be water and 20 pounds of it would be your tobacco that you're extracting. Q. Okay. I understand that, but -- A. There's a lot of water, what I'm getting at. Q. Originally, though, what you add is 100 percent water? A. Yes, yes, yes, yes. Q. I Okay. And it goes through the tobacCo in whatever form and comes out 80 percent watex and 20 percent nonwater? :; A. Yes. Okay. Now The final -- the final extract that we're applying back on the sheet, yeah. Q. Right. When you apply back on -- A. Yes. Q. When you apply back on, is anything HUSEBY & ASSOCIATES (800) 333-2082
Page 237: raj82d00
I 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. What differentiates the 12 types? A. Some of Jt•is.in the -- the starting materi.als that we use to prepare the -- the -- the recon -- reconstituted sheet. Generally we use somewhere between 60 -- about 60 to 65 percent stem and so much lamina and -- or dust. And so, the type of stem, the composition of the types of stems and the type of lamina, which is either in the form of scrap or -- or dust, that makes a big difference in the type of sheet you -- you use. And, then, during the processing, some of the different reconstituted sheets are the -- the -- the extract is heated slightly longer than -- than others. And then some of them are not only heated, but we've added some diammonium phosphate and ammonia in there. So -- and getting back, there's three things; the composition of the raw materials going in, whether the material -- whether the extract is heated, and whether the extract is heated with diammonium phosphate and ammonia. So, those are the three things that make the difference. Q. How many different plants make this reconstituted tobacco? A. We have -- our plant up at Whitaker 240 HUSEBY & ASSOCIATES (800) 333-2082
Page 238: raj82d00
233 1 2 3 4 5 6 7 A. Yeah; the a7A method, yeah. Q. That's the' metliod that was used from the beginning of time until when? A. Till we were -- I said -- I guess -- I think earlier in the testimony I -- I said it was -- we hadn't used it for eight or eight or so years. Q. . Okay. Now, how -- or how.soon after 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 the -- Reynolds began using the a7A process did they come to realize that the ammonia disappeared after two to three weeks? A. I don't think that they understood that until Lawrence Hayes did some work where he actually monitored it. Q. How many -- A. I think they believed -- I think generally people believed that it stayed there and did something beneficial. But at some point it was discovered that it left after two to three weeks? A. Yes. Q. When I say "left," in layman's terms, does that mean that if you did a chemical analysis of the tobacco when the cigarettes were made and W co m 25 1 then you did it three weeks later, you'd find 333-2082 HUSEBY & ASSOCIATES (800
Page 239: raj82d00
248 1 2 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Okay. That gets pumped to vats where it is sprayed then •onto._-the -sheet . Q. And there's still nicotine in that spray? A: Yes, sir. Q. And there was nicotine in the water that was condensed? A. Yes. Q. What percentage of nicotine actually makes its way from, once it's extracted and then reduced, what percentage of nicotine is lost? A. I think there may -- there's very little, if I reckon. There was about -- I think it was less than 5 percent at that point. Q. And regardless of the -- I mean, you have 12 different types of reconstituted tobacco. But regardless of the type, it's all still the same process up to the point in time where there's additives put in? A. Yes. Q. So, you could make all your reconstituted tobacco at the same place and all you do is alter what is put in or the method by which it is put in at the end, the additives? A. That's correct. You can use the same ~ ~ HUSEBY & ASSOCIATES (800) 333-2082
Page 240: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 taken out of that extract or is it still the 80 percent water and 20 percent-nonsolubles? .A. There is nothing taken out. There is some stuff added. I mean, you'll lose a little bit of volume, I guess, when you're -- when you're concentrating and -- and taking off some of the liquid. But after you've reduced this to -- after you've.concentrated to 20 percent solids, that's when they, if they were going to add.the diammonium phosphate and the ammonia, it -- it would be at that point before it's applied onto the wet web. Q. Okay. After the water passes through the tobacco and it's 80.percent water and 20 percent solubles -- A. Uh-huh. Q. -- is that 80 percent water and 20 percent solubles put back on the tobacco? A. Yes. Q. So, there's ne'ver any point in the process whereby you have to drain off excess water and dump it out somewhere? They're always being reused? A. There is -- there is something called the white water where there is extra water around to wash off the felt, because once you've done your I HUSEBY & ASSOCIATES (800) 333-2082
Page 241: raj82d00
245 1 initial extraction of as much water soluble as you can get off this stem and scrap and stuff, there more water added to these -- this extracted pulp that's left. And that's what goes through they conical refiners to -- to grind it up to a very, is 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 very fine mesh, so that it will be laid down on a sheet. Now, that's called your refining water. And that water is then.separated from the pulp at the head box and excess -- the water that drains through is used to wash the felts again where this,r- this material is being laid down on. So, there is -- there is more water available. I mean, there's a lot of water in this system. Q. What other than diammonium phosphate is added to the extract before it's reapplied to the sheet? MS. FEE: Object to the form. THE WITNESS: As I mentioned, the extract, after it's been reduced to 20 percent solids, you'll add diammonium phosphate,in and/or m BY MR. MAISTROS: ~ N 25 I Q. Let me stop you there. You -- you HUSEBY & ASSOCIATES (800) 333-2082
Page 242: raj82d00
250 1 2 3 4 5 6 7 8 9 10 11 12 13 14 , 15 16 17 18 19 20 21 22 23 24 25 Reynolds? MR. O' HARA': TYianks. THE WITNESS: Yes, this is the -- the review that I talked about when I first came to Reynolds that I did. BY MR. MAISTROS: Q. Okay. And this four-page document appears to be a complete and accurate version of your January or February 9th, 1978 memorandum? A. Yes, it is. Q. And you authored this document? A. Yes. Q. And you kept it in the course of your employment at Reynolds? A. Yes. Q. You filed it with your other employer or records? A. Yes. Q. Now, is there or is there not a list of the documents you reviewed when you did this 170-year review? A. There -- there should be a listing of that under this nicotine -- under one. This was a way that they used to tell where these boxes of documents were in the library. 1977, and I think HUSEBY & ASSOCIATES (800) 333-2082
Page 243: raj82d00
249 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 facility to make different types of G7 s.heets. Q. Do the ----does the nicotine content of the•G7 sheets vary? A. It does -- yes, it does vary a little bit and it depends on the starting material that you put in. Q. Is that the only variable, the starting material? A. That is the only variable, yes. Well, there -- there's one other variable, and that is whether it has diammonium phosphate and ammonia or not. Because if you -- if that's into the process, you will lose an additional 10 to 15 percent nicotine when it's being dried. Q. Is there anything that's used in the reconstituted process which has the purpose or effect of changing the pH of the smoke? A. No, not -- not really, not really. (PLAINTIFFS' EXHIBIT NUMBER 9 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 9 is entitled "Nicotine Review." I'll ask you if this document is a summary of the literature review you testified about previously that you did when you started at HUSEBY & ASSOCIATES (800) 333-2082
Page 244: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. But the -- did the end -- or the end ammonia content of the.Q3garette as a whole change when it transferred from the a7A to other tobaccos? A. If it was not in a sealed system, yes. You -- you -- you could put this in a very tight system in a vacuum and just let this go on and it would still be in there, but, you know, when it was in ambient conditions, there was ammonia that did leave. Q. What did you mean by the last sentence of this memo, "It is our belief that if ammonia is incorporated into our sheet in its preparation, that both amidation and salt formation will occur and will afford a better, more stable reconstituted sheet exhibiting the properties of the Philip Morris sheet and hopefully-increasing the nicotine transfer." A. Well, we thought that -- that if you formed a -- a real compound -- ammonia is a gas. Ammonium salts are ionic compounds. If you're actually able to form a amid, which is a co-valent bonded ammonia-containing compound, that it would -- it would stay there forever. I mean, it would be -- it would be stable. And, additionally, that, in this 235 HUSEBY & ASSOCIATES (800) 333-2082
Page 245: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 operation, we thought we could prepare stable - we'd be able to get some'salts formed from this operat•ion also. And with -- with a straight -- a stable form of ammonia and with some salts formed, we thought that it would act more like what we thought Philip Morris' sheets were -- Philip Morris' cast sheet was, how it was being prepared. Q. With one of the end products being increased nicotine transfer? A. That's what we thought might happen. Q. Why wasn't this pursued? A. Well,.we did not have a cast sheet operation. We didn't have a place to make cast sheet was part of the problem. Q. Now, cast sheet you're distinguishing from what? A. Paper process sheet, which was our reconstituted tobacco sheet 07, which is made on a Rotoformer. Q. And do you have a cast sheet today? A. We have a small pilot line at -- at our Research and Development operations and then - you know -- that's the only one -- thing we have domestically. Q. Do you use that to sell cigarettes - 236 I I HUSEBY & ASSOCIATES (800) 333-2082
Page 246: raj82d00
252 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23. 24 25 Q. And the least important would be the toxicity studies related•to-nicotine? •A. That's the way I did it. Q. Somewhere in between would be nicotine and taste? A. Yeah, yeah, that's Number 6. That's -- that's how I did this. I-- I categorized these in more than -- now that I'm looking at this, I haven't looked at this in years, that there's many more categories than I thought there were. Q. Okay. Well, in the paragraph above, just so you can see I'm not reading this out of context, you note that -- you categorized it according to topics of interest to work already started or planned in-house. Do you see that? A. Uh-huh. Q. So, in 1978, Reynolds was looking at these areas or planning to look at each of these areas, correct? A. As far as I knew, yes. To my knowledge, that was what we were planning on doing. Some of the stuff where -- I had found -- I had found some•articles either in our own documents or HUSEBY & ASSOCIATES (800) 333-2082
Page 247: raj82d00
1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 releases pectin and you form a gel basically that cas.ts out on a steel belt. -If you were to do this, if you•were to -- to put diammonium phosphate in the pulping process, you wouldn't have anything to -- to lay down on the wire to form this -- this sheet. It's -- it would be like goo on a screen. So, you -- you have to have a cast sheet operation to do it in this manner. I'm sorry. There's just two different processes that -- Q. The.idea you had of adding ammonia in the form of pectate amide, was that ever employed at any step in the process? A. No; we have never -- we've never attempted that, no, to my knowledge. Q. It says in here, "What this may mean is that in our present reconstituted sheet, where most of the nicotine is sprayed onto the surface, pyrolysis of nicotine may be taking place before a suffIcient quantity is transferred." What does that mean? A. Do you know where -- where this is? Q. Middle of the first paragraph, first large paragraph. A. What -- okay. What this means - HUSEBY & ASSOCIATES (800) 333-2082
Page 248: raj82d00
241 1 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Park makes the bulk of it and I think there's a - there's another plant downtown that -- that has some c.apacity. And I think we've been making some down there over the last couple years. Q. Is the diammonium phosphate used at one or both plants? A. For a long time it was only done at one plant, but I think it's -- it's -- both of them -- both of them make it now. And it depends on their scheduling, where they make it. Q. This water extract that -- that, I take it, comes out of this process, is that stored somewhere? A. No. It's -- they -- they -- they separate out the solids or the -- the -- the water insolubles, and that's what they use to form the sheet. And, meanwhile, this dilute extract, they have to take some of the water off of it so they can.concentrate it enough to apply onto this real wet 7latent paper sheet. And then as soon as this -- this -- they form this sheet and it -- and it goes into the dryer, this -- this sheet is about 40 to 50 percent water. And then that's strong enough that they can start applying on the -- the extract, which is at about 20 percent solids. Ln ~ J m HUSEBY & ASSOCIATES (800).333-2082
Page 249: raj82d00
I 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Okay. This -- at some point the stems and lamina, watex-'is,applied to them, correct, somewhere in the process? A. At the very beginning you add the dry stem, the dust, and the lamina into this tank and then you add water to that. Q. Okay. That water that is added, does it have anything in it? A. No. Q. It's just water? A. It's just water. Q. And it wets the lamina and stems and dust, and then as -- as it goes through the lamina, stems, and dust, you have what you call a water extract, which contains the water plus whatever it picked up out of the lamina,.stems, and dust, correct? A. Q. Correct. Now, that water extract is then rediiced to make a concentrated substance, correct? The water is removed in some fashion? A. There is not a little bit of water that's -- that's -- maybe we should talk about proportions. For every -- the water that you add is, like, 70 percent water or more. Actually 80 HUSEBY & ASSOCIATES (800) 333-2082 242
Page 250: raj82d00
229 1 3 4 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know, we haven't done it, but this is-what we think is going• to -happen. And it may be increased -- for example, "Nicotine transfer may be increased. by the incorporation of ammonia in the form of ammonium -- form of the pectate amide in the reconstituted sheet." And one way of doing that is by, we -- we believe, by the addition of ammonium phosphate in either the form of -- monoammonium or diammonium phosphate in the pulping process. we felt like this might -- might increase the chances for preparing a -- an improved ammoniated-type sheet. I mean -- BY MR. MAISTROS: Q. Would your -- was your intention to still use gaseous ammonia and use this as an added process? A. No, no. This would all be done at one time. Unlike the 07A, they -- they would form the G7 in the normal process -- no ammonia in -- in the reconstituted,process -- and then take that formed sheet and put it through this gaseous operation to ammoniate it. I HUSEBY & ASSOCIATES (800) 333-2082
Page 251: raj82d00
253 1 2 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 there was something going on at the time in -- in the -- in the station I._,was.i-n that I was aware of. There might have been more things going on that I didn't know of. Q. Out of these 19 categories, how many have -- have you worked on in your 21 years at Reynolds? A. I guess maybe five Q. Which five? A. -- six. Physiochemical Properties, Synthesis and Biosynthesis, mostly just the synthesis. Not much in biosynthesis. Methods to Detect Nicotine, D&L Nicotine, Number 8, Nicotine Salts, Number 12, Tobacco Substitutes, Number 15. Q. So, you haven't looked at Number Nicotine and Taste? 6, A. No, I -- I didn't do anything in that area. Q. Well, was any of your previous work that we talked about related to nicotine and taste? A. Up to -- up to 1978? Q. No. I'm talking about up to the present. A. Oh, not in terms of nicotine and HUSEBY & ASSOCIATES (800) 333-2082
Page 252: raj82d00
255 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 what -- what level of concentration of nicotine became.krritated, you know, to •the -- to the taste, and I never did any of that. BY MR. MAISTROS: Q. Did you -- this collection of -- of literature on nicotine, did you actually make copies of the literature and put them in one set or .did you just -- A. Yes, yes. Now, there were -- it was three different kinds of things. What we did at first was get abstracts on all of the articles that we -- we found. Some of those we -- we made full copies of. And, then, if there were books, we either bought the books or we bought -- we bought the books from Rohm Haas, or we copied parts of those books from or we got them from in our -- in our -- in,our library there and just had chapters of them. So, there was not -- not -- not all of them -- of -- of the things had full -- full copies. Some of.them were only abstracts. ~ Q. But in February of 1978, if there was ~ ~ m a scientific article or a book on nicotine in the m 25 previous 170 years, you would have a -- it listed HUSEBY & ASSOCIATES (800) 333-2082
Page 253: raj82d00
I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 okay. Oh, yes. When you make our normal a7 sheet, our paper sheet, you form this tobacco web and then you sp•ray on the extract on top of it. And all of the -- the water solubles on -- on the surface of the -- of the sheet, where if you were to -- to heat something up, it's going to -- this first time -- the first place that the heat sees is the surface obviously. But in terms of a -- a-cast sheet, it's pretty much uniform all the way through. From the -- from the top of the cast sheet to the bottom of the cast sheet, you have the same composition.of materials, and this is what I was getting at here. Q. This water extract, is that what you called it? A. Yes. Q. Contains nicotine, right? A. Yes. Q. How many different types of reconstituted tobacco does Reynolds employ? A. I think there's about 12 times -- 12 types that we make. Q. Is the makeup of the water extract the same for all 12? A. Pretty much the same, yes. 239 j HUSEBY & ASSOCIATES (800) 333-2082
Page 254: raj82d00
259 1 copied. Do you recall.receiving a copy of 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 this memorandum in 1978? A. No, but I probably did. Q. Does this appear to be a complete and accurate copy of a February 14th, 1978 memo from Fredrickson to Stowe? A. Yes, it does appear to be complete. Q. And would you keep, when you were given copies of memos such as this, would you keep. them in your files at Reynolds? A. Oh, yeah. Q. Does this accurately describe the work you were doing in this time period? A. Yes. I was working with -- I was coming down to the one, two, thre'e, fourth paragr•aph where it talks about Mr. Hayes and myself, we were doing aqueous extracts of cigarette filters and looking at the pH of those. Q. Why? A. Mr. Hayes thought that there was -- that this would be a better way of -- of looking at what was -- materials that might have been trapped more efficiently.on there than trying to take this smoke aerosol and condense it onto the surface of HUSEBY & ASSOCIATES (800) 333-2082
Page 255: raj82d00
251 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that XII means something. I'm not sure what it means. And RE with a l.ower sp is a special report or a special request. Q. Why does it say '77? A. That's when we started. Q. Okay. Now, your review, you -- underneath "A" you categorize these, correct, in areas of or in order of importance and depth to which each was surveyed. How did you decide the listing of these in areas of importance? A. Basically, I -- I made the judgment. It was -- there was really no -- no criteria. I knew more about chemistry -- since I was an organic chemist, I -- I-- I favored that more than any of the work on toxicology studies and flavor enhancement and filter additives. I•didn't I wasn't -- that didn't turn me on as much as the chemistry. So, that's why the chemistry ones are first. Q. You decided, though, in February of 1978 that if you had to categorize all the L, . r v literature, the most important category would be m the physiochemical properties of nicotine? 1w ~ a A. For me, yes. l HUSEBY & ASSOCIATES (800).333-2082
Page 256: raj82d00
258 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 updated? A. Not that )L, knqw . of , no. ,Q. After 1978 was anyone, to your knowledge, assigned at Reynolds to catalog nicotine research? A. Could -- could you be a little more specific, sir? Q. Well, was anyone charged with the task of keeping track of literature that was out there insofar as nicotine was concerned? A. I think in certain areas, yeah. I think in certain areas, our -- our head librarian will -- if you went -- if you went up and said that you wanted to do a specific search and keep up-to-date on topics associated with nicotine and tobacco or nicotine and smoke, she would -- she would keep on forwarding you everything that -- that was published on that; that she would be the one who would know who has searched to those that are active. (PLAINTIFFS' EXHIBIT NUMBER 10 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 10 is dated February 14th, 1978 from Fredrickson to Stowe with you being HUSEBY & ASSOCIATES (800) 333-2082
Page 257: raj82d00
254 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 1'7 18 19 20 21 22 23 24 25 taste. Nicotine and odor, yeah, but not nicotine and taste. Q. So, none of your ammonia research was related to nicotine and taste? A. It was related to taste, but -- but not, you know, to nicotine and taste. I mean -- Q Well, the topic is Nicotine and Taste, correct? A. Yes. Q. Has any of your research focused on nicotine and taste? MS. FEE: Asked and answered. BY.MR. MAISTROS: Q. Doctor, has any of your research focused on nicotine -- A. Oh, I'm sorry. Q. -- has any of your research focused on nicotine and taste? MS. FEE: Same'objection. THE WITNESS: The work that -- the work that this -- this relates to is some of the work that Chuck Ricks has done on nicotine and taste where they actually, you know, would make sapid solutions of nicotine, apply them to the tongue, and see HUSEBY &'ASSOCIATES (800) 333-2082
Page 258: raj82d00
256 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16, 17 18 19 20 21 22 23 24 25 in your title? A. At least -the abstract and the title of it,, yes. Q. Okay. So, any scientific research that had been undertaken on nicotine, you would have had a listing of it? It would have been in the Reynolds library by February of '78? A. Well -- MS. FEE: Objection. THE WITNESS: -- I mean, I-- that -- I mean -- BY MR. MAISTROS: Q. Assuming you were through with your research. A. To -- to the best -- to the best that we could do, yes. Looking -- looking through chem abstracts, chemicals, chemical abstracts, biological abstracts, dissertation research, the Beilstein, the review of the government documents that were available to us from the FDA, some agricultural documents. So, I-- I really left this pretty much up into the hands of the head librarian that was there at the time to do as thorough a job as he possibly could in -- i HUSEBY & ASSOCIATES (800).333-2082
Page 259: raj82d00
261 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 there was a difference between Winston and Winston A's and Winston -- and Marlboros, see if there was a change in smoke pH when we looked at the extracted filter extracts. Q. During the recon process, why are some of the extracts heated when reapplied, as opposed to just reapplied? A. Some of the -- some of the heated -- heated reconstituted tobacco sheets have a slightly different flavor. That's why not -- not -- well, they're not used in all -- all of our products. But if you need something that had a slightly more tobacco taste, then you would use one of these heat-treated or ammoniated G7's. Q. Well, you have 07 that's -- uses ammonia that's heated and G7 that uses ammonia that's not heated, don't you? A. No. We have -- we have -- we have -- we have G7 that's not heated, G7 that's with added ammonia, and then G7 that's heated with added ammonia. Maybe that's what you said. I may have -- but in terms of the ammoniated ones, one -- one is heated and one is not heated and then one is plain. Q. And that's done just for taste? U1 ~ ~ ~ m co 1 HUSEBY & ASSOCIATES (800).333-2082
Page 260: raj82d00
265 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. This is a February 17th, 1978 memo that you authored? .A. Uh-huh. Q. Looking at the use of d-nicotine in tobacco, correct? A. Yes. Q. And it is an accurate copy of your original memorandum, correct? A. Yes, yes. This is a -- this is a memorandum from a -- a team of three of us that were asked to review an invention disclosure by Calvin Neumann. And we did this at the request of -- of Dr. Mansfield and this is our reply back to Dr. Mansfield. Q. And this was kept by you during the course of your employment at Reynolds? A. Yes. Q. And the three suggestions you make to the CIM Evaluation Team are, number one, to study nicotine's effect on pH, correct? A. Uh-huh. Q. Number two, study -- I'm sorry -- d-nicotine's effect on pH. Number two, to study gross physiological effects of d-nicotine, correct? HUSEBY & ASSOCIATES (800) 333-2082
Page 261: raj82d00
262 1 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Mostly, and stability of the --. of the material in terms o_t.processing. .Q. Which one is more stable? A. The G7's that -- that have DAP on them seem to be a little more easy to handle in terms of manufacture. -A11 of them can be manufactured, because we've been making this for a very, very long time, but the patent -- the -- what do they call it, the -- the -- the flexibility of the sheet and its cutting is slightly better on the -- the ones that have DAP on them. Q. And how about the heat? Does that add to the stability? A. Yes, because, as -- as you heat it, you're•able to release some of the pectin. Part of the -- part of the things that we've said in our patents on these is that you release some of the pectin, which improves the strength of the sheet. It appears to be true. Difficult to determine, but appears to be true. Q. What is d-nicotine? A. D-nicotine is -- is an -- is an enantiomer of -- of 1-nicotine, which means that it's like the mere image of 1-nicotine. Q. Well, what's 1-nicotine? 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 262: raj82d00
1 1 2 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. And did you ever go back and utilize that information? .A. From time to time, I -- I -- I-- I-- in the first couple years I was here, yes. Q. Do you know if the list or catalog of nicotine-related research was ever provided to the FDA? A. I'm --•I'm not sure. Q. Do you know if -- if it's ever been provided to anyone? A. I -- I'm not sure. Q. when was the last time you looked at that literature review? A. Probably about 1981. .Q. For what reason? A. I think I had a question about d- and 1-nicotine at the time. There was a -- probably a paper -- there must have been a paper in the literature and I was going back and they referenced something and I-- I figured it would probably be in'this set of documents we had. Q. Was it? A. I think it was, yeah, yeah. So, think I was able to pull that out. Q. Was this literature review ever 257 F" 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 263: raj82d00
263 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. L-nicotine is the naturally occurring nicotine in tobacco, natural occurring isomer of nicotine and tobacco. Q. So, d-nicotine is similar to an analog? A. Yes, but it's -- it really is - has -- has the same -- the same geometry as 1-nicotine except it's a mere image of it. The same number of hydrogens, carbons and nitrogens and the same chemical arrangement except it's the mere. image of it. Q. Well, where does it come from? A. To have d-nicotine, you generally have to synthesize it. It's not a natural form of nicotine in -- in tobacco leaf. Q. Did Reynolds look at the use of d-nicotine in tobacco? A. No. I did some experiments on d-nicotine at one time, looking at the sidestream aroma associated with -- with it. But other than that, I -- I know of no other time when Reynolds has -- has -- has used d-nicotine. Q. You were looking at it solely to determine the effect on sidestream aroma? . Sidestream irritation, sidestream HUSEBY & ASSOCIATES (800) 333-2082
Page 264: raj82d00
266 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. That's what it says here, yes, sir. Q. In relation to'd-nicotine transfer, correct? A. Uh-huh. Q. And attempts to measure the degree of -- what is that? A. Racemization. Q. What is that? A. This is a process where one isomer like 1-nicotine is transformed to a -- a mixture of d- and 1-isomer. And they normally do that either by chemical heating.or by or -- or treatment with strong base and heat. There's a number of ways to -- to racemize something, but it's -- it's to go from one -- one pure isomer to a mixture of almost 50/50 of the two isomers. Q. Okay. Was this work carried out? A. To my knowledge, no, it was not. Again, the things -- I -- I did write.this, but it was the -- it was the suggestions of both Stew Bellin and Bob Moates. I'm -- I'm not -- I can't remember on which of these were, if any, of these were my ideas, but I was in charge of writing this. To my knowledge, none of this work was done, mainly because of the difficulty in obtaining d-nicotine. HUSFBY & ASSOCIATES (800) 333-2082
Page 265: raj82d00
267 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. And the second page, second line, although you signed it,,_.somebody states, "We also believe that work in this area may lead us to a better understanding of nicotine and may be helpful in eventually finding new compounds that mimic the action of nicotines.° Do you know who circled.the portion "and may be helpful in eventually finding new compounds that mimic the action of nicotine"? A. No, I don't. Q. Do you know who wrote on the left of that, it looks like "omit X,° "omit cross"? Do you know who wrote that? A. I -- I don't know, sir. .Q. Memos such as this, would they be reviewed by the Legal Committee? A. Well, that -- on the distribution was Dr. Bluhm. So, he was one -- he was on the -- I mean, these are -- these are invention disclosures and they would eventually get to the -- you know - the -- our legal people, because they're the people who would write the -- the patents, I would imagine. Q Well, who is Dr. Bluhm? A. He was a -- one of our patent 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 266: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 irritation. Q. A. Is that a_.physi,ological effect? I'm -- I'm sorry. Does -- Q. The sidestream aroma a physiological effect? A. It's -- it's a sensory thing. We had -- we had a -- we had a sensory panel that will look at sidestream aroma. Q. Did you look at d-nicotine in terms of its effect on pH? A. No, we did not. THE VIDEOGRAPHER: We have five minutes on the videotape. MR. MAISTROS: Okay. We can change them while I'm marking this. THE VIDEOGRAPHER: This concludes tape number three of the deposition of Dr. Thomas Perfetti. The time is 5:03 p.m. (Off-the-record discussion.) (PLAINTIFFS' EXHIBIT NUMBER 11 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: This is tape number four of the deposition of Dr. Thomas Perfetti. The time is 5:05 p.m. BY MR. MAISTROS: 264 j I HUSEBY & ASSOCIATES (800) 333-2082
Page 267: raj82d00
1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 d-nicotine's effect on pH is a separate priority or separate parameter thark_.taste; itself; is it not? .A. Yeah. I don't know why they were combined there in that fashion. It does seem a little strange. Q• Again, this was not carried forward in any sort of future research? A. No. And -- and again, I -- I think the -- the major problem is because they're very they're very -- the -- the difficulty in getting d-nicotine is very difficult to get it, very expensive. (PLAINTIFFS' EXHIBIT NUMBER 12 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 12 is dated January 28th, 1978. It's a four-page memo which appears to me to be a typed version of what I previously showed you as your handwritten notes, but you can correct me if I'm wrong. Is this a document you authored? A. Yes. Q. And`it appears to be a complete and an accurate copy of an original document you ' authored? 271 1 HUSEBY & ASSOCIATES (800).333-2082
Page 268: raj82d00
269 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 even exploring the use of d-nicotine in tobacco? A. I'm not sure except that the only thing that I can remember that -- that was different for d-nicotine is that it was -- it was -- it was less irritating. Q. In what way? A. I mean, sensorywise. Sensorially it was less irritating and this was done on -- this was known for a long time on studies. on mice and rats and rodents. I mean, not -- not on humans but on -- on animals,:appears to have less sensation or irritation. Q. Why was the first listed priority in looking at d-nicotine is reference to understanding d-nicotine's effect on pH? A. Oh, I don't know if'these have any -- any particular priority. I guess it does. The outline say -- I'm not sure why. I'm not sure why. I do remember typing this up, but not -- I don't know why that was important, why that was put number first. Q. You don't know why when you were looking at the possible use of nicotine d in tobacco, that the number one listed priority was its effect on pH? m HUSEBY & ASSOCIATES (800) 333-2082
Page 269: raj82d00
1 2 3 4 5 6 7 9 10 . 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the use of nicotine salts on -- on -- on -- on reconstituted sheet.. I_,think. we -- we did do that. And --.but those did not -- they did not meet the -- the requirement here in terms of increasing nicotine transfer. I mean, part of it is true, we did -- we did, you know, file for a patent on the use of nicotine levulinate on -- on reconstituted sheet, but didn't do what we were saying here in terms of increased nicotine transfer. It just doesn't do that. Q. Okay. But the -- when the patent was applied for and obtained, correct? It was obtained? A. The nicotine levulinate patent. Not -- this wasn't even filed for, my -- my ' recollection. Q. Right. The nicotine levulinate patent was applied for and obtained with the intent of increasing nicotine transfer? A. No. It was for in terms of -- in terms of nicotine yield. I think there's a difference here between nicotine yield and the smoke of nicotine transfer. I know there i 273 HUSEBY & ASSOCIATES (800) 333-2082
Page 270: raj82d00
260 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 an electrode. And I -- I agreed with him that, if you did have a trapping_.medium, why not just track -- extract the material from a trapping medium like cellulose acetate. It seemed very reasonable to do. So, we were doing some experiments on looking at the pH of these aqueous extracts of cigarette filters. Q. Why were you looking at the pH? A. There was a lot of -- of smoke pH data that had been collected over the years on this arginine electrode system that showed that on a puff-by-puff basis, the pattern of smoke pH for Winston was very different than it was for Marlboro. For Winston, the last puff always - you'd get this pattern that looked like a -- a sawtooth and then the last -- the last bits of sawtooth would drop in pH. the For Marlboro, you'd have the same sawtooth pattern through most of the puffs and then it would increase at the last puff. And I'm not sure exactly what all that meant, but it was collected for a long time. And we were looking into seeing if HUSEBY & ASSOCIATES (800 333-2082
Page 271: raj82d00
1 2 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 attorneys. Q. This•was Qriginally proposed in 1974 before.you joined the company? See the reevaluation heading? A. Yeah. I -- I -- I guess. I'm not -- the numbering system on these CIMs, I'm not sure how it goes. Oh, I see. Okay. It was, yeah. I guess that is•. The first evaluation is May 2nd, 1994. I guess that's what that does stand for, the year. Q. Now, you say in here, or somebody says in here, that d-nicotine has been found to be a major component of smoke. Is that true? . In 1978, I-- there was a report that there was racemization of the 1-nicotine to form some d-nicotine in the smoke. One -- one of the authors found up to, I think it was, 8 percent racemization or 8-- 8 percent of the total nicotine was d. And they had -- and -- but, then, again, there were other authors subsequently after that that did not find any racemization of -- of - of -- of nicotine. I think it's fair to say today that there is. Q. Why in '74 and then '78 was Reynolds 268 HUSEBY & ASSOCIATES (800) 333-2082
Page 272: raj82d00
1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 maybe -- maybe it isn't nicotine that's the bad guy, maybe it's tar. .Q. Based on your 21 years of research at Reynolds, have you arrived at any conclusions as to can. whether or not the benefits of nicotine outweigh the risks of nicotine? MS. FEE: Objection, assumes a fact not in evidence. You can answer, if you THE WITNESS: Okay. I don't think nicotine's so bad. Smoke nicotine, I -- I don't think that's -- that's the bad guy in terms of a -- if there is a bad guy in terms of cigarette smoke. I mean, I don't think that -- that -- that -- that nicotine is - is as bad as people are making it. BY MR. MAISTROS: Q. Are you familiar with the benefits of nicotine in cigarette smoke?' A. I -- I know some of them, yes, sir. Q. Are you familiar with the disadvantages or health consequences or adverse effects of nicotine in cigarette smoke? MS. FEE: Object to the form. THE WITNESS: I've read some of -- of HUSEBY & ASSOCIATES (800) 333-2082
Page 273: raj82d00
270 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Yeah, because I don't know why it would have -- why -- why.-it.would have an effect. ,Q. How about -- the number two priority is gross physiological effects. MS. FEE: What -- what's your question? BY MR. MAISTROS: Q. Why was that listed as a priority? A. I'm really not sure. Q. Is there any reason that taste isn't listed as a priority in determining the potential use of d-nicotine? MS. FEE: Well, it is on number one. THE WITNESS: Well, it is. It's like number one, and then there's the taste -- flavor-taste in the smoke. BY MR. MAISTROS: Q. Do you -- do you equate taste in a sensory sense with the pH level of the smoke? A. Only in the fact that -- that -- that acids taste different than bases. It would probably affect the -- it probably would have -- if you had a real basic smoke or a real acid smoke, it would affect the taste. Q. Let's see. The specific priority of HUSEBY & ASSOCIATES (800) 333-2082
Page 274: raj82d00
27 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 use if nicotine becomes prohibited. Why did yctu say.that or why did you believe there was a possibility that nicotine could become prohibited? A. The only thing that comes to mind is, you know, there was a lot of talk at -- at this period where nicotine was the bad guy out there. It was causing a lot of problems. It was -- it was being blamed for all kinds of diseases and deaths and all kinds of stuff. And, I mean, things have changed since this date, I think. A lot of the things that were originally thought to be -- that -- a lot of the studies where they -- they -- they were thinking that nicotine was the bad guy haven't really come to fruition. In fact, in doing those studies, I remember some bf the reports from one of these nicotine conferences that I went to that said that,' hey, there are some benefits, real benefits in terms of things like colitis and cognitive properties and some blood pressure things. I mean, there was a number of -- of studies that they had -- they had -- they had started that actually showed some real benefit for nicotine that -- and -- and then they said, well, Ln ~ J J m HUSEBY & ASSOCIATES (800) 333-2082
Page 275: raj82d00
272 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 117 18 19 20 21 22 23 24 25 A. Yes. Q. While you,_-were employed at Reynolds and kept in your records while you were employed at Reynolds? A. Yes, yes. Q. Now, earlier I showed you Exhibit 7, which was your handwritten notes. A. Yes, sir. Q. Does this appear to be just typed version of those notes? a - MS. FEE: Can he look at that? MR. MAISTROS: Yeah, he can. THE WITNESS: It looks like I may have - - MS. FEE: Hang on. THE WITNESS: -- added a couple more things to it, but it had to do with the same content. Thank you. BY MR. MAISTROS: Q. And, again, this idea, whether it was typed or handwritten, to your knowledge, was not carried forward in any sort of research or patented device? Well, yeah. I mean, it depends on what we're -- we -- we did finally patent some - HUSEBY & ASSOCIATES (800) 333-2082
Page 276: raj82d00
282 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 some reason something happened and I was laying on the floor. I wanted thQm to know how to -- how to treat me here. Q. And so, you put in this memo the lethal dose of nicotine if taken orally, correct? A. Uh-huh. Q. You put in here toxic levels depending upon the purity of the nicotine; that is, the form it was in, correct? A. I'm -- I'm -- I'm losing you here. Where -- where -- where are you, sir? Q. The first paragraph I'm reading from, the different - A. Ohl Okay. Yes. Q. -- things you're advising your employees. A. Yes. Q. And you put in here that a few milligrams of nicotine may produce illness or even death, correct? A. This comes out of -- of some books I-- that I -- I was reviewing. Q. Was this, your idea to warn your co-employees of the dangers of nicotine or somebody else's? HUSEBY & ASSOCIATES (800) 333-2082
Page 277: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 answer a,question until I get a document. BY MR. MAISTROS: Q. Does it appear to be an accurate copy of your original memo of March 2nd, 1978? MS. FEE: The second page has a different date. MR. MAISTROS: It does. I can't explain that, other than that's how it was produced. THE WITNESS: Okay. BY MR. MAISTROS: Q. Having read this memo, can you tell me why you sent this memo to Dr. Piehl? A.' I have no idea. Don may have asked me to update him on -- on -- on what -- what was going on out there. I'm really not sure. Q. At least if you read your memo, you were concluding that Philip Morris may also be interested in the direct physiopharmacological response to the effect of nicotine and thus satisfaction in general. What did you mean by that? A. Well, you know, the -- I remember reading some of these papers. There was a -- they seemed to be doing a whole lot of work on nicotine 275 HUSEBY & ASSOCIATES (800) 333-2082
Page 278: raj82d00
283 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. It was to just have someone available just so as you have MSDS,sheets around. We didn't have them back then. And I just thought it was important to have someone else know that these were -- these were not your -- these are chemicals that you -- you have to respect. Q. Was this memo posted, do you know, in the factory where the workers were working on the reconstituted tobacco? A. No. This was -- I was dealing with much, much higher concentrations and was dealing with pure nicotine. And so, it's more serious, I think, at that point. What -- what happened was, I had talked to -- to Bob -- Doctor -- Dr. Heckman and -- and I told him that I wanted to get some -- some things in the laboratory that -- they're very -- they're very -- they didn't want us to have our own first aid kits that weren't approved by the medical department. And I asked Bob, you know, "I think we need to have some.syrup of epicack and some carb in there available." And he said, "Well, why don't you -- why don't you write something up on safety precautions of this thing," and he said, "then we HUSEBY & ASSOCIATES (800) 333-2082
Page 279: raj82d00
1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 could go down and see if there's anybody at the safety department that 11as aproblem with -- with supplying some of this in the safety kits that are located in the lab," because syrup of epicack is not normally found there and you don't normally have charcoal in those -- in those first aid kits. Q. You can breathe nicotine in, correct? A. I'm sorry, sir? Q. You can breathe nicotine in? A. If it's in a vapor, I guess. Q: Well, if you have a vat of nicotine open and you bend over and breathe it in, can you breathe it in that way? A. Yes, you will get some. There's some in the vapor -- vapor state at that point. Q. Is there enough to make you sick? A. If you did it in prolonged time periods, yes. Q. The -- the workers that work with the reconstituted tobacco, has there ever been any test undertaken at Reynolds to determine the amount of nicotine that they breathe in? A. I think that that's routinely done by our occupational and safety people. Q. Do they wear masks when they're 284 i HUSEBY & ASSOCIATES (800) 333-2082
Page 280: raj82d00
276 1 2 salts and nicotine isomers and nicotine analogs in terms of the synthesis.of these things up there. They also had done -- filed for a 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 number of patents that -- that had to deal with the formation of nicotine salts and their effects on - on aphids and the like. And, I mean, you might want to -- I mean -- I ask -- I just ask the question, why would -- why would he want -- why would somebody be doing -- interested in doing this. And I guess what I came up with, maybe they're involved in -- they may be interested in the physiopharmacological response to the effect of nicotine and how that would -- and I guess -- I don't know. And satisfaction general, I mean, I'm really not sure how -- how I got -- why I was asked to write this or why I wrote this. Q. Do you know why you thought there might be a connection between looking at the direct physiopharmacological response to the effect of nicotine, enough satisfaction in general? MS. FEE: Object to the form. THE WITNESS: Well, structure activity relationships do tell you a little bit about the pharmacology of -- of the -- of related structures. HUSEBY & ASSOCIATES (800) 333-2082
Page 281: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. What does_.that have to do with satisfaction? A. Well, I-- I guess the -- the premise was, if nicotine had some degree of satisfaction, maybe a compound other than nicotine that had similar structure activity relations might have some similar effect. I don't know. Q. Satisfaction in what sense? A. Again, we -- we bantered that around. I don't know exactly the -- the definition of what it is, but it's that entire smoke ritual sensory, highly acceptable experience that smokers are getting. .Q. And you think it has something to do with the physiopharmacological response? A. Well, I thought -- I must have thought that Philip Morris was interested in that for some reason. -I -I can't remember the -- the -- the -- the content of these papers that I read or the work by Rondahl up there in Sweden, but perhaps it's -- I must have gotten a clue in some of that work, some of.those readings. Q. You state in here that they may be looking at these analogs because -- for eventual 277 HUSEBY & ASSOCIATES (800) 333-2082
Page 282: raj82d00
286 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 literature review where Reynolds had conducted tests involving nicotine.tests on animals? A. No. Q. When you joined Reynolds, did they have an in-house animal laboratory? A. No, they didn't. Q. Did they ever; do you know? A. I think they did, yes. Q. What years? I A. Well, it was before I got there. I'm really not sure. I think it was -- they may have had it in the early '70s, somewhere near. Q. Do you know why it was closed? A. No, I don't. Q. Did you ever hear any stories as to why it was closed? A. Q Yes. What did you hear? That the type of work that they were doing over there at the time just wasn't in -- in keeping with what Reynolds wanted to do, I guess. And -- and that they thought -- the other thing that they were telling me was, again, this is all hearsay, that -- that perhaps that the work could have been done at -- at some other location by, you HUSEBY & ASSOCIATES (800) .333-2082
Page 283: raj82d00
288 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MS. FEE: That's fine. MR. MAISTROS:. Okay. Thank you. THE VIDEOGRAPHER: This concludes THE WITNESS: We done with this one? THE VIDEOGRAPHER: -- day one of the deposition of Dr. Thomas Perfetti. The time is 5:40 p.m. ~ (Signature reserved.) (Whereupon, at 5:40 p.m., the taking of the instant deposition ceased.) ----------------------------- -- Signature of the Witness -------------------------------- NOTARY PUBLIC SUBSCRIBED and SWORN TO before me this ------------ day of --------------------~ 19 My Commission expires: ------------------- ---- HUSEBY & ASSOCIATES (800) 333-2082
Page 284: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 E R R A T A S H E E T RE: Small, et al. v. Lorillard Tobacco, et al. DEPOSITION OF: Thomas A. Perfetti, Ph.D Please read this original deposition with care, and if you find any corrections or changes you wish made, list them by page and line number below. DO NOT WRITE IN THE DEPOSITION ITSELF. Return the deposition to this office after it is signed. We would appreciate your prompt attention to this matter. To assist you in making any such corrections, please use the form below. If supplemental or additional pages are necessary, please furnish same and attach them to this errata sheet. Page ____ Line ____ should read: Page ____ Line ____ should read: - ---------------------=------------------------ Page ---- read: Page ____ Line ____ should read: Page ___ Line __ should read: Line should 289 I HUSEBY & ASSOCIATES (800) 333-2082
Page 285: raj82d00
1 2 3 4 5 7 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Page ____ Line ____ should read: - ----------- --------- ~~----------- .~...f--- Page Line ____ should read ------------ Page ____ Line ____ should read: Page ____ Line should read: ---------------------------------------------- Page ____ Line ____ should read: ---------------------------------------------~ Page ____ Line ____ should read: Page ____ Line ____ should read: Page ____ Line ____ should read: ----•------------------------------------------ Page ____ Line ____ should read: ------------------------------------------------ Page,~,-._Line __ should read: Page ____ Line __~- should read ---------------------------------------------- Page ____ Line ___,_ should read: ---------------------------------------------- GML 290 1 I HUSEBY & ASSOCIATES (800) 333-2082
Page 286: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CERTIFICATE OF REPORTER STATE OF NORTH CAROLINI~-') COUNTY•OF GUILFORD ) I, GERALYN M. LAGRANGE, the officer before whom the foregoing deposition was taken, do hereby certify that the witness whose testimony appears in the foregoing deposition was duly sworn by me; that the testimony of said witness was taken by me to the best of my ability and thereafter reduced to typewriting under my direction; that I am neither counsel for, related to, nor employed by any of the parties to the action in which this deposition was taken, and further that I am not a relative or employee of any attorney or counsel employed by the parties thereto, nor financially or otherwise interested in the outcome of the action. Registere Professional ReIN&ter Notary Public in and for County of Guilford State of North Carolina RALYN M ,/~AGRANGE e-.-.V,L)`%, M. L-iGPM; :r .':07t;RY PUL+_iC Co.rm's::ian Ex^i a :Gly 13, 2001 ! HUSEAY & AS:SOCIATES (800) -333-2082
Page 287: raj82d00
287 1 2 3 4 5 6 7 8 9 . 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know, people that have labs built for this. That was not --.I did use that same facility over there and it wasn't real -- this was not a palace. This was -- this was like a garage over there. So, the facilities weren't really great. Q. Well, weren't -- weren't the attorneys housed in this garage as well? A. I don't know. I don't know. Where were the attorneys housed? MS. FEE: Object to the form. What attorneys? MR. MAISTROS: The in-house Reynolds attorneys. THE WITNESS: I'm -- I'm not sure. I don't know where the -- the -- the earliest attorney that I ever had a dealing with was Herb~Bluhm and I-- I don't know where Herb was located. I think he was down at the Reynolds building. MS. FEE: Jack, it's after 5:30. Can we - MR. MAISTROS: Sure. How about -- when do you want to start, at 9:30? HUSEBY & ASSOCIATES (800) 333-2082
Page 288: raj82d00
274 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. What is the difference? A. The nicoti,ne transfer talks about the rate of something that transfers, but yield talks about the total load that gets transferred. If you start out with more in the tobacco, you will get more in the smoke, even though the transfer rates are the same, whether you have a little bit or you have a lot on the tobacco. Q. So, the nicotine levul.inic patent was related specifically to the nicotine yield? A. Uh-huh. To my understanding. That's what we were -- that's what it was -- it was useful in -- it was a -- it was a useful means of increasing the yield of nicotine in the smoke and -- and -- and obviously the -- the flavor. (PLAINTIFFS' EXHIBIT NUMBER 13 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 13 is'a March 2nd, 1978 memo from you to Dr. Piehl. Again, this was kept by you during the course of your employment at Reynolds? A. Uh-huh. Q. This appear to be an accurate - MS. FEE: Hang on, hang on. Don't 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 289: raj82d00
280 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that material, yes. BY MR. MAISTROS: Q. And do you think the benefits of nicotine outweigh the adverse effects of nicotine in cigarette smoke? A. Yes, but let me add something here that -- that these -- a lot of this has to do with -- with how cigarette smoke and the individual that smokes them and whether they're, you know, smoking, you know, mass quantities of -- of cigarettes every day and whether you're smoking for enjoyment and the -- the number that you smoke. It's not -- it's not that everything is always bad. It's like the degree, I think, and -- and how many -- how many cigarettes one might partake in a day and how he or she smokes those cigarettes. I think that's also important. I mean, there's -- there's risks in terms of doing everything. And, for me, and this is my personal opinion, the benefits far outweigh the risks associated with it. (PLAINTIFFS' EXHIBIT NUMBER 14 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 14 is a memorandum dated i HUSEBY & ASSOCIATES (800) 333-2082
Page 290: raj82d00
281 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 April 13th, 1978 authored by you entitled "Safety Precautions for Handling.Nicotine." Do you recall authoring this memorandum? A. Yes, sir. Q. And why did you,author this memorandum? A. This -- the memorandum was -- was - was -- was written so that I had something on hand. This -- it's a safety measure. When you're dealing with -- I was dealing with nicotine to prepare these nicotine salts and this was just some general information on -- on nicotine that I thought was important that people in the laboratory know -- knew that I was -- first of all, I -- I'd have a sign. I would say, "I'm dealing with nicotine in here," because people knew that -- that not to disturb the flask that I had in the -- in the hood and the light, and just some general safety things. And I thought it was important to have this information around. Q. You thought it was important for who, your fellow employees? A. Yeah. I was working in a lab with -- with a couple other people and -- and -- and for Ln H 1 -4 ~ m ~ kth N co HUSEBY & ASSOCIATES (800) 333-2082
Page 291: raj82d00
285 1 2 - 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 making the reconstituted tobacco? A. No, because it's not -- it's not at a level high enough to require that. Q. Did you ever have any accidents in the nicotine you were working with? A. I don't believe I ever did, no. Q. Did you require your people to use gloves when they were working with the nicotine? A. Well, I was really the only people that I-- I'm -- I made all of these. I-- I didn't -- I was in charge of -- there was no one else making these compounds except me. Q. Did you wear gloves? A. Oh, yes, yes, and goggles, you know. Q. Did you ever do any animal tests - testing involving nicotine? A. No. Q. Do you know of any work at Reynolds that did animal testing involving nicotine? A. I can't think of any. Q. Did Reynolds, during the time you worked there, contract out any animal tests involving nicotine? A. Again, I'm -I'm not aware, sir. Q. Did you read any literature in your 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 292: raj82d00
A laboratory instrument for measurement of CORESTA paper permeabilities has been designed by us and parts for its construction have been ordered. We do not consider any instrument now available to be satisfactory for this measurement. Work on a CORESTA instrument at TD.has been delayed due to higher priority projects; therefore, we have chosen to build'our own instrument. For our studies the CORESTA permeability will be superior to the Gurley porosity. A study of the inherent variability in cigarette paper porosity is underway. Historical data on Ecusta 856 and 853 papers and Schweitzer 856 paper have been obtained from Quality Control. Bobbins of several lots of each of these papers have been obtained. An analysis of the variance of Gurley porosity is being undertaken. a A study of basic properties of cigarette papers, including surface area analysis and pore volume analysis is underway. No results are yet available. ~ C. Low-CO Prototype (Norman, Whee'ler, Smith,,Massey)• The development of a prototype low-CO cigarette is proceeding on or ahead of schedule. Seven hand-made prototypes (90 mm in length) including two blends (CAMEL NF and NOW), two filter systems, two paper porosities, and two cigarette diameters were.prepared. FTC 'tar' ranged from 3.1 to 6.5 among these and main- stream CO 004lways less than one-half FTC 'tar' delivery. There are almost no commercial.Ai*" cigarettes for which mainstream CO is less than FTC 'tar'. i nceE the level), the results in Table I were obtained. It is seen that again the mainstream CO is alway-sAss than one-half the value of the FTC 'tar'.. le of pr~a.~...t~ypes kepe s and-made prototypes achieved the CO reduction desired, the overall igarettes was reduced to 85 am to facilitate machine-making of the en this was done, and other construction parameters (in c:eneral) except air dilution, which was adjusted to produce the desired.'tar' TABLE I SMOKE ANALYSES FOR MACHINE-MADE PROTOTYPES Prototype FTC 'Tar' (mg/cigt) Mainstream CO (mg/ciot) FTC 'Tar'/CO ~ 1 5.3 2.4 2.2 AMA 2 4.8 1.1 4.4 oftl~ owl M-V 3 5.5 0.9 6.1 4 4.3 ' 1.2 3.6 r N R JR16440 J IV
Page 293: raj82d00
target of this work) could be removed. It is planned to discontinue work on this additive. , :b KV}~:M\ 13d • Silver permanganate (AgMn04) supported on alumina has been shown to remove both HCN and NOx from smoke. No CO reduction has been observed. Up to 73% removal of HCN and 26% removal of NOx from regular Lark cigarettes has been achieved. Some further work is planned. b. Silver Permanganate c. Copper Oxide-Tin Oxide Gels . Several copper oxide-tin oxide mixed gels have been preDared. These have been tested for activity toward HCN, NO and CO in smoke HCN, and to a lesser extent NOX, are affected by t9ese materials. Further work is planned. d. Palladium-Copper Oxide Catalyst Several years ago, preparations of this agent with an alumina suppo'rt were found to remove CO from cigarette smoke but cost was .pv.Wbitive. Recent work has been directed toward (1) reducing the APpY9t of palladium required, (2) reducing the amount of high-purity na support required, (3) reducing the density of the catalyst, .A"nd '(4) attemating to make detailed X-ray and electron microscopic nations of the catalyst to better understand its properties. New rative techniques have so far not yielded satisfactory catalysts. ct staff are currently acquiring expertise for the microscooic -ray work. Encouraging progress has been made in the use of X-ray ima.~ ng for examination of location of particular elements on the surface .",~the support. e. Activated Bauxites Nine activated bauxites have been ordered. These materials will be re-evaluated for HCN and NOx removal activity and taste tests on cigarettes with the materials in the filters will be performed. :~ (3) New Additives (Townsend, Norman) ~ . a. Union Carbide No new samples of CO-removal agents were received in the past quarter. Mr. Norman and Dr. Reynolds visited the Union Carbide laboratories in January to discuss Union Carbide's experimental techniques. Recently, Union Carbide has reported to us results of a new test performed with improved techniques. They claim to have an agent that will reduce the concentration of CO in smoke by about 6%. However, owing to an omission of experimental details, it was not possible to evaluate their report. Additional details will be sought. RIR16438
Page 294: raj82d00
TABLE III BLEND ANALYSIS , CIGARETTES CONTAINING Si SUBSTITUTE ' x x x x . x u914 Blend Nic otine Nitro en T. Su ar NH Na ~H Cu Ni Cr Fe Pb WINSTON ~ _ 1.76 2.51 10.8 S 0.26 0.060 5.50 36.2 3.6 8.3 622.6 15.6 Contol l4 1 1.61 2.38 10.5 0.28 0.066 5.45 29.4 4.8 7.6 649.0 19.1 0 1 1.67 2.31 10.1 0.25 0.098 5.48 25.8 5.7 . 8.3' 590.8 18.2 ' 1.46• 2.14 9.1 0.22 0.156 5.41 29.4 5.0 7.6 508.1 9.8 Cigarettes were made from the above blends without difficulty. Firmness, pressure drop, and burn rates were within acceptable limits without modification ~ of the making process (Table IV). Smoke analyses (Table V) showed little change Aft, ~ in cigarettes containing 10 and 25% substitution but significant reduction of TPM, ~.... nicotine a C tar in those containing 50% substitution. Cigarette panel tests showed no differences or preferences. . TABLE IV i , U7 M *Kax ~ ~ %• BURN RATES OF CIGARETTES CONTAINING S1 SUBSTITUTES . ~ * ", ~~Mw POW Mu". . . . V m WINSTON Cdntrol 10% S1 25% S1 50% S1 0 m mia mm min 59.8 4.6 61.8 4.9 63.8 5.1 55.5 'S.0 TABLE V ~.... _ ANALYSI OF MOKE FROM IGARETT ONTA NIN 1 E • Puff Count TPM (op)• Nicotine (mq) FTC 'Tar' (mq) Blend (cigts smoked) cigt up ff cigt puff ci.t puff WINSTON Control 9 40 26.2 ~ 2.92 1.39 0.155 20.5 2.28 10% S1 8.8 45 26.6 3.03 1.46 0.166 20.9 2.38 25% S1 9.0 45 .26.0 2.89 .1.41 0.157 20.2 2.25 50% S1 8.2 35 23.5 2.85 1.17 0.142 18.0 2.19 TPM H20 (a 4.3 4.3 4.3 4.3 R JR16447
Page 295: raj82d00
VIII. IN-HOUSE TECHNOLOGY ~., ~ A. New Filter Concepts (Project 1246 - Reynolds) An outsider idea for a filter additive which would oxidize carbon monoxide to carbon dioxide enzymatically was evaluated in consultation with Dr. Lee. While the idea was found to be interesting, research data which were available on such systems did not show promise for development of a practical filter system for cigarette smoke. Research on•such enzyme systems will be monitored via the scientific literature. B,_„Smoke pH (Pro3ect 1245 - Fredrickson) (1) Multiport Smoke pH Determination (Harris, Brame) L puff volume and clearing puffs has been completed. effects o . The multiport smoke pH method is being re-investigated to learn more about the effects of puff volume, number of cigarettes smoked per determination, quantity of water in the stirred trap, and the volume of air drawn through the trap after smoking. A study of the effect of puff volume on 'tar' delivery is included to provide data for the application of the method to air-diluted cigar . WINSTON ci garettes are being smoked.with 10-,17-,35-,50-,65-and 80-cc puffs~ ~ number of clearing puffs of air drawn through the stirred trap for each rolume is being varied from 0 to 100. All determinations are being carried o in triplicate. Work with 17-,35-and 50-cc puffs has been ~qmpl" ed Data obtained with the 17-cc puff volume differed sic~nificantly esfmlrom t ata obtained with either the 35- or 50-cc ouff volume. The smoke *Wo va ere about 0.4-0.5 pH units higher. The number of puffs per cigar •ncreased from 9 to 11. Approximately a third'of the work on the (9'1"MBrand Comparisons • pH of Aqueous Extracts of Cigarette Filters (Hayes, Perfetti) Work on the method described previously (QRR. December 22, 1977) has continued to establish whether the data are a useful supplement and/or alternative to the twenty-port smoke pH values. Comparison of the data for some commercial cigarettes with the multiport smoke pH data, Table VI, showed the differences in pH are generally greater for the filter extract than seen in the nultiport smoke pH method. This provides an expanded scale for characterizing differences'among commercial cigarettes. 41 RJ R1644g N J J m ~ L„ K.)
Page 296: raj82d00
.61 ~ CONFI9ENTIAL Physical Science Section Author: Mary E. Stowe ...~~.~~~ pL...NW.''.I'IF~ -`~ .I81 / To: Dr. Donald H. Piehl Period Covered: January 1, 1978 - Manager, Chemical Research March 31, 1978 Y Re: Quarterly Section Research Report No. of Pages:' 15 0 I. GAS PHASE (ProJect 1246 - Reynolds) A. Investigation of Systems to Reduce Gas Phase . (1) Diffusion (Townsend, Norman) A substanL•ia1 effort to understand the-various aspects of the diffusion pf CO from cigarettes has been made in the past two quarters. During this quarter, a study of the mass balance of CO generated by CAMEL tobacW.i*s with varying amounts of air dilution (supplied by mouthpieces) was c ed. The res-ults showed that as air dilution is increased, the A credses No other re orts of th d i t i t f CO f li t percec}~agQ•of C0 lost by diffusion from mainstrew smoke through the wrapper ~. . p e erm e na ion o rom garet es t c ~e k ~ The amount of mainstream CO decreases in excess of that expected 91th is labor and s i t. has cigarette decreases as dilution increases. I s of dilution alone. This is only partly accounted for by diffusion. has been noted before. However, owing to the development in. our ory'of a method for capturing all of the CO from a smoking cigarette, ~ l idtifi iiiil eyenyngts sources as manstreart, sidestream and diffusona, (2) Proprietary Agents (Townsend, Norman) a. Sodium Bismuthate ~ J ~ m r m ~ 0 N m w a' . Several new and improved preparations of sodium bismuthate (Na6i03) on various supports have been made. Tests of these preparations as filtration additives showed that substantial amounts of HCN could be removed from smoke but only a very 9mall percentage of NOx (the principal The decrease in total CO occurs because (1) the mainstream CO (i.e. that exiting the mouthend) decreases, (2) the amount of CO diffusing from the wrapper remains almost constant (note that this makes the ~oercenta _e of mainstream that diffuses increase) and (3) the amount of si est~ ram - CO (defined as that entering the air directly from the coal or the 2-3 mm directly behind the coal) increases sli ghtiy, but not enough to counteract the precipitous decline in mainstream C0. Continuation of the work on.CO diffusion will include the thorough investigation of the effects of various types of cigarette papers. At this time it seems likely that the study of CO diffusion will prove interesting and fruitful enough to continue its study beyond July 1978. q possible to show that the total amount of CO generated by a R IR 16437
Page 297: raj82d00
b. Pyrolyzed Ion-Exchange Resins Rohm and Haas Company recently advertised new sorbents con- sisting of pyrolyzed ion-exchange resins. These amount to hard, spherical beads of activated carbon. In cigarette filters, they performed just as one would•expect carbon to do. They were no more effective than a commercial cigarette-grade carbon. No further work is planned. .~,. c. Ascorbic Acid-Ascorbate Salt 0 British Patent No. 1,484,663 to Hoffman - LaRoche described the use of an equimolar mixture of ascorbic acid and sodium ascorbate as a tobacco additive for reduction of NOx in smoke. The patent suggested that removal of NOx from smoke was occurrina as the smoke passed over the treated tobacco. This additive was tested as a filter additive in our laboratory in these forms: deposited on filter tow, on A1203, and on Pittsburgh BPL Carbon. No reduction in HCN or NOx was noted except for some HCN removal by the A1 203-supported material. This may be due to the support itself. No furtFier work on this ..r..ial is indicated. ' :. Fact Cigarette Filter Additive ;0~ ~~ftu ;~ . act cigarette filters contain one of the few non-carbon filter ves used commercially. A study of some of the properties of the ve showed that it is capable of removing some.HCN,.acetoldehyde rolein from smoke but does not affect NOx, isoprene, or CO. In ct cigarette only about 30 mg are used. The reductions of these components achieved are as follows: HCN - 37%, acetaldehyde - 26%, an`dr~Urolein - 25x.' Additional information about the Fact cigarette was also obtained. B. Refine Predictions (Townsend, 5inith) The commencement of a new, more extensive study of the effects of cigarette i i i h d i b ow aaa n, ng construct on parameters on smoke c em stry has een postpone d uct and principally to a new assignment dealing with the development of the N-pro :~ secondarily to a need for basic knowledge and expertise in the area of measuring and understanding cigarette wrapper porosities. In regard to the second of these, a new Gurley densometer has been obtained for our use. Considerable time has been devoted to learning to use it and in com- paring data obtained with it to data obtained with identical paper samples at Whitaker Park Quality Control: So far we,have observed that our instrument yields consistently lower porosity measurements than Whitaker Park'Quality Control. The Ln ~ ~ ~ m effect of humidity on the measurement does not account for the discrepancy. Further work to attempt resolution of this problem is ongoing. V RIR16439
Page 298: raj82d00
evaluate its performance. A second type of seal, a ferrometric rotary seal, was considered to be too expensive. The cost was $330.00. (2) Alternate Methods of Smoke Collection A trap utilizing a bed of glass beads vibrated by ultrasound has been tested as a possible substitute for the stirred trap. Various quantities and sizes of glass beads, liquid volumes, and energy levels up to 450 watts were tried. No useful combinations of glass beads, liquid volumes, and energy levels were found. (3) Smoking Laboratory , Renovation of Room 201M has been started. The furnishings and • utilities have been removed; the new duct work has been fabricated; and the new furniture has been received. Delivery of air-handlinq equipment is expected in•April. Hood design was reviewed with the designer and project coordinator on March 20. III. SMOKING AND HEALTH (Project 1246 - Reynolds) tii ~ . ::ti 'v i . . } . A. I0. iation on Gas Phase (Reynolds) 1 OR ~~ Up-to~dati information on research on the gas phase of cigarette smoke doc~p~tsi.e R R labs has been examined as it appeared in the scientific literature. A k,e~word exed file is maintained of this research for use in meeting requests fw_v.A-qformOW. on specific topics. IV. Ln F_ EXPAND _. OBACCO (Project 1211 - White) _J ;~ J m A. Flui"Nzed Bead Bed (White, Worrel l) 110W ~ ~ Assistance has been given to.Mr. Merricks of Tobacco Development in ~ x~~=A rn accumulation of data on the fluidized bead bed process and product. Since disclosure of the porous belt puffing technique (see below) efforts have been Swo concentrated on evaluation of the PBP process and product,and work.in Research n on the FBB has been limited to supplying information to Dr. Bluhm in regard to possible patent applications. B. Porous Belt Process (PBP) (White, Worrell) O-A A new puffing process was disclosed in CIM, 1978, No. 1. The process, termed the porous belt puffer (PBP),and product have been evaluated on lab-scale equipment built in the Mechanical Development Department. A variety of expansion agents including pentane, ethyl alcohol, acetone, and isopropyl alcohol have been shown to effect expansion of flue-cured tobacco in this process. Increases in filling value ranged from 63% to 183% depending on the expansion agent used. Excellent expansion of flue-cured tobacco and G13-A blend tobacco was obtained under the following conditions which were established by a parameter study. Y RJR16443
Page 299: raj82d00
1. Expansion Temperature --- 200°- 215° C 2. Residence Time in Heated Zone -- 25 - 30• sec 3. Moisture --- 20 - 25% 4. Expansion Agent --- 30 - 40% Isopropyl Alcohol (dry basis) . oil analysis is pending. Following the recommendations of Mr. Merricks of Tobacco Development, G13-A blend and uncased burley tobacco expanded under the above conditions were used for product evaluation. Filling value of the G13-A blend was increased from 403 ml/100 g to 815 ml/100 g. The product did not show a significant increase in fines. Nicotine was reduced by 50% in the product and total suaars by 36%. When the product was added at the 12% level to WKS blend containing no G13, rod weight was reduced by 7.4%. Routine smoke analyses on these cigarettes showed nothing unusual. Booth panel tests showed a directional preference for the -product containing the PBP tobacco over a product containing the same level of tobacco expanded by.the G13 continuous process in the category of flavor. Essential V. SATISFACTION (Projects 1250 and 1245 - Fredrickson) to b0b le' The investigation of "free" nicotine in tobacco will include ~cotine is Bound in Tobacco (Fredrickson) - A. H~„~ ~~ The 4~l work consists of investioations of (1) the "free" nicotine ~'. tobacco7andN(2) the distribution of nicotine in the•cellular structures of ~~ ~: stue~s of , extraction and distillation methods in the literature which have beevwUsed r fine the term, "free" nicotine. In the investigation of the distributi nicotine in the cellular structures of tobacco leaves cytochemical ~ techniques wi be used to search for sites of high nicotine concentrations and . ~~ for diffe s in the binding of nicotine within the various cellular structures. ~ . Work in progr s includes the testing of nicotine reagents and development of procedures for these studies. f B. Factors Affecting Nicotine Transfer Efficiency (Hayes, Perfetti) o (1) Efficiency and helease Profile W ~ Initial work will be concentrated on the release of nicotine from CP various organic nicotine salts at elevated temperatures. Pyrolytic gas a chromatography and pyrolytic gas chromatography-mass spectrometry will be employed in these studies. The necessary instrumentation has been ordered. The Yarian 3700 gas chromatograph has been received. Delivery of the pyrolysis probe is expected soon. Installation of the facilities for the gas chromato- graph in Room 103M is nearly finished. A variety of organic nicotine salts will be needed for this study. The nicotine salts prepared by Dr. John Diffee have been obtained. The commercially available salts have been ordered. The preparation and/or purchase of the remaining salts is under study. The syntheses of a wide variety of nicotine salts have been found in the literature. • RJR16444
Page 300: raj82d00
Project: 12S0 Smoking Satisfaction and 'Tar"/Nicotine Control (Cont'd.) smoker satisfaction will be determined throughpane 1 testing. Information developed in this manner should be most useful in designing an experiment involving the consumer and directed toward defining smoker satisfaction and the impact of various p3rameters on smoker satisfaction.': Long-Range Plan: - r nicotine/"tar" ratios and smoker satisfaction should be obtained in 1978:" through 1980. Expectations are that significant information concerning ~~. ~ .. Personnel: ~ J. D. Fredrickson 1001 T. Perfetti 1001. R. B. Liv. . ~ 1001 C. L. Nevnann 901 J. P. Dic~ 20% T A Harp~fr .. 25~ ~' ~ . ~ M. Wagd~,~ : 40% g.~ ~ .-. _ . . RJR7289 Project effort is expected to remain at approximately the current level ;
Page 301: raj82d00
b. Heat Treatment of Tobacco Preliminary work on the modification of tobacco by heat is in progress to observe the effects of moisture, temperature, and time. Samples (500 g) of tobacco at 10, 12 and 14% moisture are being heated at 125° C and 15 psi in a pressure vessel for 30 and 60 minutes. Evaluation of the treated samples includes the determination of nicotine, total alkaloids, ammonia, total reducing sugars, and moisture in the tobacco samples and nicotine transfer to mainstream smoke. of additives and treatment of individual blend components on • nicotine transfer. This preliminary work prefaces a larger study which wiil inctude a more thorough examination of the effects of moisture, temperature, and time in addition to investiqations of the effects C. Smoking Parameters (Project 1246 = 94x,-t4assey) A study of, the effects of smoking parameters on nicotine filtration and delivery is being undertaken. This study is designed to give information on nicotine dl~y under smoking conditions which cover a range of conditions found for s. Smoking variables are: . ~~' D~.ff 1/wt~rne 7G 49 AD an Ana 4A ml Y. 1. V\Y.11~ --- (.V, VV, TV, VV Y.'Y Y4 .I.. 0*11~'_N uration --- 1.15, 1.50, 2.00, 2.50 and 2.85 sec ~~ ~ P requency -- 30, 45 and 60 sec ~ . W~w A RSM des1JWM being used for the study. Data collection for WINSTON is comolete anLA*a will be sent to Mr. Bill Line for computer analysis. Similar . ~ studies are pUpned for other cigarette types. ~ VI. TOBACCO SUBSTITUTES (Project 1188 - Squires) ~ A. C_ onsultation on Develoyment of J10 (White) ~ ~ At Dr. Bluhm's request samples of J10 with and without tobacco dust added ~ were prepared. Cigarettes made with these samples were used for taste panel ~ tests to provide informetion for patent purposes. ~ An alternative method for application of tobacco dust to J10 was developed. ~~ Double-strength caramol color was omitted from the binder formulation and invert sugar was used instead. Dust coating was uniform and adhesion was good. B. Extruded Extender (Squires, Spence, Cody) ~. the extruder. " . Extruded composition S-1, a mixture of starch, glycerine, water and acid- proof caramel coloring expanded by incorporation of citric acid and NaHC03 into the mixture to generate COZ was used to replace 10, 25 and 60% vol/vol of WINSTON blend. -Analysis showed decreases in all major constituents except sodium and nickel (Table III).Sodium increased because of the use of NaHC03 and nickel in- creased as a result of the action of acids on the hot nickel-bearing alloys in RJR16446 ~
Page 302: raj82d00
RJR16451 U ~ew.. w The method was applied to the study of the transfer of materials from the cigarette rod to the filters with age. The values for freshly prepared cigarettes continuously decreased for a period of 25 hours and eventually leveled off implying an equilibrium had been attained. The migration of volatile acids is believed to have produced the observed change. Rates for the transport'of acidic materials into the filters were identical for WINSTON and WINSTON A, but different for Marlboro.• •In a long-term (35 days) study of filter changes, packages of Cigarettes were opened and exposed to the atmosphere in the laboratory. The previously observed decrease from the initial value and subsequent leveling off at the data was again observed. After about seven days, there was a steady increase in the values with time. The kinetic studies showed that the migration of acidic material from the rod was characteristic . of the blend. The role of ammonia, if any, was not.demonstrated by the data for WINSTON and WINSTON A. The rate of migration of acidic materials was greater for WINSTON-type blends than for the Marlboro blend. I IX. SERVICES • A. lare-Ua Problem (Harris, Brame) ~ ~"^,4 Work ~ in".duaT~,c . •thmpper obsowed f, w e proble^i has been completed. A study of tipping papers and onents of the dye system showed that the brown dye used to overprint factor in the occurrence of flare-ups. No flare-ups were garettes fabricated with a 32-g tipping paper colored with the stem or the regular 36-g brown-back tipping paper which used a standard ~ different 4 A Mr. Larry ~ eIA) ystem. A memorandum summarizing the results has been sent to of Tobacco Development. B. Assistance to Analvtical (Harris) Assistance was given to Miss Campbell in the redesign of a smoking and sampling system for the GC determination of sulfur compounds in smoke. Ln ~ ~ ~ ~ C SEM d X A l ~ . an -ray na yses (Squires) ~ Ln ~ Examinations included snmples of foam filter materials, bauxites, catalyst ' residues, "Free" brand cigarette filler engulfed with mold, "Styraqel", cigarettd wrapper foils made by Archer and by Reynolds Aluminum Company and glass 3ars used for packing Chicken and Noodles b RJR Foods y . Energy dispersive X-ray analyses of interest revealed: (1) the presence Of iron, copper and sulfur deposits in glass jars which caused an unacceptable coloration of the College Inn Chicken and Noodles packed by•RJR Foods, (2) the presence of aluminum,silicon, sulfur and chlorine in Styragel. The wave length dispersive X-ray automated programs do not function properly. ETEC Corporation is being pressed to correct this_problem. V . / ilti ~• , Mary E. towe ,,?IVS176' ~ Date
Page 303: raj82d00
Both the hand-assembledand machine-made prototypes were submitted for taste- panel tests versus the True 5 mg cigarette. The hand-assembled prototypes did not fare well compared to True but the machine-made cigarettes showed improved performance in panel tests. A collaborative effort with Dr. 0. P. Dickerson to evaluate belnds for use with low-CO cigarettes has been initiated. Dr. Dickerson recommends blends', while this group recommends the remainder of the construction parameters and filter systems. So far, two sets of cigarettes have been produced. Dr. Dickerson sub- mitted both for taste tests versus the True 5 mg cigarette. Improvement in per- ~~ formance of the second set over that of the first was observed. This collaborative ff i e ort s expected to continue ~ . ~. Results of work on low-CO prototypes as well as the basic information ~~ utilized in the design of these prototypes wee feported to interested staff from Tobacco Development.in mid-February. Their advice has been sought on evaluation of the taste of these prototypes. ¢., ~• . ;:~.:.::., ~.. ~~: D. Sidestream Gas Phase (Harris) . 4 Droject waibedun in March. A stu~ the effect of the amount and type of tobacco burned and the effect cigarette type on sidestream smoke formation is being postponed pending completion> e Chemical Division smoking lab Some work on this construction w1m. Ner~•`"pi~lters and Advances (Wheeler, Norman, .$mith, Mass•ey) e ,00M. - ~~ A spe roJect to aid the development of the N-product was initiated ~ ~ in February.. ans for this work inicude the following: (1) Exam`nation of the puff profiles of a panel of smokers using WINSTON, NOW and N-cigarettes in order to determine whether there is a consistent change in s.oker's profiles with N- cigarettes as compared to full-flavor cigarettes and/or other low-tar cigarettes. If such a difference exists, it might indicate a role for the puff profile in the N-product taste problem. Discovery of such a profile difference would be grounds for further investigatioe of the causes and effects of it. (2) . N-type cigarettes with filter plugs of 10, 20 and 30 mm will be made with tobacco rods of CAMEL (NF) and N-product blends. All will be made to deliver the same 'tar'. These cigarettes will be taste-tested by a special panel to be run by Tobacco Product Development. Additionally, these experimental cicarettes will be tested on the puff-profile panel. The present status of this work is as follows: (1) Profile testing of 8 smokers has been completed for WINSTON, NOW, and Regular-N-cigarettes. Results obtained so far show a trend of smokers takirlq larger puffs with N-cigarettes than WINSTON or NOW. RJR16441
Page 304: raj82d00
The expanded extrudate rvithout color added is snow white.. Addition of 30% (by wt of the starch) of 60-mesh tobacco dust produced a suitable color but would not pass through a die small'enough to form a useful strand. Tobacco extract, even when concentrated and added at the maximum level tolerable,produced only a light tan color. Caramel coloring produced a tan color which may suffice. It is Currentiy used as the colorant of choice. Other colorinq agents have been unsatisfactory because of their GRAS status, heat lability, •thermal setting or lack of inherent lubricity. A sample of North Carolina peat has Just been received for testing as a natural source of dark-brown coloring .atter at low cost. , When citric acid was removed from the extrusion mixture, the acidity of the starch and caramel coloring generated enough C02 for blowing. Control of blowing was accomplished by the amount of NaHC03, temperature • profile and screw speed. It was thereby possible to predetermine the pH of the extrudate from about 6.5 to about 9.7. The pH of the extrudate used in first (Sl) test series was 6.5. Thc• second test series (S2) contains extrudate made without citric acid. The pH was 7.4. These cigarettes have been, submitted for analysis and panel tests~ expect the nickel content to drop back to near normal. Of pa ~1ar interest will be any change in taste and preference which may b re ted to the change in pH and absence of citric acid. ~ ~ ~ on filament die was designed and constructed through the cooperative for Research Department, Mechanical Development Department and Machine op Mnel. Initial trials were fraught with problems in'start-up and leaka . odification is being attempted. VII. ANAC~IL SERVICES A. Specialized Anal.yses Air Dilution and Filtration (1) DPF Determination (WfjLlgf) Ln ~ ~j Work on evaluation of an optical microscopic method for DPF m determination is ongoing. Samples of tow items ranginq from 1.6 to 16 ~ DPF have been Obtained. Work will continue as time permits. Ln ~-A (2) Study of Monsanto Foam Filter Norn~an)• The efficiency-versus-flow rate behavior of the foam filter is being determined. It is hoped to elucidate the principal mechanisms by . which this filter operates. RJRJ644g
Page 305: raj82d00
. TABLE VI pH VALUES OF AQUEOUS EXTRACTS OF'CIGARETTE FILTERS . Filter Filter from Fram Cigarettes After Smokin Mul tiport Brand Unsmoked Cigarettes ettes _re Mean Smoke e oH WINSTON 4.74 5.05-5.23 5.14 6.1 ~ Marlboro 4.81 5.92-6.36 6.11 ' 6.3 WINSTON A 5.15 5.28-5.49 5.44 6.2 CAMEL FILTER 4.93 . 5.40-5.60 5.50 REAL 5.13 5.40-5.46 5.44 6.5 Merit 5.18 47-6 6 58 6 51 6 6 k~~r VANTAGE . 5.54 . . . . 5.23-5.30 5.28 6.2 Kool 4.93 I 5.60-5.82 5.75 6.2 40 SALEM 4.91 5.23-5.27 5.25 6.6 NOW* 5.15 5.49-5.63 5.57 6.7 Carlton* 6.43 6.35-6.59 .6.42 6.8 *6 pu~er cigarette,. 8 puffs per cigarette . for all other brands PO-4 - he thod provides an easy way to'measure some differences in com- i s t f smoke from different ci9arettes. The data in Table VlIindicate at cision of the method Is gnod although the data were not collected ~der' lled conditions of room temperature, humidity, and air flow. The accur y is not known. No standard has been established under carefully contrq~~condi ti ons. ~-d • T~& r1.1 ... WINSTON Marlboro WINSTON A CAMEL FILTER eAL Mrit VANTAGE SALEM Kool NOW* Carlton* pH VALUES OF AQUEOUS EXTRACTS OF CIGARETTE FILTERS .~ No. of Determinations Meui Variance iance Standard Deviation 25 5.14 0.003 0.051 22 6.11 0.014 0.122 6 5.44 0.006 0.081 .11 5.50 0.005 0.070 4 5.44 0.001 0.027 8 6.51 0.001 0.035 4 5.28 0.001 '. . 0.031 4 5.25 0.0002 0.016 7 5.75 0.005 0.080 7 5.57 0.003 0.054 10 6.42 • 0.008 0.093 *6 puffs per cigarette, all other brands 8 puffs per cigarette • RJR16450
Page 306: raj82d00
3 • Little nicotine transfers to saliva - Experiments to measure how much nicotine is transferred from 'the smoke to the .outh have shown that S2 average 20-40% (by difference) of the nicotine taken into the mouth remains there, but only 2-9% of available nicotine transfers to the saliva. This residual nicotine in the oral cavity may be further implicated with taste or aftertaste.' tobscco and_, rWferred to smoke so that specific means for Qr tncr~asina _transfer Good information on the.contribution of individual blend components and tobacco types to "tar" and nicotine delivery has been obtained. It has been demonstrated that blendino 1l~^p~TDat?y al*^n.JPl.rat3o, wfhilc other ~ techniques^ such as adding nicotine or other additives are less effective. No breakthrou.ghs in substantially increasing nicotine transfer efficiency ;~~~t;~ y~c~. Work in 1978 is aimed at determining how nicotine Is bound in were achL ~~ . -.--_ ._..._ _......_._ ...._ _ .r_ _ ~. ~ Thes~:4ion of what T/ti ratios are optimum at various tar deliveries is stillhtl0ft'e olved. Most of the evidence suggests that full flavor cigarettes (>15 mg "tar") have sufficient nicotine. In fact, Marlboro continues to show increased T/N ratio. At low tar delivery (c 10 ug "tar", 0e most acceptable Rosa~nr.d, experimental blends have T/N ratios no lower than 9 or 10. 0ur best 1977,1 low tar cigarette designs have T/N ratios of 10 and 11 at a tar delivery of 7 mg. • Flue-cured tobacco most irrportant nicotine contributor • Data collected on major blend camponents show that flue-cured tobacco has the highest tobacco to smoko nicotine transfer efficiency (14.".). Flue-cured tobacco also has the N 0 %A N A w V %A P ~.;lowest smoke T/N ratio (10) aiid is usually the largest blend component. Therefor•e, despite !he fact that burley tobacco usually has a higher nicotine level, flue-cured tobacco contributes more nicotine in most blended cigarettes than any other blend colnponcnt. G7 has the lo:.:est nicotincr transfer efficiency (0.4'') and a high smoke RJR4885
Page 307: raj82d00
Subject: To: ~'JM',~ ~~ ~r~ ~ %WWONOW010 _ :~- Nicotine and Smoker Satisfaction W V -/ 3' IntPr-office Niem~~andum : Date: ilenlt Y SfawQ - Okoeneh FrdrisIts•r+ Nvqn+*AA Fat;e't4i LYhM 't,x Frosm SA#A.oA S4hNMaUr ..., , COpY . osJE_,cTly_EJ: ' EXACT The ultimate goal of this research is to provide the means to maximize ....... ;<:~ rtnffer efficiency. n;i:cc~tine ~~-~--s,~~~.~~~ _....~.. ' P.M 3. As.0l:e the op ine,m nicotine level in cigarette smoke reQuired. to maximtize ~ t smoker satisfaction for all RJR cigarette brands, with particular emphasis on low tar cigarettes. Specific 1977-78 objectives are: 1. Determine the taste characteristics of nicotine and factors that affect its perce 2. ;<:flttirmine the means to alter and control tar/nicotine ratio and increase ^.}ex.+•aqxK; smoker sa~f~ction. Determine the existence of a minimum or threshold value of nicotine'~quired for satisfaction. 4. Identify any other factors that are important to smoker satisfaction. Good progress has been made on defining the taste and perception of nicotine and this objective is nearly ;=:y met. However, future work will be aimed at an attempt to establish nicotine limits with respect to irritation and more direct correiation with smoke. , •Nicotine is irritating • All of the evidence on the taste of nicotine, either in solution or in aerosol form, supports the conclusion that it is harsh, particularly in the back of the throat, and contributes to tongue bite and nasal sting. Tho intensity of irritation is related to concentration. Panel tests with a new monadic ballot also show that smokers highly associate perceived irritation n,n, ronk, ~.:...,,.~. p,m R J R4883 /~ --~ I -FiA~NT~FFs EXHIBIT
Page 308: raj82d00
An extensive literature search on the chemical, physiological, pharmacological, and medicinal properties of nicotine has been completed. The collected information is available either in the library or from Dr. T. A. Perfetti. (2) Means to Alter Nicotine Transfer . a. Sugar Levels in Casing Materials Variation of the sugar level in a tobacco blend was the first ` method examined in an exploratory study of means to alter nicotine transfer to mainstream smoke. WINSTON-type cigarettes fabricated from WINSTON blends containing 42, 70, 80, 100, 120 and 135 percent of the B-4 sugar level in regular WINSTON blend were obtained from Mr. Michael Shannon. The cigarettes were smoked under standard • conditions. The filters and Cambridge pads were analyzed for nicotine. The data (Table II) show the effect of sugar level. Minimum nicotine transfer occurred at 70% of the normal sugar level in WINSTON blend. Maximum transfer occurred at about 120% of the normal sugar level. Below the 70% sugar level, nicotine tran fer increased again since more toba`cco and less sugar was med. This work provides additional data on the manipulation ~~gar levels in tobacco blends as a way to alter nicotine transfer. TABLE_ II 0 . , EFFECT OF SUGAR LEVELS ON NICOTINE TRANSFER. ~. Nicotinea Fil B- •~ugar ter am r ae a ..4 g/lOO g tobacco ci t gt mg a to acc_o urne_ m c _, 7.39 0.59 1.25 2.38 6.57 0.59 1.29 2.35 .i' 48c 5 0 57 1 25 17 2 ~Mi . 4.38 . 0.53 . 1.15 . 2.06 3.83 0.52 1.13 1.85 I 2.28 0.55 1.21 2.03 Awo MON : a Specific nicotine determination b mg/g tobacco burned less casing materials c Normal level of B-4 sugar in WINSTON blend RJR16445
Page 309: raj82d00
2 IldMPINV1R - and nicotine strength with actualA nicotine level. Nicotine irritation can be masked by the addition of certain acids and sugars. • Some nicotine irritation is necessary - Most panel smokers describe their _...~. ideal cigarette as having some irritation and moderate nicotine strength. However, most test cigarettes and competitive brands are rated as too irritating. This - suggests.that there is a desired nicotine level for optimum taste,'but`'it may , or may not be related to the level required for op Nmum satisfaction. • There is a threshold value for detection of nicotine - Tests with nicotine- water solutions show that very low concentrations of nicotine are sti11 detectable (ti.005Y w/w compared to 4% for smoke) and buffering capacity of saliva is sufficiently great to offset any differences in pH of the solution. However, when nicotine.;,~.~;~In -~erosol form, similar to smoke, a higher concentration is required to be det-eMd. It is clear that nicotine taste is concentration dependent, but #<i4 s naI i r how this relatos to smoke, and the threshold value for nicotine ,4 ;~tatioa jos not been established. important~1a.,t.the perceived taste of nicotine. In triangle tests with sma11 panels • Tar masks ni in taste - The "tar" level and .tar./nicotine ratios are and the Reynolds fl cigarette, smokers can distinguish a cigarette wi'th 11.1 mg "tar" and 1.; mg nicotine (T/N = 7.9) from a control cigarette with the same blend^ nicotine) but surprisingly cannot distinguish a cigarette with higher tar (265 mg) and nicotine (1.76 mgj (T/N = 15.1) from a control o cigarette without nicotincl ti'WP ~'* 0at0O~41aM~" ~//sOng Qf~C+- ~ .Puff volume affects taste - Harshness was found to increase linearly with o In eiqlroNcd Pu:1Ft Le%ver*l vww t.360ksrs. N the concentration of TP?1 per puffn Nasal sting and tongue bite also increase, - but not as sharply at large puff volumes. Flavor and preference increase linearly up to the TPM level delivered by the average puff then preference decreases and flavor, shows marked curvature at larger puff volumes. RJR4884 MEL
Page 310: raj82d00
4 ,. , . T/N ratio (23) and therefore contributes the least nicotine to the smoke. Experimental blends with T/N ratios down to S were prepared demonstrating that very low T/N ratios can be achieved at low tar delivery, but all of these cigarettes were disliked by smokers. •Added nicotine transfers less efficiently - Experiments with nicotine a .; added as-the free base and as malate salt to various blend components show that it. transfers less efficiently (6-8%) than inherent nicotine and with little difference ~ ~ e3 . ~• : between tobacco types,hese Papokus do not agree with some literature reports. <.~ However, much higher transfer efficiencies were achieved when nicotine malate was added to the denicotinizod tobacco used in the Reynolds ll cigarette. I •Reduced casing lowers "tar"/nicotine ratio - A comprehensive RSI•1•designed casing st0 ~ho:.ed significant preference for a NINSTON•type cigarette wi:h dT.i~sh re~rqced casin~. The cigarette4with a mini.ura "tar"/nicotine ratio and also low ~ Marlboro still having a higher value. ~ .~ Somehow annual crop variations are leveled 4xO ~ very effectively in t•1arlboro N free nicotine values fer both WIN„TON and Marlboro are now muc c oser, t e phase. c,^el..::°very had approximately a 30% reduction in total sugar, licorice and cocoa:?'r~4&0'•Marlb~~V~increases T/N ratio while HINSTON remains constant - A historical .,~ ... study of HINSTOtI and t•tarlboro "tar" and nicotine values showed that with the except4on of ±nnual crop variations and a gradual decrease in "tar", WINSTON T/N ratio has remained relatively constant since 1972. However, there have been several apparently intentional major changes in Marlboro since 1969 that have caused its T/N ratio to inr•rease significantly. This was achieved.by reduction in "tar", but even greater reduction in smoke nicotine. It would appear that the Co-Vf" •.-J is dtioeZ7vN. Qempeetao-hon Marlboro T/N ratio is trending in the opposite direction frompoeibi e~+ for an . ~ilicreased T/tt ratio by increasing smoke pH and therefore higher free nicotine is not t~e tc-ta's axplanation.# because'WINSTON pH has increased to the point that the ' ~ h 1 h %A V
Page 311: raj82d00
R D u D n n Inter-office Memorandum '`-Subject: PROJECT PLANNING MEETING FOR PROJECTS 1245 AND 1250 Date: December 14, 1977 To: Dr. Mary Stowe From: J. D. Fredrickson An informal meeting was held at 9:00 a.m., Thursday, December 8, 1977. Personnel attending were J. D. Fredrickson, J. L. Harris, T. A. Perfetti and L. E. Hayes. Dr. Harris first reviewed the work carried out in 1977 on sidestream smoke, smoke collection traps, nicotine transfer, gas chromatographic analysis of He described the difficulties nicotine on Cambridge filter filters ads and i ett p . gar c e ~., encountered in relating smoke analyses to the quantities of tobacco burned. He found the error in experimentally determined burning rates was too large to permit a correlation of the data with weight of tobacco burned. A new apparatus for burning rate determination is under construction. Dr. Harris then discussed ! the three specific undertakings for Project 1245 assigned to him for 1978. Since P-M&IN. the smoking facilities will not be ready for use until some later date, Dr. Harris w plans to direct his initial work to the determination of the cause of the increase ~~010. in smoke pH with air dilution (Item 4, Project 1245) and subsequently start work on a proto igarette which has optimum nicotine transfer to mainstream smoke, has minimu d stream TPM, etc. (Item 2, Project 1245). Mr. Ha3'es ~riefly reviewed his work on toasting and pH of filters containi{g ~ ~ smol~ond '. He outlined the work he intends to carry out on the effect o ~ toa~g und arious temperatures, times, moisture levels, etc., on nicotine an~t ~P#1 lev: f smoke (Item 3, Project 1245). He also will continue the study ~ of the use ~garette filters in the determination of pH of smoke condensate. Enj Dr. Peo0i reviewed his literature search on nicotine which covered the " 'date. Most of the papers covered physiological, pharmacotogical, • period 1835 to and medical topics. However, some of the papers covered relevant topics including ~ biochemical and chemical syntheses, physical properties, toxicity, degradation, ~ and nicotine substitutes. Dr. Perfetti has ordered a pyrolysis-gas chromatograph combination from Varian which will be used in the study of factors influencing iwjm~ nicotine delivery efficiencies (Item 3, Project 1250). In his preliminary experiments the unit will be interfaced to a mass spectrometer for a study of *4w, pyrolysis products. A series of nicotine salts•will be synthesized for the initial If experiments on nicotine release. Differences in pharmacological properties of D- ~, ~ and L- nicotine and their salts has suggested that the release and delivery of both ~_4 ~ isomers should be examined in studies of means to control 'tar'/nicotine ratios ~ and to increase nicotine impact. m ~ General discussions of various topics including analytical methods for W nfG.otine and smoke pH, equipment for treating tobacco, composition of filters-on ~ com~nercial cigarettes, panel testing of cigarettes, and remodeling of the laboratory reserved for smoking machines were interspersed among the presentations of proposed work. /mm Xc: Dr. J. L. Harris Mr. L. E. Hayes Dr. T. A. Perfetti RlR/ IORM ?I?J - R.v. 7/7O R J R728g
Page 312: raj82d00
6 ACF:yOWLEDGMENIS: The work to date represents the combined effort of several different groups in two sections. The following individuels have contributed: Dr. W. M. Henley Or. M. E. Stowe Or. J. P. Oickerson Dr. C. E. Rix 0r. C. L. Neumann Or. 0. Lynm Mr. N. 0. Shannon Or. T. A. Perfetti Mrs. M-J. Wallace 0 ~ r w~i:a ~.ws :ki *9* ~ Ln Ij ~ ( Ij ~a 1 - Wr _ J T ~ . . , . , • . . ! . . . • . . •I4 . ~ - ,.~. ~.. •., ~ . . t
Page 313: raj82d00
n.. . .~ru."r. EMS i 2 I respectfully submit that the evidence available to date in this area is now conclusive but I feel that if we are to pursue satisfaction we need to have a basis in science. Goldstein's approach will determine n cot ne satisfaction has its bases in chemistry. I have no doubt that the work will be done and relatively soon, since nicotine is the next naturally occurr ng alkaloid used in appreciable amounts which has been implicated as an addictive drug. I can't stress this fact enough, since its results could be devastating to the to6acCo industry as a whole: This work could have far reaching effects for us. I feel the work should be funded. If the results found are to our advantage, so much the better. If we do not fund the proposal and information detrimental to RJR is found, our position directed toward public safety in making a safer smoking product could be in jeopardy, tfiey, the pu6lic, realizing we were not sympathetic in research directed at their safety. I realize that I know little about making these types of decisions and for that matter the policies of RJR in.these matters. I, therefor•e, accept and will stand behind the Company and its final decision. :ki . R J RoQ(~2A .. . T .... . ~ 1 \ . •.. . . . . • • . . . ~ .. . • ... ..r T . . • ~ .
Page 314: raj82d00
Calibration for N-cigarette configuration with 20 mm of tow and C-9 blend is in progress. (2) Perforation parameters have been established for one configuration (20 mm tow and C-9 blend). Cigarette preparation and selection is in progress for this N-configuration. All filter pieces have been cut for the 30-mm tow and C-9 blend configuration and cigarette preparation will begin on March 17. II. ENVIRONMENTAL SMOKE (Project 1245 - Fredrickson) . A. Effect of Cigarette Parameters on Sidestream Smoke (Harris, Brame) r ' Completion of the work on the effects of various cigarette papers on side= ~ stream smoke has been deferred until the renovation of the smokin9 lab (Room 201M) ' is complete. The papers used in this work are Nos. 853, 855 and 856, MORE and , , WINCHESTER wrappers'and nine experimental papers of which six have been perforated electrostatically. B. Reduced Sidestream Smoke Prototynes (Harris, Brame) . Work ot~< ee cigarettes with low sidestream deliveries continues. Some preliminar ji ~tlytical data for two of the prototypes have been received . ~ , ~~ Fabricatioryyof the tobacco rods and adjustment of the air-dilution filter tip -rV_N to uce`8 fs and 10 mg 'tar' per cigarette are in progress. Collection ~~ of ~~ on `~ e cigarettes will not be completed until the smoking laboratory (R0Q.W2-01M ".been renovated and assembly of the static burn rate apparatus has been c'ed. ~ An inv~gation of the effect of calcium carbonate levels in cigarette W." papers on sibstream smoke delivery.is under consideration. Previous work has shown that WINCHESTER cigar wrapper produced significantly lower sidestream smoke deliveries than conventional cigarette papers. The calcium carbonate levels in WINCHESTER cigar wrappers and standard cigarettes are 18-21% and 23-39%, respectively. ~ Samples have been acquired and placed in storage for study of the effects Ln of various blend components on sidestream smoke formation. ~ ~ ~ For both of these studies it will be.necessary to have static burn rate m data determined under conditions as close as possible to those under which the ~ sidestream smoke is generated. For this reason.equiument is being built for ~ MOO determination of burn rate. All the parts for the apparatus have been received, Ln and assembly is in progress. The electronic components will be fabricated in the Model Shop. ' C. Improved Smoke Generation and Collection (Harris,'Brame) (1) Stirred Smoke Trap * Modification of stirred smoke traps continues to eliminate problems caused by the 0-ring seal. A mechanical rotary seal has been incorporated into one trap by Mechanical Development. This trap is presently being used in routine smokirpH determinations by the Analytical Division to RJR16442
Page 315: raj82d00
8 Although it appears that T/N ratios below 10 are not required, these results are based primarily on taste and limited smoking. An extented-use consumer study hopefully will be more definitive in identifying o and minimum nicotine levels. Increased nicotine may not be required in the near future, particularly with record high nicotine values for flue-cured tobacco in 1976 . •. ;'r and 1977; but we must be prepared for those low nicotine crops that will surely - come. We have made substantial progress in obtaining general knowledge, but as in 40 a11 new research areas, we have probably raised more new questions than we have answered. OM RJR4890
Page 316: raj82d00
NUMBER CONTROL PAGE BATES NUMBER NOT USED 517701486
Page 317: raj82d00
- «., ~' ``'~Mi Distribution: I Dr. A. H. Laurene, Dr. M. Senkus(f11e) Dr. A, Rod9aan, Dr. H. J. Bluhm, Library (file) Mr. R. H. Cundiff Dr. D. H. Piehl, Dr. N. E. Stowe (file) ": Mr. J. A. 8iles, Mr. J. P. Clingun, Dr.. W. L. Ciapp, Dr. C. fi. Mi*nsfield, Dr. J. T. Dobbins, Dr. W. M. Henley Dr. J. N.'Schumacher, Library (file3 Dr. T. A. Perfetti Mr. L. E. Hayes . ..,• 'r RJR23810 .
Page 318: raj82d00
, ._...._ ........r......•........ .....~.._.__ - LITERATURE CITED: 4 1. Perfetti, Thomas, A., Nicotine: A Review. 77, XII, ResP. 2. Diffee, John and Sheppard, Mary E., Th~ Pr rarrn, d PrMrlLiSs_ of Salts and Coordination Com ounds ~onta nins !licoline: A Review. i0t;~T93 , tio. 0ugust 25). 0 0 P" L R J R2M , . , ... ..,... . . . ... . . , .. .. . ... .. .. . . . ... ~
Page 319: raj82d00
i W ==0i , X= ZZO) S eSmokin behavior is bein activel studied • An increasing amount of researt in t e wor d ls being devoted t0 smokln9 behavior. Unfortunately most of it is aimed at smoking cessation. The importance of smoking behavior and basic motivations for smoking could be critical to understanding smoker satisfaction. Unlocking the key to smoking pleasure or the positive motiva- tions for smoking whether they be physiological or psychological, could mean the difference between success or failure of future tobacco products. RJR is funding some basic research on the relationship between personality and snlokin9 behavior and we will stay abreast of that research as well as staying up-to-date through the use of outside consultants. Together with these consultants we will decide on the desirability of hiring our own in•house behavioral scientist. eNicotine pharmacology • There are no plans to do any in•house research related o ' nicot nep armacolo , but recent research on brain chemistry suggests that certain chemicals, some o~which are nicotine-like alkaloids, act on the "pleasure centers" of the brain. In fact, some researchers are actively working on nicotine and its role in brain chemistry in an attempt to identify how it works. This research could provide breakthroughs in understanding nicotine satisfaction and we will at least try to keep up-to-date with the literature. CON0.U~5TINS: - -_-"~mS4 ?'We•;have yet to adequately understand smoking satisfaction. Obviously, ;Wnica;,i_n,&~'is important but just how important has not been defined. The relation- +smtship'VMeen nicotine taste and nicotine satisfaction is not clear. Smokers a =a app be able to identify nicotine on the basis of its taste, which they assq~~ with irritation, but surprisingly cannot detect, on the basis of taste alone, v ey high levels of nicotine when accompanied by high "tar" delivery and ther,ey~ high T/N ratios. Whether upon extended smokin~ they would be able to dist~n~sh different nicotine levels on the basis of n cotine response alone is not known. Nicotine taste and satisfaction may be totally independent responses. Although it appears that T/N ratios below 10 are not required, these results are based primarily on taste and limited smoking. An extended-use consumer study hopefully will be more definitive in identifying optimum and minimum nicotine levels. Increased nicotine may not be required in the near future, particularly with record high nicotine values for flue-cured tobacco in 1976 and 1977, but we must be prepared for those low nicotine crops that will surely come. We have made substantial progress in obtaining general knowledge, but as in all new research areas, we have probably raised more new questions than we have answered. R3a2110
Page 320: raj82d00
~ E~A ~~,'i~* ~ ~ iect: Research Dealing with Nicotine and Enkephalins To: Dr. D. H. Piehl From: T. A. Perfetti . ef I strongly agree with Dr. Goldstein in his work with enkephalins and endorphins. Several weeks ago I discussed with Jim Dickerson this same approach in relating chemistry to satisfaction, a word having rather subjective connota- tions and having little to-'do Wi'tTi science per se. There are several reasons to believe the work in this area would benefit R. J. Reynolds and the tobacco industry in general. 1. Opiates, like nicotinicg;agents have rather non-specific receptor sites. These sites in opiates comprise b7Oth tightly and loosely bound sites. Techniques are now available to sort out these different types of binding which could, as in the study of opiates, lead to the stereospecific sites of action of nicotine. 2. ~es,like nicotine~ have receptor sites throughout the body,. primarily : ting their pharmacological effects in the smooth muscles. The "` binding si n the brain and in the smooth ruscles are essentially the canr in ~~ the two ti~"sue . If indeed, endorphins are found for nicotine then a' more ~ exa~~nethbr studying its concentration effects, pharmacological action and . phy ogiq ffects could be handled. This could relate directly to the . related to nicotine-type molecules. crll'MWr MMtisfaction and relieve us of the gross subjective generalization we now use etermWe satisfaction. 33 aps the most important reason that this work should be pursued concerns the s 1milarities in structure-reactivity the scheme for opiates as R' . Ketobemidones (1) exhibit the cornnon features of all opiates, these are Ar.- a. a quaternary carbon (X) `^ o Date: January 5, 1978 i R . R " (C FiL)4 (- 'r,3 ~ b. a phenyl ((Ar) or bioisotere] ring attached to this carbon (X) IA°' c. a tertiary amino group, 2 saturated carbon atoms removed ~ The most potent ketobemidones (analgetics) having a methyl or pentyl group for R, being extremely active. .7 Comparing these ketobemidones to nicotine and nicotine-like drugs we find that the similarities are quite sinilar,_,Sp similar that it would not be surprising if the same endorphinsth,t bind ketobemidonEs and opiates also bind ~ nicotine. :`\I Inrer-office Memorandl , 4
Page 321: raj82d00
2 eThere is a threshold valve for detection of nicotine - Tests with nicotine-water so utsons show that very low concentrat~ons of nicotine are still detectable (~.0055 w/w compared to ti6t for smoke) and buffering capacity of saliva is sufficiently great to offset any differences in pH of the solution. However, when nicotine is in aerosol form, similar to smoke, a higher concentra- tion is required to be detected. It is clear that nicotine taste is concentra- tion dependent, but it is not clear how this relates to sr+oke, and the threshold value for nicotine irritation has not been established. e"Tar" masks nicotine taste - The "tar" level and 'tar"/nicotine ratio are important to t e•perce ve aste of nicotine. In triangle tests wtih small panels and the Rkynolds /1 cigarette, smokers can distinguish a cigarette with 11.1 mg "tar" and 1.4 mg nicotine (1'/N • 7.9) from a control cigarette with the same blend without nicotine, but surprisinq 1y cannot distinguish a cigarette with higher "tar" (26.5 mg) and nicotine (1.76 mg) (T/N • 15.1) from a control cigarette without nicotine, due to an apparent eiasking effect. ePuff volume affects tast • Harshness was found to increase lir-early with ~ the concentration o per puff in controlled puffs delivered to smokers. Nasal stin9 and tongue bite elso increase, but not as sharply at larpe puff ~...:~ votum Flavor and preference increase linearly up to the TPM level delivered -`~ by th~ra9e puff then preference decreases and flavor shows marked curvature at lart"puff volumes. W Lit~1e nicotine transfers to saliva • Experiments to neasur•e how much ~picot s trans erre0 from the smoke to the mouth have shown that on average '~70-40~ difference) of the nicotine taken into the mouth remains there, but ~~on1y of available nicotine transfers to the saliva. This residual nicotine in thP"1 cavity may be further implicated with taste or aftertaste. ~ . A ~ ;~ 2. "Tar~Nicotine Ratio and Nicotine Transfer Efficiency ~ Good informatio~ on the contribution of individual blend components and ~ tobacco type to tar and nicotine delivery has been obtained. It has been demonstrated that blending alone can greatly alter T/N ratio, while to date ha been less h dditi ve ves, er a %~i other techniques, such as adding nicotine or ot ozlk expedient. No breakthroughs in substantially increasin9 nicotine transfer efficiency were achieved. Work in 1978 is aimed at determining how nicotine is e bound in tobacco and transferred to smoke so that specific means for increasing ~ transfer efficiency might be developed. -The question of what T/N ratios are optimum at various"ter" deliveries Is still unresolved. Most of the evidence suggests that full flavor cigarettes (>15 m9 "tar") have sufficient nicotine. In fact, Marlboro continues to show increased T/N ratio. At low "tar" delivery (<10n~ "tar") the most acceptable experimental blends have T/N ratios no lower than 9 or 10. Our best 1977 Research low "tar" cigarette designs have T/N ratios of 10 and 11 at a "tar" delivery of 7 mg. . . . RJR21O7
Page 322: raj82d00
and although the changes that are probably intentional are seemingly in the wrong direction, the consumer appears to have proven them right. We must admit that they likely know something that we do not. 5 Little progress has been made on defining the optimum nicotine value to maximize satisfaction and no progress has been m.ade on defining the existence of a threshold or minimum value. However, a consumer study planned for 1978 is intended to help shed some light here and progress has been made on designing test cigarettes for this study. •Experimental blends prepared - Ideally, a series of test cigarettes with the :LK'v}:.i:{•:aA same taoW very and taste characteristics, out varying nicotine level is required to dete5p ne optimum +md mimimum nicotine requirements. The same test series should ~ted at edifferent tar delive)j~so that both high and low tar cigaretta: be':, * M ova \ 0. If'possible, pH should also be controlled as an independent variable. Except for.:.~ynolds 11 cigarettes with various levels of added nicotine, test : cigarettes`4f this type, meeting all requirements, have never been successfully prepared. In 1977 some success was achieved In preparino test cigarettes at "tar" levels of 5, 10 and 15 mg/cigt with various nicotine values and T/H ratios from 9.8 to 22.S. Taste characteristics were held reasonably constant so that trends could be observed with the Research booth panel and a new munadic ballot. As reported under nicoi~e tosta a high correlation was observed for reported irritation 31t000 and nicotine strength with actual,, nicotine level. No success was achieved in the , variation of pH independent of nicotine level. \ oi~reliminary optimum nicotine value identified •~Tb~+ .1proliminary data A6ouo- apparently reveal an optimum nicotine level of 0.12 mg/puff. These W*A4a result: should be regarded as unconfirmed at this point. However, it is of interest to sueculate since the value for WINSTON has usually been over 0.15 mg/puff and RJR4887
Page 323: raj82d00
C•~ w lnter-office Memorandum , To: Dr. Alan Rodgman OBJECTIVES: . SECRET O.ate: January 4, 1978 From: 0. H. Piehl The ultimite goal of this research is to provide the Teans to maximize smoker satisfaction for all RJR cigarette brands, with particular emphasis on low "tar"cigarettes. Specific 1977-78 objectives are: yIT". ' Identify any other factors that are important to smoker satisfaction. 4 : 0 1. Determine the taste characteristics of nicotine and factors that affect its perception. ~.,.~ Determine the means to alter and control "tar"/nicotine ratio and incr4'asoNicotine transfer efficiency. T«""= ,.3.•t Define the ~timum nicotine level in cigarette smoke re;uired to y;~~maxisni=e snaker satis action. Determine the existence of a minimum or .....thre!"g value of nicotine required for satisfaction. ~ . Subject: NicotLne and Smoker Satisfaction -~r 1. Nicotine Taste and Perception Good progress has been made on defining the taste and perception of nicotine and this objective is nearly met. However, future work will be aimed at an• attempt to establish nicotine limits with respect to irritation and more direct correlation with smoke. BHicotine is irritatin • All of the evidence on the taste of nicotine, ' either in so u on or n aerosol form, supports the conclusion that it is harsh, particularly in the back of the throat, and contributes to tongue bite and nasal sting. The intensity of irritation is related to concentration. Panel tests with a new aronadic ballot also show that smokers highly associate perceived irritation and nicotine strength with actual smoke nicotine level. Nicotine irritation can be masked by the addition of certain acids and sugars, but high levels are req:,ired. eSome nicotine irritation is necessar - Kost panel smokers describe their ideal c garette as hav ng some rr tatjon and moderate nicotine strength. Hc.,ever, most test cigarettes and competitive brands are rated as too irritating. This suggests that there is a desired nicotine level for optimum taste, but it may or o may not be related to the 1eve1 required for optimum satisfaction. ~ v ~ J K_/•••///,A' OVr/!~~ LYYI~ITIJ~1 t~• V 0l011 tootM 142t•QM. 1/10
Page 324: raj82d00
~ 2MTFTfmf= O 0 EIONATUR! AND DAT[ l . t Ir...w«...r..m w. w~.w. wen. M. a -"- r`~~//1`/i O qAD ANp uNDqSTOOD if . . .1ui..ri~ Coh1 AZ i R~R24583
Page 325: raj82d00
4 e.Ex erimental blends reoared • Ideally, a series of test cigarettes with t e same tar de ivery and taste characteristics, but varying nicotine level is required to determine optimum and minimum nicotine requirements. The same test series should then be repeated at different "tar" deliveries so that both high and low "tar" cigarettes are evaluated. If possible, pH should also be controlled as an independent variable. Except for Reynolds 11 cigarettes with various levels of added nicotine, test cigarettes of this type, meeting all requirements, have never been successfully prepared. In 1977 some success , was achieved in preparing test ci 9arettes at "tar' levels of 5, 10 and 15 mg/cigt with various nicotine vatues and T/N ratios from 9.8 to 22.5. Taste characteristics were held reasonably constant so that trends could be observed with the Research r booth panel and a new monadic ballot. As reported under the section on nicotine ~~ taste a hi 9h correlation was observed for reported irritation and nicotine strength •. with actual smoke nicotine level. No success was achieved in the variation of pH independent of nicotine level. ePreliminar o timum nicotine value identified • The preliminary data above apparent y revea an op n+um n cot ne evt o . mg/puff. These results ~ should be regarded as unconfirmed at this point. However, it is of interest to speculate since the value for NINSTON has usually been over 0.15 mg/puff and the valueZ&wAll-arlboro 0.13 mg/puff or less. ,_.. "ioloAical response to nicotine difficult to 9.uantifZ - Measurement of thre• physiological Tesponse to nicotine by some ra5id and non•invasive technique ,_,_~avould b convenient indication of nicotine satisfaction. Nicotine is kno:+n to &tause mber of small changes, such as increased pulse and heaft rate, decreased ;e ~=tempe~, e of the fingertips, and altered EEG. Pilot studies on the measurement ~ of fi~~~~ip temperature and pulse rate for a small group of Research subjects showe ferences before, during and after smokinp, but they were almost impossible ,to qu ate. Individual differences and day•to•Eay variations are great. There is 1i, expectation that a successful technique will be discovered, but we will continue to search. eConsumer study beino olanned • To9ether with Yarketing Research a special consumer stu~y is e ng es gne at will involve the use of the experimental cigarettes described above. Smoking habits, cigarette consumption and preferences will be followed for a large representative consumer panel with the aim of establishing optimum and minimum nicotine levels as will as obtaining a better understanding of smoker satisfaction. Final plans will be completed in January with results scheduled for 4th quarter 1978. We will work closely with !!RD through- out this study and with.their consumer psychologist, if they hire one. 4. Other Factors Important to Smoker Satisfaction e1 ortance of smoke H is unclear - The role of smoke pH in smoker satisfac- tion is no c ear. t s o v ous y mportant to taste, but how this relates to nicotine level and T/N ratio is not well established. It has also usually been assumed.that smoke pH determined "free nicotine" content of the smoke, and it is calculated on that basis. However, recent evidence suggests that "free nicotine" in the mouth is determined by the pH of the smoker's saliva. It is hoped that ~, experimental ci qarettes can be desi qned with smoke pH as an independent variable, ~ but the probability for success is low. ~ s ~ . ~o ~ ~ ~ RJRVO9 •. ~
Page 326: raj82d00
, Dr. M. E. Stowe . 2- NICOTINC: A REVIEW (7) Nicotine and pH (8) Nicotine: d vs 1 and a vs 6 (9) Nicotine Absorption and Adsorption 10) Nicotine Trdnsfer and Removal in Smoke 11 Denicotinization and Recovery Processes 12 Nicotine Salts 13 Nicotine and Cotinine: A Relationship 14 Tobacco-Pyrolytic Products 15 Tobacco Substitutes 16 Tobacco and Blood Sugar 17 Effects of Y-Radiation on Tobacco 18 Flavor Enhancement and Filter Additives 19 Toxicity Studies February 9, 1978 The chemical literature covers a number of areas and many minor toc+ics are M 04'" hic orms are discussed. obviously obscured by the headings chosen. The author will be glad to discuss any and all information he has reviewed and direct persons interested in more specific detail o pertinent articles. 6.~ ~iolooical and Medicinal Aspects of Nicotine ThA pa t of the literature deals with the biolonical effects of nicotine ~the ons and vital processes of living organisms. Effects on nearly ~ of t 76 dily functions and vital processes of animals f rom the lowest to This~ ~* -t of the literature has not been divided into specific sub-sections. The autlei,i~ s unable to classify these areas under specific sub-sections since the artic in each of these parts represented data which were concerned with the combined overall effects of nicotine. That is, in considerino these effects basic principles from the areas of physiology, pharmacology and medicine were used together in the discussion of the results. Differentiation of each area into specific sub-sections became very aifficult and was not undertaken. The medicinal aspects of nitotine and nicotine-like molecules have been investigated on a number of types of animals. Their biological functions were examined, e.g., with respect to central nervous system activity. The nicotinic effects of nicotine and nicotine-like agents were determined. Areas of action and receptor-site theories were also developed. As in the previous sections, many years of work has been devoted to trying to elucidate the effects of nicotine. The questions of why people smoke, chew or snuff and why such a drive even exists have been pursued diligently. Over a hundred years of work has produced little tangible supporting evidence to answer questions. Perhaps the nost interestin4 aspect of the review was followinj the logic of the investigators in their pursuit of the problems and the continued development of techniques used by them to find answers over this 170-year period. , . . - : - . JR2113
Page 327: raj82d00
4 Xc: Dr. J. Harris Dr. T. Perfetti Mr. L. Hayes RJRI 1100
Page 328: raj82d00
%Flue•cured tobacco most imoortant nicotine contributor • Data collected on major components s ow that ue-cured tobacco has t e ighest tobacco to smoke nicotine transfer efficiency (14S). Flue-cured tobacco also has the lowest smoke T/N ratio (10) and is usually the largest blend component. There- fore, despite the fact that burley tobacco usually has a higher nicotine level, flue-cured tobacco contributes more nicotine in most blended cigarettes than any other blend component. However, uncased burley tobacco has a nicotine transfer efficiency comparable to that for flue-cured tobacco. G7 has the lowest nicotine,transfer efficiency (8.4%) and a high smoke T/N ratio (23) and therefore contributes the least nicotine to the smoke. Experimental blends with T/N ratios dowrr to 5 were prepared demonstrating that very low T/N ratios can be achieved at low "ttr" delivery, but all of these cigarettes were disliked by smokers. eAdded nicotine transfers less efficientl • Experiments with nicotine added as t e free ase an as na ate sa to various blend components show that it transfers less efficiently (6-8%) than inherent nicotine and with little difference between tobacco types. These results do not agree with some litera- ture reports. However, much higher transfer efficiencies were achieved when nicotine malate was added to the denicotinized tobacco used in the Reynolds #1 cigak~wt,i~. ` ced casiny lower "tar"/nicotine ratio'• A comprehensive RSM-designed casiag swed signiT'icant preTerence or a WINSTaV-tyoe cigarette with ~;:~redu esing. The ci9a.rette design with a minimum "tar"/nicotine ratio and ;r~;;also gas•phase delivery had approximately a 30% reduction in total sugar, e coo* PAnd cocoa. ~ boro increases N ratio while WINSTON remains constant - A historical .studY.~N N andmAr oro tar'r'and n co ne va ues s owe tFiat with'the excep'1~i4~ of annual crop variations and a gradual decrease in "tar", WINSTON T/N ratio has rer.+ained rel_atively constant since 1972. However, there have been several apparently intentional major changes in Marlboro since 1969 that have caused its T/N ratio to increase significantly. This was achieved by reduction in "tar", but even greater reduction in smoke nicotine. It would appear that the t4arlboro T/N ratio Js trending in the opposite direction compared to t4INSTON. Compensation for an increased T/N ratio by increasing smoke pH and therefore higher free nicotine is not the total explanation, because WINSTON pH has increased to the point that the free nicotine values for both WINSTON and Marlboro are now much closer, the 'q riboro still having a higher value. Somehow annual crop variations are leveled out very effectively in Marlboro and although the changes that are probably intentional are seemingly in the wrong direction, the consumer appears to have proven them right. We must admit that they likely know something that we do not. 3. Optimum and Threshold.Nicotine Values Little progress has been made on defining the optimum nicotinr value to maximize satisfaction and no progress has been made on defining the existence of a threshold or minimum value. However, a consumer study planned for 1978 is intended to help shed some light here and progress has been made on designing test cigarettes for this study. RJR2i08 . ..• .
Page 329: raj82d00
.. If there were but one all-encompassing conclusion that could be drawn from reviewinq the work in nicotine, it would be this: the handle for which we have been grrspinq has, to date, not been found. It would appear that the number of alternatives left to try are few but technoloqy has been supplyinq us with tools to achieve our goals for decades. Finally, it is the author's feeling that within the next decade we will satisfactorily answer manv, if not, most of the problems of nicotine satisfaction and its effect on us and our environment. L . REFERENCES: Because of the larne number of references associated with this review, its bibliography will not be attached. A copy of the bibliography is available from the library or the author. ti-t-7ac.r.eO H. VUC;' .2 -~ ~ 6at e FBMs A. ~'eri e ~ IL Dr, Dr. . Piehl 1. Henley Dr. J. . Dr J L Fredrickson Harris Mr. L. E. Hayes rDr. J. N. Schun;scher Dr. J. P. Dickerson Dr. C. L. Neumann Mr. J. J. Whalen
Page 330: raj82d00
Mlriw-'ii& - s":.zzffh-~*~ 2 Considering the facts that: 1. The blends of Marlboro and WINSTON are very similar except for the type of reconstituted sheet, 2. WINSTON A and Marlborp ¢oth use amaroniated sheets and resemble each'other in t~ste, and I 0=0 major difference. 3. On heat treatment WINSTON A reverts to WINSTON but Marlboro retains its identity, the composition of the two different reconstAut'ed~sheets represent the a better, more stable reconstituted sheet exhibiting the properties of the Philip Morris sheet and hopefully lncreasing the nicotine transfer. preparation, that both amidation and salt formation will occur and will afford I . It is our belief that if amnonia is incorporsted lnto our sheet, in its ...; 0 Z. Distleutio ~; ~ f Submitted: January 26, 1978 ~ . Completed: From manuscript:mm Read and understood by me: - ne:: e .
Page 331: raj82d00
Dr. M. E. Stowe - 3 - February 14, 1978 Nicotine Delivery Tobacco subjected to treatments determined by previous studies will be used in nicotine transfer.work. Possible treatments might include extraction, addition of nicotine salts, or relocation of nicotine by moisture and heat. Thermal analysis, other pyrolytic techniques, and cigarette smoke analyses will be used in this phase of the work. Specific Undertakings 3: r, . Mechanism of Nicotine Transfer ~ Dr Perfetti expects the gas chromatograph to be deliveredithi tht .. wne nex month. The pyrolysis unit will be delivered later in the year. The tentative work schedule is as follows: miSecond Quarter: ~~~~ Install of equipment and familiarization with the techniques of capillary gas chromat y(GC), pyrolytic GC, pyrolytic GC-mass spectrometry, and operation o*N*` microprocessor module. ~ecoc~,lr Thifcd Qtkrters: 01""N ~ theld%jOnd analysis of assorted nicotine salts. Third Fourth Go~rters: .J .Y..W v.Y i'YYY.~.i Y. to ~YYY.11G iGilYi AINI VV-IIIP7J .7MCbbIV111G1.1 iM Ollaqvi/7 V1 ~ pyrolysates. Exploratory work on tobacco pyrolysis. X1W First, Second Quarters, 1979: ~ In-depth study of the pyrolysis of' tobacco to establish condition under which ~ the smoking process can be simulated and to develop program for the microprocessor. ~ GC of whole smoke. WW IftS Second, Third Quarters, 1979: X"% GC-mass spectrometric study of pyrolysates of tobacco with added nicotine sal ts. _ .' Fourth Quarter, 1979-1980: Pyrolysis of tobacco blends. Effect of casing materials on nicotine transfer. / RJR11099 Ln I I- _J _J m ~ ~ CO 00
Page 332: raj82d00
7 Subject ' • ~EIdNATUItE AND DATE , 306354 D % i ~~ ---- !/.L1~~! i _-- ~:-~-~~t~~ 0 ~ T~ ~~i-•-.T7f .~ 0 - w e~r..ce as~c.v ~ ~ '. --- ----~ WM .YIY. 7i.... R J R24580 M: % • 0I a 0 D V p . „~., . ., ~• : • . READ AND YNDQ3fO0D (S~n~r~un.nd-4 .
Page 333: raj82d00
293 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPREME COURT OF THE STATE OF NEW YORK COUNTY OF NEW'YORK X SHARLENE HOBERMAN and AUDREY . HULSE, as Executrix, on behalf of: the Estate of Lewis Hulse, . individually, and on behalf of . others similarly situated, . Plaintiffs, ndex No. VS. . 110953/96 BROWN & WILLIAMSON TOBACCO CORPORATION, B.A.T., et al., Defendants. . -------------------- ---------- X ROSE FROSINA, ELIZABETH COLAVITO : and ANILDA ROSS, individually, : and on behalf of others similarly: situated, : VS. Plaintiffs, : Index No. : 110950/96 PHILIP MORRIS, INC., et al., Defendants. : -------------------------------- X CATHERINE ZITO, PETER HOBERMAN, . and GEORGE ELISSEOU, : individually, and-on'behalf of . others similarly situated, VS. . Plaintiffs, : Index No. s 110952/96 THE AMERICAN TOBACCO COMPANY, INC., et al., Defenda,nts. . : X HUS-EBY & ASSOCIATES (800) 333-2082
Page 334: raj82d00
7 ~ X= of research in the world is being devoted to smoking behavior. Unfortunately most of it is aimed at smoking cessation. The importance of smoking behavio r and basic motivations for smoking could be critical to understanding smoker • S.oking behavior is being actively studied - An increasing amount satisfaction. Unlocking the key to smoking pleasure or the positive. mQtivations for smoking whether they be physiological or psychological, could mean+the , difference between success or failure of future tobacco products. RJR is funding some basic research on-the relationship between personality and smoking behavior and we will stay abreast of that research as well as staying up-to-date through the use of outside,consultants. Together with these consultants we will decide on the desirability of hiring our own in-house behavioral scientist. •N-A&Wiie Pharmacolog,Y, - There are no pla:+s to do any in-house research : ~ : relate~ricotine pharmacology, but recent research on brain chemistry suggests at c rta. chemicals, some of which are nicotine-oibair alkaloids, act on the 0-ha tr leasy"nters" of the brain. In fact, some researchers are- actively r.orking on nico ine'and its rolle in brain chemistry in an attempt to identify how it vro rks. This~r~r~~uld provide breakthroughs in understanding nicotine satifaction and 0 iA* we will at least try to keep up-to-date withdliterature. ~ 0 ~ N r w 0 CONCLUSI4NS: _ "WOO . ~', pw~* We have yet to adequately understand smoking satisfaction. Obviously, o nicotine is important but fust how important has not been defined. The relation- ship between nicotine taste and nicotine satisfaction is not clear. Smokers appear to be able to identify nicotine on the basis of its taste, which they associa te with , irritation, but suprisingly cannot detect~on the basis of taste alone, very high levels of nicotine when accompanied by high tar delivery and therefore high T/N ratios. Whether upon extended smoking they would be able to distinguish different nicotine levels on the basis of nicotine response alone is not known. Nicotine R J R4$89 taste And satisfaction may be totally inclependent responses.
Page 335: raj82d00
. 0 iUJ nM Ei~ CON FIDENT.lALoffice Nemo~~.~ ic'1.~,;, . Subject: CIM Evaluation Date: February 17, 1978 To: Dr. C. T. Mansfield From: T. A. Perfetti CIM Evaluation Committee S. A. Bellin R. F. Moates ~Kpert of this study. '. 2. Gross physiological effects should be measured in relation to d-nicotine transfer. 3. Attempts to measure the degree of racemization with variations in mechanical parameters (e.g., filter, rod, degree of air dilution, etc.) should also be attempted. It is the opinion of this evaluation team that on completion of the first priority (1) a reevaluation of the work should be made to determine its potential. st eva uat on y 2, 1974. 0.. ~.~ Reevaluation:* CIM, 1974, No. 2 Use of d•Nicotine in Tobacco . a v n L. Neumann MEMORANDUM: The C1M Evaluation Team concurs that the investigation of the properties of d-nicotine should be started,.pending the preparation of d-nicotine. While the evaluation team realizes that the inavailability and economic costs associated with f ddition of d-nicotine to tobacco, is not feasible at this time: it also belieV ,,.~~hat work in several areas ortance should be started and that perti'r~ ni;~`information on d-nicot s c emicil, pharmeco'To9ical' and physiologicalJ ffec:fs sh uld be gathered for future reference,, ~.'""' . . . . ~WMIA om Te •M Evaluation Team has thus outlined suggested priorities for this ~ :~tudy. ~Nicotine's effect on pH should be determined as well as its flavor- :~ ~ : aste in smoke. Panel testing of cigarettes should represent an integral RJ R17805 RJ111 FORM JIJ2-MwV. 7/10
Page 336: raj82d00
Subj.et 11rm oa..r vwY Ya.1r1.rM1G& N. • MAD AND YNDLWOOD ~WY :~ RJR24,%1 ~ ~=_-......:.• De+. 306355 ~ ~ 7 ~ a 0 I 0e ~Z~O! , ~.I~ .---- O 0 0 ~ z S •s t~1s. _ O • a 0 O 0 me 0 SIGNATURE AND_DATt ., r •/. Jf A . m.hir..ea Daf.) ' .
Page 337: raj82d00
inter-office Memorandum ;ubject: WORK PLANNED FOR 1978 - PROJECTS 1245 AND 1250 Date: February 14, 1978 To: Dr. M. E. Stowe From: J. D. Fredrickson Drs. Harris, Perfetti, and Fredrickson and Mr. Hayes met at 1:30 p.m. }3 Thursday, February 9 to discuss their work for 1978. Their plans are summarized in the following paragraphs: PROJECT 1245: SMOKE FORMATION AND PERCEPTION Dr. J. Harris has had to postpone work on the delivery of mainstream and sidestream smoke until the smoking laboratory has been renovated and the static * -,~ burn rate apparatus is ready for use. Most of the parts have been purchased, 4 but Mechanical Development has not begun assembling the apparatus. His im~~~~.~te attention has been directed to the 20-port pH determination. The obJectir~~~"iIto establ ish whether the measurement is a function of the cigarette smoke compo=~-*-Mn or the procedure. The work will include studies of the effects of the volurge o air drawn through the traps after smoking, the quantity of water ' in t. rap pu volume, and the number of cigarettes smoked per determination. A ~ stud th ect of,puff volume on 'tar' delivery will be included to provide dat~ th ication of the method to air-diluted cigarettes. Estimated time ,~ for complet two months. Other work to be carried out as time is available ~ includes re es ing the stirred smoke trap in current use and a study of cigarettes with low si,, am delivery. w. : •~ When the new smoking facilities are completed, the study of the mainstream, ~ ~~ sidestream, and nicotine deliveries per weight of tobacco burned will be carried OD ~~ out. Data will be collected for twenty-eight cigarettes fabricated from various ~ ~ grades, blends, and cased blends, eight commercial cigarettes, and fourteen ~ cigarettes fabricated from WINSTON blend, WINSTON filters, and fourteen different ab ,' ~~ cigarette papers. °; ti o :,rftk 4~tj Mr. Hayes and Dr. Perfetti have been collecting pH data for aqueous extracts of cigarette filters after cigarettes have been smoked mechanically. The objective is to determine whether the data are a useful supplement and/or alternative to moke pH data. Comparison of data for some commercial'and experimental cigarettes is in progress. The differences in the data for current WINSTONs, WINSTON A's, and Marlboros are greater than the differences in smoke pH data for these cigarettes. Th,is provides an expanded scale for characterizing differences among these cigarettes. This work may extend into the second quarter if the results of current experiments warrant further study. Mr. Hayes and Dr. Perfetti have also initiated a study of the effects of heating tobacco under controlled conditions of moisture, temperature, and time primarily on nicotine transfer to mainstream smoke. Other variables being studied include casing and ammoniation of blgnd components. Changes in tobacco pH, smoking qualities, pH of aqueous filter extracts, and possibly nicotine transfer to sidestream smoke will be determined. This work will extend at least into the the second quarter. RJRI FORM 2422-Rw. 7/70 RJRI 1097 51770 1485 PlJ11NTIFF'S EXHIBIT /
Page 338: raj82d00
S SECRET Authors: Division: Chemical Research CIM, 1978, No. 2 No. of Pages: 2 Disclosure No: Notebook Pages: 306351-306353 Dated: January 26, 1978 Previous Reports: ,None IMPROVED AMIONIATED R,ECO_ftSTITUTED SHEET SUMMARY : 'OF Chemically bonding ammonia as the pectate afiide and nicotine as the Lawrence E. Hayes ~~ ~ Thomas A. PeriPl~Qt ~`'~ Y anuary 30, 1978 pectate salt into ammoniated reconstituted sheet should improve the nicotine transfer awor of RJR tobacco products. MEMORANDUM:. ~ 0• .P01 coti'~~.nsfer may be increased by the incorporation of ammonia in ieee•~~forfi ~"~the pectate amide, in reconstituted tobacco sheet. This may be,f~eved;i~e addition of ammonium phosphate either in the form of the ~~ mono- or di'~: ium phosphate in thepu iping process. It is known that ammonia is use •o break down:the pectin in tobacco. It Is believed that ~..- pectin chem, binds the ammonia and available nicotine as the amide and ~~ nicotinic s i,•respectively. Th!se compounds, therefore, will be chemically m bound into the s"6et. The transfer-of nicotine may be enhanced by this process since the nicotine pectate is relatively thermally stable. The temperature needed for the release of free nicotine frw this salt occurs at ~ a temperature higher than that needed for pyrolytis of nicotine. What this may mean is that in our present reconstituted sheet where most of the nicotine':::: ~_4 is sprayed onto the surface, pyrolysis of nicotine may be taking place before a ~ sufficient quantity is transferred. The proposed asmoniated sheet should resist nicotine pyrolysis and merely cleave the salt releasing more intact, :~ free nicotine into the mainstream. Our present annoniated sheet uses ammonia :W~l gas. It has been shown in our laboratories that this ammonia Is oredominately adsorbed in some manner onto the sheet. This ammonia is released on standing M.M."and can be removed entirely by heating at 80-90' C for a short period of time (1 hr.). The Philip Morris sheet also releases some adaonia but seems'to transfer more nicotine than our sheet. It is our belief that a portion of the ymnia and most of the available nicotine are che:nically bound in the sheet. The taste of WINSTON A using the ammoniated sheet resembles Philip Morris' Marlboro but on heat treatment the WINSTON A reverts back to WINSTON while the Marlboro retains its same taste.
Page 339: raj82d00
Sub/.c7 ' x ~rn ~~.~ 3 OG SS3 0 0 ozol a 0 ?.2<i{~!L: i: _ _ _ - - 6 0 .; ,~.. ~ Do+. ® - LLt S t ~ r -z D ~ ~ , J r /. R~y~ /~iGfi'C,. K/GS•;4P , !!~~a;iL! SIGNATIJR! AND DAT[ ~ % ~/ j~` 8 ` !a w. a , lbne w1YO NM Wn WWOW*MIft ReAD iwo ur4D1t ~ :~:_ • 306356 ~~ t V J m ~ N t!~ ~ .I P-7 S/r RJR24582
Page 340: raj82d00
29` J TLLrL.1'nc.e 1 SUPREME COURT OF THE STATE OF NEW YORK COUNTY, OF NPW' 'YORK 2 3 PHYLLIS SMALL and DENISE FUBINI, individually, and on behalf of 4 others similarly situated, X 5 Plaintiffs, : Index No. VS. : 110949/96 6 LORILLAgD TOBACCO COMPANY, INC., 7 et al., . 8 Defendants. : -------------------- -----------X 9 MARY ANN HOSKINS, Executrix of . the Estate of Edwin Paul Hoskins,: 10 WALTINA BROWN and DANTE AUBAIN, : individually, and on behalf of . 11 others similarly situated, VOLUME II PAGES 292 494 12 Plaintiffs, : Index No. . 110951/96 13 VS. 14 R.J. REYNOLDS TOBACCO COMPANY, et al., 15 Defendants. 1 6 - - - - - - - - - - - X 17 18 Videotaped Deposition of THOMAS A. PERFETTI, Ph.D 19 (Taken by Plaintiffs) 20 Winston-Salem, North Carolina 21 January .21, 1998 22 NMl -0+"+.3. 23 HU~EBY ~t ASSOCIATES 2 4 R e p o r t e d b y: G e r a 1 yn M. L a G r a n g e An .rf aTIm Legal services Company Oak House : 1316 Harding Place Registered Professional Report~'~ Charlotte,NC2s2oa 2 5 N o t a r P u b 1 i c 704)333-9as9 y Fax~704)372-4593 http://www.huseby.com : email rpr©huseby.eom Atlanta, GA / Gainesville, GA / Asheville, NC / Greensboro, NC / Raleigh, NC / Winston-Salem, NC / Columbia, SC / Greenville, SC / Florence, SC / Chattanooga, TN
Page 341: raj82d00
41 ;.~~ V ~H>w~ I'ro ect: 12S0 Smoking~ Sutisfaction and 'Tar"/Nicotine Control Discussion of Commitments: Marketing has identified the low "tar" cigarette category as a hi hh growth potential area. It'is clear that simply decreasing "tar" and n~cotine•' levels together may not be satisfactory to the consumer. Consequently, it would be very desirable to control nicotine delivery so as to adjust the "tar"/nicotine ratio of low "tar" cigarettes and improve smoker satisfaction. To accomplish this, a number of long-range (3-S+ years) efforts, with prospects • of short-term payoff, have.been outlined. An essential feature is first to., determine the controlling variables in nicotine delivery. Ourrently approxi-'• mately 10-11 percent of available nicotine in an average 8S ma filter cigarette. is transferred to smoke. It should be possible to evaluate that transfer. efficiency under various conditions and ultimately, the relative amounts of "free" and "bound" nicotine in smoke and its relevance to smoke quality and satisfaction. Investigation of various factors that could influence•nicotine delivery (rod parameters, tobacco types and blends, additives) is in progress or is planned. - , In a~n, there is the question of what is the'optimaa nicotine delivery at a givei-..;,; level and is there a minimum or threshold value for nicotine • necessary: .smoker satisfaction.- G1urrent and future efforts are being made to d,e elo th information via in-house paneling of special cigarettes, ta. ed ~rticular pEl and "tar"/nicotine ratios and levels. emnloyinb new ri eling techniques. Additionally physical measurements of the , Aoms r e to these cigarettes will be made. Such information should permit deant of a technique for measuring nicotine impact which, in turn,' " - Wrould be us evaluat oranyo in developing a smoker satisfaction index. In evolvir~.-and ' a techniques it will be necessary to employ.the assets of IMtD er ivailable source. . , . ;. Methods of controlling "tar".and nicotine'while maintaining quality and~ , brand identity will be investigated. 8nphasis will be placed on methods that are not used to control "tar" and nicotine delivery:of current blends. Since casing increases the "tar"/nicotine.ratio, a determination of optimum . levels for cigarettes with low "tar"/nicotine ratios would be desirable. The:.' - • ,, current T&f study of the effect of casing on "tar" and nicotine delivery provided ~ excellent data on tar and nicotine delivery over a range of casing levels for the j WINSIbN-type blend and on smoker preference. Some related experiments are. anticipated, however, the level of effort is expected to be low.,• . • . . . . . . .• A wide range of nicotine concentration is found in foreign and experimental a, type tobaccos. Therefore, the effect of selected samples of these tobaccos on ,. "tar" and nicotine delivery of blends will be examined. . . • . . . . ;;, . •,. . .. Preliminary work indicates that nicotine effect is an important factor:' ;; ' which influences panel acceptance of low "tar" cigarettes. A study of the effect, o of varying nicotine levels of low "tar" cigarettes through blend manipulation is ~;;.° in progress. In.conjunction with this work, niinimsn "tar"-nicotine levels' for~";~ RJR7288 Ln
Page 342: raj82d00
295 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPERIOR COURT OF WASHINGTON FOR KING COUNTY CASE NO.: 96-2-i5056-8 SEA STATE OF WASHINGTON, Plaintiff, VS. AMERICAN TOBACCO COMPANY, INC., et al., Defendants. x Videotaped Deposition of THOMAS A. PERFETTI, Ph.D (Taken by Plaintiff). Winston-Salem, North Carolina January 21, 1998 Reported by: Geralyn M. LaGrange Registered Professional Reporter Notary Public m HUSEBY & ASSOCIATES (800) 333-2082
Page 343: raj82d00
6 the value for Marlboro 0.13 mg/puff or less. • Physiolooical response to nicotine difficult to Quantify - Measurement of the physiological response to nicotine by some rapid and non-invasive technique would be a convenient indica±ion of nicotine satisfsction. Nicotine is known to cause a number of small changes, such as increased pulse and heart rate, decreased temperature of the fingertips, and altered EEG. Pilot studies i: the measurement' of fingertip teeperat.ure and pulse rate for a small group of Research subjects showed differences before, during and after sookiniy but they were almost impossible to quantitate. Individual differences and day-to-day variations are great. There is little expectation that a successful technique will be discovered, but we will continue to search. • Cons`ltudy being planned - Together with Marketing Research a special consurk r s is being designed that will involve the use of the experimental ~ y~. :fi,~•,4 cigarettes~des~ribed above. Smoking habits, cigarette consumption and preferences ~A ~ wi;~~e fo~d for a large representative consumer panel with the aim of establish- ~:: ienq optirm minimcm nicotine levels as well as obtaining a better understanding W-" wt n14 ~~ of smoker ~action. Final plans will be completed in January with results ;~ :.~ A °' scheduled for 4 quarter 1978. We will work closely with NRD throughout this N study and with their consumer psychologist, if they hire onw. '' ~ .....r..~...+ O~r Factors _Imoortant to Smoker Satisfaction w 0 ~ 0 .Im ~ortaf k H il r k H i i f f k T l r • ~ nce o soo e s unc ea e n smo he ro smo e p er sat action e o s ~' is not clear. It is obviously important to taste, but how this relates to nicotine <NA ~ ~t sAify level and T//t ratio is not well established. It has s~~ A p been assumed that smoke ==M pI1 z3oo• determined "free nicotine" content of the smoke,)and it is calculated on that qasis. However, recent evidence suggests that "free nicotine" in the mouth is determined by the pll of the smokei1s saliva. It is hoped that experimental cigarettes can be designed with smoke pH as an independent variable, but tho probability for success is low. RJR4888
Page 344: raj82d00
Dr. 0. H. Piehl • 2- February 28, 1978 NICOTINE ANALOGUES: SAR STUDIES ON NICOTINE ONO Pao REFERENCES CITEO: 1. Whidby, J. F. and Seenan, J. I., J. Org. Chem. 41, 1585 (1976). 2. Pitner, T. P., Edwards, W. B., lII, Baisfield, R. L. and Whidby, J.f., J: Ain. Chean. Soc. ~, 246 (197A). 3. Sanders, E. B., Secor, H. V., Seeman, J. I., J. Org. Chem. 43, 324 (1978). 4. Rondahl L., Acta Pharaiaceutica Suecica 14, 113 (1977), 13, 229 (1976), 9_, 221 11972) and references therein. u x ~ RJR12505
Page 345: raj82d00
Within the scope of this inventlons the addition of nicotine salts to tobacco products is inesnt 1nclude the addition of n cQttne selts qt }lnple oro tnic acids, amino !clds~s),~Fetty tcids, pepttde: f), orot.in: t11) and potrnerie acids (5,10) as xell as .lxtures•ot thes• st ts. The addition Is netnt to Include all types of tobacco yroducts such as eifsrs, ci4ar.ttes, snuff. mokin4 and chew/n~ tobaccos as well as.additions to tobteco,extenders, substitytes, , filters and wrappers. The concepts and procedures taught in this fnvention are thought to be novel and presumably patentable. : otstr ibutt Or. A. H.Awftne, Dr. N. Senkus (file) : H~_Ervn~tfr. H. J. eluha, Library (itle) : ~:~. H. . Ie 1, Or. N. E. Stor+e tttle) , I~ . A , Dr. W. L. Cltpp .Or. C. T. NtnsFteld Nr. 3. npnan, Dr. J. 1. bobbins, Dr. 11. N. Hente$, Dr. 3. N. umscher, Library (file) •Or. T. A.., tti . Mr. L. E. ~t ' 'Subeitted: February t, 1978 ;~:! 1400 Completed: Nsrch 8, 1978 ~ From eunuseript: sa • Retd and yrders by me: e. . 'ar:/A ~~L/l f na . 0 .P ~ RJR23807 `°
Page 346: raj82d00
298 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CONTENTS The Witness: Thomas A._.Perfetti, Ph.D Examination By Mr. Maistros 300 By Mr. Sobol 419 By Mr. O'Hara 464 By Mr. Maistros Re-Examination 486 INDEX OF THE EXHIBITS For the Plaintiffs 15 Handwritten Notes - June 22, 1978 16 Handwritten Notes - July 19, 1978 17 Handwritten Notes - 1979 Program 18 Memo Dated September 20, 1979 19 Memo Dated September 8, 1980 20 Memo Dated October 29, 1980 Page 329 331 337 341 345 351 21 Position Papers sent to Dr. DiMarco 355 22 Notebook Pages - May 9, 1983 363 23 Draft Dated December 1, 1986 368 24 ' Memo Dated October 20, 1988 370 25 Memo Dated November 28, 1989 378 26 Memo Dated July 30, 1990 387 27 KDN Extract Dated March 11, 1991 389 28 Processed/Reconstructed Tobacco 393 HUSEBY & ASSOCIATES (800) 333-2082
Page 347: raj82d00
294 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 SUPERIOR COURT OF THE STATE OF CALIFORNIA FOR THE CITY AND COUNTY OF SAN FRANCISCO CASE NQz: 980864 x THE PEOPLE OF THE STATE.OF CALIFORNIA, et al., Plaintiffs, VS. : PHILIP MORRIS, INC., et a Defendants. x Vi'deotaped Deposition of THOMAS A. PERFETTI, Ph.D (Taken by Plaintiffs) Winston-Salem, North Carolina January 21, 1998 Reported by: aeralyn M. LaGrange. Registered Professional Reporter Notary Public I HUSEBY & ASSOCIATES (800) 333-2082
Page 348: raj82d00
297 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17' 18 19 20 21 22 23 24 25 Videotaped Deposition of THOMAS A. PERFETTI, Ph.D., taken by the Plaintiffs at Womble Carlyle Sandridge & Rice, 200 West Second Street, Winston-Salem, North Carolina, on Tuesday, the 21st day of January, 1998, at 9:39 a.m., before Geralyn M. LaGrange, Registered Professional Reporter and Notary Public. HUSEBY & ASSOCIATES (800) 333-2082
Page 349: raj82d00
{l . ~ ~ . .r Subjcct: N1C0T1NE:•A REVIEW To: Dr. M. E. Stowe • St1t-F•1ARY:. m< t ft ]' ' I ' ' Datc: Febru•ary ?, 1978 From: T. A. Perfetti A review has been'made of the literature on the chemical, physiological, pharmacological and medicinal properties of nicotine. Studies reported over this 170-year period dealt with nearly every conceivable aspect of nicotine. Thousands of references to nicotine were reviewed to determine if the work was pertinent to research underway or planned in our laboratories. The collected material is availa ble either in the library (1) or from the author. This report is intended to provide an outline of the types of studies which have been made of nicotine rather than a comprehensive review of the results.of t ose studies. The author will be willing to discuss in greater detail *Vic areas of interest to other staff-members on a one-to-one basis. 0" A c~te review of literature on nicotine has never been made although sand o articles (2) and books have been written. This review of the a` rat~ecame necessary because of the larroe number of staff working in MEt•10P,kt2 this ar the large number of diverse areas in which each is or will soon be workin Jt was thought that if one individual reviewed the literature, his i:no\•p could help others in directing them to literature that could be of assistan~. Finally, it was thought that such a review would serve as a source of information to spawn new research ideas. Topics reviewed will be presented in two parts: chemistry and physiology and medicine. The major emphasis will be in the chemical area. A. Chemistry ~ ' this part of the literature were classified as falling into The papers in ~ ~ nineteen areas. Each area concentrates on specific topics of interest to work already started or planned in-house. Several other topics., not mentioned below, were abstracted from the literature. These topics were not thought to be pertinent . to work planned or in progress and were not further investigated. These ancillary references can be•found in the compilation of references in the library (1) but are not included in any of the areas iisted below. The chemistry Dart reoresents ; the backbone of the literature survey and was of the greatest interest. The areas of major emphasis are listed below in order of importance and depth to which each was surveyed. Ln ... . i Physio-Chemical Properties ~ 2 Synthesis and Biosynthesis 3 Degradation, Fermentation and metabolism of Nicotine ~ 4 Chemical Degradation of Nicotine '~ 5 Methods to Detect Nicotine 00 (6) Nicotine and Taste PMA a~ R JR 2112 Nl~t foA~~ t4tJ•Rw. 1I10 t~, o- r. . . _ . .. .. 1 117
Page 350: raj82d00
..w~ .~.r ~.~. . •4a LZTERAIURE CIT€0: 1. delltn, S. A., CIM, jM, No. 10. . 2. Turkov/c, Ivo~Y~.stnfck, Ka (isgrob 16/16s63•66s 1491•4?s Ce:eltc M., iC-va:tc ..n C, S., lULL. aOC. CNO1. ANo TECH., ~rasevo~, i3-5s~ ~1963~. 3. Klenflskfl, I. S. and Prokovlew, E. 8., atOCHEM. 2. 376•9 (1933). . 4. 0iffee. J. and Shoppard, M., RCl1, 6!. 6. Perk/ns, P. Re and M1e, C. R., Canel/an Patent 977,9,13 (1975). r 6. Tonpsoa, C. C., RDR, JM, - No. 11. ~.. 7. Perfettl, T. A. and ltayes, t.. E.. C111, IM No. t. 8. Pictet, A. and Rotschy, A., CHEX. EER. U, 1tt6•35 (1904). 9. Y.echmkov. J. GE!!. CHEM. (USSR) JL, 970-1 (1935). 10. Scholler, R., FACHL. MITY. OSTERR. TAdllptEilE, Dec., 193a, 15•17t entr. 1959, 31 1602. 11. l,00 tn. M. A., RIOCHEM 2. M. :6-S t19333. 4 ~ ro, Coestantln, French Patent 719,a13 (1930). PM. 'doM , E. R., Science LX ja, 16 (1924). . ~ :`'~utt~ Sb1R' • RJR23$08 0
Page 351: raj82d00
299 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 INDEX OF THE EXHIBITS For the Plaintiffs Page 29 Report Dated December 15, 1993 401 30 Distribution List 404 31 Projects Dated October 7, 1988 413 32 Memo Dated May 7, 1986 411 33 Mission Statement/NRC Membership 436 34 Memo Dated February 23, 1989 447 35 Nicotine Research in R&D 451 36 Memo Dated March 10, 1983 465 37 Memo Dated January 6, 1987 471 38 Memo Dated July 30, 1990 476 HUSEBY & ASSOCIATES (800) 333-2082
Page 352: raj82d00
Treatment: 1. •For ingested poison, vomiting should be induced with syrup of ipecac solution, 15 cc of syrup with 15 cc of water, then administer 6 to 8 heaping teasponsful of activated charcoal as a slurry in water. 2. Gastric lavage with 0.5 percent solution of tannic acid or a 1:5000 solution of potassium permanganate should be performed using 1 liter of solution, 120 cc/dose. • If nicotine is spilled on the skin, wash thoroughly and immediatel•Y with cold water. Artificial respiration and oxygen therapy until spontaneous breathing is adequate or until the heart ceases to beat. Central respiratory stimulants are rarely if ever indicated. Keep the airway clear. . If severe or persistent, convulsions may be controlled with small intravenous doses of barbiturates . . , 6. Most of. ral manifestations can be controlled by various combinations of' autonom c: cking drugs, such as atropine and phenoxybenzamine (Oibenzyline). ~• Caramip arpanit) hydrochloride and diethazine (Diparcol) hydrochloride, ~~ which h$tl'e en extolled in the control of the experimental nicotine poisoning ~ "not' able in the U.S.A. for parenteral use. LabelM• r R%Aid: ~' ~ In constr ing this memo, Dr.,Shirley.K. Ostuhout, Clinical Director of ~ the Duke Poi4ontrol Center and Dr. W. S. Garland of RJR Medical Department were consulted:-~ In the treatment of nicotine poisoning - s eed is im erative ~ and those working with nicotine or nicotine salts should be aware o t e symptoms p" of nicotine poisoning and its treatment. It is recommended that each laboratory ~ that handles nicotine or its salts should have syrup of ipecac, clean activated charcoal and a solution of potassium permanganate on hand. If an accident happens first-aid should be administered and then the person should be transported to Avi*, a hospital immediately. R J RI 1085
Page 353: raj82d00
301 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Awards Committee. That's what it was. It was called the Awards Committee..~.I was on the Library Committee and I-- I did serve a -- a short time on the Human Resource Review Committee, I believe. Yeah, I was an alternate on that. Q. How about any outside organizations? A. Yes. I -- I was -- I had worked with two graduate students. I had two graduate students at the University of California, Davis, and that was during the '80s. I was on their Master's Thesis Committee. Q. Who.are those students? Did they ever do work for Reynolds? A. No, no. They -- they -- they were -- they were never at work or paid for anything that we did around -- Q. Any other outside committees, organizations? A. I can't think of any more right now, sir. Q. Any professional chemist organizations? A. Yes. I'm a fellow of the American Institute of Chemists, I was a member of the American Association for Advance in a Science, Ln ~ ~ ~ m r un m HUSEBY & ASSOCIATES (800) 333-2082
Page 354: raj82d00
306 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 higher nicotine content tobacco? A. In - in -.T in one part of the patent, yes, that was one of the -- the -- it was one of the pieces of the patent. It -- it ranged over the entire range having low nicotine delivery at the end of the cigarette or high nicotine delivery at the end of the cigarette.There was a very wide range in terms of the nicotine delivery profiles for these prototypes we were preparing. Q. And wasn't one of the goals or end products of this patent to attempt to eliminate the problem that had been detected in cigarette smoking that -- that is, the nicotine content of the puffs varied from the beginning to the end of the cigarette? There -- there was a concern during this time period that -- that -- that -- that people wanted -- that smokers were interested in having a constant.delivery cigarette that did not change from -- from the beginning to the end. And thi-s particular cigarette could be designed to -- to deliver a constant delivery of tar and nicotine at least theoretically during the entire smoking process. 25 1 Q. Well, didn't Reynolds determine that HUSEBY & ASSOCIATES (800) 333-2082
Page 355: raj82d00
303 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 chemist, senior staff scientist, master scientist, principal scientist, have a].l.those been under R&D? A. Yes, sir. Q. Were you ever outside of R&D? A. No. Q. Is New Product Development inside R&D? A. Yes, sir. Q. Is that a different entity than or a subentity of R&D? A. It -- it it -- it -- it's -- it's a division under -- well, it's a division that was normally under Product Development and Assessment Division and that -- that title for that particular applied R&D area has changed a number of times over the last 20 years, but basically doing.applied R&D research there. Q. Okay. I want -- if you can give me a thumbnail sketch of what type of research you were doing from 1980 to the present. Categorize it. Ln N A. I-- I would say the -- the large -J majority of it is under product development, is I ~ N _ f.., think that's what I'd call it, product development. Q. And what type of products? A. Cigarettes products. HUSEBY & ASSOCIATES (800) 333-2082
Page 356: raj82d00
1 2 3 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 turned into commercially used products? A. Not -- no.t •-- .not all the invention disclosures were on cigarettes. Some of them were on parts of -- of -- of cigarettes and on reconstituted sheet modifications and things like that, but one of the -- one of the patents was commercialized into a cigarette. Q. Which one? A. I'm not familiar with the -- I can't remember the US patent number, sir, but it had to do with two-stage blended cigarettes. Q. That was an idea to provide the same amount of nicotine at the beginning of the cigarette and at the end? 'A. The invention disclosure dealt with preparing a cigarette that had two -- that the tobacco rod had -- had two -- two segments that could vary in terms of the -- the length of each of the segments. It would also change in terms of the density of each of the sections and the -- the composition of the tobacco blend in each of the sections and -- Q. Didn't it also provide that the end of the cigarette would have a low nicotine content versus the end closer to the filter which had a HUSEBY & ASSOCIATES (800 333-2082 305 i
Page 357: raj82d00
304 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. New cigarette products? A. Some of the --. •some -- some -- some of the.projects were dealt -- dealt with with new cigarette development and other ones were in terms of product improvements from -- for our existing brands. And you referred to yesterday as invention disclosure memos or what were they called? A. Yes, sir. They were titled CIM, and that was Conception of Invention Memorandum, is what that -- that -- those -- those were. And then there is another -- they changed the name a little later on, late in the '80s, I guess, to just invention disblosures. Q. How many of those CIMs or invention disclosures did you file since you've.been employed at Reynolds? A. Oh, 50 or 60 maybe. Q. How is that compared to other Ln ~ chemists in Research and Development? ~ A. I probably have more than -- than most. Q. Of the 50 to 60 CIMs or invention disclosures that you filed, how many actually HUSEBY & ASSOCIATES (800) 333-2082
Page 358: raj82d00
307 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 .17 * 18 19 20 21 22 23 24 25 the smokers actually had a problem with the varying levels of nicotine and not the tar? It was -- the entire smoking experience became very -- very hard at the end, and it was a component both of the tar and of the nicotine, sir. Q. Did your patent disclosure disclose that the patent would attempt to produce a cigarette that had constant nicotine.delivery or constant tar delivery? A. I-- I think that there were several patents that we had on this. The one that I think -- one of them, I think, did talk about having a constant delivery of -- of smoke nicotine as -- as a factor that was different from other -- and I think it was one of the way'-- ways we were able to get the patent allowed. Q. And what cigarette did this end up being incorporated into? A. It was a product manufactured in Germany called Reynolds II Stage Blend, I think is what it was called, Reynolds II Stage Blend. Q. why wasn't it sold in this country? A. We -- we had done some -- we had made experimental prototypes and we had tested those out HUSEBY & ASSOCIATES (800) 333-2082
Page 359: raj82d00
296 1 2 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 APPEARANCES.: For the Plaintiffs (Stat.e of New York) : JACK D. MAISTROS, Esq. KATE M. McNAMARA, Esq. Climaco, Climaco, Lefkowitz & Garofoli, L.P.A. The Halle Building - Ninth Floor Cleveland, Ohio 44115 (216) 621-8484 For the Plaintiffs (State of California): MICHAEL SOBOL, Esq. Lieff, Cabraser, Heimann & Bernstein, L.L.P. 275 Battery Street - 28th Floor San Francisco, California 94111 (415) 956-1000 For the Plaintiff (State of Washington): CHRISTOPHER A. O'HARA, Esq. Hagens Berman & Mitchell, P.L.L.C. Suite 620 2425 East Camelback Road Phoenix, Arizona 85016 (602) 840-5900 For the Defendant R.J. Reynolds Tobacco Co.: DENISE A. FEE, Esq. Jones, Day, Reavis & Pogue 1450 G Street, Northwest Washington, D.C. 20005-2088 (202) 8 7 9 - 3 9 3 9 Also Present: Brent Troublefield, Videographer HUSEBY & ASSOCIATES (800) 333-2082
Page 360: raj82d00
3;? , CQNFID1LPJr:tce . ~s „ -~: ~MFreran d u rr 4 I Subject: Nicotine Analogues: SAR Studies on Nicotine Date: March 2, 1978 To: Dr. 0. H. Piehl a " From: T. A. Perfetti V During the last two years Philip Norris has published several papers on nicotine (1,2,3). The work concentrated on the configurations of nicotine in the crystalline, liquid and gaseous states. TAe~r have also published a paper (3) on "Preparation of Nicotine Analopues." M~ile this information is interesting and important, perhaps insight into the underlying current of this research would be of greater interest. Having been familiar with the history of what has been done with nicotine in the past and being abreast of current trends in this area, these papers seem to indicate that Philip Morris is Involved in the area of Structure Activity Relationships (SAR). Interest In the configurations of nicotine in the gas and liquid states is of great importance when trying to formulate SARs but this information, except on a purley acadesic basis, is rather impertinent. Philip Morris' interest in nicotine analogues is the second step in the forawlatior ARs. For if one knows the preferred configuration of a molecule to achieve ~ Aax mum activity, then compounds can be synthesized to achieve this goal. SARs OWAO been used extensively as a means of finding new compounds that mimic the rac ion of apa rent compound. A considerable data base on the SAR for nicotine ' has atready been established by the Ro al Ins en, in their series of papers on e yn t c na opues of Nicotine" (4). 4s my impression that Philip Morris is involved to a large degree with finding r•nicotine analogues, for eventual use, if nicotine becomes prohibited or for in perhaps a new smoking material where nicotine would not be 4wsuitabie. ~ Finally as a note on enother area, it has been brought to my attention that ~ Pharamcology Department at the Medical College of Virginia (f4CV) is involved in the study of the,pharmacological effects of d-nicotine and that a successful synthesis of d-nicotine has been achieved. Since MCV has been involved with work for Philip Morris previously and since information on the pharmacolo y of d-nicotin is important for the cigarette industry in general, perhaps this work has also been sponsored by Philip Morris. It should also be noted that MCV has been interested in the investigation of certain compounds,•their activity and enkephalins that may be related to nicotine. If this is the case then Philip Morris may also be interested in the direct physio-phar+nacological response to the effect of nicotine and thus satisfaction in general. N v v ~ :ki ' Xc: Dr. M. E. Stowe /11H1 fO11M y<2l-/1M. 1/70 RJR12504
Page 361: raj82d00
308 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 on some consumer panels, and there did not appear to be a -- a large enough number of people that thought that they were acceptable. And there wasn't any -- you know -- after -- after we had attempted a-- a couple consumer tests and modifications, we still never were able to -- to get a product that was acceptable to the consumers. Q. Do the cigarettes that Reynolds markets today still have that phenomena of varying levels of nicotine from the beginning puffs to the. end puffs? MS. FEE: Object to the form. THE WITNESS: The -- the general pattern for delivery of -- of tar and nicotine is a -- a -- a shape where you have lower deliveries at the beginning, moderately small changes in the middle, a number of puffs, and then increase at the -- the last couple of puffs. That is the general shape of -- of delivery of smoke components per puff, puff count on the X-axis that you'll find for almost all smoke components, nicotine as well as tar, nicotine CO, C02, and a variety of other smoke products. HUSEBY & ASSOCIATES (800) 333-2082
Page 362: raj82d00
I 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 directly back to the material. BY MR. MALSTROS-t .Q. Is the REST process something that's been employed commercially at Reynolds? A. No, sir. Q. And,why is it being looked at? MS. FEE: Object to the form. BY MR. MAISTROS: Q. First of all, when was.it first developed? A. The REST process was, I believe, developed sometime in the early to mid-'80s. Q. For what purpose? A. One of the charges of our -- our process technology development area was to explore new processing technologies and equipment. Some of the scientists in that area thought that, -- that this would be a good thing to -- to look at in terms of preparing a new means to uniformly -- prepare uniformly uniform taste and -- and properties of all the cut filler at one time. It would lead to a more uniform smoking experience for the -- for the -- for our consumers. And work was done to explore equipment and bring that equipment in-house and test it. 312 w ~ J J m HUSEBY & ASSOCIATES (800) 333-2082
Page 363: raj82d00
! P R 0 C E E D I N G S 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Whereupon, THOMAS,_,A. PERFETTI, Ph.D., having been previously sworn, was examtned and testified as follows: THE VIDEOGRAPHER: This is day two of the deposit-ion of Dr. Thomas Perfetti. The time -- the date is January 21st, 1998. The time is 9:39 a.m. EXAMINATION BY COUNSEL FOR PLAINTIFFS BY MR. MAISTROS: Q. Good morning, Dr. Perfetti. How are you? A. Pretty good. Good morning. Q. Couple of things. During your employment at Reynolds, were you ever a member of any ad hoc committees or groups, other than the Nicotine Committee you referred to yesterday? A. Yes. There were several committees, like the Peer Review Committee, the.Publication and Presentation Review Committee, the -- there's a -- there was a committee to honor employees in R&D, and I was on that. I can't think exactly the name of it, but it was at -- we -- we would review employees for particular honors and awards. Oh, 300 HUSEBY & ASSOCIATES (800) 333-2082
Page 364: raj82d00
311 1 2 3 4 5 6 7 .8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the -- the -- the extracted tobacco, and then you can apply the extract b.&ck onto that material to create.a real uniform smoker -- smoking material where -- where all of the different pieces, the pieces of Turkish and flue-cured and sheet would all have the same extract from that blend all -- all across the -- the tobacco. .How -- how is that different than the recon process? A. There is not a maceration of -- of the particles to form a sheet in this; that we're dealing with cut filler where some of the material is extracted off and then reapplied.across the entire cut filler. So, there's no destruction and there's no refining of the -- of the -- of the tobaccos before an extract is reapplied to it and also no sheet formed. Q. And is all the extract reapplied to the tobacco? A. Generally speaking -- MS. FEE: Object to the form. In which, in REST or in -- MR. MAISTROS: In REST. THE WITNESS: In the REST process, generally all the extract is applied HUSEBY & ASSOCIATES (800) 333-2082
Page 365: raj82d00
Dr. M. E. Stowe - 2 - February 14, 1:73 PROJECT 1250: SMOKING SATISFACTION AND 'TAR'/NICOTINE CONTROL Specific Undertakings 1: Initial work by Fredrickson on how nicotine is bound in tobacco will include studies of (1) extraction and distillation procedures which have been used to determine the "free" nicotine in tobacco, and (2) the distribution of nicotine in , the cellular structure of tobacco. ~ "Free" Nicotine Determinations ~.• In previous studies in the literature "free' nicotine has been defined as the quantity of nicotine extracted by petroleum ether or chloroform or as the W quantity of nicotine steam distilled from tobacco without the addition of alkali . " Although the analytical data frcm the extraction and steam distillation experiments ;gg},v,a~ do not agree, both methods suggest that nicotine is present in tobacco in various ~ forms. In the present work the removal of nicotine from tobacco by extraction with organic solvents under varied conditions of temperature and time will be investigated. Relationshi the yields of extracted nicotine to the quantities and types.of acidic toba ~ nstituents will be studied. A similar study of the effect of pH on the yiel~ •icotine steam distilled from tobacco will be carried out. Estimated ,:ime for th~se studies is 6-12 months. V n~ Distftwtion~Nicottne in Tobacco 0 :. Aist • ical investigation of the distribution of nicotine *within the ,4 cellular struct es of tobacco leaves is planned to search for sites of high ~, nicotine corations. This approach is based upon the assumption that ~~ different nicblWe compounds may be located in different parts of tobacco leaves. ~ For example, nicotine in cuticle wax may simply be dissolved in the wax or it ~~ may be in the form of fatty acid salts; whereas, nicotine within the cellular ~~ structure may exist partially as salts of stronger acids, e.g., citric, malic, ~'"~ oxalic acids. If this approach demonstrates distinct distribution patterns, it will be a lied to different tobacco t es, grades, etc., and to treated samples ~ ph tt which may ave altered distribution pa erns . 1%0 The initial phase of the'work will involve the testing of various nicotine ;~ ~ reagents and development of procedures. Picric acid, Dragendorff's reagent ~ ~~(KBiI4), and cyanogen bromide-aniline have been used to detect nicotine in ~ ;:~imilar studies so these reagents will be tried first. m Estimated time to developed procedures and to determine the utility of this approach is 4-6 months. " Nicotine Salts ~ ~ ~ ~ In this work the emphasis will be on the types, distribution, and relative amounts of nicotine-containing materials in tobacco. Properties of nicotine ~ salts will be studied as needs for additional information develop. In subsequent m ~ work on nicotine transfer, thermal analysis will be applied to the study of the ~ 00 -behavior of nicotine salts at elevated temperatures. m RIR11098
Page 366: raj82d00
310 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 experimental prototypes that we were developing. These have never• been used.. .. .Q. Were they used anywhere? A. No. They were tested in consumers in the United States and -- and I believe in Denmark, but -- but -- but,again, they were not -- they didn't have the consumer appeal in taste profiles that -- that consumers liked. Q. Has Reynolds ever'attempted and used commercially cigarettes that contained tobacco containing different levels of nicotine compartmentalized in the tobacco rod? A. Again, the -- just -- we did -- we made experimental prototypes based on this -- on the -- the TSB-type technology, which -- which did do that. You'd have a -- one kind of blend on the front end, one other blend on the back end of the cigarette which could have very different nicotines, if you'd wish to -- to do that. Q. What is the REST process? A. The REST process stands for the Re-equilibration of Solids on Tobacco or Solubles on Tobacco. Generally, what one does is -- is does a mild extraction of the tobacco -- of a tobacco cut filler and then have the -- the extract in HUSEBY & ASSOCIATES (800) 333-2082
Page 367: raj82d00
313 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 What's the current status of the REST Their -- the REST process is - was not found to be feasible and was not -- it doesn't exist anymore. Q. When was it abandoned? A. I believe it was abandoned for good about five years ago. Q. So, it was -- it was experimented with from the early '80s to about 1993? MS. FEE: He said mid-'80s. THE WITNESS: Yeah, about -- about -- aboutthe -- the mid-'80s. I think there was about maybe five years of -- of actual working with -- with -- with the process itself and getting equipment in and doing a lot of testing. There was a -- a number of pieces of equipment that were, you'know, were on loan to us from a variety of companies to -- to just to experimentally see if -- if this was feasible first. And -- and then after we thought it was a feasible thing to -- to attempt, we had to go and make a little bit more than just a handful, because originally we were HUSEBY & ASSOCIATES (800) 333-2082 ~ r v ~ m ~ Ln N) N
Page 368: raj82d00
318 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 useful in terms of what they'd like in a cigarette, I guess. I forget exactly the question we asked, but we,lost -- we were trying to find out what -- what else they would like in a cigarette and -- Q. I'm sorry. A. Just what else they would like in a cigarette. And one of the things that came back in terms of that thing was different shapes, because we -- we had -- I'd been in Europe and a lot of -- there's a lot of fat cigarettes over there. And when I travel around, I look at different products that are on the markets in different areas. And we saw some real fat cigarettes over there, which kind of appealed to me and we thought maybe there would be a market here for something like that. Q. Was that the only design change, the cigarette was wider? A. Basically, yes. It was a change in -- in the -- in the diameter, you know, the girth of the -- of the product. Q. Everything else being equal to cigarettes exactly the same except one is wider than the other, which will deliver more compounds of concern? A. Well -- HUSEBY & ASSOCIATES (800) 333-2082
Page 369: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. Has Reynoj.ds employed any process or methodp in an effort to achieve the same thing that your patent you testified about sought to achieve? Your patent was attempting to modify the ordinary low, moderate increase levels of tar and nicotine in the smoking process, correct? A. Yes. Q. To try to even them out perhaps? A. Yes, yes. Q. ' That patent wasn't employed in this country. Were any similar efforts ever employed by Reynolds? A. Oh, yes. There -- there -- there was -- there was another technology that -- that -- that appeared to -- to work along these same lines, and that was in a filter -- a filter technology. This filter technology had small tubes that were in the filter that were able to level out the delivery of tar and nicotine as -- as the cigarette smoked. Q. And that's been employed in was commercially sold cigarettes in this country? A. No. These were -- these were HUSEBY & ASSOCIATES (800) 333-2082 309 m i
Page 370: raj82d00
314 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 only making handfuls of material and then we Q. wanted to get to_.a point where we could make enough to -- to make some cigarettes on a real cigarette machine. It was a -- it was a -- it was a slow growing process. BY MR. MAISTROS: What has been your involvement in expanded tobacco? MS. FEE: Object to the form. THE WITNESS: I've had really very little, you know, involvement in -- in the expansion of tobacco over the years. BY MR. MAISTROS: Q. Are you familiar with the process? A. I have some familiarity with -- with the process, yes. Q. What is the primary agent that Reynolds uses to expand its tobacco? A. The primary agent is carbon dioxide. Q. How long have they used carbon dioxide? A. Gees. We started using it -- I can'tt give you an exact date, but I guess it was early in the '90s, somewhere in that time frame when - 25 1 when -- when we knew that we had to get out of HUSEBY & ASSOCIATES (800) 333-2082
Page 371: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. You have identical smokers with identical puff habits. _ ,A. Okay. They -- they both deliver actually about the same. In -- in the -- the beauty of that is that you have a -- the tobacco rod is -- is a filter itself and it appears to burn slower per puff, but it filters more as you're burning the thing. So, we -- we've looked at the full range of things that we can -- we can analyze generally, we normally analyze. We couldn't find any real change in the -- in any of the smoke components. Q. Did you find any change in the nicotine yields of cigarettes, everything else being equal, what the circumference of the cigarette has to do with the nicotine.yields? A. No. The -- we didn't see any real change. The tar-to-nicotine ratio for a -- a -- a skinny or a normal or a -- a wider girth, prototypes are all about the same when you have about the same amount of tobacco that you're burning in those rods. They don't seem to -- to change dramatically. Q. So, it would be your testimony that 319 HUSEBY & ASSOCIATES (800) 333-2082
Page 372: raj82d00
i 1 2 3 5 6 7 8 10 11 12 13 14 15 16 1 T 18 19 20 21 22 23 24 25 Sigma Xi, the American Chemical Society, and there's -- there's anotljer fraternal, something like Sigma Xi that I -- I was a member of. I can't think of the name of it right now, but it was a scientific fraternity in college in graduate school. Q. What is CORESTA? A. CORESTA is a -- it's an international committee dealing with standards and.testing methods for the cigarette industries. Q. Have you ever been a member of that organization? A. No, sir. Q. How many publications have you participated in? A. I -- I'm not sure of the exact number; 12, 15, somewhere in there maybe. Q. Have all those publications been since you were employed at Reynolds? A. No. Those are just the ones that -- that -- that -- since I've been at Reynolds. There was -- there was three or four other ones when I was a graduate student and a undergraduate. Q. The different titles you've held over the years; research chemist, senior research 302 HUSEBY & ASSOCIATES (800) 333-2082
Page 373: raj82d00
315 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 using Freon. Q. And does Reynolds use Freon in its tobacco process today? A. No, sir. Q. And the last time it used Freon was in the expanded tobacco process? A. Yes. Q. Did it use Freon in any other portion of its tobacco processing? A. No, sir, not that I'm aware of. Q. Well, do you know what the initial primary reason expanded tobacco was used? A. I-- I think there -- my -- my understanding of that is that there -- there were two -there were two things. One -- one of them was that, if you burned less -- less -- less total mass in -- in a cigarette rod, you will produce less tar. And this was introduced, I guess, somewhere in, I think, in the '60s, early '60s when we were working hard in terms of reducing the tar and nicotine delivery of our cigarettes. One of the inherent properties, of course, of -- of -- of expanded tobacco is that it has a -- a real low bulk density and it -- it is a excellent way to adjust pressure drop in the HUSEBY & ASSOCIATES (800) 333-2082
Page 374: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarettes and has -- has an additional tool for the design of cigarette8.. .Q. And what role did cost savings play in these expanded tobacco? A. Expanded tobacco did have a reduction in cost. I mean, it was -- it was certainly significant enough to -- to -- to have a return on investment that was a-- you know -- really appeal -- appealed to the company. Q. And do you know if the cost savings was the primary motivating factor in use of expanded tobacco or was the fact that you were burning less tar the primary factor? A. I -- I wasn't here at the time, sir. I'm -- I'm not sure. Q. The one invention disclosure that you cited that ended up in a.product that was not sold commercially in the United States was this dual blend tobacco rod. Were there any other invention dis'closures that you filed that ended up being used in a commercially sold product in the United States? A. There -- there were a couple of other improvements that -- that -- that I think were 316 I HUSEBY & ASSOCIATES (800) 333-2082
Page 375: raj82d00
1-4 SECRET Authors: Thons A. Perf~~~ February 24, 1978 Lawrence E. N~+W, 13 EJY...~ .. Division: Chemical Research _~ obook Pages: 306964-57 CiMI, .1978, No. 4 Wedr ,knuary 28, 1978 Ho. of Pages: 4 Previeus Reports: Nona Disclosur. No: H-10S•R F SU IiNARY: . 1'La ~~~~ .• ~IAW .~,.. ~ .:.,L W'&1L~::!3 !j itilL:L'1:1~&1i%;l L'1ll,l4W.IJ'.V re are com Th ble that whe d ll a kl h l d 1 poun e va a s n pyro n t e smo np process yze my tntroduce flavorants and lncrease nicotine transfer. This tnventton concerns itself with such compounds - nicotine salts of flavorants and nicotine anf f 1t f d idl 1 t 1 ~ :a or9 c cornpoun s con n9 ac s o n a c unctlons tn parttcular. ~ .' ~ M MORAl10UN: . Ftirty c acids ere known to be flavorentt In tobacco and tobacco sa:oke, e.9., phe Ic acid and tsovalerle actd. AlthouDh Maqy flavorants have an 0 ~k~ ~ ntcotlcin nne ~iihodorlot=ttnNleotl~easol t~s s~utA asberiotinotottrit:~ ,.~iliti aW'brtr• e.been used previously for the purpose of transferring exopenous nte~ltine nstrea~o smoke. Exparlments have :howe two iuportant tfilngs. ' ;1 ~t~ :., 1n se of nicotine tertrite the salt rnt thenrally unstable In the' smonp p • deoompos/n ot aro! nd ~00• C(8), a taperaturs far below the . pyrolysis ature of to~cco. CSaTts such as nicottne citrate and nicotine ealate tn tob o also dissociate at rather low teAperaturys.) Durtno the smoking :~ process t sfer of uco enous nicotine was not constant. llberatton of free nicotine M1Mf°nox regulated tn the smoking process. fnttially, larger concentrit/ons ~ of nicotine kero expertenud by the smoker and resutted In greater harshness for the smoker. The transfer rate did not Increase in a linear fashion In relation ~~ to the amount of nicotine salt added. ~~ Secondty, the unregulated dissociation of the nicotine salts lncru sed the concentration of tirtartc, citric and malic actds. This sistent release of ~ acids led to an Irritating and bitter taste in the sNoke ~1 . This Is because ~ -nicotlne ts known to tora: salt complexes having a ratio o enles of acid to 1 ~ role of nl;otine rather than the normal 1 to 1 or t to 1 rwttos expected for # salts (2,4). Not every acid has 4ood flavor characteristlas, but there are many ~ known tobacco flavorants that ere acids or have acid functional Sroupt. ~j
Page 376: raj82d00
I 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MS. FEE: Object to the form. THE WSTNE$S : .I.k think one of the .points we're missing here is that the weight of the fat cigarette and the weight of the normal circumference cigarette are not really different. So, mass of material burned with the fat cigarette versus the normal circumference cigarette is about the same; therefore, it will deliver about the same tar-to-nicotine ratio, the same -- the same tar and nicotine delivery. BY MR. MAISTROS: Q. So, again, is it your testimony that there is no difference in.tar and nicotine yields that are dependent upon the circumference of the tobacco rod? MS. FEE: objection, asked and answered. BY MR. MAISTROS: Q. Is that your testimony? A. My testimony is, if you have two cigarettes, regardless of the circumference within reason, if they have about the same weight, you will deliver about the same tar and nicotine yield 321 HUSEBY & ASSOCIATES (800) 333-2082
Page 377: raj82d00
320 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 circumference of the tobacco rod has no effect on tar yields or nicotine .y.ields1 .A. No. I -- I would say that it had little effect. Q. What is the little effect that it has? A. There is a-- there is always a -- some variation in -- in -- in the tar and nicotine yield, even between cigarettes, within two in one pack of cigarettes. So, they're -- they're not always dead-on no difference. Q. Everything else being exactly equal, if you have two tobacco rods with the exact same blend and one has a greater circumference than the other and you tested a thousand of them, which tobacco rod would you expect to have greater nicotine and tar yields? I would expect neither one of them to have any different difference. any real significant Q. I'm not looking for the degree of difference. Which one would have a greater tar and nicotine yield? When was the last time you read Townsend's design book? HUSEBY & ASSOCIATES (800) 333-2082
Page 378: raj82d00
322 1 for those two prototypes. Q. Forget yottr wide cigarette for a 3 4 5 6 8 9 10 11 12 13 14 15 16 1 7' 18 19 20 21 22 23 24 25 moment. Does the circumference of the tobacco rod effect the tar and nicotine yields? A. No. The -- the tar and nicotine yield of a cigarette is generally most impacted by the mass of material burned within that -- that -- that circumference. Q. Okay. So, the circumference -- would the circumference of the tobacco rod be a design specification? A. In some prototypes, yes. Q. Yet, it plays no role in tar and nicotine yields? MS. FEE: Objection; asked and answered about five times. THE WITNESS: I'm -- I'm sorry. The -- the -- that last question, could you - BY MR. MAISTROS: Q. The circumference of the tobacco rod plays no role in tar and nicotine yields? MS. FEE: Same objection. THE WITNESS: Generally, no. HUSEBY & ASSOCIATES (800) 333-2082
Page 379: raj82d00
323 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q Study?. Were you *ver -involved in the Chemsol A. I'm sorry, sir? Q. The Chemsol Study? A. I -- I guess not. I can't remember. Q. How about Project RAN, R-A-N? A. No. Q. Do you know what Project RAN was? A. Yes; yes, I do. Q. What was it? A. RAN stood for Reduced Ames Numbers. And it looked at a variety of experimental prototypes. And I -- and I believe what they were doing is running Ames tests on the cigarette smoke condensate. I believe the objective was to determine what -- what really -- was there anything that we -- we -- that we know about a cigarette that actually influences the Ames activity. Q. Did you ever meet Alex Spears? A. No. Q. Did you ever meet Wallace Hayes? A. Yes. Q. Did you ever hear anyone at Reynolds, including yourself, complain tY}at the lawyers at HUSEBY & ASSOCIATES (800) 333-2082
Page 380: raj82d00
t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 incorporated into Premier Menthol that were incorporated into that .r--.int'o that project. .Q. What were those? A. I believe that that particular patent had to do with mentholation of a number of the pieces and part.s associated with that cigarette, so that -- that you would not have this tendency for migration of menthol across the cigarette. And that was important in Premier. And that -- I think those modifications were made into the -- the menthol Premier product that was introduced. Q. Anything else? A. Yes. We -- I hold the patent with with, I think, some -- another scientist on the Wide Camel. Q. The what? A. There was a -- a cigarette called I think it was called Wide Camel. It was a -- a little bit fatter cigarette.' And -- gee. Q. What was the consumer benefit, if any, of that patent? A. There was -- there was some consumer research done, I guess, again, in the '80s looking at some of the -- the wants that consumers - - that were -- certain wants that they thought could be 317 m HUSEBY & ASSOCIATES (800) 333-2082
Page 381: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 they wanted me to -- to keep m,y ears open; and,if I had a good idea, always.--keep 'on putting them in. Q. Did you ever attend any meetings of the Council for Tobacco Research? A. No, sir. Q. How 'about the Tobacco Industry Research Committee? A. No, sir. Q. Have you ever heard of the Committee of Council? A. No. Q. Have you heard of the Scientific Advisory Board? A. is that a particular committee, sir? I mean,' is it -- Q. If you haven't heard of it, then, it doesn't matter. A. I mean, there -- there are -- there are just general scientific advisory boards. I mean, there -- there are scientific advisory we've had at Reynolds, but -- boards Q. Have you been a participant in any of those? A. No. 25 1 Q. I noticed in the documents we'll get 325 HUSEBY & ASSOCIATES (800) 333-2082
Page 382: raj82d00
326 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 to that a lot of time was spent first identifying and then obtaining nico,t.ine.a-nalogs; is that correct? MS. FEE: Object to the predicate. THE WITNESS: Yeah, nicotine analogs are -- are not -- weren't easy -- easily obtainable materials generally. And some of them had to be prepared. There wasn't a whole lot that could be just bought from -- from chemical companies. BY MR. MAISTROS: Q. And although we can go through all the documents, what was the primary motivating purpose in Reynolds gathering over 250 nicotine analogs? MS. FEE: Object to the form. THE WITNESS: There was -- there was -- there really isn't a large number, first of all, I'd like to say, because there's -- there's literally millions of organic compounds out there that -- to -- to choose from. And -- and a lot of the compounds that we're trying to get procured, I think, is what we were calling them, procuring HUSEBY & ASSOCIATES (800) 333-2082
Page 383: raj82d00
Nicotine salts of llevorahts could be used In situations where the larger concentrations of acid would enr/ch the flavor of the snoke. Such a situation exists In the need for Turkish substitutes. Nicotfne !•sa tltylbutyrate, nieotine b•methylvelerate and nicotine isovalerate would appear to be carpounds of tnterest In our search for new Turkish Substitutes. Other Mcotine salts th}t might be of interest would be nicotine talicylate or ~tcotine phonylacretete (4). The particular needs that we my have In the future for incressed tlavoranta or mixtures of flavorants as txed nicotine salts Is not known but a variety of pure and mtxed salts of nicotine could be used to enhance flavor and secondly increase nicotine transfer. Nlcottlsilts and/or nixed silts of t'1' avorents should enhance the t,aste and arorna of tobi~co and tobacco sNake. Mixed saitt MY be prepared to give the characteristics of several flavorants. Finally, Niwtine :alts of flavorants should also increase nicotine transter. 550• C(5) eraally stable and tulFills chancteristic (d). thermbl s , e.q., nicotine alqinatt, whose pyrolys/s temperature is 500• Ideal nicotine salts have several eharaeteristiest C13 Compound; should have low vapor presares. Ct) Compounds should preferably be crystalline solids. oous should exhiett thermal etabllf~r , /.ef the nicotine C33 Cas+ nd salt should ron~in Intact duriep the brnlysls o~ the tobacco and be liberated Ideally as the trN ee/d and nicotine durin0 the smoke formation process. The enerp,y associated with the p3rotysio ot the toa cco would Ideally only cleave the coordinate covalent bonds associated wlth tatt torriat/on and leave both the acid and ntcotine Intact. [4] lo,"nds should be easy to synthesize. Most ,Wic nicotine salts characteri=tieally are solids and have low vapor presiures: The vapor pre=sure of those salts that are oils exhibit va_ ~.A,... pres4ures'exrch less then the parent acids, e.'., VallriC acid n:o • 0.0274, nt~ne e r,=o • 0.5165•. Most nicotine salts aro easily prepared in one : ynthe 2). Thermal stability Is dittitutt to determine +~A thout expert- . ~~~ton, • iph boiling and high melting nicotine salts usua~ly exhibit. . •Y/scos/ty (n and surface tenston (Y are directly related to vapor pressure (po;. Nicotine salts IMve sOher viscosity values than their correspondin0 acids or Mcotine, exMbi wuch hipher surface tensions and thus.6ave low vapor pressures (!1. ' Nhere R is a constant M is a molecular we1 ht r ts radius of drop ~trom the statapuorntric method) end p ts the denstty. • .
Page 384: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 headings such as on the fourth page at the top, "Factors effecting nicotine.transfer efficiency"? ,(Mr. Sobol exits the proceedings.) THE WITNESS: Jim'wasn't involved in that, but Jim was my supervisor at the time, and I believe this is why Jim wrote this. He was reporting results of work -- I -- my supervisor was -- I was reporting how I was doing and how Mr. Hayes was doing. BY MR. MAISTROS: Q. Okay. Under the heading B, "Factors affecting nicotine transfer efficiency," does Dr. Fredrickson actually set -- accurately set forth the work you were doing during this time period, June of '78? A. Yes, I believe he does. Q. How about a couple pages in where it says, Number 2, "Means to alter nicotine transfer"? Do you see that? A. Yes, sir. Q. Were you working on that? A. This was generally work that Mr. Hayes was doing. (PLAINTIFFS' EXHIBIT NUMBER 16 WAS MARKED FOR IDENTIFICATION) HUSEBY & ASSOCIATES (800) 333-2082
Page 385: raj82d00
330 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the end of the day. A. Excuse me,.• MS. FEE: What number are we on? THE WITNESS: Number 15. BY MR. MAISTROS: Q. Let.me see the first page. A. Oh, I'm sorry. this Do you recognize the handwriting on I believe this is Jim Fredrickson's Is there any portion that's yours? I'm -- I'm not -- I -- I need a -- a minute to -- to look through the rest of it, sir. . Q. handwriting A. Q. My only question, yours? No, sir. is any of the Okay. Did you assist him in any of the work that's set forth in this document? A. I'm sorry? Q. Did.you assist Mr. Fredrickson in any of the work set forth in this document? A. No, I did not. In -- in the work that Jim did, no. Q. Why is your name under some of the HUSEBY & ASSOCIATES (800) 333-2082
Page 386: raj82d00
2 F"~ .. «,- i. Once data on d-nicotine is collected and correlated with the data on 1-nicotine we believe this data could be implemented in the eventual use of synthetic racemic nicotine in tobacco. We also believe that work in this area maylead us to a betteryrlQe sta~l~iD,q Q ~Q e may u ~ ~ tuall ~( ~ ~e th~ Actio~+ nicotine fiodioB new compoun s that mim c a ~ , h eg d ess t ough a dati base on d-nic'otfini is necessary an wT1TTe useful since d-nicotine has been found to be a rajor component of saroke. This fact can not be ignored any longer. It is the evaluation team's belief that work on d-nicotine not be set aside and that work on a full-time basis should be performed. #Approv ~ 71 n Rod9men :kt Distribution: Dr. A. H. Laurene, Dr. M. Senkus, Dr. H. J. Bluhm (file) Dr. A. Rodgman, Library (file) Mr. R. H. Cundiff Dr. D. H. Piehl Dr. C. L. Neumann Dr. W. M. Henley Dr. S. A. Bellin Dr. R. F. Moates R3R178~6
Page 387: raj82d00
328 A. No, I don't think that was ever, you 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know, the end-result we.were -looking for or that being an objective. Q. Nobody ever suggested using the by-product of the KDN process to reapply it to tobacco to affect nicotine yields? A. That was suggested. Q. Who suggested that? A. I'm really not sure, I mean, of an of an individual, but I do remember that was a suggestion that came up. Q. And was it tested? A. I think some experimental tobacco sheets were made with -- that had some of the affluent from the -- the KDN process on the tobacco sheets. Q. And were they test marketed? A. No, sir. Q. When I say "test marketed," they were not ever put into cigarettes and sold to people out ~. in-the public? A. No, they were not. Q. Were they A. To my knowledge, they'were not, no. Q. Were they given to test panels? HUSEBY & ASSOCIATES (800) 333-2082
Page 388: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I believe that they were tested in some experimental proto.t-ypes 'that might have been sent out to consumers, yes. Q. How,were they sent out to consumers? A. They would have -- we would have, you know, worked with our marketing people that set up consumer panels and, you know, recruit smokers and that under a project. And - - and then they would have -- we would have'made those prototypes, put them in packages, and sent them down to marketing, I guess, to, you know,`to take them to the -- send them out to smokers. Q. Wasn't the primary motivating purpose of the REST program to control the nicotine in the cigarettes? levels A. No, I don't think that was the -- the motive for -- for that. I believe I told you what I thought the motive was, which is to prepare a very uniform tobacco that would have an extract from -- from a blend applied uniformly.across all of the tobacco strands. (PLAINTIFFS' EXHIBIT NUMBER 15 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. I'm going to steal a stapler before 329 i HUSEBY & ASSOCIATES (800) 333-2082
Page 389: raj82d00
.0 0'' _~ .A no Infier-off ice Memorandum w2v'l Subject: SAFETY PRECAUTIONS FOR HANDLING NICOTINE Date: Apri 1 13, 1978 To: Dr. Robert Heckman From: Thomas A. Perfetti Memorandum: Safety measures for the handling of nicotine are important. Toxicity • levels, symptoms and treatments are given in this memo. Nicotine can be ' ° absorbed from the alimentary tract, respiratory tract and intact skin. Taken ~ orally the mean lethal dose of nicotine is about 60 mg in'malla adult (1 mg/kq), but a few milligrams may produce illness or even death. Nicotine salts are much less toxic than nicotine itself. Toxic levels vary depending on the purity of the nicotine, the form it is in, e.g., type of solution, form of salt, ;>-0, tobacco extract, etc. and how it enters the body. It is difficult to determine ~ is dependent on the body chemistry of the"indiv.idual and the exposure that individual 4` a priori whether a person will become ill when exposed to nicotine. Nicotinism ziM has had wi :~otine. It has been known that people have become nearly immune to nicotine a tar working with it for long periods of time. Resistance to ~. nicotinism e achieved but in the same sense an individual's resistance may ry t4 day since detoxification is relatively rapid, complete within 00'•4vary from d$ ~ 16 hlW.s. Syamat". 1. Burning' se ' tion in mouth and throat, salivation, nausea, abdominal pain, A ~' vomitin ,, diarrhea. (Gastrointestinal reactions are less severe but do ~ occur afteH.cutaneous and respiratory exposures.) ~ 2. Systematic effects include headache, sweating, dizziness, auditory and visual ~ disturbances, confusion, weakness, and incoordination. ~ 3. At first respirations are deep and rapid, the blood pressure is high, and AZa, the pulse is slow. Intense vagal stimulation may cause transient cardiac ~ standstill or paroxysmal atrial fibrillation (Ahn, 1952; 1953). The pupils ~ are generally constricted. Ln 0"~ .4. Central nervous excitation is also evidenced by tremors and sometimes by ~ cronic-tonic convulsions. m 5. As depression develops, the pupils dilate, the blood pressure falls, and '.. the pulse becomes rapid and often irregular. Faintness, prostration, and ' dyspnea progress to collapse with loss of reflexes. 6. Death from paralysis of respiratory muscles. RJPt1 FORM Z122-Rw. 7/70 •,~r. ~.~. •.......~..~.r.rw~+~~.........~..~.~w..r.w......+..wn~~~ ~...~....w.~.~~..~....~. ~.~~ ~~...~.~.~...~~~~.~..~ . ~
Page 390: raj82d00
I 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Reynolds or outside of Reynolds was preventing internal scientists, suc.h as yourself, from doing appropxiate toxicology tests? Q. . No. Were you ever counseled, warned, talked to about the language you used in any of your memorandum? A. I -- some of my -- some of my supervisors have. I'm -- I'm not a very good speller and I -- I didn't do real well in terms of my -- my grammar. Generally, the -- I used to get papers back from Alan Rodgman that looked like they were bloodstained from.his corrections. Q. Other than your -- your grammar and your spelling, were you ever counseled to not use certain phrases or words in your -- in your memorandums or papers? A. No. Q. Were you ever counseled about the number of invention disclosures or CIMs that you f iled? A. Yee. And -- and -- and generally, we -- my supervisors, they were always encouraging me to do more. And it -- sometimes it's tough to, you know, to -- to be creative. But, you know, HUSEBY & ASSOCIATES (800) 333-2082 324
Page 391: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY.MR. MAISTROS: Q. No. You. can -.-..you can read it. I can't read the writing. MS. FEE: Sure you can. THE WITNESS: Let's see. BY MR. MAISTROS: Q. Could you read it out loud, please? A. "This invention is a method to enhance the delivery of desirable smoke components by the filling of'holes or openings produced in modified smoking materials with various additives to the materials mentioned." Q. And what type of additives were you exploring with respect to this research? A. I'1], have to read the -- the memorandum now, eir. The memorandum -- the memorandum doesn't describe exactly what types of additives, but it's -- that I -- that I intended in -- in this memorandum, except that they could be salt, liquids, or gases. Q. Including nicotine? A. Well, I guess it would fall under that classification. There is -- there is a line which is unreadable on the second thing, which I'm 333 I , HUSEBY & ASSOCIATES (800) 333-2082
Page 392: raj82d00
337 1 2 3 4 5 6 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MR. MAISTROS: Okay. BY MR. MALSTRQS o. .Q• You've testified that nicotine would fall within the classification of materials set forth in your summary, right? MS.,FEE: Objection, that misstates his testimony. BY MR. MAISTROS: Q. Is that your testimony, it would fall within the classification of materials in the summary that could be added? A. I would like to -- to say that it would be a tobacco extract that might contain nicotine as one of its components. .Q. Okay. A. I would certainly not want to be putting pure nicotine on -- on these materials here. (PLAINTIFFS' EXHIBIT NUMBER 17 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Do you recognize the handwriting in Exhibit 17? A. It appears to be the same handwriting as -- as the last document, and it may be Jim HUSEBY & ASSOCIATES (800) 333-2082
Page 393: raj82d00
r 1 2 3 4 5 6 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 (PLAINTIFFS' EXHIBIT NUMBER 18 WAS MARKED FOR IDENTI_F.ICATION) MR. MAISTROS: If you can, bear with me. I'm going out of order on some of these to hopefully skip through a lot of them. So, I have,to find the copies. BY MR. MAISTROS: Q. Showing you a September 20th, 1979 memo from a Mr. Casey to a Mr. Lloyd. Q. First of all, do you know Mr. Casey? . Yes, sir. Who is Mr. Casey? A. He's a senior research scientist at -- at Reynolds Tobacco. Q. And Mr. Lloyd was who? A. He was a manager in the Tobacco Division, I believe. Well, he's held a lot of positions. I don't know where he was at this point. Q. Do you recall receiving a copy of thi"s memo in September of '79? A.. Not offhand, no, sir. Q. Could you take a look at the memo and see if that refreshes your recollection? 25 I A. Yes, I've read the memo now. HUSEBY & ASSOCIATES (800) 333-2082 342
Page 394: raj82d00
341 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 reconstituted process? A. No; no, it,.• nevex was. Q. Was there ever an extract applied to the KDN tobacco? A. No. Oh, casing materials. There would be casing materials perhaps applied to it. Q. The KDN tobacco by-product, if you will, were there ever any additives or processing aids used to effect the nicotine yields or transfer efficiencies of the nicotine? MS. FEE: Objection, vague. Could you read that question back, please? MR. MAISTROS: I'll rephrase it. BY MR. MAISTROS: Q. KDN is a type of tobacco Reynolds has used over the years? A. Correct. Q. At any course during the processing of KDN, does Reynolds or has Reynolds used processing aids or additives to affect either the nicotine yields or the nicotine transfer efficiencies of the KDN tobacco? A. No. Can I get a glass of water? HUSEBY & ASSOCIATES (800) .333-2082
Page 395: raj82d00
327 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7' 18 19 20 21 22 23 24 25 them,'were some nicotine salts and some - some nicotine mol_ecule-s that have the shape of nicotine or some kind of shape associated with nicotine that -- that had substituents on them, meaning other chemical moieties, little nitro groups or chlorides or something, on different positions on the range. And there was a tremendous variety out there and 250 isn't a whole lot to start with. BY MR. MAISTROS: Q. Okay. Did you understand my question? A. Why'did we -- why were we doing this, I think, is what you asked. Q. Right. Can you answer that question? To have a variety available for someone to -- to do some testing on. Q. And was it the thought of Reynolds at any point in time that, if they could develop nicotine analogs that could be applied to tobacco, they could thereby -- thereby affect the nicotine yield of the cigarettes? HUSEBY & ASSOCIATES (800) 333-2082
Page 396: raj82d00
343 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Do you recall why you were being sent a copy of this memo.? _ ,A. I -- I was working with -- I guess at that time I was working with Bill, and we were lab mates. We had to -- we were in the same office and the same laboratory. Q. Now, what were you working on in September of 179? A. Let's see. I can't recall, sir. I'm not sure. Q. Well, Mr. Casey is, in this memo -- I'11 paraphrase it -- is attempting to figure out why Philip Morris has lower nicotine levels and more constant nicotine levels, correct? A'. Yes, that's a question -- Q. And the end of his memo, he states, "A probable or deduced answer to these two questions is that Philip Morris has a means of controlling cigarette nicotine content while other tobacco companies do not. Mechanism most likely involves flue-cured tobaccos, since currently it is the largeste single contributor to tobacco smoke and tobacco blend nicotine content." Do you know if Mr. Casey or anyone else at Reynolds ever did any research to determine HUSEBY & ASSOCIATES (800) 333-2082
Page 397: raj82d00
1 BY MR. MAISTROS: Q. Exhibit 16., is"dated July 19th, 1978. 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 My first question will be, is that your handwriting? MR. O'HARA: Thank you. THE WITNESS: Yes, sir. BY MR. MAISTROS: Q. And is this an accurate copy of a memorandum you prepared in July of 1978? A. I think it is in order, yes. Q. And that was kept in the ordinary course of your employment at Reynolds? A. These are -- these are pages out of a laboratory notebook. It is kept by the company. Q. Okay. What is the title of this? And this is a invention disclosure memorandum or conception of invention disclosure memorandum,?. A. Yes, sir. Q. What is the title at the top? A. "Method to Enhance Delivery of D.es-irable Smoke Components." , Q. And what is the summary? A. The -- MS. FEE: If you want to read it into the record, Jack, you can. HUSEBY & ASSOCIATES (800) 333-2082
Page 398: raj82d00
347 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Okay. And what work are you aware of that Reynolds did to inc,reaee..the free nicotine in the tobacco smoke of its products? MS. FEE: Object to the form. THE WITNESS: I don't know if we did -- ever.did any work on that. In fact, I think that's not -- I think if there was anything, a -- a lot of the work that we did was to reduce harshness which would have produced less -- what they call -- free nicotine in the smoke. BY MR. MAISTROS: Q. Are you saying you never did any research aimed at attempting to increase the free nicotine in tobacco smoke? A. I think that was never the aim of what we were trying to do. Q. Doesn't the amount of free nicotine affect the nicotine satisfaction of the smoker? A. No. I think -- I think it does just the opposite. Q. So, free nicotine plays no role in nicotine satisfaction? A. Free nicotine is associated with a irritation of tobacco smoke, and there is certainly HUSEBY & ASSOCIATES (800) 333-2082
Page 399: raj82d00
346 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 president of Research and Development, I believe. He was the main man for,a number of years. ,Q. And Dr. Rodgman headed your group for a number of years; did he not? A. Yes, sir. Q. Now, in the footnote of the first page of Dr. Rodgman's memo, he states, "Most, if not all, nicotine in tobacco is present as a salt. The reaction product of nicotine and an acid generally referred to as bound nicotine, most of the nicotine in smoke is present as a salt or bound form and a small fraction is present as free nicotine." First.of all, do you agree with that statement? A. Yes. Q. Then he goes on, "The percent free nicotine depends on the smoke pH." Do you agree with that statement? A. Is one of the factors, yes. Q. Then he goes on, "Free nicotine is absorbed more rapidly by the smoker than is bound nicotine." Do you agree with that statement? A. Yes. HUSEBY & ASSOCIATES (800) 333-2082
Page 400: raj82d00
336 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in these holes? A. Yes. Q. So, now your testimony is that nicotine wasn't even within the realm of possibilities as being added? MS. FEE: Objection to the -- it's argumentative. MR. MAISTROS: Well, he first testified that nicotine was. Then after you instructed him on how to answer, he said nicotine wasn't. BY MR. MAISTROS: Q. So, was it or wasn't it? MS. FEE: I didn't -- I -- I made no instruction, Counsel. We can -- we can read that part of the record back, if you like. MR. MAISTROS: Read the very first question. I'll do that. Could you read the first question after I asked him if it was his handwriting? (QUESTIONS AND ANSWERS WERE READ BACK) MR. MAISTROS: Okay. Let's go back to the question. MS. FEE: I would say that reading supports what I just said. HUSEBY & ASSOCIATES (800).333-2082
Page 401: raj82d00
348 1 2 3 4 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 some irritation, which, I think, consumers expect in their cigarettes., but,ther.e is irritation contributed by other smoke components. Trying to increase the amount of free nicotine in a cigarette smoke, I think, is -- would have been deleterious to anything we were trying to do to improve consumer acceptability of our products. Q. .Well -- so, did Reynolds undertake research to limit the amount of free nicotine in its tobacco smoke? A. This whole concept of free and bound nicotine really was -- wasn't talked about a lot in my circles at -- at -- at -- at Reynolds during this time period in -- I think this memo says it's 1980 or '90, sir. I don't know what the date is. Q. '80. A. Is -- is it '80? Q. '80. A. We did talk about -- sometimes in terms of having an issue in reducing irritation harshness. And the way that one -- one would and probably do that is to reduce any amount of free nicotine that was around, because we do know that is irritating. Q. So, again, is the amount of free HUSEBY & ASSOCIATES (800) 333-2082
Page 402: raj82d00
335 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 at -- at this particular time in '78, we had room, I guess, or.- we .c-ould apply slightly -- .slightly more material into the -- as -- as solids onto the -- onto the reconstituted sheet. Unlike other -- other people -- I mean -- we never put anything in our extract except the starting material that was there. But you could -- you could have taken the finished sheet and sprayed on casing materials or other types of flavorant to make the stuff taste better -- taste better. I mean, our reconstituted sheet does not have the best flavor associated with it, and we never spent a whole lot of time in terms of improving its flavor. One way of doing that, to make sure the material stays on there, is to provide wells for this material to rest in. I think that's what this is about. BY MR. MAISTROS: Q. Let me ask it a different way. When you developed this conception of invention memorandum, did you exclude nicotine as one of the potential additives that could be placed HUSEBY & ASSOCIATES (800) 333-2082
Page 403: raj82d00
334 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 not sure what.that -- but it says, "To include all types of additives generated°.-- something -- "as tobacco or smoke isolates," and -- and I'm -- Q. But among the additives you had in mind with this conception of invention disclosure was nicotine? MS. FEE: Object to the form, misstates his testimony. THE WITNESS: I -- I don't think that that was -- that was the -- the intent of this. We were trying to produce -- BY MR. MAISTROS: I'm not asking the intent. I'm asking among the added, if you had in mind, was nicotine? MS. FEE: Same objection. THE WITNESS: No, I don't think so. The -- BY MR. MAISTROS: So MS. FEE: Let him finish his answer.. THE WITNESS: I believe you could use tobacco extracts, just like the kind that we were applying back on the G7. What occurs to me when we had this is HUSEBY & ASSOCIATES (800) 333-2082
Page 404: raj82d00
350 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 • 22 23 24 25 that it's his belief that Philip Morris denicotinizes its flue-curecl.tobacco but does not discard the nicotine. Do you know if that's something that Reynolds ever determined was or was not the case? MS. FEE: Can you show us where -- MR. MAISTROS: Footnote D. MS. FEE: Footnote D. MR. MAISTROS: Page -- THE WITNESS: That's the Footnote D, sir? BY MR. MAISTROS: Q. Yes. A. And -- and the question was? Q. The question is, did you ever figure out if Philip Morris discarded its nicotine? A. No, not -- I don't remember ever proving that. Q. Dr. Rodgman also says in his footnote, "RJR denicotinizes a part of its tobaccos from high nicotine crop years but does not discard the nicotine." Do you know why Dr. Rodgman would have said that? A. I-- I don't know what they were HUSEBY & ASSOCIATES (800) 333-2082
Page 405: raj82d00
349 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 nicotine in tobacco smoke a factor which Reynolds has attempted to control.over.the years? A. Not in a direct manner, no. Q. How about in an indirect manner? A. I think it is -- it is a -- it was - it would be a direct consequence of adding casings that would reduce that. You might inherently reduce the -- the free nicotine, but it wasn't done in a -- an -- in a direct fashion. Q. Has Reynolds done analysis to determine the amount of free nicotine.that affects tobacco smoke? A. There was and I'm -- I'm not real an analysis attempted for, up on this analysis, because I wasn't part of it, but to determine free nicotine in the smoke. And I assume that's what you're talking about, sir. Q. Right. A. And some of that work was done by some of our research scientists and they found very l.ow quantities of it in the smoke, about 1 percent or less is what I-- what I remember. And that is 1 percent of the total nicotine. So, it's a pretty small quantity. Q. Dr. Rodgman goes on to note in here HUSEBY & ASSOCIATES (800) 333-2082
Page 406: raj82d00
338 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18, 19 20 21 22 23 24 25 Fredrickson's. Q. And w.hat.'s,, this-_"1979 Program" that's outlined at the first page? A. The document says that "Project: 1250 Smoke Formation and Ni'cotine Control." Q. Okay. And you were still working on these projects personally in 1979, weren't you, a year plus after you had started at Reynolds? Project 1250 that we talked about yesterday -- A. Yes, yes. Q. -- began when you started at Reynolds? A. I-- I assume that was the project. I can't remember back. I mean, I -- there was sometimes it appeared to be 1250, sometimes 1245, but there was -- my name is under this thing as supporting a hundred percent of my time. So, that's what the document says here. Q. So, in 1979 you were still working on attempting to identify factors that would influence nic-otine delivery efficiency? MS. FEE: Object to the form. THE WITNESS: Whatever that particular objective was on 1250 that we looked at yesterday, that -- that is what I m ~ ~ ~ m HUSEBY & ASSOCIATES (800) 333-2082
Page 407: raj82d00
339 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was supposed to be working on. BY MR. MAI,STROS.: ,Q. Okay. Do you -- do you know if in 1979 you were working on research to identify factors influencing nicotine delivery efficiency? A. I think that, yes, that was -- that was part of what I was doing, yes. Q. Go to the third page, paragraph number three, does Dr. Fredrickson accurately set forth what you were doing in 1979 in that third paragraph? MS. FEE: Objection, assuming this was written by Dr. Fredrickson. THE WITNESS: This is a statement that we saw, again, yesterday, and that does describe what Jim had plans for me to do. BY MR. MAISTROS: Q. And that is, "Determine nicotine transfer efficiency and nicotine release profiles for various tobaccos, such as flue-cured, burley, G7," KDN, tobaccos with varied levels of nicotine, treated tobaccos, nicotine salts, and combinations thereof." That's accurate -- accurately describes the work you were doing in '79? HUSEBY & ASSOCIATES (800) 333-2082
Page 408: raj82d00
351 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 doing. That's -- that's kind of interesting to me. I -- denicotinizes -- I.don'.t• know what they were doing back at that time frame, sir. Q. So, when you testified yesterday that Reynolds has always discarded or incinerated its nicotine, are you still certain that that was the case? A. To the best of my knowledge, that's -- that's -- I-- that's what I believe they've been doing for all this time. I don't know where -- where all this nicotine would h&ve been and I don't know where -- how that is framed in what you said, since I didn't read the memorandum. Well, you read the footnote, didn't you? A. Yes, sir. (PLAINTIFFS' EXHIBIT NUMBER 20 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 20 is a October 29th, 1980 memo from a Dr. Chin Lee to Alan Rodgman. Do you know who Dr. Lee is or was? (Mr. O'Hara exits the proceedings.) THE WITNESS: Dr. Lee was a principal scientist that worked at Reynolds. HUSEBY & ASSOCIATES (800) 333-2082
Page 409: raj82d00
1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Did you ever determine that Philip Morris was controlling t.he ni-cotine content of its cigarettes? A. No, I don't believe that was something that we could, you know, prove. Q. Did you ever do research to determine how or why Philip Morris used ammonia in its tobacco processing? A. I never did work along those lines, but there were -- we -- we did try to -- to -- to prepare reconstituted sheets that -- that were much stronger and used some of the -- a similar type of technology that Philip Morris used in terms of making their released pectin sheet. (PLAINTIFFS' EXHIBIT NUMBER 19 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 19 is a September 8th, 1980 memo from Dr. Rodgman to Dr. Morse. Dr. Rodgman is a respected scientist at Reynolds, correct? A. Yes, sir. Q. Or was? And who is Dr. Morse? A. Dr. Morse held a position of vice 345 Ln ~ V V m HUSEBY & ASSOCIATES (800) 333-2082
Page 410: raj82d00
344 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 if that was true? A. I, as far .as I know,. I -- I don't know if that question has ever been answered. Q. You never worked on that issue? A. I did work with Mr. Casey on -- on a investigation of competitive brand study of -- of Marlboro versus Winston. Q. Did you ever research to try to figure out if or how Philip Morris controlled cigarette nicotine content? A. There was, over the years, there were several attempts to -- to try to determine if there were differences between processes that Philip Morris uses and processes that -- that we use in -- in their -- their Marlboro versus our brands. Before you could do'anything, you had to come up with a hypothesis. And they were really difficult to come up with, a hypothesis to try to work on. o, a lot of times what we did was j-uet investigate broad-brush what our obvious difference is based on some of the tobacco and smoke chemistry differences that we saw. I don't know if we ever found any reason why this phenomenon took place. Ln ~.. ~ ~ m HUSEBY & ASSOCIATES (800) 333-2082
Page 411: raj82d00
352 1 2 3 4 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q If you coua.d take a look at this memorandum, and by reading it, can you tell me what it is that Dr. Lee was attempting to describe in this memorandum? A. The,subject of the memo says it's an "Ames Test on Ammoniated Tobaccos." Q. And under Table I, he describess two different processes, A and B, correct? A. There are two processes described here, yes. Q. Do any of those look familiar to you? Either of those? A. Yes. Process B looks like the -- the way that we are making O7A, gaseous ammonia in a denic plant is probably how we were preparing the -- the ammoniated 07 -- ammoniated reconstituted sheet, the general process there for that. Q. And it describes Reynolds general processing of ammoniated reconstituted tobacco sheet? A. That's what it looks like here, sir. Q. By the gaseous message -- method which was employed during what years? HUSEBY & ASSOCIATES (800 333-2082
Page 412: raj82d00
354 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 T 18 19 20 21 22 23 24 25 flue-cured tobacco produced varying degrees of mutagenic activity in tho siaoke condensate." Were you aware of that in 1980? A'. No, sir. . Q. Were you aware that the Process B, the gaseous ammonia process, employed by Reynolds from the '60s to the early '90s produced higher mutagenicity in the tobacco smoke? MS. FEE: Object to the form. THE WITNESS: Under this one type of testing, I think that is correct, but the NCI in our -- in their -- in their studies showed that reconstituted sheet had the -- the lowest biological activity of any tobacco type. So, again, this is only one aspect of one type measurement of biological activity. BY MR. MAISTROS: Q. Were you aware-of this in 1980? A. What Dr. Chin said, sir? Q. Yes. A. No. Q. Does the Process A appear to be related in any fashion to the application of ammonia that is currently employed by Reynolds? HUSEBY & ASSOCIATES (800) 333-2082
Page 413: raj82d00
356 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. This is Dr. Charlie Nystrom, and Charlie hold a -- held a,variety of positions, scientific affairs. I think Charlie is a organic chemist by training. So, over the years I was there, he held a whole lot of positions. Q. And how about Dr. DiMarco? A. Yes, sir, I know him. Q. Who was he? A. He was a vice president of Research and Development. Q. And the second page reflects that this memorandum was a draft of 8-9-82. Do you see that at the top? A. Is that a'92, sir? Q. Right. '82. A. '82? Q. Do you see that? A. I -- I -- I see it. I didn't know what the last numbers were of the year. Q. Okay. On the first page is a ref-erence to, in the second to last paragraph, "Based on a discussion of July 16, 1982, we did prepare a position paper on Coumarin." What is Coumarin? A. Coumarin is -- it's a flavoring not HUSEBY & ASSOCIATES (800) 333-2082
Page 414: raj82d00
353 1 2 3 4 5 6 7 A. I guess -- I think -- I thought it was somewhere around 196.0 to -- to about, you know, several years ago when we shut it down, because the plant had -- you know -- was getting very, very bad. We weren't using it any longer. Q. Until the '90s at some point? A. Yes, I believe so. (Mr. 0!Hara enters the proceedings.) 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. What is the -- does this Process A look familiar to you? A. There was a process that -- that -- that this might have been, and I think it was called the FS2000 or 2001, something along those -- those lines, something like that, where they would put on ammonium hydroxide onto its tobacco and then pass it on this -- pass it into this box that -- that had steam coming up from the bottom. And as it passed through there, it -- it had real hot steam, 250 degrees. It took about 8 minutes to travel down this belt. And then this was another way of denicotinizing tobacco. Q. Okay. In the first paragraph of his memo, he states, "Previous tests have shown that various conditions used for ammoniation of .HUSEBY & ASSOCIATES (800) 333-2082
Page 415: raj82d00
1 2 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 surprising. Q. Why is that? A. I -- I didn't know it was a tobacco. It was a -- it was an additive. Q. Pardon me? A. I did not know that ammonia was an additive in RJR tobacco flavorant formulations. Q. In fact, yesterday you testified it was only a processing aid, correct? A. Yes. I didn't know that. Q. Okay. If you turn to the fourth page of this document, there's a summary of "Ammoniation of Reconstituted Tobacco." Do you see that? A. Yes, sir. Q. And it talks about some studies in the '50s and '70s, and then it goes on to list that "the studies led to the following observations and conclusions. Number one, the pH of cigarette smoke is important to smoke quality and can be used as a mea'sure of the physiological strength of smoke.". Do you agree with that statement? A. I think -- not altogether, no. Q. What do you disagree with? A. I -- I think that smoke pH can be 358 1 HUSEBY & ASSOCIATES (800) 333-2082
Page 416: raj82d00
340 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Not all of it, no, because this is a -- this is like an obj.ective of what -- of what he wanted us to -- to try to do. Not everything was accomplished here, but this is a general scheme of -- of what he thought could be done in that time f rame . Q. So, this is what he laid out as, if everything went right, what you should be doing in '79 with your time? A. if -- if it was possible to do this, yes. Q. And why were you looking at the nicotine transfer efficiency of KDN? (Mr. Sobol enters the proceedings.) THE WITNESS: KDN, sir, is is -- is a tobacco type. It ies d-nicotinized burley tobacco in this instance here. BY MR. MAISTROS: Q. Does d-nicotinized imply that there's no 'nicotine in it or very little? A. That there's about a -- somewhere between a 50 and 60 -- 50 and 60 percent reduction in nicotine after it went through the KDN process. Q. Was the KDN tobacco used in the HUSEBY & ASSOCIATES (800) 333-2082
Page 417: raj82d00
359 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 used as an indicator perhaps of smoke quality, and I don't believe that it_.is a-measure of the physiological strength of cigarette smoke. I do not believe that. Q. Number two, "Ammonia in smoke is one of the major pH controlling components." Do you agree with that statement? A. No. Q. What do you disagree with about that statement? A. There is so little ammonia in tobacco smoke, that it could never affect the smoke pH. That is, in R.J. Reynolds products. Q. We11, how about "ammonia occurs naturally in tobacco ranging from trace amounts in flue-cured tobaccos to over 1 percent in high quality cigar tobacco." Do you agree with that statement? A. Yes, I do. Q. Number four, "Philip Morris i-nt"roduced the use of added ammonia in their cigarette products in 1965. They used diammonium hydrogen phosphate in their reconstituted tobacco process to liberate ammonium pectinate prior to casting a reconstituted tobacco sheet." HUSEBY & ASSOCIATES (800) 333-2082
Page 418: raj82d00
360 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Do you agree with that statement? . Q. A. Yes. Number five, "Philip Morris brands, especially Marlboro, began growing in sales very rapidly after the introduction of added ammonia." Do you agree with that statement? I think that's -- that's just a fact. So, yes. Q. Six, "Correlation studies related increased smoke pH to sales trends showed a very strong positive correlation; RDM, 1973, Number 17." Were you aware of that fact? A. I'm not - MS. FEE: Object to the form. BY MR. MAISTROS: Q. Do you believe it's a fact? A. I'm;not familiar with that particular RDM, I don't think, and I think it's kind of bizarre that anyone would make a correlation between the smoke pH and -- and sales trends. I dori't -- I mean -- I don't believe that's -- would tell them anything. Q. Number 7, "Studies of the effect of ammonia on smoke composition showed a reduction in aldehydes, especially formaldehyde, in an increase HUSEBY & ASSOCIATES (800) 333-2082
Page 419: raj82d00
361 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in the levels of pyridines, pyrazines, and minor alkaloids. Smoking pan_e.l results showed a decrease in smoke irritation and harshness and an increase in physiological satisfaction with increasing ammonia content." Do you agree with that statement? A. Most of that statement I -- I -- I agree that you will have a reduction in formaldehyde as a -- when there is ammonia in the smoke, that you will get increased levels of pyrazines, pyridines, and other flavorants, and that that will probably reduce the smoke irritation, but having this increased, I don't agree with the increase. I'm finding it hard to read this -- Q. Physiological satisfaction. A. Satisfaction, I don't agree with that. Q. Then the author goes on to state, "Based upon the above observations, it was decided to'investigate the use of ammoniated reconstituted tobacco, G7A, as a means of increasing the smoke pH of RJR cigarette products." Were you aware of that? A. Since I wasn't aware of -- of this HUSEBY & ASSOCIATES (800) 333-2082
Page 420: raj82d00
362 1 3 4 5 6 7 8 13 14 15 16 17 18 19 20 21 22 23 24 25 memorandum, I -- I -- I mentioned yesterday that I thought that they used.it, th.ey had some preconceived notions of why it was important to use G7A. Q. And is it your testimony that you were aware or you',re not aware that they were doing it as a means of increasing the smoke pH? A. I didn't know that. No, I did not know that that was their aim. Q. Were you aware that at the time of this memo the author stated that, since th'e introduction of Camel filter in 1975, G7A has been tested and/or introduced in 19 additional brands? A. If that's what the memo says. I mean, hopefully this person knew what they were talking about. Q. Did you ever have the opportunity to gauge the work of either Bernasek or Nystrom? A. No. They were always my superiors. They were -- I never had a chance to do a peer review on -- on Dr. Bernasek or Nystrom. Q. Did you have the opportunity to make a determination as to their scientific abilities? A. I always believed that Dr. Bernasek was -- was a -- a very good scientist, as well as Ln ~ ~ -j m 1-1 Ln -3 m HUSEBY & ASSOCIATES. (800) 333-2082
Page 421: raj82d00
364 11:15 a.m. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 (Recess 11:15 a,.m.•to 11:24 a.m.) (PLAINTIFFS' EXHIBIT NUMBER 22 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: Back on the record at 11:24 a.m. MR. MAISTROS: How many pages do y.ou have there, Denise? MS. FEE: Four. MR. MAISTROS: The last one blank? MS. FEE: Last one's blank, yes. BY MR. MAISTROS: Q. Exhibit 22 is a May 9th, 1983 memorandum from Chin Lee and Elizabeth Reed. Do you know who Elizabeth Reed was? A. No. Q. And you knew -- obviously you know who Chin Lee was, right? A. Uh-huh. Yes. Q. Have you seen this document before? A. No, I have not. Q. The title or the object says, "To compile and review all the past work and memos concerning Ames test" -- I think it says "results on smoke condensate and smoke-related HUSEBY & ASSOCIATES (800) 333-2082
Page 422: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 compounds." Do you see•- that'? .A. I see that, yes. Q. Were -- if you look through this document, were you aware of the eight tests that were done looking at smoke condehsate, components, and specifically the one cited here in dealing with ammonia? A. This document is supposed to have 36 pages to it. This is an incomplete document. Q. All right. There may be more Ames tests on mutagenicity of ammonia that aren't in this document. I'll concede that, but are you -- are you familiar with any of the tests that are summarized here in this document? A. I'll need to read the document here. Hold on. Okay. I've read the memorandum. Q. Okay. Between 1978 and 1983, were you aware that Reynolds had done internal Ames tests on the mutagenicity of ammoniated flue-cured tobacco, as set forth in this memorandum? A. Not that I was aware of, not that I was involved in. Q. For example, in the number two listed 365 HUSEBY & ASSOCIATES (800) 333-2082
Page 423: raj82d00
357 2 3 4 5 6 7 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 material. Some companies use it, some companies don't. .Q. What was it used for? A. It's -- it's used like as in the top dressing normally. Sometimes it's -- it's used in a solid form. I t.hink in -- in a -- in a material called Deer Tongue. It's a -- just a constituent of a natural product. It's used as a flavoring. Q. Did Reynolds use it? A. I think at one time we might have used it. Q. And why did Reynolds stop using it? A. To my recollection, and I'm -- I'm speaking secondhand here, to my recollection, there was --.there was information that was in the -- in the literature that said that there was some adverse effect on using Coumarin in products. So, when that was discovered, it was removed. Q. Okay. Now, this cover memorandum states that these individuals are enclosing for Ln ~ Dr.' DiMarco position papers on RJR's rationale for ~ using the following additives in RJR tobacco flavor Ln m Ln formulations, and included is ammonia. Do you see that? A. Yeah, I do see that. That was quite HUSEBY & ASSOCIATES (800) 333-2082
Page 424: raj82d00
367 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 condensate, you would have taken no action? A. Would -- MS..FEE: Objection, asked and answered. BY MR. MAISTROS: Q. That:'s your testimony? A. Yes. Q. How about the number four test, in 1980, that found that the use of aqueous ammonia and contrasted gaseous ammonia does not increase the mutagenicity of flue-cured tobaccos? Would you have taken any action based on those test results? A. I would have to know more about what -- what this -- this memorandum was about, because this is too vague under -- to make -- to take any action on. Q. You were not aware of any of these tests that are set forth in this memo? A. Not that I can recollect, no. Q. On the third page, it lists or it states that -- appears to say photo for Pat Perfetti. Do you know why your wife would have been provided photos related to this research in HUSEBY & ASSOCIATES (800) 333-2082
Page 425: raj82d00
371 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Exhibit 24 is an October 20th, '88 memo. I t' s f rom a Tammi.e ar.eene. Do you know who that is? A. Yes. Q. Who's that? A. Tammie Greene was a sensory analyst at Reynolds. Q. What department? A. Sensory Evaluation Department. Q. This memo is entitled "Intercepted Philip Morris Products, Nicotine/Flavor Enhancement Technology." Do you see that? A. Yes, I do. Q. In the executive summary on the first page, the author states in talking about "increased flavor and impact at low tar seems to. be the development objective for the intercepted test produ.cts. Most reviewers of the product data and a recently published Philip Morris European patent application believe that these deliveries have been achieved by using nicotine flavor enhancement technology. "That hypothesis is supported by the usual blend compositions, high nicotines and low HUSEBY & ASSOCIATES (800) 333-2082
Page 426: raj82d00
372 1 2 3 4 5 6 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tar-to-nicotine ratios of the test products. It is important to note that these -products represent technology fairly --.fairly -- very similar to Project XGT in that RJR is preparing low tar and nicotine blends which are then enhanced by the addition of natura.l tobacco extract containing high levels of nicotine.° Were you aware that research was going on? Q• I was aware of Project XGT, yes. And the natural tobacco extract, where did RJR get that? A. I'm not sure exactly.what Ms. Greene was talking about here. .Q. You were not aware that RJR was preparing low tar and nicotine blends which are enhanced by the addition of natural tobacco extract containing high levels of nicotine? A. I was aware that Reynolds was preparing low tar-to-nicotine prototypes. Q. Were you aware that Reynolds was adding natural tobacco extract containing high levels -- levels of nicotine to its tobacco? MS. FEE: Object to the form. THE WITNESS: I was aware that HUSEBY & ASSOCIATES (800) 333-2082
Page 427: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7' 18 19 20 21 22 23 24 25 panels? A. I wasn't.in charge of that not sure how far they went. Q. But your testimony is that area. I'm some of the KDN extract by-product from the KDN process was used and reapplied to the reconstituted tobacco sheet? A. We were preparing experimental prototypes, yes. Q. And that was different than Project XGT? A. There were -- XGT -- there was Project aT, XGT, and I'm not sure where one of them left off and the other one began. Q. Was any of this experimental tobacco ever used in Merit 85? A. I -- I doubt it, since -- since we don't produce Merit 85. Q. Who produced Merit 85? A. This is a Philip Morris brand. Q. Now, Project XGT, are you saying that was never -- none of the results of that project were ever sold commercially? That is correct. And it's your testimony that the HUSEBY & ASSOCIATES (800) 333-2082
Page 428: raj82d00
355 1 A. No. MR. MAISTROS :. We have to change 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 ,tapes. THE VIDEOGRAPHER: We're going to -- tape number four of the deposition of Dr. Thomas Perfetti. The time is 11:02 a.m. (Off-the-record discussion.) (PLAINTIFFS' EXHIBIT NUMBER 21 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: This is tape number five of the deposition of Dr. Thomas Perfetti. The time is 11:04 a.m. BY MR. MAISTROS: Q. Now, Exhibit 21 is a memorandum from a Mr. or Ms. E. Bernasek and C.W. Nystrom. Do you know either of those individuals? A. Yes. Q. Who are they? A. Dr. Bernasek was a principal sci'entist at -- at RJR. Q. What department? A. In the -- he worked most -- most most of the time in the applied research area. Q. How about Nystrom? HUSEBY & ASSOCIATES (800) 333-2082
Page 429: raj82d00
376 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 It's an inorganic compound. Q. And what_'s.ite .-- is it used in tobacco? A. It's generally not used, not -- no. Q. Has it ever been utilized in tobacco, to your knowledge? A. We may have produced some research cigarettes that had -- had that in -- that had potassium carbonate in the cigarettes. Q. Do you know, other than Reynolds, you know if other tobacco manufacturers have employed potassium carbonate for any purpose? A. Not that I can remember right now, no. Q. What was -- it was used in, to your knowledge, it was used as an additive in tobacco for what purpose, if it was used at a11? A. The -- I think there was experiments done on -- on -- on using potassium carbonate in some reconstituted -- reconstituted tobacco sheets. I can't remember whether they were paper sheets or cast.sheets. I think they were cast sheet materials. Q. For:what purpose? A. It was -- I think that they were HUSEBY & ASSOCIATES (800) 333-2082
Page 430: raj82d00
366 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 item, it's Ames test on smoke condensate memo to Mr. Giles. Who is Mr. Giles? A. Mr. Giles is an analytical chemist that worked at Reynolds. Q. Were you aware that in 1979 Mr. Giles was sent a memo that deals with the comparison of the mutagenicity of ammoniated flue-cured tobacco and nonammoniated flue-cured tobacco that stated that ammoniation increased the mutagenicity of flue-cured tobacco? A. I was not aware of that memorandum, no. .Q.* In 1979, if you had been apprised that there was research which indicated that ammoniated flue-cured tobacco had higher mutagenicity levels than nonammoniated flue-cured tobacco, would that have caused you to take any action as a scientist at Reynolds? A. No, because we do not.make a hundred percent flue-cured tobaccos -- hundred percent flue-cured tobacco products. Q. So, if you had been apprised that or had conducted research that ammoniated flue-cured tobacco increased the Ames results of the smoke HUSEBY & ASSOCIATES (800) 333-2082
Page 431: raj82d00
377 1 2 4 5 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 using that in the Eclipse part -- part of the Eclipse substrate sectio.n of the -- of the capsule, and I'm not sure exactly what the purpose of that was. Q. And, to your knowledge, potassium carbonate has not been employed for the purpose of increasing smoke smoke nicotine? pH and thus increase the yield of A. The -- there -- there -- there was some work done where potassium carbonate, I believe, was added to either in the sheet or on the blend to see if that would affect nicotine transfer yields. Q. And did it? A. No, it did not. Q. Did Reynolds ever try to do that? A. In our -- in the research area, I think we have experimented with that, yes. Q yield?' As a means of increasing the nicotine I think that was one of the things that -- one of the effects that they were looking at, as well as nicotine transfer. And I think it was in conjunction with smoke pH, if I'm not mistaken also. HUSEBY & ASSOCIATES (800) 333-2082
Page 432: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. Yes. 25 1 Q. And does this appear to be an Q. What was Project GT-X? A. ago, there As I menti.oned Just a few minutes was a project called GT, and I believe that was trying to improve the quality of Vantage. And then it went to GT-X where we were looking at the reduction of low tar-to-nicotine.prototypes. And that -- most of that work centere- d on production of.blends that -- high nicotine blends as a means of -- of increasing the total quantity of nicotine in the rod. (PLAINTIFFS' EXHIBIT NUMBER 25 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Exhibit 25 is a November 28th, 1989 memo - A. Oh, yes. Q. -- by you A. Uh-huh. Q. -- to Dr. Suber entitled "Request for Scientific Affairs Review of Potassium Carbonate as a Tobacco Additive." Do you recall drafting this memorandum? HUSEBY & ASSOCIATES (800) 333-2082
Page 433: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 carbonate is a base that can increase smoke pH and thus increase the yield.of smoke nicotine." You were aware of that, I assume, 1989? A. I guess. Q. And then, "Secondly, as the melting point of this salt is below the fire coal temperature, it acts as a heat sink and can reduce. the level of combustion and promote the formation of char," and you go on. Now, in 1989 you, at least as indicated by this memo, were aware that potassium carbonate could increase smoke pH and that smoke pH had a relationship to nicotine yield, correct? MS. FEE: Object to the form. THE WITNESS: I was aware that potassium carbonate could affect the tobacco pH and that it was used in tobacco products and that there were some reports written on use of it. BY MR. MAISTROS: Q. And you were also aware that by increasing smoke pH, you can increase the yield of smoke nicotine? A. I guess that that would be true if 380 I HUSEBY & ASSOCIATES (800) 333-2082
Page 434: raj82d00
363 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Dr. Nystrom. Q. Does this memor.andum or the comments contained in this memorandum change your testimony or beliefs in any way as to why Reynolds first began using ammoniated reconstituted tobacco? A. I -- I think that it's just new information for me, but I-- I trusted Dr. Bernasek and Dr. Nystrom, who have been there a lot longer than I had or position, I guess, in the right framework. Q. Would you agree that at least that this memorandum would suggest that Reynolds first began using ammonia, not as a processing aid, but as a flavorant to increase the pH of the cigarette smoke? A. That is what it -- it says, yes. I mean, -that's what the memoranda say. THE WITNESS: Is that all for this one, sir? MR. MAISTROS: Yes. MS. FEE: He'a like to take a break. MR.'MAISTROS: Sure. THE WITNESS: Would that be all right? THE VIDEOGRAPHER: Off record at HUSEBY & ASSOCIATES (800) 333-2082
Page 435: raj82d00
I 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 1 7' 18 19 20 21 22 23 24 read this memorandum. Q• Okay. I read"t.he memo. Does Dr. Lippiello accurately set forth the purpose of the Nicotine Analog Research Committee as being a research program to i investigate known -- known nicotine analogs or to identify new ones that have minimal cardiovascular activities? A. Based in -- on this.memoranda in 1986, I think this is -- this is a fair statement of what Dr. Lippiello thought this committee ought to be doing. Q. And you were a member of this committee? A. Yes. Q. And why was Reynolds and yourself attempting to identify known nicotine analogs that had minimal cardiovascular activity? A. As I mentioned•yesterday, there was -- there was literature out there about p.latelet aggregation that some of the members of this committee had information and knowledge about, and I suppose that was why they were working on this. 25 1 Q. Well, did the purpose of the HUSEBY & ASSOCIATES (800) 333-2082 369
Page 436: raj82d00
381 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 there was a high enough level of the material. Q. Or, in fact, the increase in any base could increase the smoke pH, and thus increase the nicotine yield, correct? I think the -- the operative word there is yeah, depending on the level. If there was a high enough level, one would think that it would do that. Q. And why were you looking to use or get permission to use potassium carbonate in an effort to increase the nicotine yield of a prototype cigarette? A. As a general policy, I always check with our -- the -- I -- I guess I was working at this time in the Flavor Division. And there was a general policy in the Flavor Division to -- if you were going to be looking at any new c.ompounds, that you would touch base with someone in -- in the scientific affairs. That was always done. Just a general policy. Q. And why were you attempting to increase the nicotine yields of the cigarettes? MS. FEE: Object to the form. THE WITNESS: We were trying to change the pH of the tobacco by the use of HUSEBY & ASSOCIATES (800) 333-2082
Page 437: raj82d00
1 2 .Q. 4 5 7 8 9 .10 11 12 13 14 - 15 16 17 18 19 20 21 22 23 24 potassium carbonate as a base. BY MR. MAI.STROS.:. You weren't attempting to increase the nicotine yield? . It was never a foregone conclusion that that would be. the effect. Q• pH? Why were you trying to increase the A. I'm really not quite sure why this was undertaken. Q. Well -- A. I was in the -- I was in the -- I was in the Flavor Division at the time. Q. And the Flavor Division was looking at ways to increase smoke pH? A. I need to read this memorandum more closely here before I go on. Okay. What was the question, again sir? Q. Having read the memo, does the memo refresh your recollection as to why the Flavoring Division was attempting to increase the pH of the smoke? MS. FEE: Object to the.form. 25 1 THE WITNESS: As it states in the - 382 I HUSEBY & ASSOCIATES (800) 333-2082
Page 438: raj82d00
375 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 other process you described, where the KDN by-product was used and.reapplied to reconstituted sheet, that was never used commercially? A. That is correct. Q. And you're absolutely certain of both of those? A. To the best of my knowledge, yes. Q. Do you know why you were copied on this memo? A. I need to read the -- the entire thing so I-- to determine why I might have been copied. I was probably sent a copy of this memorandum -- my best guess is that I was part of this brainstorming session. Q. Were any of those brainstorming ideas on that last page yours? MS. FEE: You mean, any of the hypotheses? MR. MAISTROS: Yeah. THE WITNESS: I'm really not sure whether -- whether any of these were mine or not. This is quite a few years ago. BY MR. MAISTROS: Q. What is potassium carbonate? A. Potassium carbonate is a weak base. HUSEBY & ASSOCIATES (800) 333-2082
Page 439: raj82d00
1 2 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Reynolds had some natural tobacco extracts that had varying_.ievel,s of nicotine in it, yes. I was not aware -- I -- I-didn't know exactly how they were applying this or where they were applying it. I assumed it was on the reconstituted sheet. BY MR. MAISTROS: Q. And where did they get that natural tobacco extract containing high levels of nicotine? A. The one that I'm familiar with is that they obtain that from the KDN process. They -- they -- they took the very, very dilute KDN extract,,and then they had to reduce some of the water out of that and take it to a -- a level of nicotine of about 8 percent, if I'm not mistaken. Q. And then applied it where? .A. Onto the reconstituted tobacco sheet. Q. And then what was done with it? A. That was used as a portion of the blend. Q. And then what was done with the cigarettes? A. We -- we looked at the physical and chemical properties of those cigarettes. Q. And did you place them in test 373 i HUSEBY & ASSOCIATES (800) 333-2082
Page 440: raj82d00
385 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 correct? A. Could you._.repeat that one more time? Q. Was one or both of the goals of this research to reduce the tar or increase the nicotine yields of the tobacco? MS. FEE: It's compound. THE WITNESS: We were -- it's all -- these are both responses to a change from a variable -- I mean -- we start with tobacco and these are -- are responses from the burning of tobacco. We started with a high nicotine tobacco as part of G -- of XGT or GT-X, whatever. And we're just using high nicotine tobacco to determine if you could produce a reasonably flavored low tar-to-nicotine product that had smoke chemistry that was in -- in keeping with -- you know -- it wasn't out of bounds, things that were normal at the time in terms of CO -- CO to tar level, total carbon monoxide yield and smoke component deliveries. BY MR. MAISTROS: Q. Is it your testimony that no portion of this research was premised upon the belief that HUSEBY & ASSOCIATES (800) 333-2082
Page 441: raj82d00
368 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1984? Or maybe a photocopy. I don't -- I don't know what it means., That's'j.ust what it says. A. I'm not sure why that was here. Q. Did your wife ever discuss with you research that she was aware of that the ammoniated treated flue-cured tobacco had higher mutagenicity numbers than nonammoniated flue-cured'tobacco? A. No. Q. Do you know if the fact that ammoniated flue-cured tobacco by the gaseous treatment method had anything to do with Reynolds not using that method anymore? A. No, I don't know any -- anything about that. (PLAINTIFFS' EXHIBIT NUMBER 23 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 23 is a December 1st, 1986 memorandum authored by Dr. Lippiello copied to you. Do you recall receiving a copy of thi-s memorandum in 1986? A. Patrick normally did not send out drafts, and this is a draft memorandum. Q. So, your answer is "no"? A. I -- I can't remember it. I need to HUSEBY & ASSOCIATES (800) 333-2082
Page 442: raj82d00
1 2 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the table below, we were trying to test the two hypothes-es tb.at were put forward in .the -- in the reference memos that I'm referencing here. Since this memo does not contain the data tables,,it's very difficult for me to -- you know -- I would have loved to have seen that, since this is a not a.complete memorandum here. But it did -- the data, based on what I've -- I've written here on the analytical review, would indicate that the potassium carbonate, as it increased nicotine delivery decreased. And that as expected, based on the work of Mattina, that C0 and C02 -- CO and C02 levels decreased as expected based on his -- his report that he made at the Tobacco Chemist Research Conference in 1985. BY MR. MAISTROS: Q. Before you obtained the results from this research, wasn't it the goal of this research to determine if potassium carbonate could be used to increase nicotine yields of cigarettes? A. The use of a-- no, that was not the entire intent of this, first of all. 383 HUSEBY & ASSOCIATES (800) 333-2082
Page 443: raj82d00
1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 potassium carbonate could be used to increase nicotine yields? A. No, because there was hypothesis out there that, if you added a base to this thing, that you would increase the nicotine yield. And, in fact, what.we found out was that you did not increase the nicotine yield relative to tar. Q. Isn't the fact or one of the reasons you chose potassium carbonate was its potential to increase nicotine yields? A. I chose potassium carbonate for two reasons. One of them was that Charlie Mattina had used that material and that -- as an example as a carboxylate salt, and it's -- and because it had effects in terms of altering the combustion of tobacco, which I thought was important, and, secondly, because it was a solid. You could meter out exactly what you wanted and wouldn't have to worry about looking at liquids or gases. Q. So, is it your testimony that the fac-t that the literature indicated that potassium carbonate could increase nicotine yields had nothing to do with your selection of that as a potential flavorant? A. No. That did -- 386 I HUSEBY & ASSOCIATES (800) 333-2082
Page 444: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17* 18 19 20 21 22 23 24 25 accurate copy of the original November 28th, 1989 memorandum signed by you, on the second page? A. Yes. Q. Kept in the ordinary course of your employment at Reynolds? A. It would have been kept in my records, yes. Q. And in this first paragraph of this document, you describe that "historically K2C03" which is what? A. Potassium carbonate. Q. "Historically, potassium carbonate has been used in the tobacco industry as a tobacco additive and wet snuff product. The intent for its use in wet snuff was to increase the tobacco pH and therefore increase the availability of tobacco bases, pyrazine flavorants and notably nicotine. Its use level range from about .25-5 percent, depending on the type of snuff product. Its use in smoking tobacco products is also known in the l,it-erature. "Again, it was employed in the range of .25 to - 5 percent. In tobacco smoking products, the intent was twofold. First, carbonium" -- I'm sorry -- "first, potassium HUSEBY & ASSOCIATES (800) 333-2082
Page 445: raj82d00
387 MS. FEE: Object to the form. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 THE WITNESS: That did hurt -- no. .That did help. There are other types of basis that one could have used. I chose that one. (PLAINTIFFS' EXHIBIT NUMBER 26 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTftOS: Q. How long had you been in the Flavorant Department by November of '89? A. I -- I only had a short time in that division. I think I was there perhaps a year, maybe a year and a half. Q. And the document I'm handing you by Jack White -- who.was who? A. Jack White is a research scientist that works at R&D. Q. Exhibit 26, your -- is this you being copied on this memo in July 30th of 1990? A. Is this -- is this me you're asking? Q. Yes, yes. A. Yes, this is me. Q. Do you recall receiving a copy of this memo from Jack White to Mary Stowe? A. I need to -- to read it first. HUSEBY & ASSOCIATES (800) 333-2082
Page 446: raj82d00
388 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Yes, I remember this memoranda. Q. Why was Ja~k White attempting to identify sources having the capability of supplying large quantities of 95 to 99 percent nicotine in July of 1990? A. I -- I -- I suppose that Mary Stowe felt that Jack had the wherewithal to -- to do this request that she had for him. Q. Okay. Do you know why Mary was looking for large quantities of 95 to 99 percent nicotine in July of 1990? A. This would have probably been in in relationship to Project XB, which is an extension of XGT. Q. And the primary goal of XB was what? A. To produce a low tar-to-nicotine cigarette prototype. Q. And do you know which of the four identified sources, if any, were selected? A. None of these -- none of these sources, as stated here, were selected. Q. Do you know why that was? A. I'm not sure. Obviously the -- he had some -- he did say here that this does not seem practical under number two. He states under number HUSEBY & ASSOCIATES (800) 333-2082
Page 447: raj82d00
389 1 2 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 four that supplies may be limited from Eastman. You know, that's what tlxe memoranda said. .Q. Do you know if large quantities of 95 to 99 percent nicotine were acquired by Reynolds in the 1990 time frame? A. To my recollection, no, there were none of that was obtained. Q. What is Avoca? A. Avoca is a -- it's a farm that we that -- that -- that we own down in the eastern part of the state. Q• And -- and do you know how Reynolds obtain 95 percent nicotine from was going to condensate by use of equipment out of Avoca? A. At Avoca there is some chemical processing equipment down there. Q. Do you know if they've ever processed the KDN extract at Avoca? A. I'm really not'certain. Q. Do you know if Freon was used in the processing of that KDN extract at Avoca or the extract at Avoca? MS. FEE: Object to the form. THE WITNESS: No, I'm not aware that they did work with Freon to get nicotine HUSEBY & ASSOCIATES (800) 333-2082
Page 448: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 variables can be applied alone or in combination with G7 extract during the sheet making process. The combination of KDN extract and levulinic acid on G7 is referred to as G7-18. And has been -- it has been hypothesized that levulinic acid will provide a smoothing effect to overcome the perceived harshness that may occur from the addition of the KDN extract which provides a higher nicotine" -- something -- "sheet in our current G7-1.° Were you aware if 07-18 was ever produced, as set forth in this memo? A. That was an experimental reconstituted sheet that was produced at -- at Reynolds, yes. Q. And the purpose of G7-18 was what? A. It was to prepare a -- a tobacco sheet that had nicotine:.and'levulinic acid on that sheet. Q. Are you instrumental at all in this particular research? A. I'm not sure. I need to read the memorandum to find out. Q. Well, just -- without reading the memorandum -- not the memorandum research, but the 391 i HUSEBY & ASSOCIATES (800) 333-2082
Page 449: raj82d00
1 2 3 4 5 6 7 8 9 .10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Yes, I was,involved in the XB What was the extent of your I consulted and presented some -- was used as a resource for information on work that we had done on Project aT and XGT. Q. And it involved the use of a concentrated KDN extract? A. Some of the work that was.done in Project XB did, yes. Q. And these cigarettes with the concentrated KDN extract were tested on consumers but not sold commercially? MS. FEE: Object to the form. It's compound. THE WITNESS: We prepared prototypes that had certain levels of 07-18 in them that contained KDN extract with varying levels of levulinic acid. That was usually in combination with our normal C37-1 in these prototypes. These experimental prototypes were tested on our sensory evaluation panel, to 392 i HUSEBY & ASSOCIATES (800) 333-2082
Page 450: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the best of my knowledge, and we did do some consumer eva,luatipns".w.ith XB prototypes that contained -- at which some of them contained some level of the G7-18 in them. BY MR. MAISTROS: Q. What.is neat nicotine, N-E-A-T? A. Neat is a term that's -- that's synonymous with pure. Q. Was it one of the purposes of the XB project, to increase the nicotine levels of the tobacco? A. Of the XG -- Q. B product -- project. A. What project was it? I'm sorry. Q. XB. A. XB. Yes, we wanted to increase the tobacco, the -- the nicotine level in the tobacco. (PLAINTIFFS' EXHIBIT NUMBER 28 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 28 is a multipage document that's entitled "Processed/Reconstituted Tobacco." The first page lists various G15, G16, G17, et cetera. Do you see.that? HUSEBY & ASSOCIATES (800) 333-2082
Page 451: raj82d00
394 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 page? . A. Yes. 4. Are you ,familiar with this first MS. FEE: I just want to state that the -- the document is -- seems to be a collection of different documents. The Bates numbers aren't sequential. I don't know if this was assembled by plaintiffs or if it was produced in this fashion. MR. MAISTROS: I don't know either, but the third page, fourth page, and fifth page appear to be consecutive -- MS. FEE: Right. MR. MAISTROS: -- which is really what I'm going to get to. I just -- want to ask him if he's familiar with any of the lettering or numbers on the first two pages? MS. FEE: Which may or may not have anything to do with what's on the subsequent pages? MR. MAISTROS: Right. THE WITNESS: I'm familiar with -- with some of these numberings, like a15. Those are cast sheet operations, as -- as stated, and that 16 is what -- your Kimberly HUSEBY & ASSOCIATES (800) 333-2082
Page 452: raj82d00
395 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Clark formulations. BY MR. MALSTROS-: Q. Okay. On the third sheet, do you see that one that's entitled "Project Explanations"? A. Yes, I have this in front of me. Q. Were you familiar with Project G7-KDN, a process by which nicotine from the KDN process is added to G7? A. Yeah; I've -- I've heard of that terminology, yes. Q. In what context? A. This was -- I believe that the G7-KDN was -- what it was called before was G7-18. Q. And then on the last page, do you see the list of paper sheet processes, G7-1 through G7-26? A. Yes, sir. Q. Are you familiar with all those processes? A. I was aware that there was a tremendous number of G7s at the time, in '91. And I usually had to have this -- this cheat sheet with me to determine which ones they were talking about at the time. There were so many, it was difficult to remember which G7 went with what descriptions. HUSEBY & ASSOCIATES (800) 333-2082
Page 453: raj82d00
390 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 with -- I -- I'm not aware that that work was done at Avoca,with,.Freon to collect nicotine. (PLAINTIFFS' EXHIBIT NUMBER 27 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: Q. Exhibit 27 is a March 11th, 1991 memo from Margaret Savoca to J.H. Reynolds. Do you know who Margaret Savoca was? A. Margaret was a sensory analyst at Reynolds Tobacco, manager of the Sensory Evaluation Division. Q. And J.H. Reynolds was who? A. Principal scientist at R.J. Reynolds Tobacco Company. Was he ever your supervisor? A. Yes, he was. Q A. Development Exp1oratory Q. states, and the several In what group? In the Product Division -- Product Division. We had a group called Research Technology, I believe. In the second paragraph, the author she's talking about Project XB, "Among technologies being considered for XB are KDN extract and levulinic acid. These HUSEBY & ASSOCIATES (800) 333-2082
Page 454: raj82d00
396 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• Do you know what the difference between G7-1 ammoniated'.-- regular G7-1 ammoniated and isolated G7-1 ammoniated is? A. Yes. G7-1 ammonia, which is G7-2 here, what they're calling, is -- we produced some of this for Tobacco International. That's what the TI stands for. So, materials that were produced for Tobacco International were normally kept separate. Q. Why is that? A. I think it was for inventory purposes. Q. Do you know what the difference between G7-1 ammoniated extract was and DAP treated G7-1? A. We're talking about 07-7, sir? Q. Right. A. The difference between G7-7 and G71? Q. G7-10. A. G7-10. Yes, G7-7, some -- the ext-ract before it was applied back onto the base web, there was ammonia added to it. I forget exactly the level. There was some ammonia added to it and it was warmed up and then that warm ammoniated extract was applied back onto the sheet. HUSEBY & ASSOCIATES (800) 333-2082
Page 455: raj82d00
399 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Now, you didn't mention G7-6. You don't_beli.eve that that had ammonia in it? Additive free ammonia. A. Additive free. Okay. I thought it said free from ammonia. I wasn't -- I'm really not -- I wasn't familiar with G7-6 to tell you the truth, but it says, "Additive free ammoniated.". This probably does contain some ammonia then. Q. So that at least in 1991 of the reconstituted sheets that have the "C" by them, although not -- not representing what that "C" means, one, two, three, four, five, six, seven use ammonia, correct? A. That's -- that was what we went through, yes. Q. All right. And about six or seven do not, correct?, A. That is correct. Q. Now, yesterday-you testified that it was your belief that ammonia was used in the pro-cess for two purposes; one was taste and one was for workability of the sheet? A. Yes. Q. Did Reynolds have problems with the taste and workability of the six or seven sheets HUSEBY & ASSOCIATES (800) 333-2082
Page 456: raj82d00
397 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 That's -- that's what G7-7 was -- was about. G7-10 had.diammonium phosphate added to the extract before -- before it was applied back to the base web and there was a -- a step in that where they added ammonia first before they added the DAP, if I'm not mistaken. Q. And why did they do that? A. They wanted to have the -- you had to be able to do reduce -- release the pectin so that, it would react with the diammonium phosphate to form a slight gel so that you could increase the strength of this paper sheet. Q. Now, out of these listed paper sheet processes, which ones could you identify for me have either ammonia or some form of ammonia compound in them? Not the experimental ones. The ones with the "C" by them. MS. FEE: Object to the form. What -- are you making some representation about which ones of these are experimental and which ones are not? MR. MAISTROS: Well, the "C" means currently being used and "E" means experimental on a document we'll get to in two minutes, but HUSEBY & ASSOCIATES (800) 333-2082
Page 457: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 When -- when you use by-products associated with, and I t.hink we were using by-products in -- in -- in some of this GT-X work, you would generate -- there were high levels or higher than wanted levels of carbon monoxide and carbon dioxide. The burning of the thing was - was slightly different than we had anticipated. So, there was a couple of aims at this. One was to reduce the CO and C02 by using a -- by -- by the use of this -- of this additive. Q. Well -- A. And they were obviously tested with two -- two different types of blends. One was a high nicotine blend that we were using in -- in X -- XGT and the other one was the control cigarette. So, this is part of a -- must have been a response from a request of -- of difficulties and they came to the Flavor Division and they asked for something we could do. So, this i-s what I proposed to do. Q. One of the goals of this research, was it not, was to do either one or both of the following: Decrease tar or increase the nicotine yields of the tobacco by the use of this additive, 384 I HUSEBY & ASSOCIATES (800) 333-2082
Page 458: raj82d00
403 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Underneath the summary, the first page. .A. Oh, okay. Q. Do you see "the -- the addition of L-arginine to increase the pH of RTC substrate and thus aid in releasing the nicotine present in the tobacco utilized to make RTCS was accomplished." •Do you see that? A. Yes, I do. Q. And,RTCS is the Reconstituted Tobacco Sheet? A. Yeah, I think that's the abbreviation from -- for that. Q. And then below, "Sensory evaluation also indicated that addition of L-arginine via top dressing increased mouthfeel and strength. This was confirmed by the increase of both puff-by-puff smoke pH and nicotine yields." Do you see that? A. Yes, I do. Q. And do you know what, if anything, was done subsequent to these tests? A. No, I was not part of that project. Q. What are the GTC cigarettes? A. I'm sorry, sir? HUSEBY & ASSOCIATES (800) 333-2082
Page 459: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Steve Sohn -- I believe Steve Sohn was still working for mo.. .Q. And in what areas were you working April of '94? A. We were looking at reconstituted in tobacco types, improved reconstituted tobaccos is one of the areas of the division I was in. Another area that we were looking at were particle sizes of tobacco -- tobacco by-products. Q. On the last sheet, it lists the current experimental and di.scontinued reconstituted sheets. Is this an accurate summary of what sheets were currently being used by Reynolds in April of 1994? A. I believe this is correct, yes. Q. And how many different.types of reconstituted sheet was Reynolds using in April of 1984? A. That would be all of those designated with the "C" on them; is that correct? Q. Right, if you believe the -- the document. - A. It would appear that Reynolds had 15 -- 14 or 15 R-.- C37s that they were producing 406 I t HUSEBY & ASSOCIATES (800) 333-2082
Page 460: raj82d00
370 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 committee ever change over time? A. The -- the.comm.ittee has -- has discovered a number of nicotine analogs that have -- that appear to be useful in -- in terms of dementia diseases. So, it was expanded, I guess. Q. When did the committee stop looking at nicotine analogs for the purpose of identifying ones with minimal cardiovascular activity -- MS. FEE: Object to the form. BY MR. MAISTROS: Q. -- if ever? A. I'm not sure, because I was not part of that -- I was not on that branch of the team. My -- my duties were outlined on the final paragraph of this.memo here. Q. How.long were you on thia committee? A. I think I was on the committee for a year and a half. I did very little work on the committee', though. Q. Did the committee continue after you were -- ceased being a member? Ln ~ A. I believe it did, yes. m . .., (PLAINTIFFS' EXHIBIT NUMBER 24 WAS MARKED FOR ~ 00 24 25 IDENTIFICATION) BY MR. MAISTROS: HUSEBY"& ASSOCIATES (800) 333-2082
Page 461: raj82d00
404 1 2 3 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23- 24 25 A. What are the.GTC cigarettes? GTC, thos_e..--.tbose were improvements that they were trying to -- to make on Premier. MR. MAISTROS: Bless you. THE WITNESS: Bless you. MR. MAISTROS: Bless you. THE WITNESS: Bless you, MS. FEE: Thank you. BY MR. MAISTROS: Q. In 1993 Reynolds was exploring means to improve Premier? A. Well, it wasn't Premier any longer at that time. That project was killed a long time ago, but the -- but they were still looking at new technology prototypes that -- that addressed some of the deficiencies that -- that Premier had. Q. And one of the deficiencies was the nicotine yield? A. Actually not. 'Well, the major deficiency was the flavor of the thing was very, very bad and the sidestream odor was -- was not real good, lightability was very, very bad. So, there was lots of areas to improve upon. (PLAINTIFFS' EXHIBIT NUMBER 30 WAS MARKED FOR IDENTIFICATION) HUSEBY & ASSOCIATES (800) 333-2082
Page 462: raj82d00
410 phosphate is added to tie up that pectin and 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 o produce a ga1_.that will increase the strength of the sheet being prepared. BY MR. MAISTROS: Q. Isn't the ammonia added to really affect the pH of the extract? A. Ammonia is added to.affect the pH through the extract for the sole purpose of precipitating out free pectin. Q. So, it's your testimony that the processing aid use of ammonia -- that is, what, to increase the streng'th of the.sheet? -- is accomplished by increasing the pH? A. Yes. Q. And how is that different than the - the function of the DAP? A. It is -- it's a two-step type of reaction, sir. One of the -- one of the things that you have, calcium pectate that ammonia -- it's -- it's in a soluble solid. You add ammonia. Tha:t becomes solubilized and you release the free pectin. The second step.of the reaction, then, is to tie up the free calcium with the ammonium -- diammonium phosphate. That produces an HUSEBY & ASSOCIATES (800) 333-2082
Page 463: raj82d00
409 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Correct. And the reason that is, is because if they had to g.repare materials for prototype development that went out to consumers where you had to produce more materials than, you know, a couple pounds, you had to have a number associated with that to get a run done in -- in the pilot plant. They had to order up materials. Someone had to be charged for the preparation of materials. And they would be given a number, a G7 number when it was either experimental or used in -- used in experimental prototypes. Q. What is G7-25? A. That is a heat treated extract we're -- we're -- there ammonia added to that. that is diammonium phosphate and Q. And is the diammonium and ammonia -- those are two different compounds, right? A. Correct. Q. Those are both'added for the purpose of affecting the pH; are they not? MS. FEE: Object to the form. THE WITNESS: The ammonia is added -- as a processing aid, as I had stated previously in my testimony, to reduce -- to release the pectin. The diammonium HUSEBY & ASSOCIATES (800) 333-2082
Page 464: raj82d00
412 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MR. MAISTROS: I skipped 31. I'll go back to 31. MS.`FEE: Oh, you had something else marked 31? MR. MAISTROS: Right. MS..FEE: Okay. All right. BY MR. MAISTROS: Q. This is 32. This is a May 7th, '86 memo you're copied on from D.W. Eaker to C.R. Green. Who is David Eaker? A. David Eaker was a research scientist at R.J. Reynolds Tobacco, R&D. Q. In your group? •A. No, sir. Q. Do you know why you were copied on this memo? A. No, I don't. Q.. Could you read this.memo? Maybe that will refresh your recollection. (Mr. O'Hara enters the proceedings.) THE WITNESS: I have read the memo. BY MR. MAISTROS: Q. Do you have a recollection of receiving a copy of this memo now? HUSEBY & ASSOCIATES (800 333-2082
Page 465: raj82d00
I A. No, I don't. 2 3 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Do you rec.all.w-ork that you were doing in 1986 relating to attempting to apply nicotine to filters.of cigarettes to increase nicotine yields? A. No, I don't. Q. Do you recall research you were doing in an effort to reduce the nicotine content of sidestream smoke? A. No, I don't. Q. What is nicotine freebase? A. That is neat nicotine. Just pure unionized nicotine. Q. Did you ever work with free nicotine? A. Yes, I did. Q. But'you don't recall working in the context of applying free nicotine to filters? A. Actually I don't, no. Q. Do you know if -- if Reynolds ever experimented with cigarettes that had filters that coritained nicotine in the filters? A. No, I don't know that. (PLAINTIFFS' EXHIBIT NUMBER 31 WAS MARKED FOR IDENTIFICATION) BY MR. MAISTROS: 413 ~ ~ ~ ~ ~ HUSEBY & ASSOCIATES (800) 333-2082
Page 466: raj82d00
398 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 MS.'FEE: Well, I -- I don't -- I don't know that. I don't know that the witness knows that. MR. MAISTROS: Well, your previous counsel stipulated to it, but you can -- you can debate it. MS. FEE: I'm not -- I'm not -- MR. MAISTROS: Just forget what the connotation is. MS. FEE:, I'm not debating it. I just want to see what you're relying on. MR. MAISTROS: Forget the connotation. BY MR. MAISTROS: Q. What -- which of the -- the processes that have the "C" by it contain ammonia or ammonia-related product? A. This is on page 3, sir? I'm trying to find -- Q. Last page. A. Ahl In this column here. Okay. G7-2 says it has ammonia; G7-4 had ammonia; G7-7 had-ammonia; G7-9; G7XXA; G-- G7-10. Q. Okay. That's the end of the ones with "C" by them. m ~ rn m rn HUSEBY & ASSOCIATES (800) 333-2082
Page 467: raj82d00
401 1 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20. 21 22 23 24 25 Q. You'have found smokers that both like the taste of ammoniated_.tobac~co and those that do not like the taste of ammoniated tobacco? A. There are smokers that -- that like the taste of it and there are certain smokers that do not like the taste of it, yes. That is, of tobaccos that contained ammoniated tobaccos. (PLAINTIFFS' EXHIBIT NUMBER 29 WAS MARKED FOR IDENTIFICATION) MR. MAISTROS: Do you have an extra copy of that one? No? BY MR. MAISTROS: Q. Exhibit 29 is a December 15th, 1993 memorandum. MR. MAISTROS: I'll have to get you guys a copy, okay? MR.'0'HARA: Fine. BY MR. MAISTROS: This is from a Gonzalez and Stafford. Do you know who they are? A. Yes. Q. Who are they? A. Al Gonzalez is a-- is a flavorist and Ted -- Ted -- Ted Stafford is a technologist that work at Reynolds R&D. HUSEBY & ASSOCIATES (800).333-2082
Page 468: raj82d00
415 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Okay. And you were part of this group? A. Yes. Q. What group were the other individuals in? I know they're all R&D, right? A. Yes. As noted by the asterisk on the first page, Patrick Lippiello was in the Biochemical and Biobehavioral Group, as well as William Caldwell, Don deBethizy, and John Robinson. I was in the Applied R&D Group, as well as Steve Sears. And R&D Administration Services, Richard Williams was in that -- in that particular division. And Sam Simmons was in the Smoking and Health Group Division for R&D. Q. And -- and, again, what was the purpose of this program? A. The objective, as is stated here on the first page, would say, "The development and initiation of an integrated in-house/ex-house -- I program to increase our understanding of the" can't read that word. Q. It looks like basic -- A. -- basic -- yes -- "basic physical, chemical, pharmacological, and toxicological properties of nicotine and its analogs." HUSEBY & ASSOCIATES (800) 333-2082
Page 469: raj82d00
414 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1? 18 19 20 21 22 23 24 25 Q. Okay. Exhibit 31 -- Exhibit 31 is a October 7th, 1988 memora.ndum authored by eight individuals including you. Do you see that? A. Yes, sir. Q. Without -- I mean, you can look and see if the pages go consecutively, and without reading the entire document, can you tell me if the document appears to be a complete an.d accurate copy of your October 7th, 188 memorandum? A. Some of the figures are not in here and some of the -- these bar codes over on the side, these -- these numbers start with 51233557, I guess, some of them are penciled in. But besides that, it looks like that it is a complete document. Q. Do you recall Unintegrated Research Program for the Study of Nicotine and its analog -- Analogs? A. Yes, I remembe'r this. Q. And what was this? A. This was -- this was a -- sort of like a status report on the nicotine analog research program that -- that Pat Lippiello put together, and then he submitted it to the committee to look over and see if it was accurate. un ~ ~ ~ m ~ m N N HUSEBY & ASSOCIATES (800) 333-2082
Page 470: raj82d00
405 1 2 BY MR. MAISTROS: Q. Wind -- wi.nding..down, as they say. MR. MAISTROS: I don't know what 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 happened to my copies, guys. MR. O'HARA: That's all right. MR. MAISTROS: They got out of order somewhere. BY MR. MAISTROS: Q. The document I've handed you has previously been marked as Plaintiffs' Exhibit 1154. It's a three-page document, which, although the Reynolds Bates numbers in the right are in order, the first sheet is a distribution sheet and the second sheet is actually the memo itself. And you're on the distribution sheet on the right-hand corner. Do you see that? A. I was looking for myself and I -- Q. About halfway down. A. Ah, I see it. Yes. Q. Do you -- why -- do you know why you had been provided a list of the different reconstituted tobaccos in April of '94? A. Yes, I do. Q. And why? HUSEBY & ASSOCIATES (800) 333-2082
Page 471: raj82d00
416 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q• was. Is taste included in any of those? A. I don' t--,. no ,. I don' t be 1 i eve i t Q. And how long did this program continue? A. I believe it continued for this section of this that I was connected with. I believe it -- it continued for about three years. There is other work that Dr. Lippiello has continued in terms of determining some of the -- of these nicotine analogs in terms of for dementia diseases, and that is still continuing. Q. Now, were you aware, then, in,the course of this work, that Dr. Lippiello determined that levulinic acid -- I'm sorry -- yeah- levulinic acid could enhance the binding of nicotine to nicotinic receptors? MS. FEE: Object to the form. THE WITNESS: I remember only that Dr. Lippiello mentioned that to me, that he had been doing some work in terms of looking at binding of -- of nicotine and he'd used a seri,es of different chemicals to see how well they -- to see if there was competitive binding or -- or inhibition of binding when HUSEBY & ASSOCIATES (800. 333-2082
Page 472: raj82d00
407 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 and using currently. Some of these appear to be duplicates, because we're -- we were attempting to give these new numbers at this time, as why that why -- why -- you'll see 07-31 was basically the same as G7-1. And then-it goes down there at the -- the higher-number of "G" -- the higher number of G7s, they were being redesignated at this point. Q. And on the right of each different type of reconstituted sheet, it tells the type of cigarette was used then, correct? See -- see where it says, "where used"? A. Yes, I see that. Q. R&M is Regular and Menthol, right? •A. Yes. Q. FF is Full Flavor? A. That is the -- yes, that's the designation. Q. LT is Light? A. Low tar. Q. All right. And ULT is what, Ultra -- A. Ultra Low Tar. Q. -- Low Tar? What does it indicate that the C37-18 was used in? HUSEBY & ASSOCIATES (800) 333-2082
Page 473: raj82d00
402 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. In 1993, were you aware of a project they were working on to._.expior.e the addition of L-arginine to reconstituted tobacco cast sheet substrate and its effect on GTC cigarettes? A. I-- I had heard this about this project, yes. Q. What was the purpose of this project? A. Al believed that L-arginine had some particularly good flavor characteristics associated with it, in that in combination with the preparation of the reconstituted tobacco sheet, that it -- it gave this -- this -- this tobaccoo taste that they had been looking for for a long time. This is some of the work, I guess, they were doing on GTC at the time. Q. The primary benefit of the addition of L-arginine was to increase the nicotine yields; was it not? A. I think that was something that they were attempting to do, but I'm not certain. Q. The first page on the summary, it says, "The addition of L-arginine to increase the pH of RTCS substrate" -- that's the reconstituted tobacco, correct? A. Where are we here? HUSEBY & ASSOCIATES (800) 333-2082
Page 474: raj82d00
417 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 he was comparing that to nicotine, I guess. BY MR. MALSTROS : .Q. And is it your testimony that the knowledge that levulinic acid could increase the binding of nicotine to nicotinic receptors had nothing to do with Reynolds' use of levulinic a.cid in its tobacco? MS. FEE: Object to the form. THE WITNESS: I also remember that Dr. Lippiello went back and tried to repeatt that experiment and he did not -- was not able to repeat the work that he had prior -- that he had discussed earlier. BY MR. MAISTROS: Q. Do you -- are you testifying here to this jury that there is no association between Reynolds' use of levulinic acid and Lippiello's initial findings that indicated levulinic acid increased the binding activity of nicotine to nicotinic receptors? MS. FEE: Object to the form. THE WITNESS: The work that Dr. Lippiello conducted relative to why we used levulinic acid were not connected in any way. HUSEBY & ASSOCIATES (800) 333-2082
Page 475: raj82d00
1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 ammoniated pectim -- pectin that -- that gels and gives additional strength to -the sheet when you apply that -- that treated extract onto the base web. MR. MAISTROS: Let's take a break, if we can, just a short one and see if I can sum up here. MS. FEE: All right. THE VIDEOGRAPHER: Off record at 12:45 p.m. (Recess 12:45 p.m. to 1:21 p.m.) (PLAINTIFFS' EXHIBIT NUMBER 32 WAS MARKED FOR IDENTIFICATION) THE VIDEOGRAPHER: Back on record at 1:21 p.m. BY MR. MAISTROS: Q. Exhibit -- is that A. Yes, air. MS. FEE: Is it? 32 T gave you? MR. MAISTROS: I skipped 31, but I'll go back to it. BY MR. MAISTROS: Q. What was the last one? A. It was Number 30, sir. MS. FEE: Yeah, this is 411 i HUSEBY & ASSOCIATES (800) 333-2082
Page 476: raj82d00
408 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. It was used in regular prototypes and ultra low tar, but -it wa.s dis-continued. ,Q. Where does it say it was'used in the prototypes? A. I'm sorry? Q. Where does it say "prototypes"? A. This does not indicate that these were -- that these were marketed as ULT. A -- a XGT prototype were ULT prototypes. That is why it is designated as this. It doesn't say that -- this was the formulation of the blend types. Blend types used were full flavor low tar and we made full flavor -- I mean -- ultra low tar, we configured that into ultra low tar configuration only as regular. Q. Where does it say "prototype" on this sheet? A. It does not, because this means also prototypes. Q. How do you know that? A. Because I was aware -- I was working at in using some of these. Q. So, it's your testimony that where used could refer to both type prototypes and -- and/or commercially sold cigarettes? Ln H J ~ m ~ m ~ m HUSEBY & ASSOCIATES (800) 333-2082
Page 477: raj82d00
418 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. Now,.this_.memo •is dated October of '88. When did this program actually begin? A. I'm not sure. I just don't know. Q. Is it connected to your work in gathering a list of available analogs, the documents we -saw earlier? A. Yes, this was part of the CONAR project -- CONAR Committee. These are similar there were the same people that were on the -- on the committee on -- Analog Committee on nicotine analog research. MR. MAISTROS: What I would like to do is just let these gentlemen ask questions. If I have follow-up questions, I'll be permitted to, but I won't duplicate any questions or I won't ask questions I .could have asked now. Is that okay? MS. FEE: That's fine. MR. MAISTROS: Thank you, Doctor. Switch -- MS. FEE: Why don't we go off the record for.two minutes while people change HUSEBY & ASSOCIATES (800) 333-2082
Page 478: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1'7 18 19 20 21 22 23 24 25 seats. THE 'VIDEOARAPHER: Of f record at 1:34 p.m. (Off-the-record discussion.) THE VIDEOGRAPHER: This concludes tape five of the deposition of Dr. Thomas Perfetti. The time'ie 1:35 p.m. This.is tape number six of the deposition of Dr. Thomas Perfetti. The time is 1:37 p.m. EXAMINATION BY COUNSEL FOR PLAINTIFFS BY MR. SOBOL: Q. Good afternoon, Dr. Perfetti. My name is Michael Sobol, we met yesterday, and I've been presented during the first part of your deposition here. Q. A. Yes. I represent,the Plaintiffs in The Peoole of the State of Qalifornia versus Philip Morris and R.J. Reynolds, et a1. Do you understand you're still under oath? A. Yes, sir. Q. I have just a few follow-up questions. You have been here a while. HUSEBY & ASSOCIATES (800) 333-2082
Page 479: raj82d00
421 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Virginia Polytechnic, RJR has been your only job; is that correct? A. Correct. Q. Has your only professional work in your career been with RJR? Let -- let me ask it a different way. Did you have professional employment prior to your graduation from Virginia Polytechnic in 1977? A. I-- I have not worked with any other company since my graduation from Virginia Tech. Q. What about before that? A. I -- I was -- at Virginia Tech, I I worked as -- under contract -- not under contract, but as a grant from NASA and -- and then I-- I -- I'd worked earlier as a-- in -- as a produce manager when I was in college. Q. What's your current salary at RJR? A. I really -- I-- I don't know the exact -- the exact salary. It's about $100,000. Q. A year? A. Yes, sir. Q. Do you participate in the bonus program? A. Yes. HUSEBY & ASSOCIATES (800) 333-2082
Page 480: raj82d00
420 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Can you tell me again where you received your Ph.D? .A. I received my Ph.D at Virginia Polytechnic Institute and State University in Blacksburg, Virginia. Q. When was that? A. In 19 -- 1977. Q. And what was the nature of your degree? A. My degree was in --. a Ph.D degree in physical organic chemistry. Q. Did you study pharmacology at Virginia Polytechnic? A. I had a course in medicinal chemistry but no pharmacology. Q. You studied pharmacology anywhere else? A. No, sir. Q. What about at RJR? Have you been apprised from time to time on pharmacological developments? A. I never had any training in pharmacology and I'm not real familiar with that field. Q. Now, since 1977 when you left HUSEBY & ASSOCIATES (800) 333-2082
Page 481: raj82d00
423 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 A. Yes, there has been. Q. What.about , last..year? Did you receive more than your base pay last year? A. I -- I believe that I -- I received my base pay last year. Excuse me. Q. What about the year that Camel Wides came out? Did you receive more than'your base pay that year? A. I think -- no, I don't believe I did. Q. When have you received more than your base pay? A. I believe two years ago I got -- I I received a little bit more than my base pay. Company did very well that year. Q. Is the 20-percent plus, in addition to your 80 percent base pay which you receive during the course of the year, determined at all on individual merit? A. Part of it is on how well we achieve our objectives and then part of it is on, as I mentioned before, the -- the company performance. Q. Who establishes your individual objectives? A. The objectives that a scientist has 25 1 are usually based on a joint agreement between the 333-2082 HUSEBY & ASSOCIATES (800
Page 482: raj82d00
1 2 3 4 5 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 implications -- excuse me. And he is -- he is prepared and willin'g to answer the question, but we would request that this part of the deposition be put under seal, because this is work for which Dr. Perfetti understands that Reynolds has not sought patent protection yet. So, for that reason we would this part of the deposition to be under seal. MR. SOBOL: I'm not aware of the procedures in the other actions that I'm participating in this particular deposition, but in California, as you're probably aware, we're under a confidentiality order and there's a-- an agreement and a mechanism there to designate matter highly confidential. And I certainly think it's within your choices to designate whatever portions you want as highly confidential. MS. FEE: Okay. Well, we're so designating for this -- for this part of the testimony. MR. MAISTROS: Okay. BY MR. SOBOL: Q. The -- the question pending HUSEBY & ASSOCIATES (800).333-2082 426 i
Page 483: raj82d00
1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 supervisor and the -- the individual, based on some company objectives that_.are.out there, they may be at the time. Q. What time of year is the employees? whatever AIAP paid to A. Generally it is paid in February, in the spring. They say -- the spring of the year. that just precedes it. For example, for 1997, it will be paid in -- well, 1998, it will be paid this year in February or March. Q. Who's your current supervisor? A. My current supervisor is Dr. Brad Ingebrethsen. Q. Have you had a discussion this year with Dr. Ingebrethsen regarding what your objectives would be for the following year, this coming year? A. Yes. Q. What are your *objectives this year? A. Part of them are to continue the -- the work that we've been doing on some -- on some projects that we started a number of years ago. It's -- part of them are to continue what -- what we were doing last year. And -- I'm trying to think what -- and then to look at some additional 424 i HUSEBY & ASSOCIATES (800) 333-2082
Page 484: raj82d00
428 1 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25. the tobacco it is being mixed with and to determine any unusual smoke and p.bysica'1 properties associated with tnaterial. Q. Do you intend to investigate the effect on the level of free nicotine that the addition of these materials will occasion? A. No. Q. Have you performed yet other studies regarding nicotine transfer efficiency, transnicotine yield, and nicotine delivery with this material? A. Yes. Q. And what results have you found with regard to nicotine transfer efficiency? A. The nicotine transfer efficiency of this material is a lot lower than normal material when it is placed in a blend with tobacco. The yield of the -- the yield of nicotine from blends, having~,this inner -- inner material in it, the start of extruded material are lower than blended. Ln ~ ~ It does not have this extruded material in it. I m . , ~ think those are the two aspects. W m Q. What -- what's your understanding of the term "nicotine delivery"? A. My understanding of nicotine delivery HUSEBY & ASSOCIATES (800) 333-2082
Page 485: raj82d00
400 2 3 5 6 7 8 9 1,0 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that didn't contain ammonia? A. Yes. Q. But they still used those tobaccos? A. Yes, because they have a particular flavor characteristic. If -- when you remove -- we had very -- very -- a very rough time changing the flavor of our cigarettes. Once -- once a smoker gets used to smoking G7-1, for example, making the change to an ammoniated sheet like G7-2, it was not always acceptable. There is a number of tobaccos, and all -- not all tobaccos have great flavors to them, but the -- the -- the marriage of -- of all these tobaccos sometimes does have a -- a flavor that is acceptable to smokers. And smokers do get.used to a flavor like G7-1. And when you remove that or try to replace it, they miss that and they will down rate the product. So, we -- we -- we still make a tremendous amount in terms of our total poundage of unflavored, straight, run-of-the-mill 07. Q. Unflavored, meaning unflavored with ammonia? A. I'm using that without any glycerin or diammonium phosphate or ammonia. Sorry. HUSEBY & ASSOCIATES (800.) 333-2082
Page 486: raj82d00
432 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. MAISTROS: Q. How long h.ave.you been working on these prototypes? A. The low temperature smoke generating -- smoke generated prototype, we've been working on that for about three months. The ambient temperature smoking device, we've only looked at it for about a month and a half. Q. Why are you looking at an experimental prototype,for smoke flavored ambient temperatures? A. We have some cigarettes known as -- I I'm trying to think of the name of them -- Smoker's Choice that really aren't cigarettes at tall. They're just flavored filter materials that a smoker can puff on or suck on that deliver a cinnamon or a mint flavor to -- while.you're -- while you're sucking on these things. And we -- we thought that there is some technology available today where we might be able to have that -- have that -- a smoke flavor that they could suck on rather than just.the mint or the cinnamon flavor. Q. Is nicotine delivered in the use of Smoker's Choice? HUSEBY & ASSOCIATES (800) 333-2082
Page 487: raj82d00
1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Are you familiar with a study published last summer by•Jame-a Pankow that appeared in the,Environmental Science and Technology Journal? A. I remember seeing that article. Q. Did you review that article? A. No, I did not review it. Q. How did you come across that article? A. It just came on my desk. There's a lot of articles that I request. Normally they get hundreds of papers from a library on -- on a variety of topics that they think if I'm interested, they send them down to me. Q. Did you request a copy of this article? . No. Q. And have you read it yet? A. I've -- I have not -- I have not done a good reading of it. I've looked over it. Q. Have you formed any opinions regarding the results of that study reported by Dr. Pankow? A. No. Q. Has anyone asked you to review that document? 430 I HUSEBY & ASSOCIATES (800) 333-2082
Page 488: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Dr. Perfetti is, what is this material? A. The extruded material that I had mentioned that we were preparing off site is an extruded material prepared from rice flour, calcium carbonate, potassium nitrate, potassium carbonate, and a heat treated tobacco suspension. Q. What is going to be the application of this extruded material? A. The application is used -- is used in experimental prototypes as part of the cut filler material. Q. Have you examined or do you intend to examine the effect of this extruded material as incorporated into a tobacco cigarette on nicotine transfer efficiency? A. Yes. Q. Do you intend to investigate the effect of the addition of this extruded material on nicotine yield? A. Yes. Q. And on nicotine delivery? A. Yes. 4. Why? A. When we use a artificial material like this, we need to know how it interacts with 427 HUSEBY & ASSOCIATES (800) 333-2082
Page 489: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. No. Q. You also'_1-isted -as one of your objectives for the upcoming year additional experimental prototypes; is that correct? A. Yes. Q. Those additional experimental prototypes different or a part of the work that you're doing with this extruded material? A. They are different. Q. Can you tell me about the nature of the additional experimental prototypes that you're working on? MS. FEE: Same concern? THE WITNESS: Yes. MS. FEE: Okay. We'd continue to treat this as highly confidential. THE WITNESS: The -- the two types of prototypes th,at I've been working on this year, in addition to the extruded artificial smoking material are -- is a prototype that delivers flavor at ambient temperature, smoke flavor at ambient temperature. And the second prototype is one that delivers a -- it generates a smoke aerosol at a low temperature. HUSEBY & ASSOCIATES (800) 333-2082
Page 490: raj82d00
434 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Q. And who oversaw the incineration of the nicotine produced by,,the KDN process, if you know? A. I do not know. Q. How would you find out who was in charge of that? A. I -- I really don't know. I don't know. Q. Who operated the KDN process. Was - was there an operations manager for the KDN process that you know of? A. There was an operations manager, but I do not know his name. Q. And how would you find out his or her name? A. I don't know. Q. How did you find out that the KDN plant was in shambles? A. The -- it was -- from my window, you -- I could see the -- the KDN plant from the Research and Development laboratories. It was rusting. It was obvious to see that from -- from even from my vantage point. Q. Could you see into the plant from 25 1 your office? HUSEBY & ASSOCIATES (800) 333-2082
Page 491: raj82d00
1 ~ Q. What's the name of the bonus program? 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. The progr_a_m is known as the AIAP, but it is not a bonus program. Q. What is it? A. The program exists as -- there is a base pay that we get as -- at a particular level and at -- at that particular level, based on the performance of the -- of the company and of the individual, you're paid, for example, at a principal scientist level, it's a 20 percent incentive. And based on the -- the company's performance and the individual's performance, you will get paid up to this $100,000 if you do fine, which is my base pay, total base pay. So, during the year I get paid about 80 percent of my base pay. Q. Have there been years when you receive less than 80 percent of your base pay? A. Not less than 80 percent of my base pay,, no. Q. Have there been years where you receive less than 100 percent.of your base pay? A. Not less, no. Q. Have there been years when you receive more than your base pay? 422 I HUSEBY & ASSOCIATES (800) 333-2082
Page 492: raj82d00
435 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17' 18 19 20 21 22 23 24 25 A. No. We could see the outside of the plant. .Q. And the outside of the plant was rusting? A. There were areas where there was lots of rust deposit. I was also on a committee that looked at the -- the -- the plant and reviewed authorization requests for funds for a number of different processes and we reviewed the -- an engineer's report that gave us the condition of the plant itself. Q. Is there other use of the Whitaker Park portion of -- of that plant where the KDN process took place or is there something else going on there now? A. To my knowledge, that plant has been shut down and -- and I believe the -- the building has been removed. Q. Has your office moved since they shut down the KDN process? A. Yes. No. Wait a minute. No, it hasn't; no, it hasn't. Q. Okay. So, if you looked out your window today, would it be there or not? A. I have moved so many times, I'm HUSEBY & ASSOCIATES (800) 333-2082
Page 493: raj82d00
437 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Correct. MR. SOBOL,.. I'.m _going to mark Exhibit 33 here. I guess I can do it. (PLAINTIFFS' EXHIBIT NUMBER 33 WAS MARKED FOR IDENTIFICATION) BY MR. SOBOL: Q. Ask you to take a look at that. Have you seen this document before? A. I really need to look it over for a second. I've looked over the document. Q. Have you seen that document before? A. Yes. Q. Did you write it? A. No. Q. Did you participate in writing it? A. I -- yes, I think I did.. Q. The entire document or just portions of it? A. We -- I believe that somebody was taking notes and -- and then formulated a draft that we looked at, and I think we came back as a committee and looked over it. Q. Let me direct your attention to the first page of that document. HUSEBY & ASSOCIATES (800) 333-2082
Page 494: raj82d00
429 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 is that amount of'milligrams of nicotine that get transferred to mainstreo-m smoke that is trapped on a Cambridge pad under FTC smoking conditions. Q. Is nicotine delivery different under your understanding than nicotine transfer efficiency? A. The -- the term that I use is percent nicotine transfer I have used prior to this, and, yes, it is different. Percent yields is a quantity of material that is delivered to the mainstream smoke under FTC conditions. The percent transfer is -- is that quantity divided by the total available nicotine that could be transferred to the mainstream smoke times 100, of course. Q. Is there a difference between nicotine delivery and nicotine yield to your understanding? A. No. That -- in -- in my work we use those pretty much synonymous'ly. Q. It is possible to measure on a Cambridge pad f ree nicotine versus nicotine that is in the proteinated form? A. No. The amount of --.the nicotine that is trapped on a Cambridge pad should be all particulate nicotine. HUSEBY & ASSOCIATES (800) 333-2082
Page 495: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7' 18 19 20 21 22 23 24 25 gauge. And I'm not -- I was not in the Brands R&D Brands -- brand devo;lopment area. And so, I mean, ~n terms of -- of prototype development, prototype testing, and consumer testing of wides, I would have had no involvement in that area. Q. What -- did you review any marketing data prior to your work on developing a wide-gauge cigarette for which you are listed as a co-inventor on the patent? A. No,'I did not, because they -- they weren't available. There -- there wasn't any other cigarettes out there in the United States that had the real wide gauge at the time that I knew of. That's the only reason we were able to get a patent. Q. What marketing information were you referring to earlier today when you testified that it was the development of the Camel Wides came in response to certain marketing information? A. Ah! There was -- we had asked -- we had asked consumers to look at their particular wants that they would like to have in a-- in prototypes. Is there something that you would think would be novel enough to go buy? There was the -- the normal routine things of they're skinny, 440 HUSEBY & ASSOCIATES (800) 333-2082
Page 496: raj82d00
433 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. No. Q. Would it_be with the incorporation of this smoke flavor at ambient temperature*s? A. I'm not sure. I don't know. Q. You've testified both yesterday and today regarding the KDN process and that the nicotine produced by the denicotinization process in KDN has -- is incinerated; is that correct? A. To the best of my knowledge, the -- as far as -- as far as I can remember, we used to , incinerate all of that material when it was being used. Q. Did RJR have more than one plant where the KDN process was employed? A. No. I think there was only, to my knowledge, there was only one plant where that was being done. Q. And where was that? A. In the Whitaker Park Complex. Q. And where was the incineration of the nicotine produced through KDN? Where did that happen? A. The incinerator was adjacent, very close to the plant, within feet of -- of the -- of the plant itself. HUSEBY & ASSOCIATES (800) 333-2082
Page 497: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that nicotine is a key design parameter in RJR cigarettes? A. No, I don't agree with that. But in terms of research, tobacco nicotine can be a key design parameter, tobacco nicotine, because you can measure it. And you have materials that you can blend to get a particular tobacco nicotine. Q. Do you disagree with the statement contained in that paragraph, and I'm going to paraphrase now, that research regarding nicotine would put RJR in a position to maximize volume and share growth? MS. FEE: I object to the paraphrase. THE WITNESS: The concluding statement there has to do with nicotine is inherent to tobacco and is a well-known constituent tobacco smoke. Nicotine is important, contributed to taste, as I've said before, and organoleptic properties of tobacco smoke. And I think that is -- this is what this is about here. BY MR. SOBOL: Q. Does your review of this paragraph 4 refresh your memory or change your testimony in -- in any regard concerning whether or not nicotine 444 Ln ~ V V m I HUSEBY & ASSOCIATES (800) 333-2082
Page 498: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 thinking back. In fact, it has moved. Yeah, I'm -- I'm now down -- L!m down a floor or two from where I was. Q. You mentioned yesterday that Sam Simmons -- it's William Simmons -- would be most knowledgeable regarding health risks and smoking is -- at RJR; is that correct? A. In my -- in my opinion, he is in the smoking and health section, yes. Q. From time to time do you receive the. memorandum and reports generated by Sam Simmons' group? MS. FEE: Object to the form. THE WITNESS: No. BY MR. SOBOL: Q. Are you aware of health effects research being conducted by third parties should say -- outside of RJR? A. No. Q. But funded by RJR? A. I'm not aware of any -- any studies. Q. Did I understand your testimony correct yesterday that irt's your understanding that RJR does not conduct nicotine research for the purpose of selling cigarettes? Is that right? 436 HUSEBY & ASSOCIATES (800) 333-2082
Page 499: raj82d00
445 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 research is conducted for the purpose of selling cigarettes? ,A. It does not change what I've said before. We do work on tobacco nicotine as it relates to improvements in taste of our prototypes and the smoking enjoyment that people get from smoking tobacco. Certain individuals like ultra low tar prototypes, some of them like, you know, full flavor low tar prototypes, some.of them like full flavor prototypes. And cigarettes are a system of which tobacco is a part of that system that can be blended and to -- to give organoleptic properties that smokers enjoy. Q. And I want to direct your attention to the•section that says "thrust." Do you know what's meant by that word in this context? A. No, I do not know. Q. And do you see'that it says "to maintain its technical leadership position and t-hereby maximize volume and share of market, RJRT must," and then there's two bullet points under that? A. Uh-huh. Q. Do you agree that in order to HUSEBY & ASSOCIATES (800) 333-2082
Page 500: raj82d00
448 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 IDENTIFICATION) BY MR. SOBOL: .Q. You have in front of you now, Dr. Perfetti, Exhibit Number 34. Why don't you take a moment and take a look at that. MS..FEE: Do you have a copy for me? MR. SOBOL: Yes, I do. Right here. MS. FEE: Thank you. BY MR. SOBOL: Q. Do you recall this document? A. I'm reviewing it right now. (Mr. Maistros exits the proceedings.) THE WITNESS: Yes, sir, I'm done reading it. BY MR. SOBOL: Q. Do you see on the first page where you're listed as the first author? A. Yes, sir. Q. Do -- do you recall seeing this document before? A. Yes. Q. Did you write it? A. I don't know. Q. Is the fact that your name appears first in the -- among the authors indicate to you un ~ ~ ~ m I HUSEBY & ASSOCIATES (800) 333-2082
Page 501: raj82d00
446 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 obtain -- well, to maintain technical leadership and maximize volume and_.shar.e of the market, that RJR must employ nicotine as a key design parameter? A. No, I don't. Q. At the time that this document was being drafted and you were reviewing it, did you make a recommendation to strike that portion of this document? A. No, I did not at the time. The viewpoint changes over the years, and I don't agree with it now. Q. Did you agree with it at around the time that the nicotine strategic plan was drafted? A. I would -- yes, I did agree with this at the time. Q. It also says that to maintain technical leadership and maximize volume share of profit -- volume and share of market, I should say -- that RJRT must prepare for the future by investigating the key properties and characteristics of nicotine. Do you see -- I'm referring to the second bullet point. Do you see that? A. Yes, I do. Q. Do you disagree that fundamental and HUSEBY & ASSOCIATES (800) 333-2082
Page 502: raj82d00
438 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Uh-huh. Q. The NRC membership is composed of marketing people. Is that consistent with your memory? A. Yes. Q. Okay.. Why would it be -- what was the purpose, I should ask, of having marketing personnel on the Nicotine Review Committee? A. The -- there were -- there were people from marketing on there, because they believed that there were existing and emerging consumer wants that had to do with nicotine, had something to do with nicotine. Q. Was the purpose in part to have nicotine research directed by marketing? A. No. We were -- we were all on a particular.team and, you know, some things were looked at and some things weren't looked at. I mean, everyone had a-- they had a say in -- in -- in discussing the types of work that was going on currently at R&D and that -- find out what merit those had based on the criteria that were set up by the committee. Q. You generally share the product of your research with people in marketing? HUSEBY & ASSOCIATES (800) 333-2082
Page 503: raj82d00
447 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 applied research into the key properties and characteristics of nicotinelw.ould not help RJR maintain its technical leadership in maximized volume and share of market? A. Now, there is a two-part thing here. There is a -- we are partners in -- you know -- we work with marketing. We're all in one company here. And there are certain responsibilities that Research and Development has and there are certain responsibilities that marketing has. One of my -- I do not have the responsibility for increasing or in terms of advertising and other means of increasing share of market. My responsibility is to make sure that, you know, I personally have a -- maintain my technical competency. And part of that means, in terms of this document, knowing as best as I can, doing whatever research I can to understand some of the properties and characteristics of nicotine. Q. Do you remember, prior to preparing this document, you having recommended that a Nicotine Review Committee be established? A. No, I do not remember that. (PLAINTIFFS' EXHIBIT NUMBER 34 WAS MARKED FOR HUSEBY & ASSOCIATES (800) 333-2082
Page 504: raj82d00
449 1 2 3 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that you have primary responsibility for drafting this document? .A. I don't know. Q. Do you remember making the recommendations which appear on page 1, Roman numerals I, II, and III? A. No, I don't. Q. When was the last time you recall seeing this document? A. It had to have been sometime in 1989 when it was written. Q. Do you recall receiving comments from any of the other listed authors on this document? A. No, I don't remember getting comments from any of the other people. Q. Is there anything on this document that's inconsistent with your memory of the recommendations made by this particular committee? A. To my recollection, a lot of the things that they said here -- excuse me -- in terms of the committee recommendations, they're not inconsistent with -- with -- with what I had seen -- you know -- with -- with what we had talked about earlier on the team. This is, again, is a guess, I mean, HUSEBY & ASSOCIATES (800) 333-2082
Page 505: raj82d00
442 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Wides -- b'roke down the, by age group, the people that were interviewed for purposes of the marketing study?, MS. FEE: He just answered that question. ~ THE WITNESS: Ohl Not only did I not review any articles, I said that I was aware of some of these needs. We had -- and at the time we were -- the individual and I that were working together were kind of restricted in terms of our -- we were in sort of like a think tank developing not only this idea, but numerous other inventions that were -- that were in the mid-'80s. BY MR. SOBOL: Q. And Camel Wides did go on the market in the United States; is that correct? A. Yes, it did. It was a -- it was a prototype -- I mean -- it is a product out there. I b*elieve it's still being produced. Q. And it's still on the market? A. I'm not sure. I-- I think it is. I'm not sure. Q. As part of your compensation, do you HUSEBY & ASSOCIATES (800) 333-2082
Page 506: raj82d00
439 1 2 3 4 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. We have reviews that they're welcome to come to, j ust as, they, have~ reviews of what they're doing down -- down in -- in marketing that they often ask us to come to. Q. Do you feel as though your research is directed at somewhat by consumer wants? A. Not -- not so much my research. I deal with a lot of basic research and development of research prototypes, experimental prototypes. Q. Did you testify earlier today that your development of the Camel Wides was precipitated by a review of certain marketing surveys? Is that correct? A. Yes, that was true in that particular instance. Q. Was the development of the Camel Wides done in response to RJR's efforts to capture the young adult smoker market? A. My involvement in the Camel Wides thing was that myself and I believe one other ind-ividual hold a patent on the production of wide-gauge cigarettes. That's it. That's all I did. We hold the patent so that we can make those particular prototypes that are wide HUSEBY & ASSOCIATES (800) 333-2082
Page 507: raj82d00
450 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 like a -- a final memo from the Nicotine Review Meeting -- Nicotine RevLew Committee. This says "your understanding." I think it's my understanding that it is like a final memo from the Nicotine Review Committee. I think these are the people that are on that -- were on that committee. Q. Well, what's Tobacco USA? Do you see that reference in the first paragraph? A. Yeah. I'm not sure what that is. Q. What's the Development Corporation? A. I -- I-- I don't know what those two things meant in this -- in this paragraph. Q. Did RJR implement a five-year strategic plan on nicotine-related projects? A. Not to my knowledge. Q. And directing your attention to the second page under "Research Programs/Projects Should be Pursued and/or Continued." Do you recall any of those recommendations of programs or projects which should be pursued and/or continued? Which A. There were projects that had to do with high T/N ratio and obviously low T/N ratio. And obviously there were -- other work that was done that -- bits and pieces here that I -- that I HUSEBY & ASSOCIATES (800) 333-2082
Page 508: raj82d00
451 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know were -- were -- were being pursued. Q. And direct.ing.your attention page 3, under "Important Areas of Research to that Should be Reviewed to Determine Fit in Current Development Programs." Do you see that? A. Yes, sir. Q. Do you recall any of those? A. Number 2 had to do with XB program, as well as Number 4. Q. What about Number 7 there? To your knowledge, has RJR made a determination of the yields of nicotine which provide optimal levels of perceived satisfaction for high, low, and no nicotine yielding products? A. To my knowledge, that has -- that not been done. ' Q. Do you know if that research was conducted after February of 1989? A. No, I do not know. has Q. Do you know if it's going on today? A. No, I do not know. (Mr. Maistros enters the proceedings.) (PLAINTIFFS' EXHIBIT NUMBER 35 WAS MARKED FOR IDENTIFICATION) HUSEBY & ASSOCIATES (800) 333-2082
Page 509: raj82d00
452 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 BY MR. SOBOL: Q. I've marked as Exhibit Number 35 a substantial size document called "Nicotine Research in R&D." I want you to take a look at that. A. Sure. MR. SOBOL: That's to share, I guess. BY MR. SOBOL: Q. I'll direct your attention to certain pages, Dr. Perfetti, but maybe I'11 ask you preliminarily if you recognize any part of this document so far? A. I'm -- I'm getting through it. I-- I do see some things. Q. Do you know what this document is? A. It looks to me like a series of presentations. Q. Is this a presentation.which you participated in; do you r.ecall? A. I may have. I'm not sure. I can -- yeah, it looks like I was here. Okay. It looks like MS. FEE: There's no question pending. BY MR. MAISTROS: Q. Have you seen this document before? ~ ~ ~ ~ m HUSEBY & ASSOCIATES (800) 333-2082
Page 510: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Boy. Q. -- Farm? A. I'm not sure. It's a fairly good size farm, though. Q. Well, what is good size? A. It may be, to me, more than ten acres. It's more than ten acres. I don't know how big it is, but it's pretty good size. Q. Do you know what "collective gene pool approach" means here? A. No, I don't. Q. And is it your understanding that the high nicotine leaf which RJR was investigating was going to be less than or equal to 14 percent nicotine? I A. It was not my understanding what level of nicotine you'd actually get out of these seed drops. Q. What percentage of nicotine does, on average, does a burley tobacco have? A. Generally, a burley tobacco will have about 3 percent. Q. And that would be from the middle stalk position? A. On average across the -- across the 455 HUSEBY & ASSOCIATES (800) 333-2082
Page 511: raj82d00
1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 , plant about 3 percent, I would think. It does vary from year to ybar and based.on a lot of agronomic and weather conditions, though. Q. And I want to direct your attention to page 5239. Do you recall participating in the Nicotine Control RSM Study or the Nicotine RSM Study? A. Yes. Q. And what was your involvement in the Nicotine RSM Study? A. I was -- I was asked by the person who was directing this to -- to help them in terms of developing a statistical design for the program and to make some experimental prototypes to see if we could hit those design parameters.. Q. Who was the person directing it? A. It was Mary -- Mary Jo Dryden. Q. And RSM refers to Response Surface Methodology; is that correct? A. Correct. Q. Is that the statistical design which you developed? A. Yes. I -- I didn't do this myself. We had -- there was a statistician there that -- I 456 i HUSEBY & ASSOCIATES (800) 333-2082
Page 512: raj82d00
454 1 2 3 4 5 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. 52 -- this page here, sir? Q. Yes. A. Okay. Q. Do you see where it says "nicotine -- high nicotine leaf"? A. Yes. Q. Is it your understanding that RJR is -- has made an effort to produce a high nicotine leaf at Avoca and East Bend? A. I think that -- I think I'm aware that Avoca was -- they do plant tobacco down there, research -- for research purposes, and I am aware that at one time we did grow some varieties produced by the USDA, Dr. Chapman's lab at -- at Oxford Station that were supposed to have high nicotine - Q. you -- what containing high nicotine gene type. And what about at East Bend? Do is East Bend,; do you know? A. I'm -- I'm not sure'what East Bend is. I know Avoca. I don't know what East Bend is. Q. And Avoca, you said, is in East North Carolina? A. Yes, sir. Q. Do you know how many acres is at the Avoca -- HUSEBY & ASSOCIATES (800) 333-2082
Page 513: raj82d00
453 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I think I've seen pieces of it. Q. Do you recall'a.ttending a presentation or a seminar on nicotine research in R&D? A. I have attended many of them. I can't remember which one this is from, sir. Q. There's been more than one presentation entitled "Nicotine Research in R&D" in your tenure at RJR? A. I don't know if I remember the title of that particular one, no, but I -- some of these -- some of the -- some of the presentations look familiar to me. Q. Did you attend this particular presentation? MS. FEE: He -- he -- he answered that. THE WITNESS: Yes. BY MR. SOBOL: Q. And did you participate in the pro-duction of any of the materials in that packet? A. I'm not sure. Q. And I'm going to direct your attention to the page Bates numbered 5235, the last four digits. HUSEBY & ASSOCIATES (800) 333-2082
Page 514: raj82d00
441 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 fat, long. People were -- had been exposed to colored cigarettes. There's normally a -- a -- a -- a pattern that people articulate when you ask them that question, is there anything new and different that you'd like to see in a-- in a cigarette product? And one thing that -- that occurred to to us was that this -- maybe we can make this fat cigarette. Q. This wider-gauge cigarette was identified through this consumer and marketing study as something that people may try? A. Yes. Q. And it's correct, isn't it, that the age group which expressed an interest in trying wide-gauge cigarettes was the young adult smoker. Is that your understanding? A. No, that's not my understanding. I -- I really can't remember who -- where that -- that data came from. It was just smokers. I mean, could have been any smokers out there. Q. It's your testimony that you don't have a memory as to whether or not the marketing information you reviewed for the Camel Wides - should say before your development of the Camel HUSEBY & ASSOCIATES (800) 333-2082
Page 515: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that was his testimony: THE WITNESS: '.I. don't think that's what I -- what I said. BY MR. SOBOL: Q. Okay. Okay. Now, directing your attention to page 5248, the page reads, "Nicotine RSM Study Objective. Begin to develop an understanding of satisfaction in actionable product development terms to improve RJR position in the marketplace Do you see that? A. Yes, I do. Q. Is that consistent with what your understanding of the Nicotine RSM Study was all about? A. This is what the objective says. Q. Is that consistent with your understanding of what the Nicotine RSM Study was to do at the time that you were involved in it? A. Yes, yes. Q. And directing your attention to the next page, it says, "Nicotine RSM Study, Background," and under the third bullet point, it says, "Independent manipulation of nicotine will result in a better understanding than ever before 459 I HUSEBY & ASSOCIATES (800) 333-2082
Page 516: raj82d00
460 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 of satisfaction pharmacologically, physiologically, and taste." Do you see that? A. Yes, I do see that. Q. Do you disagree with that statement? A. I don't particularly agree with the wording of it, but I think the study would gain further information on some of the physiological, pharmacological, and taste attributes when the cigarettes were going to be designed. Q. What is it about the wording that you don't like? A. This independent manipulation of nicotine, I guess. I don't know if I would have worded this that way. Q. Why -- why does that wording give you pause? A. Because that's not what we did. Q. You used REST process prototype cigarettes as part of this study. Do you recall that? A. I remember experimenting with some REST prototypes, but I don't -- I don't believe that we used those in the Nicotine RSM Study per se. HUSEBY & ASSOCIATES (800) 333-2082
Page 517: raj82d00
I 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. Look at the next bullet point. Do you see, it says, "The REST.p-rocess allows for independent manipulation of nicotine and tar. This, in turn, allows product developers to manipulate draft in a reasonably independent fashion." Does that refresh your memory as to whether or not you used REST prototype cigarettes as part of the Nicotine RSM Study? A. As I just said, I don't believe we used the REST process in developing the prototypes for the nicotine RSM Study. Q. Okay. How did you develop the prototypes for the Nicotine RSM Study? A. My understanding or what I remember is that we used -- there were varying levels of nicotine tobacco -- varying levels of -- of high and low nicotine containing tobaccos in formulating the -- the tobacco blend used in the cigarette design, and then we adjusted the filtration parameters to hit draft and tar. Q. Do you recal]l authoring a study regarding the sensory evaluation of nicotine level prototypes using REST process -- A. Yes, I do. 461 HUSEBY & ASSOCIATES (800) 333-2082
Page 518: raj82d00
463 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 whole point of an RSM study. And it's - it's -- it's the -- the degree that one can make a orthogonal design or actually separate out the variables will -- will give you the -- the -- the better -- the better you can separate out, the better the variables, the more uncoupled the effects that you're looking at in terms of responses will be. If you -- if you cannot give a good response surface in terms of the design, the data that you get out of that will be not very good either. It's like garbage in, garbage,out. If you -- if you -- at this .point,-I don't believe that we had attempted to actually satisfy the design criteria. This was like a wish list, that if this happens, then you might be able to uncouple these effects. BY MR. SOBOL: Q. Did the Nicotine RSM Study permit you to look at as independent data points the physiological, pharmacological, and taste effects of nicotine? A. I don't know. I was not involved in HUSEBY & ASSOCIATES (800) 333-2082
Page 519: raj82d00
458 1 2 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that was based on desire for cigarette. Do you see,that-there on that page? A. Yes. Q. What does that mean? A. That was some kind of marketing term, I believe. Q. Are you familiar with the acronym DFC? A. No. Q. Are you aware of any methods that RJR uses to determine desire for cigarette? A. No. Q. How was the Nicotine RSM Study going to shed light on desire for cigarettes? .A. I'm -- I'm not sure. Q. And I want to direct your attention to page 5241. It's entitled "Animal Research." Does that refresh your memory as to whether or not RJR has conducted an animal -- animal research? Well, let me ask a predicate que-stion. Yesterday, did you testify that you're unaware of any animal research being conducted at RJR? MS. FEE: Actually, I don't think , HUSEBY & ASSOCIATES (800) 333-2082
Page 520: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 accurate copy of this memorandum that you wrote back in 1983? . .A. It does appear to be correct. It looks like somebody else signed my name, though. guess the secretary that typed it. Q. Was that -- was that a unusual process? A. No, no. I think that was -- that was - Q. It doesn't cause you any concern? A. No, no. Q. Okay. Can you tell me in general terms what the purpose of your writing this memo was? A. John Wilson had -- was interested in the topic of nicotine and nicotine analogs, state of the art. And he asked me to write down what I knew about this -- this subject. So, I -- I prepared a -- a small memorandum for him. Q. If.I could direct your attention to the- second page of the document, the third paragraph of the second page begins, "A great deal of work has been done on isolation of neuroreceptors since the discovery of the opiate peptides (enkephalins and endorphins) in 1975-'76. I HUSEBY & ASSOCIATES (800) 333-2082
Page 521: raj82d00
425 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 experimental prototypes that are new -- new -- new -- new cigarette pr.ototyp'es. Q. Okay. What's the work that you're continuing from last year or a number of years ago? A. Part of that work is to prepare some extruded material out in -- at a off-site location. Q. What kind of material? THE WITNESS: Can we -- can I ask you something? MS. FEE: Yes, you can ask me something. Can we take a break? MR. MAISTROS: Sure. THE VIDEOGRAPHER: Off record at 1:46 p.m. (Off-the-record discussion.) THE VIDEOGRAPHER: Back on record at 1:47 p.m. BY MR. SOBOL: Q. Doctor -- MS. FEE: Mr. Sobol, the -- you asked Dr. Perfetti a question, and the reason he -- he wanted to confer with me is that your -- you've touched on an -- an area that has trade secret application or HUSEBY & ASSOCIATES (800) 333-2082
Page 522: raj82d00
443 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 receive a royalty or a bonus for any of the inventions which you're.listed as an inventor and has --,have assigned to RJR? A. No. Q. And directing your attention back to Exhibit Number 33,. I want you to look at the third page of that document. I'm going to refer you to the fourth paragraph under "background." It says, "By building our knowledge base with respect to nicotine, as a key design -- design parameter, to R -- R&D can place the company in a more responsive position to act on identified consumer wants and product ideas to maximize volume and share growth." I suppose first I should ask you, do you recall the year which you-participated in the -- the drafting of this document? A. No, I'm not sure of the year. I don't know what the year is. Q. Approximately how long ago? A. I would say ten years. I'm not real -- I'm not -- I -- I don't know. Q. Do you recall the phrase -- nicotine being referred to as a key design parameter? A. Yes. 25 1 Q. And do you agree with that statement, HUSEBY & ASSOCIATES (800) 333-2082
Page 523: raj82d00
468 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 another kind of -- another -- there are some other studies that have been.done.on -- on the minor alkaloids. So, they're -- they're separate. Q. Okay. I guess what I'm getting at is, later on in the -- in the memo, specifically the -- at the bott.om of page 2, you appear to be recommending that further research in these areas continue; is that accurate? A. Well, I'd have to read what I'm recommending. Q. Sure. Take your time. A. Okay. I've -- I've read the article now. Q. Okay. What I'm getting at is, yesterday you testified, I believe, and -- and please correct me if I'm wrong, that in your 1978 memo, marked as Exhibit 6, you recommended that RJR undertake research with regard to enkephalins -- A. Yes, sir. Q. -- and endorphins? A. Yes, sir. Q. And I believe, if I correctly, that research was not, by RJR; is that correct? . That is correct. remember in fact, funded , HUSEBY & ASSOCIATES (800) 333-2082
Page 524: raj82d00
471 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 market. Q. At the -- the .end of page 2, the document ends with the last -- or this page ends with the last two sentences. "This information might be useful if nicotine is ever banned by the federal government as a harmful substance. The possibility is real and are alternatives are minimal." Can you explain to me why in 1983 you believed that there was a real possibility that the federal government might ban nicotine as a harmful substance? A. There was, even at that point, there was a lot of press in saying that -- that nicotine was a real bad actor. And there were scientists, like Mark -- Mike -- Mike Russell and a number of his colleagues that were presenting information that implicated nicotine in -- in -- in what I consider a bad way. So, perhaps I was concerned when I wrote this at -- at the time. I must have been concerned. Q. Do you recall why you believed that this information might be useful if nicotine ever was banned? A. No, I don't -- I don't know what -- HUSEBY & ASSOCIATES (800) 333-2082
Page 525: raj82d00
467 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Most of the work has been done investigating the psychophysiological responses._of the major alkaloids (morphine, cocaine, et cetera) on the neuroreceptors -- receptor of mammals. Most recently studies have begun on the minor alkaloids (nicotine and nicotine analogs)." I want to ask you, first of all, do you recall yesterday we discussed a memo that I believe we marked as Exhibit 6, a memo that you prepared in 1978 which was quoted in the Los Angeles Times concerning enkephalins and endorphins? Do you recall that testimony? A. I remember we were discussing that. Q. Is -- is the type of research that you're mentioning here in the third paragraph of page 2 similar to the research that y.ou were suggesting in that '78 memo? . This is -- it's describing some of the work that was done on enkephalins. This is what the 1975-'76 -- the first sentence describes some of that as alluding to that kind of work. The second sentence is not related to enkephalins and endorphins, but to work on alkaloids, major alkaloids, and then there is HUSEBY & ASSOCIATES (800) 333-2082
Page 526: raj82d00
470 1 2 3 4 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Let me just ask you, in your opinion, is nicotine important in.terms of satisfying the psychophysiological needs of smokers? A. As I mentioned yesterday, the whole smoking experience is based on ritual, sensory, and mild pharmacology associated with the smoking -- the entire smoking experience. So, there is a facet that some research in this area might be able to -- to help. Q. And can you explain exactly what you mean by satisfying the psychophysiological needs of smokers? A. No, I don't know what -- why I wrote that or what that really means. Q. Okay. Do you recall why an understanding in this regard would provide a competitive edge?: A. Well, only -- only in the fact that if we get -- if we had -- we-had smokers that were smoking our product, that liked our product because af -the ritual and the smoking experience and, you know, there is nicotine in there which does have a mild pharmacological effect, if we had something that we had a real winner of a product out there, I thought that that would help us gain more of the HUSEBY & ASSOCIATES (800) 333-2082
Page 527: raj82d00
475 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 cigarette, addition of nicotine to cigarette paper, addition of nicotine to .the+.t,op dressing prior to cigarette construction, addition of nicotine to process sheet material," continuing on the next page, "injection of nicotine to the cigarette rod or filter after cigarette construction, finally miscellaneous modes of application not specifically mentioned above." The -- the description of the various ways to add nicotine is -- am I correct that that was the effort to bring the nicotine in the mainstream back up to normal; is that correct? A. These are all the possible ways that Dan thought we might be able to bring the nicotine back up into the mainstream. I don't know if any of these were tested. Q. Okay. That was my next question. Do you know where the nicotine would have come from for addition into the cigarette filter, addition to the cigarette paper, et cetera? In*other words, do you know where you were planning on ge.t -- getting the nicotine to add to the products? A. I'm trying to see if it was d or 1 that we were adding. Okay. This was -- because HUSEBY & ASSOCIATES (800) 333-2082
Page 528: raj82d00
462 1 2 3 4 5 6 7 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. -- cigarettes? And it' s,y,our .memory that that was independent of the Nicotine RSM Study? A. That little study was done to determine if there was any benefit in using the REST process versus conventional blending techniques. Q. Let me direct your attention to the next page. This is "Nicotine RSM Study, Explanation, Longer Term, To understand the role of nicotine and consumer satisfaction, uncouple the effects of tar and draft to separate the physiological, the pharmacological, and taste effects of nicotine." Do you have an understanding as to why uncoupling the effects of -- I should say -- uncoupling the physiological, pharmacological, and taste effects of nicotine would better understand the role of nicotine in consumer satisfaction? MS. FEE: Objection. I'm not sure that's what that says. THE WITNESS: The use of RSM, if there was a perfectly designed study, would give you clear direction on the responses from the independent variables. That's the HUSEBY & ASSOCIATES (800) .333-2082
Page 529: raj82d00
474 1 2 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was it nicotine and did it make a difference whether it was d- or 1-n,icotine? Q. So, is it correct, then, in -- in looking at this issue, that you were attempting to come up with prototypes where the amount of nicotine in the sidestream smoke was reduced but the amount of nicotine in the mainstream product. stayed consistent? Is that correct? A. I think that was what this was about, yes. Q. Okay. A. I think we had -- yeah, I think that's right. Q. And is it correct that the -- the manner in which the -- well let me just read towards the bottom of the first page, the last paragraph reads, "Reduced sidestream delivery of 1-nicotine will be accomplished using cigarettes made with either low nicotine tobaccos or with denicotinized tobacco. Mainstream delivery of nicotine will be brought back up to 'normal' by the application of nicot,ine to various components of the cigarette. These may include one or more of the following: "Addition of nicotine to the HUSEBY & ASSOCIATES (800) 333-2082
Page 530: raj82d00
1 2 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 those aspects of this study. Q. Did you review the product of this study?. A. I don't know if there was even a final report written on -- on the study. Q. Well, let's look at page 5253. Did you participate in*generating the data for any of these Nicotine RSM Study response variables? A. No. Q. Are you familiar with Dr. Ingebrethsen's work on levels of pH and sensory responses? A. No. Q. Do you know that he's conducted that research? A. No, I did not know that. MR. SOBOL: Could we go off the record for a minute? THE VIDEOGRAPHER: Off the record at 2:56 p.m. (Off-the-record discussion.) THE VIDEOGRAPHER: Back on record at 2:58 p.m. EXAMINATION BY COUNSEL FOR PLAINTIFF 464 I HUSEBY & ASSOCIATES (800) 333-2082
Page 531: raj82d00
476 2 3 4 these were going to be very, very few experimental research cigarettes, I i.magine that Dan would have done most of this work by injection of nicotine bought from Eastman. e Q. But, again, it's your testimony that 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 you don't recall whether any of these applications were ever, in fact, tested? A. I have no idea whether any of these were tests. Q. Okay. A. The other point of this, none of this work would have been done in -- we had not gotten approval to do the work, and I don't know if there was any approvals granted by the HRC. Q. And through this -- through this document, you were asking for approval; is that correct? A. That's the first step in these things, yes, where we weren't spending any time effort. and (PLAINTIFFS' EXHIBIT NUMBER 38 WAS MARKED FOR IDENTIFICATION) BY MR. O'HARA: Q. Okay. And, finally, I'd like you to take a look at what I've marked as Exhibit 38: I HUSEBY & ASSOCIATES (800) 333-2082
Page 532: raj82d00
477 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 apologize in advance for the poor copy. Exhibit 3 8_. is .a.. interof f ice memorandum dated July 30th, 1990 from yourself, as well as Mr. Best, Mr. White, Karen Womble, Joanne Taylor directed to Dr. Lawrence. And I'll give you a moment to take a.look at this and again ask you if you recognize this document? A. Yes, I recognize the document. Q. Do you recall participating in the preparation of this document? A. No, I -- I don't remember preparing this document. Q. Does this appear to you to be a complete and accurate copy of the July 30th, 1990 memo to Dr. Lawrence? A. Yes. Q. And is -- is that your signature that appears on the third to the last page? A. Yes. Q. Okay. Can you explain to me in general terms what -- what you were proposing to Dr. Lawrence or what the purpose of this memorandum was? A. For some time, there was -- there was some work -- there was some preliminary done on HUSEBY & ASSOCIATES (800) 333-2082
Page 533: raj82d00
465 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 1 7- 18 19 20 21 22 23 24 25 BY MR. O'HARA: Q. Good afternooii,. Dr'. Perfetti. We had a chance to meet briefly yesterday morning, actually before we got started. My name is Chris O'Hara. I represent the states of Washington and Arizona in the actions filed by the Attorneys General office in those states against RJR and others in the tobacco industry. I just have a few questions. I'll try to make this very brief, just a couple documents that I'd like to quickly go over with you, following up on some of your earlier testimony both yesterday and today. And first I would like to have you take a look at a document that I am marking as Exhibit 36. (PLAINTIFFS' EXHIBIT NUMBER 36 WAS MARKED FOR IDENTIFICATION) BY MR. O'HARA: Q. This is a RJR interoffice memo dated March 10, 1983 from yourself to a Mr. J.B. Wilson. I.'1-1 give you a moment to take a look at that, and I'll just ask you, first of all, whether you recognize this document? A. Yes, I recognize the document. Does this look like a complete and HUSEBY & ASSOCIATES (800) 333-2082
Page 534: raj82d00
478 1 2 3 4 5 6 9 10 11 12 13 14 15 16 17 18 19, 20 21 22 23 24 25 carbonized materials as fillers for tobacco. None of those had very good flavor.. And Freddie Best had a-- had a -- an excellent idea, Ithought at the time, which was to extract the by-products before you pyrolyze them, form the sheet, and then add the material back onto the -- add the flavorants and extract back onto the formed carbonized sheet. Just thought that would have -- his thoughts on that would have been to improve the flavor of this carbonized sheet that he was looking at. Q. So, is it correct that in removing the materials that the REST process used, and I'11 refer you to the summary that appears on page 1, if that.refreshes your recollection. A. Yeah, I'd need to read this in detail. Q. Certainly. A. I think I -- I read over it. Q. Okay. Again, I just want to make sure that I understand the process that is being discussed in this document. And, first of all, is my understanding correct, that the REST process was HUSEBY & ASSOCIATES (800) 333-2082
Page 535: raj82d00
480 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. Where is that located, sir? Q. Actually,_-the.-- the very first sentence under "objective" reads, "The objective this -- of this study was to provide data to support a disclosure concerning a novel smoking product with reduced TPM"? of A. Total Particulate Matter is what that stands for. Q. Do you recall why an effort was being made to come up with a novel smoking product with reduced total particulate matter? A. No, I do not. I can't remember it. Q. Do you recall whether it had anything to do with health concerns? A. No, I -- I don't think -- I don't think that had -- I can't remember the -- to tell the truth, why Fred was doing this, except for what I told you at the beginning, was a way to bring back flavor to other carbonized materials that. didn't have flavor. Q. If I could turn your attention to the fourth page of the document ending in the number 6990 in the lower right-hand corner, under the "discussion" heading, Roman numeral III, that portion of the document reads, "This report HUSEBY & ASSOCIATES (800) 333-2082
Page 536: raj82d00
472 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 what I was getting at at that point. Q. Okay. _ A. No. (PLAINTIFFS' EXHIBIT NUMBER 37 WAS MARKED FOR IDENTIFICATION) BY MR. O'HARA: Q. Okay. Now, I'd like to ask that you take a look at what I am marking as Exhibit 37. Exhibit 37 is a R.J. Reynolds Tobacco Company interoffice memorandum dated January 6, 1987 from yourself and a Dr: Kurtz, K-U-R-T-Z, to Dr. John Reynolds. I'll give you a moment to take a look at this and ask if you recognize this document? A. Okay. I've read it. Q. Do you recognize this document? A. Yes. Q. Okay. Does this appear to be a complete and accurate copy of a memo that you and Dr. Kurtz prepared on January 6, 1987 for Dr.- Reynolds? A. It appears all to be here. I've signed it. Yes. Q. Okay. Can you tell me in general terms what the purpose of -- of this memo was, why HUSEBY & ASSOCIATES (800) 333-2082
Page 537: raj82d00
469 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q. In this memo, are you again urging RJR to undertake similar.research with regard to those two items? A. No. I'm -- I'm -- I'm recommending that we get a better understanding of the neuroreceptors of -- for nicotine, how they work, where they are, how they interact with the body. So, that was what I was recommending. I thought it was a good idea for us to get some -- some knowledge in that area. Q. Okay. But if I understand correctly, that understanding would not be based upon research regarding enkephalins and endorphins? A. No, that would not be the same thing. Q. Okay. At the bottom of the third paragraph on -- on page 2, you write, "It took very few years to isolate and attempt to understand the neuroreceptors and action of the major alkaloids. This information has been extremely useful to the medical community. Any information on the action of nicotine that will help us understand why people smoke and why nicotine is important in terms of satisfying the psychophysiological needs of smokers could be very important in creating a competitive edge." HUSEBY & ASSOCIATES (800) 333-2082
Page 538: raj82d00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 was -- I was trying to work with him in terms of finding which variables_-.we could actually control and then -- you know -- in -- in a mathematical way and then getting into how -- if it were possible, to make any of these experimental prototypes. Q• it? And RJR still uses the RSM, doesn't A. We haven't used it in a long time. Q. What were the design parameters you were attempting to hit? A. I can't remember. Nicotine was obviously one of them, but I can't remember the other. A. Were you attempting to hit -- Oh, draft was one, nicotine draft was one, and I guess tar. Those were the variables. Tar, draft, and nicotine. Q. And with regard to the nicotine parameter, did you try to develop experimental prototypes with varied levels of nicotine? A. Our approach to this was to use varying levels of nicotine tobaccos and blends to try to meet the statistical design -- experimental statistical design here. Q. And the Nicotine Control RSM Study, HUSEBY & ASSOCIATES (800) 333-2082 457 i
Page 539: raj82d00
1 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 used in -- in coming up with these prototype cigarettes such that ni.aotine-and other flavorants in the.tobacco was extracted as sprayed dried extract in nicotine concentrate; is that correct? A. The REST process was used in terms of taking the tobacco pulp and separating the extractables from that, yes. Q. Okay. And -- and the -- the nicotine and the other flavorants were preserved in -- in the form of nicotine concentrate and sprayed dried extract;.is that correct? A. Based on the flow diagram, there was a sprayed dried extract that had nicotine in it and also a denicotinized sprayed died extract on -- the last four digits is 6992. Q. And that is nicotine from the original tobacco, correct? A. Yes.. Q. Okay. And then is it correct that that sprayed dried extract and nicotine concentrate is then added back to the carbonized tobacco? A. The carbonized sheet that was made from that pyrolyzed tobacco, yes -- I mean -- the carbonized tobacco. Q. What is TPM? 479 HUSEBY & ASSOCIATES (800) 333-2082
Page 540: raj82d00
482 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 these prototype cigarettes, that the quality was excellent? Or let me as.k a.different question. Do you recall what was meant by the quality being excellent? A. Yes. What -- what Freddie was talking about here is that they -- they were well-packed. There wasn't -- there wasn't holes in the -- the packing as -- as this term was placed in there. The -- the ladies that prepared these was Joanne Taylor and she does an excellent job at preparing prototypes with unusual materials. Q. Do you know what was meant in the very last sentence on this page, which reads, "Unequivocally, the products qualify as cigarettes"? Do you know what that reference is to? A. I'm not sure exactly what Freddie was getting at with that statement, no. Q. Okay. THE VIDEOGRAPHER: We have about five minutes on the tape. MR. O'HARA: Okay. Thank you. BY MR. O'HARA: Q. Do you recall that these -- these prototype cigarettes, in addition to producing less HUSEBY & ASSOCIATES (800) 333-2082
Page 541: raj82d00
483 1 2 3 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 tar and less total particulate matter, also generated less carbon mpnoxide? And if it helps, I'm --.I'm looking at the -- the last or the fifth page of the document ending in 6991. In the -- in the middle of that top paragraph there's a sentence that reads, "The test products also generated less carbon monoxide much -- (much. less based on total weight of starting material) compared to the control." A. Well, based on the data table, I guess Freddie could have stated that. I think that was where that data came from. Q. So, if I understand you correctly, does the -- does the data table support his suggestion that these test cigarettes generated much less carbon monoxide? A. I'd have to calculate out the CO tar-to-nicotine ratio. It's not included in this table. Q. The very last paragraph on -- on this page 5 reads, "The CSSDENC product provides a very flavorful smoke. It burns and ashes well with no sparking of the filter during puffing." Is it your recollection that -- that the smoke generated from these test products was HUSEBY & ASSOCIATES (800) 333-2082
Page 542: raj82d00
473 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 did you write this memo to Dr. Reynolds? A. Dr. Reynol$s was the chairman of the Human Research Review Committee, and this was a - a description of research which we're hoping to do at -- in the Sensory Evaluation Division. I must have been in the Sensory.Evaluation Division at this time. It talked -- it is very, very broad. And it asks for a number of ways to apply either or -- or combinations thereof of d- and 1-nicotine_ to a variety of positions on the cigarette and to look at a number of end points, sensory end points, as located on the second page near the bottom. And this was the first step in terms of preparing a request for review by the Human Research Review Committee. Q. And is my understanding correct, that the main purpose of this research would be to investigate ways to cut down on the level of nicotine in its sidestream smoke? A. I-- I think one of the complaints that -- that -- that Dan talked about here in the beginning was that there's irritation and it was assumed to be due to nicotine in the sidestream in the ETS. And the -- the question, you know, really HUSEBY & ASSOCIATES (800) 333-2082
Page 543: raj82d00
484 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 flavorful? A. I can't remember smoking them myself. I can't remember. Q. Do you recall the reference to the fact that these test prototype -- prototype cigarettes apparently burned and ashed well? Do you recall that? A. I remember seeing them smoke and they did ash well. Q. Okay. Were these -- do you know whether these -- these prototype cigarettes were ever commercially marketed and produced by RJR? A. They were never commercially marketed or produced by RJR. Q. Do you know -- do you know why? A. No, I don't. Q. Do you know whether they were ever tested in the -- with consumer groups? A. I -- I'm almost certain that these were never tested anywhere else, because we only produced a very small quantity of this to -- for -- to provide supporting documentation for this patent disclosure under the objective. That's why we were doing this. We only produced a small amount. Q. Would you agree that if RJR could N HUSEBY & ASSOCIATES (800) 333-2082
Page 544: raj82d00
485 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 produce a cigarette that had very flavorful smoke, burned and ashed well, g.ener.a-ted less carbon monoxide, generated less tar and less total particulate matter, would you agree that consumers may have.been interested in such a product? A. No, I would not agree. Q. Why is that? A. Because the material is black and on tests of other black sheet material that we looked at or that were looked at in the research and development on sensory panels, it would pick it up every time and comment on the unusual filler that was there. And that was, you know, something that they disliked. It does not.look like normal cut filler. Q. So, the -- the -- the test consumers could actually see black material in the cigarettes, is that -- A. Yes. Ln ~ Q. Do you know whether those test m corisumers were ever informed of any potential health benefits that may have accompanied this black material? A. I'm not aware. I don't know. 25 I Q. Do you think that if -- if those test HUSEBY & ASSOCIATES (800) 333-2082
Page 545: raj82d00
I 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 consumers had been informed of potential health benefits, that that may_,have made a difference as to whether they were concerned about the black material? MS. FEE: Objection, speculation. can't possibly know the answer to that question. THE WITNESS: I have -- I -- I have no idea. MR. O'HARA: I don't have anything further. Thank you for your time. MR. MAISTROS: I'll get you out of here Denise in five minutes. MS. FEE: No, I'm not going to make it, but that's okay. MR. MAISTROS: Yeah, you will. Greensboro airport? MS. FEE: (Nods head.) MR. MAISTROS: No more than 20 minutes. THE VIDEOGRAPHER: This concludes tape six of the deposition of Dr. Thomas Perfetti. The time it 3:39 p.m. (Off-the-record discussion.) THE VIDEOGRAPHER: Back on the record 486 HUSEBY & ASSOCIATES (800) .333-2082
Page 546: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 488 at -- at RJR has to have some bottom line to it . Some -- someL• of those things may take ,longer time, but you should have some some benefit to the bottom line. BY MR. MAISTROS: Q. I know. I'm trying to clarify what you just testified to about an hour ago, I think. .Is it your testimony that none of your nicotine research was related to increasing the sale of cigarettes, yours personally? THE VIDEOGRAPHER: That's it on the tape. This is tape number seven of the deposition of Dr. Thomas Perfetti. The time is 3:43 p.m. BY MR. MAISTROS: Q. Let me rephrase the question so we can begin the.tape. Is it your testimony that none of the Ln nicotine-related research you have done in your 20 ~ m years -- 21 years at Reynolds has been done for the ,~ m ~ purpose or effect of increasing the sale of ~' Reynolds' cigarettes? A. I don't know if any of the research that I have done on nicotine has been used directly i HUSEBY &'ASSOCIATES (800) 333-2082
Page 547: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 A. I am a scientist and I am interested in technology more than,_.marketing. .Q. So, when you use -- when you use competitive edge in Exhibit 36, you were referring solely to technological competitive edge? A. This was a long time ago. I'm not sure. I don't know. MR. MAISTROS: Thank you. I have no further questions. MS. FEE: Okay. THE VIDEOGRAPHER: This concludes the deposition of Dr. Thomas Perfetti. The time is 3:47 p.m. (Signature reserved.) (Whereupon, at 3:47 p.m. the instant deposition ceased.) the taking of -------------------------------- Signature of the witness SUBSCRIBED and SWORN TO before me this ------------ day of --------------- -----1 19-- ------------------------ -------- NOTARY PUBLIC My Commission expires: 491 HUSEBY & ASSOCIATES (800) .333-2082
Page 548: raj82d00
492 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 E R R A T A S H E E T RE: Small, et al. v. LQ.rilla-rd Tobacco, et al. DEPOSITION OF: Thomas A. Perfetti, Ph.D Please read this original deposition with care, and if you find any corrections or changes you wish made, list them by page and line number below. DO NOT WRITE IN THE DEPOSITION ITSELF. Return the deposition to this office after it is signed. We would appreciate your prompt attention to this matter. To assist you in making any such corrections, please use the form below. If supplemental or additional pages are necessary, please furnish same and attach them to this errata sheet. Page ____ Line ____ should read: Page ____ Line should read: ---------------------------------------------~ Page ____ Line ____ should read: Page ____ Line ____ should read: Page ____ Line ____ should 25 1 read 333-2082 HUSEBY & ASSOCIATES (800
Page 549: raj82d00
481 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 describes a method for making a cigarette from all tobacco or tobacco deriy.ed materials that delivers full tobacco flavor (reduced flavor, if desired). The products of the invention exhibit good nicotine transfer with tremendously reduced combustion tar." Does the reference to the tremendously reduced combustion tar have anything to do with the reduced total particulate matter t hat we just discussed? A. I believe that was what Freddie was talking about in terms of reduced TPM, reduced combustion tar. Q. And isn't it correct that the majority of the health concerns that had been raised regarding cigarette smoke concerned the tar fraction of the smoke? Is that your understanding? A. That's what I've read.. Q. Okay. Down towards the bottom of this discussion section on page 4 that we're just looking at, there's a sentence that reads, "Although the cigarettes were handmade, the quality was excellent." Do you see where I am? A. Yes, I see here. Q. Do you recall that the quality of HUSEBY & ASSOCIATES (800) 333-2082
Page 550: raj82d00
1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Page ____ Line ____ should read ------------------~_---- Page _y__ Line ____ should read: ---------------------------------------------- Page ____ Line ____ should read: ---------------------------------------------- Page ____ Line ____ should read: Page ____ Line should read ---------------------------------------------i Page ____ Line ____ should read: Page ____ Line ____ should read: Page ____ Line ____ should read• '---------------------------------------------- Page ____ Line ____ should read: Page ~___ Line should read: Page ____ Line ____ should read: Page ____ Line __ should read: GML 493 I HUSEBY & ASSOCIATES (800) 333-2082
Page 551: raj82d00
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CERTIFICATE OF REPORTER STATE OF NORTH CAROLINA_.) COUNTY.OF GUILFORD ) I, GERALYN M. LAGRANGE, the officer before whom the foregoing deposition was taken, do hereby certify that the witness whose testimony appears in the foregoing deposition was duly sworn by me; that the testimony of said witness was.taken by me to the best of my ability and thereafter reduced to typewriting under my direction; that I am neither counsel for, related to, nor employed by any of the parties to the action in which this deposition was taken, and further that I am not a relative or employee of any attorney or counsel employed by the parties thereto, nor financially or otherwise interested in the outcome of the action. -----~------ GERALYN WZ LAGRANGE Registered Professional Mporter Notary Public in and for County of Guilford State of North Carolina GEftALYN M. L_1--jR,4?~ 3c NOTA,,Y P'.;31_!C GUlLFCRD COUNTY, *!~ Comm!ssion Expires Ju!y :8, .^% 494 HUSEBY & ASSOCIATES (800) 333-2082
Page 552: raj82d00
487 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 at 3:41 p.m. RE-EXAMINATION BY C.OUNSE•L FOR PLAINTIFFS BY MR. MAISTROS: Q. Doctor, to your knowledge, in your 20 years at Reynolds, did Reynolds ever undertake any research whatsoever to develop flavorants, additives, top dressings, top coatings, processing aids that had binding properties similar to nicotine? A. I -- I don't know. Q. Did RJR ever undertake any research to attempt to determine what the binding properties of nicotine were? A. Yes. •Q. Did they ever attempt to develop additives or flavorants that had binding properties similar to nicotine? A. No. Q. And is it your testimony that none of your research ever related to or had the purpose of increasing the sale of cigarettes or no RJR nicotine research had the purpose of or was related to increase in the sale of cigarettes? MS. FEE: Object to the form. THE WITNESS: All research that we do HUSEBY & ASSOCIATES (800) 333-2082
Page 553: raj82d00
I 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in terms of our products to increase our market share. Q. I'm not talking about the end results. I'm talking about the purpose in commencing the research. Is it your testimony that the purpose in commencing your nicotine research had nothing to do with increasing the sale of RJR cigarettes? A. Yes, that is my testimony; that my research was not directly related to increasing the sales of our products. Q. Have you ever done anything'at Reynolds in your 21 years that had the effect of increasing the sale of Reynolds' cigarettes? A. Yes. Q. What was that? A. Some of the work that I did on the effect of menthol and moisture on the coolness associated with mentholated products. Q. And when you commenced that work, when you initially commenced it, there was no intended purpose of hoping to increase the sale of cigarettes through that work? A. No. We were trying to understand what coolness was. 489 HUSEBY & ASSOCIATES (800) 333-2082
Page 554: raj82d00
490 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Q And when we refer to Exhibit -- what was it -- 36, we had tal.ked.about a competitive edge that had nothing to do with increasing the sale of cigarettes? MS. FEE: Object to the form of the question. What are you asking him specifically? BY MR. MAISTROS: Q. When you said in 36, "any information on the action of nicotine will help us understand why people smoke and why nicotine is important in terms of satisfying the psychophysiological needs of smokers could be very important in creating a competitive edge," you weren't suggesting that they undertake this research for the purpose of selling more cigarettes? A. No. Q. What did you mean by "competitive edge"? A. There's a technological competitive edge also, sir. Q. So, as far as you were concerned, you were only interested in a technological competitive edge. It's not an economic competitive edge; is that true? HUSEBY & ASSOCIATES (800) 333-2082
Page 555: raj82d00
L° 13/`'/ R 12 -tF•.~'~,,.* ,s ..e.t..OQ ,y . .~ . it•f~ ..,.d ~ie "Ll ..J-- . ~ ~,.~. .~~ Gb,,...Q ' . -~.rr1?.~.1? RJ R15929
Page 556: raj82d00
. I C.
Page 557: raj82d00
..,4-. e-l •7;..4- . ,, ..,~..~..~~- _r.,~w..~.,. ' ---- -- - .o . • . r.._.w. .. .a•AA .~ ... _ .. _ . ._ ._..._.. .. ~_~_. , :. . RlR15936
Page 558: raj82d00
f . 0 -W- e. l~ ~- ~.._.__.~ PVWAWKM ~ ~ ~w ~ ln N J J m ~ v N Ut O _~.-.... ..~--.~~.--. -. _.. - . .. - ...~ A v W N • ~ RJ R15937
Page 559: raj82d00
r+ -%•.•. •ri //A. 1 +t •1 rr..~ ~..rr . ;. .~ • ~ ~' ~ "V 0 ,. . RJ Rj 5927 ,GZ.G-w .'. 'T~.A.
Page 560: raj82d00
N.:! y
Page 561: raj82d00
J -- ~.~,•a-~` .. ~. ~ . .._._. _. _._. __ _ ._._._._._.... . . M..•. i • ;x + /-Ln v ~ RJR15925 N O N P r v W • N .- f
Page 562: raj82d00
71
Page 563: raj82d00
~•~.,,. . dz,~,-~,. ;~.,, v,,~ •"Oo RIR15931 517~0 1709
Page 564: raj82d00
Page 565: raj82d00
Page 566: raj82d00
2. Lr r`---- 51770 1726
Page 567: raj82d00
A / . ~ . . .. :. . _ -- ~ ~ . .._~....j_ .. ~.~.... _.~ . ...~._~~rl.'~/.....~A~a.~..Y.- • -Y. _. _ • ._. ~.. ~ ~ ~...~. . ... ~..r_1_ ~_ .~ . . . . . .. . .. _ _ . _~. _~.. .. _.a.. [
Page 568: raj82d00
T ~w-4 ~.,....~-A ~ T! NAW ~j ,t, ~ . ;ol.. ~ ~~. . ellll-~: A .!O .~..'~.~ .~-e ~ .r.....-e ~ ,.e-~rQt ..t ~.~:-s~e%~ vz~ ., 51770 1710 RIR15932
Page 569: raj82d00
'*q. .... I r O N N O O
Page 570: raj82d00
. „ Os ~ a..t.~# ~.... RJ-R12364 .
Page 571: raj82d00
A probable or deduc4d answer to these two questions is that Philip Morris has a me~n~ of.controlling cigarette nicotine content, while other tobacco companies qo not. The-mechanism most--likely involves flue- cured tobacco since currqntly it is the largest single contributor to tobacco smoke and tobaccd blend nicotine content. :ki Xc: /or..W. M. Henley Ms. L. S. Lewis Dr. T. A. Perfetti Dr. D. H. Piehl ~ ~ RJR12925
Page 572: raj82d00
. . _. ~. _ . .... ~ .. . ~ . _ .~ .. _. .
Page 573: raj82d00
Page 574: raj82d00
RJR12368
Page 575: raj82d00
RJR12367
Page 576: raj82d00
----~-•.-.-~.......~.~...~.._........~.........._....~..,....,.._..~ ....~..~,.~.....-~_. > cz.,'.JQ . :(. l, f --- i."~•': 0 Poo ~-A ..~.. . RJR15926 I i . ._; ~ 0 N P V V W • W i
Page 577: raj82d00
RIR12373
Page 578: raj82d00
y , ' '.. 'POW` ~,# ~~.~+2.:A N~ , . .. - . .. . . _,i I~, ''.G-o" , y,"01..%C-P... e...:: . .: 12360. - eol4vil." .az. 19 80 51770 1720
Page 579: raj82d00
"Iv~ oeOV.VU • 4 ~.. 140 ~~ ~~ ~ ~ . .... .. . . . :~.. . . *S111"'l~ X ~ • ~ P•wcaww r • { ~..~ . ' ~~l `iO I, , ~IV+'riC~.7 1~ ~ A I . • • / 00 51770 1711 N 0 N a .1 r w ~ RJR15C}3 i
Page 580: raj82d00
./ f, • J . , . ~. /~/,~:r~'«:, t'«:,t 7pM X4 F~•A,- W&i ~4 ^-; ; ~'1?a ~ - __..lo•dif Ay 244 . .:'"'- -. 1.37 y,o l~.S _s.f.. . . .1 q.f ._l•.30 ..~.. Sr.!' .ay.o r-= /.4 8, o Aaf Pv ~ . Z:?. ._ _ ... 14.7 g, o AvO? .- 1.v 14a .t a.1.7 © . 3.3 16.? g. l~. Al.N --- 17.1 7.f .20 0.19 3.g 1L.3 ! • vf !fll l6.3 ~ ,2.2. 7.0 ~-- o, r' A./ . 13.1. ~ 000, ~ . . F-r-a a+ P-~ d'~•~f/V.,--•:~• r~_'`'ft .-~i.. 09' N 0 N A r r w N N RJR15935 I
Page 581: raj82d00
80LT OLLTS I ^ V . r ~ : ~ .. ...._. . a . a.o.o '6 s/c •C.) . . . .... ~ ''`~`~~ _.. . -.$~ 0£65 6a ra ! . _ a-~-'--'-r:'J.- --•, ~s. . -P--%-y-0-k. (r) 0 PEW
Page 582: raj82d00
~~• ~ . ~ a..,.:.~~ .~..u.8~... e.~~:~ . `T e ~ .; . a.. '`.S1JL RJ R' 5928 51770 1706
Page 583: raj82d00
RJR1Z369
Page 584: raj82d00
TA8EZ 11. • Smw AJ~LII.Y~S:...r . ! MIGO"f ~ ti~ '' ~'ttOSPNATE. ~....w. : I LiBht Lheet Source of Sheet Msterial ~-PJR• G7 (1980) : Msrlboro (1979) . •wetit (1980) O . ~-aj Cambri,dsa.° ~ 0) .(.~~j. Z.O; mS Cerobridp ,_ ) 0)0) 4.6=a,5. Caiobrid~~~ .. ";'". . e b ., AMW :...a No , csn sheet in asw of ~_hs Cabridn ci6amttu. 1.73 238, 1.76 .83 L 1.99`; 1.92 Dark Sheet (CGst Sheet) 1 N-i t rte : Pho~ sph, ste 2.52 4.93 2.38 4.70' - C c •c Average oLtjiplicste deteaaibstiar~. . Pesc.at ~~ ~frr of nieoti:a frai thi6. sheet to smoke 19 6..1t. Thi3 is ~ d.temitw4 _for C4zblidtt pspr•typ. sheet. . Sheet).. . ~.,.. ~...~._ Ni `' titu~ : = 1.52
Page 585: raj82d00
R:rt}?i> -% _ - ~~.~~: ~'Li~ ~~/. Lt .j~.~a ~ ~-~r ~st~-.." 71 ~_;i~i"r• r /Ai%r~~ ~~/.~~ .i t~~ 306359
Page 586: raj82d00
I he ,•» wev1/ 11b tp oletuts erlut eddtt/ona1 1ntOtNt/on ~!i111~e~.ped. ' ICeie. Tetealf0~tilttitf .:. on ovr d/tfMon en-july ld, 1ltt, v/~ ~et orea re OePer en CovlrNn. Mliltep you end Or, u11f~j hwt htd en o0dertunlty to rer/tw eNo .'' or.' c. It. olwree .. [• . - , . . ~.. T Atteehed e?e Oosi,tten'.0eoert 1eter16In0 evr•retlenetf ~or u:tnq the tollew n' edlStlves;ln itJRT toetcto.llever_tornwlft/onet S Mn~oni• ',,~ ifoel ~'bcterfellde ~--.:~ ....., ~ ~ © © ,vk•.,.-. 9
Page 587: raj82d00
n' Subject: _ To: Dr. R. A. Lloyd W, Nicotine in Philip`Morris Products Date: From: September 20, 1979 W. J. Casey Several in-house studies contain analytical data which relates to nicotine content in Philip Morris;products. Selected results-from both Quality Control reports and six-city competitive brand tests are sunmarized in Tables 1, II, and III. It will be noti;ced tfiat the six-city data (1'able III) confirms the data found in Quality Control reports (Table I), i.e.,_Philip-Morris p'roducts have lower nicotine, in both the tobacco blend and in the cigarette smoke, than comparable R. J. Reynolds products. Tabies I and II contain data for..-representative Philip Morris and R. J. Reynolds cigarette brands which are-grouped by FTC."t•ar" delivery.numbers. An overall average for each group.-was calculated and these values are compared ~~xt;,.~ in Table IV. . . . 3JCiF}:.Y}iy Ammi >0 T re two striking features,obvious from the comparison made in Table . : . varies ~ whether the balculation is.made peri-ci9arette or per puff.) . 0 jAW n f c gare tes,l t.e.,`10-19% less. (The percentage difference (. C sidering 12 P~ilip Morris brands and 16.R. J. Reynolds brands ~+lre i sistentl .es nicotine in smoke from Phil ip Morris cigarettes a- ~ ( sidering the ~obacco b]end, Philip Morris not-only maintains an overall tdwer nicotine level (9% less)!but, for the 12 brands surveyed, they were able to maintain a m~c-h more°constant nicotine level than was found for the 16 R. J. Reynolds products examined. (The relative standard deviation:fQund for nicotine in Philip Morris cigarettes [Tab1e V]'indicates.their values ere 72% more consistent than those found for R. J. Reyootds cigerette'blends.) Ywo questions arise from this latter comparison. ; (A) How can Philip Morrls maintain a more constant nicotine value than other tobacco companies are able to maintain? Should they not have the same crop to crop, grade to gradei-belt to;belt tobacco variation? (The most recent entries in Quplity Cqntroi-reports are data for certain months in 1979. The tobacco % nicotine:values.for 8"mid-range" Philip Morris products again average 1.54, valuesjfor -R.:J. Reynolds 4"mid-range" products averaged 1.93, or +5% fro(n 1978 aevels,..and the.9 Lorillard products,so far in 1979, average 1.84% nicot%ne, or an increase of +8.2% over 1978 values.) (6) It is known that{Philip Morris purchases about..15% of its flue-cured tobacco as "PM Grade 66",;which is high in nicotine. Ir1 which product do they work off this high nicotine #1uo-curetl tobacco? RJRI FORM 242:-Rw. 7/70 ~ N ~ J m ~ J W ~
Page 588: raj82d00
r . ti~~+111r~~1x ^ ; :uw.n Am. teit ~ +oWLtN teweeeNO..243-*.*'"e~,,•„ w. ». 1940 h.s ea~.t1s~nr. tAe" ahlt mr1.a .eiwt/au rtN fer wM/at1~ AI~`IW.itIfM tNeqe_irMiiet wyiM Niha af arf~M/e , eetfti{y ,. ~M: ~r11~ aetMqtefi. ' ~ . _ 1i MNiAt itMfr. MfJMq if.1~rM1et1M~ Mr'~t sIMiN r+N eJ~e ~lii+~ tet.aM t~itr.t~r.r ti~itt Zewpa ~r.r fl~e u~i.t+M:r ~;~~aiiw~r~.i~:ii.t~:l~ ~elw.. faaw+r'11MI~ZY;~i+» irMet/M eeMlt/eq uM eM NeeMItlmt af tw i1~r1tN1 t~A 1~eNAitf /e tftte i. „WU 1 Alt~IttAtt% UM11•f ~ ~.~...tiAI taiARLt1t ~fA1~Llt ~ r~,...~~,.,~~ rAMts A• t~~~ 1N tp~ i i~wep. SO~iO ./l. Nwt i!0' 1t. ~Ne. M}eniA MIt h~elt 1• MeMift 1A Neie tt~t wwtr f•!A ? fM~t~It1M : M M.1M/1tN tewea >a . 100f'A.M1aN tNWea l+y Matt A ia ; t,1rWI.W tohtM ty Preats I L•ttt1t•A CeMPO1, fAft tllter tUM (M eeMA1tt/en) L•1iTim ,O1f~ 1/1Nr t1eM Hth itf awMtetd'tewea 4 jrMUt i t-tt1)i•C tm lllttr l1eM .ItA i!S +wlmlfyl'tUNieN PLANTM . O"aff 1 - b Metti A 0090 RiR 0 ~ O • N : RWNlM1~• 7WI~R / ~ +s OI~fR •r= .•l ~f yNKw. C. b..eRet Ati~sTtRi~ ~~er. Rs.e~RtR
Page 589: raj82d00
41 ( . OWN."ad"`+ Iag. t • .... I fM E/hnetn MN. HM1tN sawtt/Mf .M •tbt wt4 aMNwtN ~MM.1. ._.1M IMef Utt Mef nM r/tA islwAtfs TA!N a,1 sYM;1/1 INiMm it _4-1 Nf/tatU1/ Srftr. Table i{ N'ttMM *0 sob li.t/tiM .f ltiA NilAttt. Topt 1t1MN Tt~ : s~cc ~a, f,,,/,r,r~ 1TC LWJW ~ ". 1:.` ~ J, >23 ~_::, 1147184 ii`:~ 0:/ ls : C qet Ms nOutN tM t1.a _t. 661016 htter frwrt~. W ~NOWM~ •.0'I~eM"'a+R uIrw, hM_ '- ~1~t1~Io1M y!. TIIf ~W1t r7. Nr nf+R~ ntti vp Mi ~ ~ i ~t M ~ l alt a r~ri i e /i N . L•1t1i•i 1.4471110 ~ N1Nti• 1111111111011 : 01'..Ah~ t.~apei ,,,~ 14 0 it W3 1 F f f10~ a I ~a 1~~0 . " 11.1 0 1!1
Page 590: raj82d00
•.: s~b~.et 0 306360 a . A .J : .'o. ~ _!•/J•c si 0 . ~ i . • I f ~IIAM T, '-~~ a 0 ! s. 0 ,. ll ® ~ ~ jit ~ e' v tr, r .. , ® iIONATYRE AND DATE r - X Y.~w i.n..- . .; „ ---~, k s. ~ • . . ~.«.,: ... . lMs . • •r ... . u Q EiT00 D F-~ v J ~ r ~ r N rK • : a o .
Page 591: raj82d00
E ffz,,t ./- i 7w ~,.,Q ~,,:.(~s•~ WT!'M W+~ T.~.~ ..TM ' ' > 1 ~1 J=..W&g : !A • ff .~A. 3. Jr•oy. 3.7y 9,Q4 . 3,74 /~ ~Sf ~~ ~.7~ . . . ~~. - . ~s 9,ys O. Sos o. 93 /. Q'~ /.QD 3. 7y I,q•A I•y )J,9 !29 7,41 ./,X fIN jo.3 6.s !. ~.. y9 . Q, y /O.f 9, P AV ~ . Irmo,-& •- f7 ~~ . I O a ~./ V W N .r RIR15934
Page 592: raj82d00
! . ; wt4r, IoC tow".Nieotinc, to R~t~lYs »mtt .~ ~i, Avtrs=t ;~ ~ Avora~t! /~ ~ ons>~Or A!lt~i ~3~1f ~ t ~ ~1~:roltrin, uQ - 4 ~~ `~o AhrniL, u; b ~lyiro;en Cyin'A"Mo; ~ k4wisoAronft, us ONA" ? `~8cn=o'.)DY'm=, nA aou: 1.111 P.12 ~ PD, tn:hea Water Su:.rs, : : Il l CO' 3 ~~: ~: ...,...r........... ..• ..~.r......_ • . +,.
Page 593: raj82d00
t IRtJlAt CUNFIDENTI~'L MtMrso Ola R. tot % tlisal.th A, t..d O4Iartsa.ce luMassstal m0 tjOM, 1913, 1/.. !0 { N.. .t tal..i 36 tr.jst !L. t ~ •' SAert tors t .a~6sy ~ w a . .0, aaat 1/ay !, 3f1).e ~ Ifat.l..ti htas 1 732•31 i 204 ~~M1! 001•2! W •11 .4! , lts-26 , 3~3il-11 OatNt t/1t/3t t~~/t!/i2 M.tNS b~.rtat ~~ree .~. ~. ~ ;.r ~ m,t ritl ow oars cxotxusts - % :ai.uu .~e..t'lle aM r~Viw v3 iM }ett vrrk aM ~er..wat~lat s.t w astss ses~asaate rY ..eta•r.1atN aa.,e..ls. .. z lam *. ~i a.rrasl.. }uraritt~ sLt =t1. taleltlla e..•rp4 Mttas tfa • . .tset 1978 tk 4440 e.:~rr. e.sela~ et st~senet..s..k~/...ds..t~ r as w .N.uts osoi Nitcuttt .sepos.ttl. 'r'M- ~Al. trtitce~ M r.re t.lM~s r.ret. ~ ~.t t.Msee t1a•.rasti`i=e e.t tselrl.d te n .~.. ~ lfLt aalt !a "1.t.. e N :1kA,firre• t~wI ~ _ ~, 0Avg WO&..10. N~eeec ~ Ate.fitte'ae1 Ag'ORTtA l_. °0089 RJR
Page 594: raj82d00
:-, The committee plans to-re-.convene in mid-January,-1987, and orga~nize the above inf.ormatiQn °-ond -+-o begin designing an program. XCi J.H. Reynolds J.H. M.F. J. D. T. A. w. S. S. B. S. L. Robinson Dubs deBethizy Perfetti Simmons Sears Jowdy am" R J R5226 j~.. - r ~ to review integraited
Page 595: raj82d00
W . 8 main rum ~~~®n ~~ ~~~qqq~~ccAp ~ pyr~p~ l`.~lPAM W wet ~V Fel]~~'tT1~ ]~-~~~~'"irc'r ~ll I'~ .L[1Ritr# 3f~{yiF --lC+ll. r~.'-rtt il~~1~yEc tG~}rilf :r~niL•!I'NE~+Srw-q~~i{-'~ti7~jF ~'74~~L~.~~ Etf-~=~ui~ii ;E c jc ir~ ~~rfi i ~t E!tE't~f ~!!"rI~ it'` t t~~t 1~ ~~.t~f'dtl6 Fi~`li 1f4:~FFFttt~riiiitiC fL f1 Eii 'E ~F ' c~~ tl@FTIFriauu;Fz3f~ EL!~ E'E 1R -~. c riEF~ i_Fr YFE13tF~ ~, F'~ t f'[., x~ [' ~ 6h[IFr~~i c t'ijf a 4 tJt( i~. a fa~tlksafrF~tzj~~pr'f~c'] ~ E , g t 4, t, F ,j t' p 4 E Ifr ~ ~ -- rE` - t 5~ cr c , irtt ~. F,IF [ _ , f c. c.-. - --. - - -r r r - ` - ' - - F(~' `s1 ®
Page 596: raj82d00
® ® ® ® ® i 71 .1 li s , ,r . . [ T. _- : _ . :. ) : _ . - .] - _ ,.. _ ..__ .... _) .. .-_.-..._.. ~ ~:=f ) ~;;,,." I nf- . y , - , ~ , ]1 -,E ,~.r „ - ,1' =. j11 -3 - n 1 I Ill I ] .1>• . ~ 1. I', ]. - 7 . :. . ~ ,.aI- _ -r_4 ][L'ni'TI'~1TZ; -]~ ]f j )~F t .21 , - ~~~[IIIL ~~'; 7. , tt_ -.1r ;'13.1YF[./i r'} 1: ..1~7r } [ . c'',f:.i --} f ,3_f--Z 1 3 1 .,~w-,] `~ r .. , . . lF ~.~~~.1~~l~1~~pJf~!3$H~fS~..~g~HH~tt-t~H.f~lipi] y~~yht{1ft6Fg'f~~~V~F~:1r t1~17~~F ~a3,Fi~q4 i~~[, 'dFt,j},~ri 1~.)~t ~ fFl~tft ~~) iy~! sAi 'u_~ie ~3$'HFfHfi'i33fpf~~iN~iiS~.qJ~91(L•~A1N~)SiS~a,~fq3i;~!rylfr9h~,f~f7Ffit1H}qiF1~i F,.~- qih~i~1~F ~z,1[,~tf~i!~'iif{~r~'~{i~t~,,' dry.'Fb ~i~f~8kEf3h~~B.f~f~8~f~9i188f¢1 H~~'i~9rtEfn~,*tfd~>i13-#lff~ff'n~F~i~~i°i3f-3i1~"r-~Z-.'~"s~f~tx3±-"~ttB.~ 4 41's 10.6 - !L- . . ~
Page 597: raj82d00
J C tM Mtvlte /11it+i~fl~..t#A i~eiei ~ 1i ~stit ienN v eti ee: .M 7O. ThA ~A!~ `A~ ~tALrl: ~/t! ~~tf~~~ tr tN~t ~~~.AA4~~Ie~c~is 1.~1 fi t Mf aN1AiA1~+Ilt~INt ~e ~~ttfr 11Atfi. :~IArtItUAr ~ft.llt• e1NmA~e ts Mw ~~ tt~~~ ~l Mt1M Nf.et .. t,f ~ t.te.+te+e« . uNMe M~A~(efll et th~ NM._-: tA tr.+ . tM ~Aeii~litM tN1et~ Rr hrAat ~ IettMtelf 1rwNea A/w~ wite tt qt~•lt~ IA#A1pMAAtiN. UM`t~rs th11 Alffereeee t• ~ 1A~i1r/ Wrf tli tAMt;tt Mh r>N Is iIY~L I/lttr tM tl i' .ii ~nAtly i 9 WaA/. 11
Page 598: raj82d00
1 - . •. I AnDnfr. !s us+:S by IU6T in tihe tollo~lM tojVeeo oreaessi>t, e4tretlais; `' . (1) Ooulootinleetia~ of Oy'ley-to6lteou (2) Aanonistien et roeMitcitutte tsbseee ~; I~ lienieetlnlatfon of arlex To-U ;; ~,= oent eotinli.~ofi`or vsk of aw eurlcy tobaoeo f:ivts us groatcr j ;~ ln our proaluots to wt the p1=jle:lpility in the types of toeieoo w oitn uso ~ ,., .r a. _At~t+stently e)rmtir~ O~nds by sens~ti`f~3t'eiR~e~te proJuau aitli oiftaront, ~1 ~ sr sr+d MeotiiIeli"`'lflis treeiis also pereits us te oartiallr ow ' Alll : dITy ...~R N~A. i•v/4-.0 M ))ti0 ;''+ • fw /a GNM't b~y:2 ~ ~r eurley toa~` ~.~ 86ep)ote)y oae~site for eht*year to year v~+rietaon !n tlw Moocine.eonter,i ~ . .a.. - ~.` ln Mi RJOBOinieotinitNi}on prootst, 1+criey tbusoo !% tiri4 trtutea , ~~ ith ~t~us oM, an~! tihen ioriLastaJ ++ah.3~ttu~ to creovo nieoilnt _'no reees! iNlbtlla^wm,~e u,c fe* florttam of otfo niootine in t!k ioaooW !s t~ %Aresent •s nie »lts (eitrAe, ouin4e, ~oleLO1, the Mjor jortion ot tba ~ y `.rl csilu:~l snreor. a.~present in ttR form of tfo cemonm solts ot the aelws. ~,~ •.Dcnieetlnif~!!6n Oreeu:~s t~e follot+ln= e)Nn=es in o)~+loyl owcWsmon ot ....,.... ... . • 40110%jrltry tobsooo,Now f~e/ N) ieerssse9 Afootino oontt'nt ot the to>veeei {2) w ~ t nieotine, rslNtad slksloias; Dyrstinoi u+0 yyHjlheu tn s o 11"k-:rosss d level ~+e swkc .;~) fnrrs+~se+l srnoei. eonet•nt of .ht teeeoos; 09 ta) insr'Os.d f~r) c' s+•.e:+iz in Uw sbrr. i .. 3 TM 0 stniwsr o! seec of ttt+ eh:a{ie1 enr 1>Ct±s u}Ct OeeU' 1n bHr)ey 4000C0 Hr e &,b».tn in 7hrsc ae t: w rc, .yen troa :~ rrper~ t+y C. R. ... ~. •;. ... ~ ..r N O A • • M O r
Page 599: raj82d00
Y f Subject: Clarification of ay 0742186 .Dat.a: Septo:rber 8, i::0 lk Ni MJdi i i r~o on cot ae t Ye eajoj1so; mo M aT M ~ e e. 07/0 f l ~ ~ . .. . p a~.. a Hy JQ1y 22 Mmo es3uped that t,he read.r was faailiar with nS's and our past activities, in 4evOloyi4 =riooti~e uthttiolo~r . To put the inforn~stion in thst ~e.a~p ' in pessp.C,tive, the following baek fromd is presented: Deveior!wft of n3ebtine tedmolopy involves the ltudy of a ho;t of faetors. eKlif ==a rrhirh u. ~ 'Tar" ds vdt7 , ' b. . I~cotiae~ayivery 1I . ; ' e«~ T/N sstio = &m mcotine 'atisfaction: Zhis is Upendmt an pattf ca2 ,W-voYuer, .TjN satio, total ~ooti4w~r~, iitodtin= ~livr~.y per ° Jat~# "l~ee . nicotite pes putf. The ~ ~atts ia+tun is Mated to tiieotiaft s'm detivel'Y 0ot' pef errd *oajc. pEt. : To dsvis adi ~l~.ih~Ee 0ft :e~td their iattrrelatio~ship:, in detail att a te 't~~~n~r lb. t2 ~ a~rsent ~tat ~e o~ ~lt~ aisaf~ '' I~ t ~P Y possible: ~4 _.. , ~ TabW&'ymd tht attu2sed ~1:3 it~ictte that .es,a re~ult of R6D - 3 efforts s3ace add•1lT7, *e baw '~ht ~p" to ~t ~tofar ae its current tu~s :>e use in the Xisibo:o of Aioqtimtodwlov is conc.raed; rv Q~ spps~ j• `•,-(~+ been pri~sfly eat o# cqatro2l~ tke's~qks pesatetsre ~t.d abavr b blead fors~slatiaa esed ,d~niaat~iution rather thea by additioK or trans- ~ ~ witioA of ~d oti : :..y~ r -1 nicotine. ~ a Zfost, if riot s11, nicbtiasn ise tobaaco.-is pr.sent es a salt, the reaction prod~iet of n4cotiae arid em aesd,. 90eally referred to as 'bastd' nicQtino; *mt of thsAicosiAe in saakm is present as a salt or "bo~s~d". fo * attd s ema]1d~~tioa is p~t, :~s' "free„ nicotine. !1r 1"~re. " Ytitotina on _ the smoke~ p1~t. "Free', rscotiae is" ebsorbed `~pidiy ~t~te aadksr t1>~ i~t "4oimd" Ni11o PoAM 2Rt-Pw. fM
Page 600: raj82d00
Analyses conc#+ct.d over the past sev.rnl ;•cars on svarioty of iM products indicated: ~ ~ s. The nitotine cor}tent of the Lisht Sheet hss been ssmsrksbiy.-orotsnt • irti theTriMe oE 1. S•1.60: ~. ~ ~ ..r --a •A d "~ , .~ , i ~ ~ i. ~ ;, :,~ ~ ,~ ~ .. `~ ~ ~ : ; ~ ' ~ The nicotins. cotitont of :vu total blend has been The CsmbridSs -o4ntaitu -At . Li ~ht Sbeet se niaotinee content (q.Q1) ;is ht~tr;:,thut previowly abserv.d for this shesb- ia at?ut~ ~F! ~roduete ($ie s.). in tt+e sNp oV1i60*1.tS/. 4. T!» nicotits, coot.nt of 'she Gobridfo blend is ti2.1t (see-b.). tlns.a„,dwta as+~ sumr~rited itt 'Iebl~ ~I. ' :~ _ Fxmdaat3oa ot theso nicotine:and phWh;te cLfa hss'led us to speculate theR FM •q be lsd_ -AiOatW-~at the t. .slt to its sheet matasiels. '1lwss N" wWt c t nicatine alt caa be extracted fma te~b~ for saqki) to detendne it,e coaposition. `ba v~tZ), `bav~t ~ound~rio edditional inforastion SIs~ ~ e~rlier es~o (Ju1ji i ~ra ivdiesti~ ~it R4 is ac~ually ~tV ~o. Ad'et sxp.riencq' ia siieotinm technology dstas bsoic to pr-196i i s± R!' e d.velop~a~t of ~eotlne t~olosy has.been cZpf.l~ aosso~ ~ts findisus traa.~ot~/c~nsuaer ~dreep~tioa _td~dies, e ~atfdr :~i,ei htw`beea Wd.rt~y-slnce the •6~ . 11dmtttid,ty~ ~lttlt R4D~hsYA bNn IsyinS ''ostok -up" in this nieotis~s tec?~nolosc ar~e_s. it. the I]~ti~S+QtV ~-;~w iifdicatiohi w. hsv. "ca*t up" to the c.utrenuy ased sltimReA. -.jfOw 10 N hasl+rei ssed;l~t rNw-tiicatine Le~olo w_are Aot I e,'~uE ~i ~tidp o~ ot~ IindiaSs. (se. Table I2~s ~at that is ~t~l, ~ lovolv.rd ia ~dw~.lop n.w -nicotiss. tech~olvSy.. ,1re sre diii t1y eeek#dj •to *tet~ad~ ib~t ~t~irsd trorillsrd) ase doing ~ in Lhts tsea _ s P:"da.e ~. Ject~l in the nir~otiae sres . of our own. /Pt
Page 601: raj82d00
. •9. . ..'. .. '• tt•~.~. j .. ~.•'~,. . D/OLm:CII. DRTA Ct pl9d11A ; , (".iq,e....M?,. *V, t ^ T i - eetabolfe snd eutsbolio proere s. E~teis syeuntt of ~ir Pra0uaed' in the ewy r.n eonverLe! tlissw e:cretrl rs ur~, in thr yrino. . ~~ +~ ' ~ - . .. . . ... AAt00n!• er lti WtA art nOL{Mil CNIPfIt.1tS Or Yiny Ot lsllr t0il0i. 11~, 1 niiaC:r we ~ ot tnn~onls•contefnln~ eosyouadt:at~ tonofOtrt! OI.A.~.~ uscd ds ~els~tt~UAtoua tr ,or I ~ r denerkl purpost toed P,iditivee.~ Tntat fneh+de a nonlw ~hydrqslde, irasnJWt "' 1 , «. ' ~t b ' JeirbernstA, Artronfut ear0ontt0 as~{iur a±ioel~irin, ~{ane~fJ~R witt, Md .Jie;AO~Jua ~hosp'~su:. Other; sDeel~tia soPl~c=tlo'v DC',1~1t 0e,,wt df s~Onllrf Useinite, tmceMuN I~kbloNde, an.eoaie laovaltr~te, ~Saaniua p~friulttta, a+ttsnlstn dult/#+, merOnive, y' ...• ~4ultite, tte. ~f~oed produett.= r .r ~ Clorrly, YJN of i~Onl~t in t1N (Ab11alti leidr/C.j in tt.la p~.pir _sr~~ axl3sr POP ts 1tsny Of tbeil"estlons 4ouieAly vi+d In t.tie tce.f indtastry. litnet, _tAert ua+i~u ee ;;ft}ttlt reaseu moMeet ony asEdiriWle ettatt. ~ am &li+,l~~tol ~eeroaJa~ln .4olceeo >pdtica t;.n be dttere~lMd, tM ~4usl for~ol - . ~M MO.1Ja li*nwOly as tAr ~i1ts of 0ertipAla aQida JaOrilerl! OQid, M1d Owr ~ ~ ~' .. . v ' •. _ Canio aOJda.P*hJi ialta or ael0s, wiib f!K .t=of'tien Ot the aslts of itrOn,j ~_ ;&4icis suel+ as heohltrle end J-Wlty-lt acid, W1 up+nlly lea irrJtatfn=,tn,t )csr~ "":to M+n treWW"a. fiortrort, if ve .aRJwrt u,e level of t.1s3 ~is In "U,arattt soo::dAJW tht kno:e ~is,lo=ittl Weot: or s.+or,la, we art no eoult ~~,pvereittrstint any effect. ~~ Tnc 1Kute eral to.lelty (of a-ftma in r,,ta as 3,) wr uci;f,:. y; , ,. . :ealma sspos.xe tor r t.n.{aro~ca•~ii~ CA1A ~lter_u~Ktr ~1 es:f~scN w 1+c* 1.04 .. .. ... ? . :._ . •~, M Of i~+swnii~ OC•' 4~y. J S.1 kt y-rue+e »uid tM•eforc es.na»s~s' t0 . .. Y i P • {v• 1:1: br Wy rrr,e:d. 'iw l'..~ if~ ND't SiUA :J't}f v Cat*TJ' ii2:T* ~. ; . ., .. ~., .. N M
Page 602: raj82d00
i PHYIAL RM Cigarette Weight Circumference Length Draft, Holes Open Draft, Holes Closed Air Dilution FILT;1t/TIPNG Tow Type ` Filter Length ~. Tipping Color Tipping Length ~ P.rforation Method ~ • Rows Perforations Holes/Etow . ,wCsnter to Center A ~~ . 8ut t L. nqt • Puf f Coun ~TC tar avci • t ~, ~TC a# ~A. nioo~e qt niqP,%M. e a" fi ~ CC mq/Oiq ;,~.) Tar/Nieot~. atio L~f TORACCQ ~ Nieotine % ~~ Total Sugar k - ~~ Fructose S Sucrose % Glucose k ~*W' Maltose k AO* Ammonia, Specifie ~`Nicotine in St.as . AM ~~Q ~N~1LYg2g _.~. ~, •C ~l d u. ur. ic w .. Puffed x Turkish x Shket x Added Stems ur l.y % not contain ammonloted eost sh..t, S ~ _ au f~ ~1c 0., 919? 0.0913 0.9519 2..ee 24.7e 24.80 03 63 •4 13p 116 131 M 1si 166 39 31 27 'AOttOt.*"_ ACetatt, Acetate K K N /WH /WN C K/WH C C °u,32 < 32 32 2 2 2 laser mechanical laser 40 40 NA • 13 13 NA 35 35 35 e.3 7.0 7.4 e.s 7.6 . 7.• 0.98- 1.08 1.04 0.lQ 0.7• . 0.63 >0.i09 01106 . 0.096 i.2 !.6 • 9.0" 9.0 10.3 12.4 2.66 13.2 't 2.7 0.2 i.6 0.96 0.02 17120 66.31 0.0 24.07 31.32 0.0 0.0 . 9.84 0.0 0.0 11.29 • 19,19 NA 11.0 NA NA , .• NA .% . . J2's level of speclfic ammonio -is typical for a product that does Due to extremely small qUantity of material availabls-for analysis, sample preparation procedure had't* be modified. if the normal procedure had been used,=thsss ~tumbors probablY would have been higher. R J R22489
Page 603: raj82d00
N.v philie xerria Pal.nt~ Today , a copy of a r.o.ntly =publ~sh.d Philip ~4or~tis iusopaan patent applioation covering th. r.-~o~1144t _-•:lsation ~Srooas~l; vas obtained by . th. Law D.partu.nt. (Th~ ,=n.tsoduo~4n and sos~a p+~4.s lroa the pat.nt ar. attaoh.d.~ ~. ~at~ d-plioation:oon irrs such soatt.r.d ~ i;bilip -~torrip~ supsroritical. . int.lliq.noe and sp.oula ipn roqa ~ niootin. extraction #roo ss a~ ~ii4o ~~Jtlavos rsslaroh. The pattnt lal~.n~ootini=ation pxoosss but also . application details a-ot,o.ss ~i disouss.s the t.ohnoloasr•'. ~ ~oatiabitv .to 4asarat. =niodtin. •nd/or ~• flavor enhanced blarid, ~io~po ts b~ ~tar o= riiootino b.tv..n oospon.nts and antrapw.nt ot~a, , ro '-lor ~atsr as.. :VMs new tbat ~ho ~nt.ro. t.d~ intosaation ivas hi h o. ••••• .~ +tho tA.o q q t ~ • t t a v t l '~~ d s uo ar. o ro a ~ niooUn./llavor .nhanooront t~logy: . ~, a iimons ~ ~ sohk. D or Threatt sn.an <=uss T. 11: P.rl.tti _ : R. 0. Raborkern T. E. Miller 0. C. aakridQ. s. Ro lsullinqs a+ L,: Nillard , a) stow. ~ ratio-broduoto sade possible
Page 604: raj82d00
t elend picking of the t.st,produots revealed the following blend compositionss ~lue•ovred Turkish Cast sbe.t Puffed 71dd.d steas ~ he high levels ot add.d .t.~rs ~{Nort• utled) and ths abs.noe o! ~ast sh..t in both produot;s w.rs.P+~r~ioularly vnusuaa. Also,_the ~.~. 4 blend was considerably less "balalfoad" -than ths J blsna since I ,it was oomposad of only:.llvs-ourod3tqbaooos in out.t_ilar, pulted, and stam to~ Th. •n ootina oontsnt Or aha atsms,arom bo biends:. ~_ vai •~,toal, ohasio~tl, and 4naiytioal data is -attaohed. sa.ntiaii~ ammonia vas, dasat/td io Y~bs ~i4 bi0nd and a normai ~~vsl 0'lsS wss dateat0'A An tbi ~Z 1hnd # tablo listin all ~ suggests icotine .xt, aot su,y U 4v. b.an addsa to the Mtams. N: •ra etual lr.! . f - _. . . . . • ormal s.n.~d~t evaluation of tha. produots-Mas not possible :~eoauss only~ ;l.w oi4axattss r.osinid after the ibove analyses. "WAn order to obtain a linit" d."soriptibrkot the flavor and oo.ptability o- tbesa pr 9 uots, tl~YS =3tip -a~okers, . o~. rienasd in ~.sat, bl.nd, ;- and _tobaooo oosssin~ J~.obnol. , as wlii as the tast. characteristics o!- 3 lip 1topris prods, ivsluated N4 and ~TZ in an intormal srokinq ~t~s~ion.. :. .y concluded thatt ~ ~ 40 0 . '' - both products 4e~iv.rsd ~Uka lull flavor ;.produots in spite of tbilair #40q Otarf . d.liv.ries, neither product bastsd ~jks typioal.Bbiiip Morris produots ~ ' at~d N4 had better llvor tbsn JZ 3n,spite of its biqh4r niootine.an~ "unbalanoed"-blen.d and wat-quiVr aoa.ptable.° •. RJR22486
Page 605: raj82d00
A J Another method to ae4omplish the cicvxtion of nicotine in toblicco sheet msttsiai i: to zecov~et aicotim ( Wlw fdavorful stiattriais) from a tobacco e ion proc,or_ a ttentc pt~ss , by trapping the nicotine in acid (phoria acid t) att4'applyiog tbe rdcotitu salt to: the shett aiteriil. t/e 'suspect thi:l is the prows PH is now testing in the Cambridge. sh.et.aaterLal. ~ ;. We laww PN produo'tv, iexcept for the C.mbrid;e,- contait: two types of a. A Dirk Sheet :'flais is s daa s1ott ~ ued by ani~ t~ *~s]~I~h.at is t ada va Vtio~rohatas prss.nt . th su ptvducu.:A)Kspt , the cablifte. :fa le It Wir.stes the high 1ew1 of r3a*t3rse ia this s~et our ~. Part o! the ;hi~t+ •~'j° ~ho~ptu~ 1~ i~ dvo u the ; _~a thi~ r.aiie s1Na-wJdt~ ~t~oca3. - ; • :ar, .,• •i a~iuei ~l~ats o~ blr R! ,ia . , b. ~~ht Shee tz Tl~is sheet .~ppKrs' to bd f.brit~tsd ~i "- psp;x~iCypo 'psoeia sixilas co ~ ~ , U*Aft dW1 t1A . A I~OverF ~p put fo++ y. i, the lt~ at the L~t 9heet in A~t products t~t t~a~h~up~uta•tsested) -' has incr.~~ sr~d the 1 1~il ~ Slydl has dis the 141/~ of . ~~tt~f~lltte•e~ ai tooaaco has inentaleLl/ith two s' ot ~amai~t Jaa ies. bler~s Ad ~oy~t to ~ coatrol t~"br 3nduaoet of .~.i t. {~od-~ste~) S~aet sAd r.d:+ction .~ of the Oesir6g+eet, roo ~ th~:`.woRis ia th. blend iatsp the .1 smoke pH ,to& i, l.wt not `dasired W sOPretta. Ad uses a+aeoei-i asxbotyieo to. e~sod .#ltez•cuzrd tobsoao,# this treataent, bectt~e of the basic ~ltim of ~s, I+lli "Mrs substantiat ~, qt~t~tla ~23•f0i) eo~u tlw-a,rp, t~~• In coatrsa, out C13 espanaion ~proe s xith'F~e 3l doess not sipti!'to~AtlY seduce (<51) the t~icotine level in thr e~.r~.d tob~+eco. . d Fron our extainstion 4 On-4ytiesl dawion blanid CwpOtItp in P-4 prod:xt~, ;+e :u:peet tw4t JWdoMCoi*dr4.j ;iRs flw-clned tobaoeo. PAt doa not discsrd rhw, rtieoU3tie. = RJR.dsnicotinises a past of its tobaccos fYOS hiph-nito~tine,rro9_Ysars but doa Aot-disear3 the niCAt~t1e.
Page 606: raj82d00
AVFJLSGE DA'fAi~Y'iD 090 ~~triNS'fON N.G1RIOORO . ; No. of "?sr" Nis T/N QO CO/T Sraoke 3S-_Pff: _MR liiNS'PON (8) 8.4 •. 15.9 Marlboro 8.4 1S•8 .,.r : 1~INSn7PJ Its.aif how thes•digsrf ties 0' i+e ~= botwe.n 1971 and ;197,, ir!d how they rarsvW essentiark to a rlo d~ferenu st.atus.in 1980 with the ~t ' ....~:.' `2. ...; _ . i:05 15,1 15.6 0.98 i.OS "1S•0 13.1 0.96 "froe" Nic, BHH ci t 6.4 3.4 -6.4 T 3.4 The WINSTaN D close~y matches the M4rlboro in the s;moke prop.rties ' irdicsted:*j.1~ever, th~~ doei not necessariiy a.ati t~ut smoking charut.r or qwiitr s~' ths sear• , 'i!-A h9 -~hw hr,r~ closely matched -texcept for "fiwi' itiiCOtiae) to ` #~I1itt~d ~(srlbot'~o ~rere in 1970, the disparities between tb.'. Y¢~b'~ ~d s~borv ~ri9r" to the irttrod~+tticn :of the wINSZ+GV 9, ~~ {. iaftt_ ~ ia.c2se Ga!brid~e led to aa Our ~~ ~y ~Q on n i +s , ~ ~~ ~ ~ r~' ig'o~atfb~st RW aq be tesetft n6+t nicotiAu• techtiology. fiis ic.~nav-: in~olu~i- tlyr obsr~v~t` !l~.rertei ~in sf~mtitsa trs~ts br ta ; c.f&tettiF*ric. froM dMerint t~ ,ntesis3st s.S., the triwfer of nicotio. • llvra~red, ~.c_9se~ steia ~thest metorial such as 07 is ~l aAd 47I _, v+sl .` N~eod~e trmtfer to 'smake is Mors eas troll.~l iooti~til_ott the low t•rsnsfes astsial; al, ahe e, t. ri are s*v.rel_,xsys to'transDose nieoti~e ~oae tobteri~ to=s~t~ey; prior to 3.~orporstion in a b ; . Q1e i1~~Vq li 3e fti' ~,~~cot~tle ~.~ '71iGotitle tObaCW to a taw~d•oaUa. ~tott dttby ,~treoa~t of : the' s2~ett wirh sn addie atterial, f~o __ ~yJ*y1", ehe:: tobeaio m d' ~i4•treated material to;etA.r. 3!e tdootfAe. ~tpa~ses ~rQa ~r tobss~o ~d ~ trapped aa the ~ ..t sheet In the fot~s o! ~li ~oot Re .~elt of tM aoidia m.eeriel wed. . , ._ _ Ia ot:c 1979 ttudie6' SA this -ae~4~ ve fotiaad this to be ; s wry effective ~ ,''proeese. Wee~tly Loril~d,ka: abtained.s pttent on a process similsr ! to that described above.: b Cigarette smob is so ~aerosol- of U04d droplets in s,as phis.. 'ihe ~as phaace cwnsiste of somr 100 •tanpb~sruls, the liqd;slreplets cnrtisist of s=a 300 lio~aands. ::'i!~ levels of sil theso eos0oWds irspsct on the smakitt!. ~qtality
Page 607: raj82d00
1 i , ~ Human Tsstinq of ~tDN ExtractJt+svulii7lo Aoid 07. ,$haalSareK811, 1991 J.H. Asyitolds ° Pass 7 ~~~I~! i= you have any a4ditioaa1 qusations, pl.ass lst mo know. 0 z 0 1mm =•~
Page 608: raj82d00
P 1 0 . , ~IfttO~ 2, ON` The At0 Os/aeto.e{ sf 1Ut lu• M•A tnt./.1 to .uttlaptsity tat~iZit •f ettetstt. •..k* t•hdaate snA t.rss..ldtttv.s by the A... .. /slr•n.lls/aer•t•O• I•tlad ttaa ll11L tntar•llia assos hsv Mws.at to eM pr•'.r 0artlas- 3s loNtt : tM g'~tsitt ~s -tiN tAs :t.•t• vtto ~'!'Lt,hst. N.1Ntl.r, p S.~t•~.0•t1l• Rial ~. b•ls' lR~,~h tcls N tll• ~j/W:et; W.Srdar t. r•vtsv all the _/a•!t vet +Aits1 vsu11 help Ovtd• tieves O~a~tul, a~0.st sawt ests"ttal es .•tt tsilsaut• ar. e.at3sd Nes s•0 Its.f a•t.. s1dsd. !As s+s.s ~i1stS0_sm eswses al4ittvs• ars`~ttsd to tkt ssstanlvs4. Al•s, t1N tt/•rt 1rf Jat 1tAita (wiOM, 4) t.b on evt t.st Towlta ts s.,t tQ•1Y1.d.° : r. ., :.o as.a ts Ot. !~. i~ts~r. Ais sos• AsaL vul t1s -al.ratt.ss .t the s+itatsatsur of 610 ss.1`s • 10_ •10 assts Vu sl•stlTViss • quK st t Matt•1 (tOQi tafasss). ,i ta~sis, tlr ts~iats. ~t J•10 st t!Oi s.a•~iEt !s stlsi s itsttias~dr ;ty~•t#0M rrriy..laty tre. tbre •1+r.r~ra t•r t~ i iisl#sss s~jttttt•• - ~ , MM ;• 1{•. J. A. Ctis• (ll/ti/~. 1~ ~ 1'~ • !._ lsts ss.•4ssu ~` t1i a.tsrtsw .t t#s wts`sisttiss .'~ est t1~ts0: ~iuas! sri a M• •.~iWstst.~ tw.-snt'N sss tr•t. ar.Mtatt•s,tsoe•a•1 ti~s s~tssstsstya;t4w~•rnt~ast.. ~..-~ .atia st lsa~lstt•s, lwsrsr, attsetN tN ats'is.tetty ~ 1s tt..i : ~r•wsts. iw.m t. '*.- a t. Flwtsssd t3ltin0). tNr••ia C, rn• ,m t.et e•tvles .a tM 'tar•' tt.. t.iity-t.vt lYis:....'i•alr with i1.•s _ Ln ~s.~•stts ks~s Ot tyttiesss utt0 .~eti~w 'tst' ~.~lsri.•. l~.es ts a ti•M i.t iw. 'ta:' sts.r0tt•s t• Nsrr USMr r•v.etast iwastC,4a .0 _j 'tOt'* tiw.pr, Os s fs iiitrstts 1a.ts, isir 'tar' etlarstts~Rili .ter ~ ~sv.r t•tai risrtast-sr.lsst. ,':~ m _ ..r ~ / t• W, tu!#s• tse to pt. A. 1Wl... l/lit/i1k ~ s~. i~` . f•. ~.~. R.. 410141 . ~ This dtat frttk the ss./seitss of ttll+.t OltR.t.qt s~.t1+*s of t•tats• $144 tttiM iN4 tMii +!l•tt ts ehs s++q.ttasstt? .t tM'v.e1~. 'tsr' tts" tAsa t.rs.tst t•4eti•s. _'11G w0 •i sw.ev s..•at: (stbads t t• 10) to s•oNm to talNHi• ars•la dsaN .et tsstwa.s tM sutslsateuy o~ . of tiw-er:.4 #t1NtNt., , O„m,.... -.. .
Page 609: raj82d00
i r 8vmari Testinq ol;RDN Ext,ract/IAvnl•iaic Mid 07, ShesVarex911, 1991 J.H. Reynolds Paqe 5 .. ~... ~.~..._.... ~ ~.._.~ ~~.. ... . ~.~ .. ~ ~.~._._ ~ ~__...~ parts'a= the sxtrsmes sot bhe dssiqs sheats. low.r air dilutiqn levels. 7~ttachmsnt X lists the analytical ~~ata that has been receivad :lo.x M10sl9'M+Ad which'labrication rurZ of Table 3 t61'IN'lI CYOi1RMM-Z L~il!~L~1~1t1~t~4~~I0 a . !A CxM Two add undsrsta extract at this for r.ss ;;00-, valu.s ! ~ pr ad th=od .r.., .,. ZI A ai,n based on t*e maximwa traitsfar rates which were found ihahs l1rst series of ; pr.ott~typ1s,: X hava~oalculatsd predictions ~or lsvulinic..aoid a~1d fiicotine par -oiq,arette.usin4, the levulinic acid and niootime rasiilta ilSfid tbove. °Tabl. 'a indicates these values. Amss testing will be--dane, for these two products and will be • reviewed with 8olsntitioAtlaixs prior #o-.tormai testing.  } 04 ."..j .Old S "ia1 41 shests wer. mads to provide us wit= an " ' of: afi s :diflmrance :b.tWaan.-: neat nicotine and Dtt ad a0d tt3soot Ievo;ll.nio aaid, These -phsats were prs p uosa#- Qn1y. This,nptior' is nqt-jsulder consider on ~otty dll Thdlil orpropssveopm~ht.e design an anaytha i..e 4hsstd` -*re `4isted - in Table a. Products wi1fLU be th*si shiots in the same manner (2s# .o! the blencF)%.as in the .desiqri study. ~; ZC'~iA
Page 610: raj82d00
0 _ •. J will be ctit~ asmokinqf~havior study. This metbodoloqy;wiil be xsvi blr" the _ fDtRC on March 36. tt the opportunitp` is availabl tsstin'q:-4ith a subset ~o! these products may. be a sep C p opossl ~n Mareh a~. The biobehavioral DivMoa ~g ' testinq . n addi ion, _measory Zvaluation 4wili also condue' a e nin y. ~he ~Srotoool for this ;method ~till be reviewe& in 0 KKXIM N2CftIn -(mQ.) z Okk Lw IN" =-t . ~ ~ 0 .33 I .a7 . The desillLn study will be evaluated by four test methods.'.Che uation Division: will . conduct,W diw~sti~ and' DA sensory S~ conducts4~ : - t Th mp a rm d! st " ontainirq nsat nicotine will be s'okad inlormalljInd .on :w111 be mads. Mhother or not to test lurtber.Me stin* is tlis only method that wili be amployed. ~ coti~ie, Co, Co , levulinic acid in smoke, smoke p 4 ine, ~! lsvulin~o aaid, 4 tobacco nicotine, tcbaccH, data lwiil be ~t~eviawsd '~rith Scientific Affairs or ~q, - , . ~ . • Human Testing of 1CDN Extrsct/Levulinic Acid 07 Sbeeltsrel®11, 1991 J.R'. Reynolds Page 6 Table 5 PRS~ICZ'!~D ~OtyNTO/C~d11~TPS ~..~....~......~.~......~ #l~CMS~t 1~MC V2D - (mQ, ) The prod onsu~ptiori information for each of : these test me t,~~ds is liste~ow i Table 6. ~ Table 6
Page 611: raj82d00
I. iaxassm ' im R0'ISED ' Oatobe* 10 ~ 1991 Cast do..t prooOaas G16-1 ReQvYts 97 R6 ps 015-2 2004 Dust Roo~ 015-3 GlS-4 Gis-s xC-JC; 07 al. KC-Lt 07 S1sn C-Mt 07 DlOfl },ntucky Ita.s Binder s Cbar=A6oi Binder, c~ar #. R.oip. ly Clark R.torsul atiooi lKc-2 t 67 a1 xC-zC: 07 216 xC-B: 07 ai.n r 16-10 6-11 ii.. t,• Dust # Etarl.y11-teit lsoips l lion pu6 -2 Dust l : am -11IMsnq6 . ! Chaftq.; ' Cl~at~ • qk~,~N1p, ToboaOa 6b6it. i0hld Sbi6t -- cn Prcouas s ; _ sla.d . =- oasti tuted {lbbsefoo #Itrasids o~i'I is;atiC n s 00o p.pr ~ _ _ ~.ano6d-protsiA tobacoo sh.a ~ x R /!l,LT Z LT ^s R J?? , R J LTAi.T A ~ LT*.T E RAM/!l,LT 6m t Rirl~/!l,LT:,~ Z 'RiK/!?.LT,~ 2 .R6X/?? 2 Rfix/??,LT ~r Z R f?? ~. 2 R /?? a 2 R /!? ,,; ... ~ L Ri~1R/!?,LT ;~•• IWO RicM/??,LT;~LT 1 r:. r R!: . ~.; .! .m
Page 612: raj82d00
1+urley vtlu: 'ContrOl Nrlt•Y s L':1l3A or f.O4SA Tcat .fJ01cY a;LZ1x1, or. L"73'Il: , b : DSttCrtneo s 1a) ~,5•>t)/! vi,we A s Ott tnirlty value; !: s; Cor•tral RJRT ft evrr.nbiy usinj 0-1t aer+eent dtnteaanlu•J bvrl.y tohe.eo, Weo aj,th: r t• 'M 0- ` ) total bleiwt, in all brands cs~ept tne JR't' lW1Y•' tCe t10'1 brsn0i eontzln 1+M2~~ ~ w © r.. w teWe~tar:a~'"'~ipkr f~rshr.rri ~ irrit~t[efi were rtduvl~ bne tasic pro;r~ttfva~e~c ~ ~ t2) A:.n~:i• !n eeo.e IS enr ot tn• er1 sr P~1 cwntrsllin„ eaR•onona. © . .:. 3t1:er• intlvu nle0tsne, safnc:, or,;+soau o:.ifs sr:ci tarb:n eiaal.+'. : v f..:wfLlZY 1to 1r0•I'L~o-rJ9,',111p !•el. :*MCP n :'~ t,K:r+t:~ ~.o a..~f q.J:1i:7 ~1_=:r .ea•:et. ..0 - •'j r prreent denleetfnfsed bw3ty 1e}aeee ba;i0 en tht:totbl wtne, " 1 , ` !1M , .^p! ileasntstlvn et. Atc"Ititvtnd SeexM: ` IUI/ , :• POIR r - ~ .. .r M} : ,,, ~ m 1m~ne~rt mnanfaiao or rsaenscfLvtee totseoo t..rt'it.rtod in tn11 ~w atuafa, j . _.. . _. ~ . V clvt por efairette adob.A - e 10 s No ditttrrnee; veluea lyll .fthfn' 1 4-itr"on eefdrs are e:p-esst0 aa ~ r ~eo rerilt of 1w~L~lea Oarrled out Dur'!nC N~c t9Y!lf a~d 'trly t;iQ. Ovrlng the y. tyyi' fnrestftteo the m:N a, Or. tea=ue, Jr:s.oniatlen of teb.:eee, tobreto f~ ~ - .r ~ ln t1,t •u~'d~s, & Mjer f~i~ pro~rnt vns Jafti•:ea;e levatlyoi~ ttu ~:yF,eol ~ r.fehc~fatry ot t~l~r eo and Iarlrt :in en t~.tewot to S~in i bttlsr uMcrstrn0itt~ ot ~~t`~t t+retor• o~Lir.s ~ero'ie Mrera+tas, 1Nftitltln eAO„itrrnitn. _ T~~t:r ;tvslcs lar to ent tolllouf rvitlens te~tlvitenb. ~'' ~ ~~ -~-, . ~ ; ~ _ : , . ... tN: pr ot elZ+ue6ti ste'~e fa MyCrta~+t to swtM ov.lftY .nd et.n tn• yM:rss ~ ~ eour.ure of tAs pf~ysfolpcfe.1 ><trtnten et l~okr. . y 4i!!<~i'~~.W~.i#+.~i.`,;:~~~# ~~ttes at~ ~rs:atle l~re~entnts !n the sbhinj oualltfes et suyonistW
Page 613: raj82d00
< . !. 4 , s e •r e t°,,ae.0 ;. Ot• Z. R.°Qteen (!/10/10). ~ This Ns0 eastlrac the r.rults tsperea1 In the prevt.w seN at i. s~ n t8, Mse t• Dr. A. UNl.ea (10/!!/W). INs4s . 1!• • In tkia tsat# tw ee.e,U etios sethNe (laseeve ii.esiao itvtwe ~' as..esia) wra tesqatei' tha~tteit at 3saluaten •t 3#tae s~...llti~w..llti~ ,~ telasea• !w a CA/tRL ttltet Mlehd as tM WR.Sesttit!_it tMe Iei!.+tsei 'tas` vu .ls.. c.a.1. ~i ,rav,lc~t i:..asuwla.st vstb 1r..iwt t.ets~ ~ Csue.va as.slettes lrNUeel ti~ae?o• v1~teM 141464 .'ta' vtius avcaiesi~eity vaa 439 f~tlt~.r tMa tAi sei e; ~'Nt'. ~Mwv.r, vb8~teae a..niacet tebss.e wtt ~tsilyl.i h a CA tile.r '13esM, tM iiltleraAee .; . is sot eateit7 wa selilsi4l.. v 1. e sam e. at. A. Da~1jw 0, ~ .r• ~ !S e..laeee the 4ut.resteit7 .I the 'ut' !as CAiRir L=lAt rrscty tDat !~1 ts=aratte eaeta}a,lyi0f i'RL i~t~ts ~1fN, !Ot NtMasai ~ tiwr~t.... !ba t.alsltar.itl l.v. 1~tsMr .atq~slstt! 1+te,.~ ut ~' 'tat'.//1111!!~~"lwa wtalalettt 1ie si;aatsa 4" ti 3wKS t~al 'ta~r' ,* vaL.. _ •.. , .am ta Dc. v . ,„.- j ~~~ . ~t t~srtbttad the ~e.~arRrt. -y! ~t«clutattew+atse t0iaq t. ;"' t00. ~M~wwr~ slatls. waa ut atNti.. itjatsat Z sl~,l ! stin=.*.aa. ~ _ _ Date Utnstti-d's" laesser 11, 103 Date CompleteNs ' tN MoN41. .1- . At,sav.l$ 841. rltw.o.. • Z. J j.:: tstrary ttlle) Actette•i M ~ra+r!'~+~ DIfltU7lIONt Dr. N. J. 8100, Clbrary (tlis) Me. !. Y. f..atrs Oe.C.R.Ne - Ke. _. A. Lad lT10/A ..i ..- #I I . , da •. ~~ p ~ 7~i&i. ~/~l/ .. Cbnt tAO~ ~IR,Tt Dr. It. 1. Masee Dr. C. 1. Dl tlnrte ~ Ds. A. !N~s~s ~bl Ot. 0. 1. \~ ~ Mr. 1. w dss ~ . Mr. J• a• 11110 Mt. 0. R» ribiettr 1~ br. C. !. !ealue, ~~. ~ v :.~ /
Page 614: raj82d00
~TR Interaf~ice Memorandum TO: FROM: DATE: ~" SUBJECT: t Dr. Mary E. Stowe ~ Jack White July 30, 1990 Feas. i tili „tv Stu , of iNjcetine Sotircaa Three sources have been identlged as having capability of supplying large quantities of 95•99% nicotine. /trr copdegsate by use of ;equipTetit at Avroca. This cost, dsay be reduced with : lbs. nicotine. Estimates by PT4D,tsf $25-3011b. to obtein.95% nicotine from . 1. Obtain condensate from 605-1 KI)$ Plant. 1988 estimated emissions 190,000; . . . p y umn equipm9nt, but solvedt residuals present problems (Freon). - -.3 . . obacco for pu~tpose of pr4ducing tticotine. Since cost per acre of is $2,000-3,0 0t) an4 ytatd ~r ~Q is approximatoly 100 lbs. of add in extra~ction cost ~j?). This does not seem pracdcal, e nicotine; source India. Available at 95% purity at '526/kilo, duty ) ~ Norfolk can deliver one container/month (19,2001bs Th~ 98% purity. Supplies from EartzYin may be limited. Buy nicotine from Fastman,at cost of ;S52.S4/100g for 99% or $60.30/SOOg foc : All four of the above sou"rcea of-riicotine would be tobacco based xc: Mr. L A. Lyerly . Mr. T. A. Perfetti 00 U1 ~ 00
Page 615: raj82d00
. Human Testing of ~CDH :Factract/Lsvulinl,c Acid 07 SheplSaraKBll, •i991 J.B. Reynolds , Page 3 t~.... ; U F present these products, for 3~tRC review. This was done in ordeR to accommodate the demandinq-XB-timatable and pr9vid. the commf,~ee with a trame . o! ;rslarar~os for -luCUrs studies -usinQ these Wne variables. The -actual -Uat rs~duata =will be produ.aad'usinq nsw s of the ci7 and iub~aQuso~qaratta p`rsparation in the Fabric~n Lab and the RiD. P artt. . _ : ~.. Table 1 indicates pth* dssillft o! . the 07 shsst mal;.acials and analeed values for nicotine -amd `Iavulinic' acid. ~ Table 1 ~ v ' "' DESIGN 07 SHUT W \.II 90-117A 0 .1.07 : 9.0«1178 4.0 4.26 r-14 0 The tsstt g~+lqr~ i~ cdrporatad..GT into -ths blend at a constant 1iSie1 of 254 (+siqh~ basis). Attachmtnt 3Z indic&tes the peres qe of each ese -s'hewts it~oludsd in the 07 ortion. As indicat~in ` ~ qn will be re-mads f or this att nt;only a subset of the dss ~ future t ~ All blancw.. 7at dry wiiqlit DAKOTA Liqhts blend (without G7-Zp). ~~ Th. i-~mw Z3~~drv ~~iehti i~a ~ae~re~~d e~ aith~r s:inerl. tvere~ _ --- - -- -~ -- - ~-. --~-- ---~---- -- ------ - ---- -- - -- Q G7 or ccmbinat4ons oi thesa. with the exception ot prototype Q,;~-+nli ntk d ts d ta''' ! FTC t ld S-6 a r. i a pro uc ara co quts y Qw o s r_ Products A1i107a2AA•An reprsssnt the hiqhsst irclusion levels oAhe ~ ~ deziqn variables.; 2`or Uis ~rea~ron, spscitia ch.mical analysesMind ~ the Ames assay -r quir.d by 8oiat~tilia Affairs was requestedWor m only thss iour,p~oduats:~Y-nitrosamine analyses were psrtorason ~ produots AJ~ and Afi and two #ampl.s of - KDN extract. All 17 pro 'ts ~ were aralysid-lorIstandaxd oh.mical and physical measures. , oo Attachments 2x `at~ii =tl •suisaarl.i. ths a~tialy£ioal data for prodsits AA-AD. Attaabment; St provides the results of the tobacco, FTC smoke and physical analy'sas. attachment II= includes the results from the analyses of ph.nols, HCN,;,iCarbonyls, and pH as wsll as nicotine and levuiinic acid it1'smokef =tobaooo and the resulting transfer rates. Table 11 also indicates the analysis ` of variance rssults and a
Page 616: raj82d00
STA'1'US: The utilization of L-Arginine has: becn recommended for future GTC product K F.Y WonnS: G1'C,1.•arginine, RTCS, smoke 0H, top-dressing. puff-by-pulY', niootine yieids. w fzjy% ~ ,?LtliksA ~ ANn.wr,ed: Reviewed: G.T NZ M !)_1,ltribution Pull Conv J. W 1.rivson "~ K. W. Srvicegood :,:a,~ . , 1 . W. Stafford A. Gowslcx Cover 1'Aec_ Oniv C. NV. M:bmAn G. T. l3ureer C. A. Biixt f2 S2 ;iG pa - Gso =A. GON 1.
Page 617: raj82d00
I 50/30 PUFF-6Y PUFF P.M.--PRE-MtXED cfs9 ~z0~s : +doN~ro~r.. . .. su num omm nr nman.vmu : :... : : H # 3 "f.D.-TOP-DRES~
Page 618: raj82d00
SUBJECT: Request for Scie60flo Attaira-'Revtew of -Potisslum -Carbonate (K,COJ as a ;Tobaono, Additivi U r• FROM: T. A. Perhtti Flavor Divition Rece ntiy, experiments were o6rxiuoted emplayinV potasaium oerbonate (K,COJ as. Awo tobacco additive. - Historio*° i4C(3,~t7ss.bRon used in the #obebco industry as a tobacco additive in wet ~i -snuff producte, The intent for its use Ir! wet snuff was to Increase the toba~H and, th.erefore,Ancrease the availabiiity of tobacco : W. bases (pyrizine flavorants andl not~bly, ntaotine). - its use level ranged from about :. of 0.25-5%.la-tobacoo smokho broduots the Intent was two4oid. First. K.CO. Is products ibi& known In the} Uterature (11). Again, it was empioyed In the range 0.25-5% dependent on the iype of snuff product. Its use in sftking tobacco base that ~anTihcrease emoke` pH and thus increase the yieid of smoke nicotine. these hyp s prototypes 'We prepared. -:The prototypes employed two differs ~ Co onty, it was b~ed that tess '~ar" would be produced. To test as4bgeat snd can reduce .the tevei of combustion and mr note the formation. .. Swdly, as melting poWdi this seit te beiow the flre ood temperature, it acts ' blend (--2. "/w). If the _' eo ee were correct, enhanced reduciions of blends: a ht bacco ni biend ~-~~f~ w/w) and a norimal tobacco nicotlne The data attached Is from ;tNro!,sets of .o(garettes prepared with two biends (high for Project QT-X. "tar'ynicoifne yield would result Theref4re, the prototypes were potential candidates: nicotine and normal nloot(rM • products (57 mm rods and tow ttem was 2.7/48,000 non-dituted. A second set effects of filter ventilation. e). The ~prototypes wereI prepared as 85 mm rnrrt filtdre). :ThB oiparette wrapper was Ref. 719, the : I aoetete. _!n(Uaiiy, the proto" were prepared inparea iaiter at so% aiwoon to qetermine the Tabie I Divsa the anaiydcad aniQke diita fior the 4bove prototypea The data indicate °E , Pe fottowinp: , • Aa K,CO, additive levei ina4asea niooflne delivery decreases as well as "tar", but not at a similar rate. Trte'r6u1t`Ia a-46llght -decrease fn TIN. - CO and 00, decrease with Incxeaslng. additive level. This is cxonstant with the theory of Increased char prOduCtlon. ~: TKe'tobecco ash was darkened, Indicating
Page 619: raj82d00
51770 1783 L-ARG I tRl IV SMOKE p]HI'ROFILE I :5 2 3 4 5 6 7 8 9 1011 12 13 14 15 PUFF# 50 c.c./30 sec. P.M.-- PRE-MlXE T.D.-- TOP-DRE fff RTCS l-ARGININE ~ Q% 1.5 °!o P i1A, -~. i'.5 % T. D. i a-3 R af(o 14 #2
Page 620: raj82d00
increased char. io } k. ;;0-4 strs(m diiveries of r~i~otine. ~iw~d "tar" were not affected by the level of FC,Ct~; Mz Attachmen.04 a the results, of the. Ames tests. The "reauits indicate no significant changes In bi icai acdvity ~ witt fncresie :1n additive level within each blend. The 42hiqh nkx~ti end (Blend Q w" sii~hdy. mori..biokWioapy aoove versus the norma( ' nicotlne level L).- The V L,blend was not significantly different from the KIR4F ~ blend In terms of Ames sr+kA#U M H RC e ch the R .~ Piease review these data, essoon 4wpo"ibie. f wouid Nke to appro for approval for ooneumer/senso.ry. teotinB. Thank you for your time. If you need ,~, further iMormatlon, piease -~II ~rie ~it 482~. ~ ;%* REFERENC@8: 1. Mattina, C. F., . - -O9th-tCRC, Montreal,=<aueebeo, Canada Attachment I tiats the results for s'peoial smoke anaiym (HCN,' B(a)P, aldehydes and:> ketones) for the 0% air diludon aeriie df protot)rp.=. The results son be summarized.: ; - as follows: - The effect of Initial blend nicottns level was slight In term of ohanEes In smoke yields except for nicotine, ~ axpectid. . No levels decreased with Increased additive. With inaeased filter ventilation the efFects (in yield of smoke components) at an level of additive was decressed (-4pt1.046). • B(a)P yield was not affected in termsnf a mg of -B(a)P/my of TPM yield basis. B(a)P, In general, though Oid decrease with Increased level Of additive. - The delivery of all aldehydfs and kotonea decr_eeaid with Increased level of additive aximum of pro~ ~taxe~y ,3C9fi decrease at a 596 load of NCO„ repardle tLlhe initial nk, tine level. . t _ (oaober, 19"• . ~2. Pyriki, C. and W. Philipp, e ir~~u_ence,_Qf,'V„~ariouslnorgA0io Saits on the Bumll3g Ca_gilg& of -,-AMA 4T&AM. 8er. In3t, Ta.bWonzch. Dresden 2: 94111 (185S)•
Page 621: raj82d00
PLAI,NTIFFS' wB(1' J.H. Reynplids , sRa1/ t Marqaret It. . savoCa A. Backerrdund DAi'E `. - .. : iilCHARD G. STiREV1fA T fiEQ. PROF. COURT REPOATER h de T ~ velopmsnt arro;t r,b znsure tns .suoass=ui ;asvsiopmsnz or~ sw r qansration uitrp 'lat~i tar ~rodaots Ths ks to' khs sucaess oZ~he ~ s ~ proqraa is dalqnad to-provide a comprehansivs researclUnd pro jsct is thii id~st~tlliution o! ~ew matar ais or inqrsdiants Vat C"' ... ~ can. prov de the osit'ive tasta, 'aatistaotian,' draw and burrtAte characts as perceived to be laokinq in -auslront ULT produ~t . onmak Amonq th veral tsvhnol4 ios being considersd for ~ are~DN +~+, extract evul~lniC aciti. .~hsss variables can; be applied alo or in combi n wi~h 07:~ctraat ~durinq the sheet n+akianq process~he ~ combinat ! iCA .-s~ttract-.and levulinio +~cid • qn 07 ; is referrid, to as G7-Z8 as '~s.n fiypothssiold that isvulinlc acid will proods a smooth !lsat: tQ.: ovsre~oms tpe psrcaved : harsht~ass that. •aay ~ occux tr a aqdition at ths 1V~N, axtrsat whicsh providss a h sr niq~ ns shs.ot than °-vur aurr.ht o7-i. =n an s!!or to syslMfoat ~. y study ~fil *!lsQts :of thts• matirials, a study as bs..~iss wh~oh eom#~i,t~si~ "shssts -aos~taininq thsss matsria ~ in various s;ei x d Vith'a sEat~dard bass blsnd `so that. indepen~ent ~ and into vi ~~lsot~s ,~ _bs --aslrsssNd. f. ~ . s'~9s , In a pr s Produat Guidance. Study, LTLT prototypes (c.'T3'~9 ~} series) co ta~ned 0'f+18 were tested with a VANTAGE tBsTRA rontrolo s-r~isults indioated that although the harshness and ~ strenqth r qs} -w+tre . aimilar. to "ideal" ratings. among low •tar smokers, . verall aoasptan , ae was.pot qr.at.r: than the contrOr as ~ judqed b taI• smoxs'r`s,: As a rssult, it is nscessary to beder s 1 d i luet! 0 conditions. It s antloLpated that : dus to '.ths _ nature o! Wiis pro jsat luture *pCotyypss~vill require some level of soient,aic Affairs or HRRC oppYo~-a`l: ~ r..~ Ths purposes of this proposal are to: l. Obtain approv4l lrom #he ooasdittes for tsstinq the 1mN extract/ • Lavulinia Acid study in aseries ol.tasts requirinQ human subjscts. It is anticipate,4 that --tin*l,~ approval -Vill bp contingent on the approval of scisntitia _ 11ilairs _ and HItRC ctial.raan of FTC and PLAJNTIF$ EXHIBIT ~ understand sss, variablss ore tttey ars emp oye n ~ r prototype dssiqns. ; ~ W Zt is the iatsnt' ot :#his proposa 1 to provide i.n ut)defstandir4;; o! , py these sheet mateYisls Attd seeK approva7, for testing of ths_ deZqn BW stud products d othir- -produots prsparad under these samo
Page 622: raj82d00
---------- DRAFT --------- DRAFT To: Dr. A.W. Haves ~ 1. Dates December 1. 1986 Froms Dr. F'.M. Lippiello Sub j ec*_ s Meet i ng of the ,Co~mi ttse °on "iVi eoti ne Anal oque Research y On Wednarsday, Novembsr 269 the first mestin9 of the Committee on Nicotine Analogue Researdh (CONAR) was ''held. The purpose, of the committee, as we undsrsta6d itt.As" ' to orqanize an sx-houss research ~. program to investigate known nicotine- analogues, or to identify new nas, that have minimal'-caediovascular activity. r The time frame for orq4nizinq this proqrom,,by request of executive I"anagemsnt, would be first-guuartpr, 1987. The following personnel have _ qreed to serve on the committess D.r. P.M. Lippiello, Dr. Thomas'~ erfatti, Dr. J. Don de8el;hi;y,:-Drv Stephen Sears, Dr. John Robinson, r. Michael Dube, Dr. Sam Bilnmons and Dr. John Reynolds (ex officio). s' During the coursf of = the.msetinq it was;, decided that the most .Aoieasbnabla approach would.bM =to organize the program around basic vesearch ~.f: •s, as 0ppos~d to croatinq a dedicated in vivo / i~ vitro screening a: stinq proQr~sm:for synthetic analoq~~es. This is because M the identi tion of unoquivopal pharmacolo9ical -and cardiovascular - dpoints iw ?"ffec"in 'en ased~ a:< sffa~~to herefore I imited by the ittotrof-ths-art, knowledge of nicotine's al. The eQns&nsu* was' that-thst #inal program should be inq the eff,*ctso# analogues as part of a more general ` h dsfi astaa ernsnd ',unddri~d the effcts • of nicotine. desirabls to=-make -uss of = laboratoriss' already funded by JF: that ar'e i a ppsition ; to tsst analogues (e.q, Collins, Deadwyler, rooks, Ves, etc.). At 1laast one-,of these laboratories has synthetic apabilities~4s€ well. It 64at felt< that-this approaCh would facilitats . tarting the proqram and ~inlmi~s the time and •:<psnse associated with ,~he organization of ne -and =indspendent pro ifcts in additional , aboratories. It was also decided that the program would most easily be structured - s two separate but intsqratsd psrtt. Onsld inl th ,,~wouvovee procurement nd/or synthesis of appropriate fahaloquesl this-should be supported by a #""sound stucture-activity (SAA) research effort. Th. 0 other would be based n suitable testing paradigms f or ths-tompounds obtainsd, relying on the ^est pharmacological and "ea)rdiovaspttiar pndpoints av/ailable. The major ifj~sk of the committse,,at p'rs sent,,is to-identif y both the endpoints and laboratories that support.r'ossarch lh.the appropriate areas. •At present, the commit,tse is gathering inf ormation. Dr. Fsrfetti will" rese*rch the identi;ty an.d- availability Qf existing nicotine analogues. Dr. de8ethizy = wiii identify suitabli' endpoints to study cardiovasct<lar effects. Are.i- l.ippisllo snd Robinsgn will identify both i n vi tro and in vivo piiarjmi~ct)loqtca lct)loqtcal endpoints, focusing pri mari ly on CNS effects. Drs. Duba an;d Se*i•3`will 1 explore thi` available ex-house expertise in analopue synthsitt and- svaluation of compounds using computerized SAR technol"y. Or, 8immonsl wi11'`serve as a consultant to the commi ttee i n support of; a1 l of - thdse arlas. RIR5225 51770 1756
Page 623: raj82d00
rxrrrtlMF.`TAt.: 1'hc following RTCS substrate formulations were used for this study. . Ammonium Alginst4 Glycerin K-Stem Tix. Pulp KG•2 1)iantmouium Phosphate I Arginino DY• 129 +/e 0.00 DY• 129 A. M. DY- 129 T.D. 4 5.00 5.00 51,00 32.50 20.00 20.00 le.s0 18.50 4.00 4.00 1.80 1'rE•Mi:ed 1.50 Top-Dressed ltTCS 1i11 M" 6.10 , 4,20 RTCS Nicot*"0.G9 0.g7 '1'hotoowir arette contiguO etion wtts`utilixed in this study: guwt Fr"on"~'-`ft.nd•1~0 11eat•Source Godc Q-8040 (S % Ks8) ~ t'al+cr/i~oii es~cmbty: - 6.64 0.68 Mouth•Fnd-Pict'e: 30 tmn G71Kt)N i % K2C43; 10 mm C.A. 10/35,000 Substrate weight: 300 mg. ANAI.YTICA1.li1-3U1:1'Si I DY-~29; Nicotine ug/Cigt. 393 Glycerin mglCigt. 7.6 !)Y-129 A.M: tIY•l29 T.A. 3;S 462 7(i 7.8 1tESU 1,TS AN I) C:ONCLt1SiONSt . '!'hc addition of 1.-ttrgininc to ATCS ~a to~•dressing increased substrate p1i from GA t to 6.64; this plii increase had aniffcct on itic+btine yields as shown on graph !t i.Thc higher iI! 1 resulted in highcr yicldg. i (.0/30 SnaklnR) 9 € i
Page 624: raj82d00
. i A1rr J~• oeateM. _ ^ . ~i.rsi lssrJ ~ aUw eesllrvollou, it tn1 tlealdid to lnvestidstr uic v3: a~ ;~ sr:naniaed r~.n$tiWtes LoWee. (G'h) as awfns of 3nortaslnS tne slate /d1 e~Jtdlr. ~i 1e... ; ... :~ algaratte pW,a~ts. ki0-te~hs indiCSN-thst' makers prafer {+roduotr Oontalnlrs w~~rovAq~ooOe~•~y~qrs~~i~,peauatarl~a r,oaaadd~t~rs~~+r.. 141J i,;* • of ^W1111 i).- Vr r • r , .. ~ Anii" ies) d u ana. ti*.At thc eurrent G"n ri3ter Asan aonteinn svn '' wisintroav:cia~ n CfiZ{, filter U 137;, `fWA t+as 0eon toste0 and/or introdusra in;,» ~ a (s) Pnilio ibrr(s IneFsoueod tAr usr 'f avjoA MWia in tt.oir etear«tt:. . . ~ ..~.. .., Proaw;, to 1y6S•,,7Mr iN1 4favvnitia t.ylrea+n pesxstt In er+eir, j reeonatstuleS toy%oeo proaoai to 4iber.tti +n_henive i+estiaaw orior 0 .\VWAw ~ - ~ - eostin. r reaanst tdtf! tolisolo AAirt. tROry, t97t, Sb. 10. ,,: (S) PbfUO mrns (xeo", lspeeinlly /brl0ore, bKdin p•ftin= in;salrs vt~• rsplc)y after t~,i; intro~;4llle:~ et ~O.~e9 erssonlh. • ,. .+.N.~.~~~ .. t- ''_0. - !.. (f) Corr.tliaian s6vliis rsltttlnl iearpssed "etce p1 ts sales trenls sNoM y - , ..: ' very ;trwN yosltw7 torrtlstien {A 4(, t.q71, 1b•14 )• -_ „ (7) Psu4is et t.~r aftrit ef aroWas en aryql:. eesOesit,lor. starwa! u " eaf~~rsnlly forswlathyda, atiJ us 1n:ressr !n ~' ~,N~ . w•... .... . _ ..~ veltMf rir;dinw~=lna, tns ~1~, ~lkl~4ldi.• 3w~dnl,.~~ ~ ~ )tl~ lnwi ilt,tid Msi rtsys so~atT tL~arJsse soerrton snrutass - lnoretso 1t. ol+ysl4le;,iwl itLit~I'aetlsr;vitA lnarrssin, ' ~ ~ Irrq1 - . . 1.441, nlnetm sodltfonil OrinJs.4 ° - ~ .., oaca .t7~. ~e'~tent fat4C en'.tOUlf 41tnQ) Ww1 C7it (lT,6u p"fstnd.:?:•J © OWN w toA WrnJ), ali.trs 4IwoitRlttly of a+"uvl w atEsrott7 Ia •t1.~ f~3~~strcn~ srut'c. A LW,~t~•.•e~y Cox1, i•tiar sn,0c•.r;)) bc eipesvi to ;~ _ : . . . . .: _ . . - ~ .. .. `_ _ .. . . . y iNly.
Page 625: raj82d00
R,Sl11.TS AND CONC1.UStONS: (CONTiNIIRD) Scnsory evaluation also indicated bet addition of L-arginine via top-dress'ing increased mouthfeel and strength especiisllyIn early.putTs; thie was confirmed by the,increase of both pulT-bypuff smoke pH (graph 4 2),snd pufY•bypuff nicotine yields (graph N 3). „, The addition of 1.•arginine prior t~ sheet formetion had ut advetse effect on nicotinc J yields primarily because during M~eet forrtution the pliQf the mixture was high enough to ccas: r o ~taSe~ o~'t1:e ~ n the d i ~ g ryt ng ~icotino loss dur cause n: . 5'. . MUM - RIXOMMI:NDATiONS: 0 T .. ;: hc addition of l.-atginine to RTCS o1'fers-a novel too1 for increasing both nicotine yields 4fiflt~ ~ and smoke pH in OTC cip,arettcs nd thus a~`ecting senso "ry attributCa in a poaitive way ,~ by increasing mouthfed and stret~Sth. 'f he ~est tinethod of apptication ia via top•dressing; `~.. ' . - IMMA ~ ..~r.' ~ . -$PAN ^O~ `,rr.aO >b ••*PA0 r"M ,0.40 Amos *W .~ Aw ,
Page 626: raj82d00
7iJR INTERaPPIGE MHORAlJDVH To: Distribution tROK: E. J. (Steve) Sohn` Da,TEs April 2t. 1994 sUSJECT: Revised Item Id. Codes for Processed/Reconstituted Tobaccos P replace and npd~~t~e~~ your`proosss.d Tobacco Item Ideatitication guide wit the attached doouol.at: Nev additions are bighlighted for your atwo*ion., . . n n ve captur c ct me at 7 up ~ the summ ~ si..[ ~ ~ ~ ~ ~ ~ ~ Ts~ ovativ. id:+ss and imptoveed materials, tbis su®asy may I -1he ovoativit in ~t.~ials dev.lopm.nt. Pl.ase, 36~ot-liad i do~umeat by yAX tO 741-7A76 which could or praMsed / reconstituted'tobaccos. ! Ca v N C" V
Page 627: raj82d00
I L.~-ARGIN - .. . ... .. ~.i.~..-..~.~..-•-. :. . ug NICOTINE IV . • 500 10 , 450 ~.... ...a~~~.'~~...._' . -.. -_-.. . . . . 50 cc/30 sec. P.M.--PRE-MIXED T.D.--TOP•DRESSED INE /~DITION fl MC+bTINE'1llElbS C RTC TO RT TO GRAPH # 1 Rs2~;~~3 _ .,, . . .. .. ,. S
Page 628: raj82d00
y 0 gROCtSBED / RaCONST2TUTZD TOBACCO REVtsSa April 29, 1994 Ciz/fl re ~J` Ex ed Tobaceo.Proo ss: G 3-18 Freon ~xpand.d Cot'Fill.r G13•23 Freon ~xpandad Cut-Fillar G13-24 Freon ~xpAndsd CXPL Blend _ G13-26 Freon Vxpandad VOL Slaad + CRS G14-1 Flu.-avred Cut-3foll Expaad.d Stems D D D D a RJRTS RiM/FF,LT,ULT RiM/FP,LT,ULT RiM/FP,LT,ULT RiM/FF,LT,ULT G14-2 Burloy ~ Cut Rol 1P cpandsd `8ttms E RiM/Fl,LT,ULT . 14•3 F-C i~ Qut-1t+oii ExpsA~.d Stams E RiM/FF,LT,ULT ~~14 4 U.B. /o fshor. Vroyn st.au: C RiM/FF,LT,OLT Proo- assd -S canadien artrift 8t.ms: ProC~ssed ~il:=~;antda RiM/FF,LT,ULT . Artie Grom ' St4rs • o isad tn °Cadada ' 3+9d 34qand.d 8toms bulk 1;Ctlshors'.Tobacao no. Expanded l+rooess (PEp) n IDioxid. Expaadtd: Cut Filler n ;Diox3,ds']:xpand.4 Cut -Piller-. n 'DiQSiE d.d Cut Filler de _ , _ ;Dioxid.=~~x~a.d Cut Filler . ± 41.5% GRES Ca=ha.t ProasiiiT' ~ G RequU~'C7 Reoip.': G 100• Dust R.ai. G Dust i ;Surl~ ~sm Recipe A xpaud.d Cut Fill.r xPandsd ~CKPL Bl.nd - xpand.d C"t. Biand + 39% CRES . ± 3$1 CRtS +-i6.5t CRES Cama.ll,dd - G - + )Q.25! CRES O!!~l t 47! CRES Binder 3 -Ch Reoip. Bind.r,° Chez s=taC03 iteaipe Burley istem, -3'4i ;-St.ftery Ous: N7G4, . ~s.A ~ar~p.dieda & t Wa.et ir Mat.rials axtrusioa Pioa.ss: G17-1 Reconstituted 2obaooo Straads Tobacco Daprotanisatioo p;ooissi° G20 R.ducad-protain tobacco sheet I C C C C C C D E E E RiM/FF, LT, VLT RiX/FF, LT, t7LT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/FF,LT,ttLT RiM/FF,LT,GLT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/!'F, LT, ULT RiM/FF,LT,ULT RiM/FF,LT,ULT RiM/FF,LT,ULT R /FF,LT R /FF,LT R /FF,LT R / LT, tTLT R / LT,ULT R /FF,LT,UfT R /FF. LT, VLT RiM/FF,LT RiM/FF,LT,ULT
Page 629: raj82d00
i . ., ~ ~ PLAINTIFFS ~.~ ~ tt.14 • r: t .r•. - ---J -Date: Decsmber 15,1993 NO' 3: otebook Praees: Nonc T. W. Stafford AoDRESft! ONt.Y ut 1ors. . onza ez AG SECRET R , A 1 I Division: New Technology Products Uepartment: Advanced Technology Products R&n : Report >t!: ATP 93•3S1 No of Pages: 7 ProgrAm N: 0218(GTC) i ~ ~ G~ cKTCS~ s(~~~T~ ANI) ~ R$CT 1 C ~IG . R Previous Reportss None . ADDITION OF L-ARGINiN~ TO RFCONSTlTUTED TOBrlGCO CAST SHEET ' ~ MVVV' ' ~ ~: ` N ' A FS 1'tir* tcrm'i~~e effect of ad~ingL•arginine to RTCS on nicotine'yields. • To dctcr:mnc t e cf'fcct c+f tnoth-Qd oi`:application of 1.-arginine to RTCS either as -~ top-dressing ot`prior to shcct.formatio~. 1'o detennine the effect of Adtdiuo"of L-'rginine to RTCS on puff-by.-puff nicotine yields and smoke pli. Sl1MMARV: :- 'k_iThc addition of 1.•arginine to incraa~the pH of;RTCS substrate and thus aid in releasing the nicotine present in the tobncco utilized to.make RTCS wats.,aecotnplished. Two nuthods of application were evalua;ed: li~st as iop•dressing and second prior to sheet formation. The top•dressing rtt6thod wke found to be the most effeotiye in increasing iilcotlllc y1C~ds. Sensory evaluation also indict~:dthrt addition of 4-arginine via top-dressing increased mnuthfcci and strength ; t1iiF vi~as u+ntinncd by thc increase of both puff-bypuff smoke p11 and nicotinc yields. I
Page 630: raj82d00
10816V1~B8901~f1/1 wwwoswolam I III 3SVHd 51770 1794 SNN1100 *J*1l ) '11ISt10!!V OwSS3li1S 51233 'S603 NO!l1/YIOOI~~IOM~ I" i OIOSMOV~O'S )
Page 631: raj82d00
Human•T.stinnq of KPN•'EKtractJLevuiintc Acid-,G7 Sheekera1c81i, 1991 J.A. Rsynolds Paqe 4 coaparison to cu#ent WKS for-- selected analyses. :Attachmarwt*~ Sv reviews the tobaelao, FTC smoke and physical analyses for,'",fh• coaplste all 3.7 paa~ts of ths~•~4'ti.udy. #.Attaclseant ~/- provides a of the minisum a,nd maximum values scross the deiiQn productsw~a subset of these "alysss# In additiori, it lists the predi~ed maximum values lor; levhl,inic -aeid at~d nicotine per cigarette bsssed ~- ` on the highest trutsfar --rates and '-% in tobacco of the levu ic ~ acid and riootino. Attaohment YI, 17I2 and YZZZ are the es results, n-nitros"ina' results for AA and AC and-n-nitrosam ne ~N .,~ results for two 3~~N ssasplis. ~~ ~ 07 runs avs been 4ompistsd~rhioh are r.paats ;ot, the 07 Is des ad ~ above. _are _ th~e exaot'shsst materi a1s which will be us • in the prod w2sict~ arill 3~=made in~•the fa-brioation lab and the iD ~ plant. fi s ara #~he.products whioh )re use for-sensory evalua on and biob~~ora7, : testinq., The design -and.v4ttalytical values-Eor ~ t2ioss sh ars ~istsd btlow ;in ~able 2. Thd 1tAN extract sa~l. (2•19-p3l~oh-wds analy~ed-.Cor.~-nitrosamines (Attachment tLL=I) ~, was take x th4 iCDN ssteact -used to make those sheets. ~ . ` p---q A comparisoL of two sheat runs indicates that less levulRic =0 acid was lost duXirQ tbs process than what hid been experie$Zed before. -Thl.s rssu;`ltad in; Upher `p.reentaqes oi:: levulinic aciP: on these-shsets.; Codverssly, nicotine levels !or these most re~ent sheets are lower ~.hah An . the previoos case. The reason f or thi,_ is under investiy~atl;o~i.`=8asad ~pon,-: the highest transfer rates xtom the f irst sat of es~,Qri prr~doots, • Itavs predic~.ad using the ac~dal data on these ne~ shdats t)ta-hiqhast level-ot levulinic acid and nicotini per ciqa~itpe tha_t ws would expect to find in the re-make of the products !~n' mithe,r t3~e !ab ,la1a or the R&D plant. Thsa are listed in fiable _~a. '~he ~sA1y ~oept.ioi~s to thsprsvious preparation of these produets are #be,-lusejof '719, eiqarette papers and slightly
Page 632: raj82d00
I • Human Tastinq of ItN Extract/Levulinic Acid G7 ;Sheeftrel®ii, 1991 J.H. Rsynolds ; Paqe 2 levulinic acid analysas on the final product sat.. z 2. Obtain approval, of lWted testing of two additional 07 s1 uts containing neat nicotine.-Aqainj linal.approval:viil be oontii4snt on approval of 6c-Aentilio ' Aftairs ;:and HRRC cbairman of rTC'.and' levulinic acid at~alys.s on thr final product set. ••~"M 3. Be provided vi~b.'a guidelines for futur." tirstinq with s44,pts comprised of KDN and lsvulinio at th. maximum isvels used in Wsa desiqns. } 0 ,aw i~ B. jin ?I Thesa st are, int.nded.to"identity_and interprat biobehavi,~ral and sena~esponl.es to tbess products. This requires the u~ of human ts e.th~bds, '' .~. r.r C. Scino" Atfa'irs „~R_ayin / ..r V :!'i owe•eC proa04ss-that is=beiitq.investiqatsa for x8 protolQ*es PZ is the a atiors}ot itDN extract and ,lavulinic; acid through tl~r 07 proosss. KDN ~sctraot sahioh ; is praduced from our current~tDN ,,,.,r shset in currfnt1°ti7 prooess... The amoun at concentratsd ~~N ''~ extract to ths G7 exfiraot resuits ~.n a dt a~~ pplication ratT o! concentratsd imN a~act based -oo the xiiqht of .;the finished stat. ~ Levulinic acid i ~lso -Xi,xed into tha 07 . extract/1CaN extr ct e mixture at the des~.rid ratio with the ~CDH extract. At the pres~t, M~1 Scientific Attaixs has limited the applied amount of levulinic .~id ~ , to 8.65%. r.. . a ~ approx sa niaotins. -This ~matazial is ft~rther concentrata~ by evaporat o yia~d'an 4xtiact which contains At nicotine, vtter and abou ot.other-ti~bacco+derivad mat.rials+ This concentrated ~ KDN extr s mi~Ced aith ai7 ax~,ract 'aad sprayed on ths 'toba6co ` A '% proaess used The sxtract Irom - this, process con counts were too 2iiwh. .As a result tha per putt deliveries were lower than : what as expected. Since this .~ras the first set o! . The intent of the x;tudy, is to examine not only ~uman responsas~to these products, bct also:the ciootl.ne transport properties, a~cks yields and nicotino,and levuiit~ic acid transfer raties. The ori al tabrioation runs ;ot `-thes. . produots; .~lid yisld the desired r r cigarette FTe smo~Ce :valuss .#or "tar"-:and nicotine but the !t products which ha~ syst.matibally varied-tbsse materials and the • "tar" yields were?appropriatae for ULT produots, it was decided to
Page 633: raj82d00
t coNFONrIA~ REST-XZ)N - Procesiti by : whiaWyholi or -jartial bler~~~~s~.~l~lY sYtraoted, -su.plaaatad ~rl~tb -~iootina - troa -i _~tr- Procass and r lied #.o the blsnd. ?, CA W.b - A paper••iik., `~altlo~,~ -aoitate Sat.rial prod~~~y xc vitb rav aate~ials .(;ibret:aq Calaasst. sat.rial is,o~suqdtod ~~orr.d inta liit.r rod!' wbieh taen ~ tbair '.o~aibhiM! tb ~ ssqsents. This ~ iset is not ~rrat~~lr oqtiw_ . ' ~ . . ' TC liiter - liitec tns-16iqh .isWtsias saoke and ~ ~ ventilating 'a~ur sspas+~ta n~ttil epeitin tbe tilter_ r thus produei nq sor~ i~etit ~ros lower 'tar~, _ •-• L .•. 11sAMn - sa,t vait -~[a add-an ~o eh.' tipper ; which can' :! ~ eleata v.iy is aqoord3~q to•type of r4iect. ~ ~ ~rovidea dew op~s s~qr~ oorai,stsnt read on truv ~ ejects due =l0oovapdi, 3ott seqreata, atc. ~ ± 'T rrantly insWlid tlor ov+lu.tion) on Pilot Pl6t ~ aksr 12. ? .~.~ . •., *"'~ths oi~taretta. r G7-TbF~- eat-tMated Of -axtsaat .nwd as ' a flavor enhaneer.. aat.. --sy tili# a~ter solLtblo tobaooo a ract ~ ~~so ted on a h~drop~~a_ substrst. tpaterial ;_(web) obaeoc. taste, oan •bs A4~i+v.rad. through tbe ;saok.z srosol. by `this "vaW 1rid ~p1 qisttsratsd while sao~Lfnq • e!a!-~olyat.r veb; ooatad vith a watar_'poluble 'tobaoc~i REST - s-.tstablisba~ ~o# Sol.ubl+~ to To~ooo' - Ths' reXDval t all vats olt~ble~r lrop a tiob&coo source. its3~ctive aatt~srt oi agvsoui~" axtraot lolloved :by L„ ~ ~•appli oation' to t.hs 1ubls -portion of the blond. ;I;- ,_, :... ... ~.. . r Ln
Page 634: raj82d00
Mr. A. J. Schirtdler. Dr. C. W. Eiuuan Mr. W. D. Dahne Mr. J. D. Philiipo •Dr.' G.' T. Burger Mr. L. J. Inman Mr. C. E. Tinsiey Mr. W. M. Dutour- ~ Mr. R. L. willard< Dr. R. A. Lloyd Ms. 8. T. HodQ• Mr. i~. R. CoOk , r%Kr. S. T. RsUstro49 ~,Mr . J. 8. Thomasso0 w 1[r. P. E. Slrazten ; ` . J. 8. Re.oe, Mr. R. H. Rrdtlco aTsTAIES;SreH pL111N1`IFF$_EXHIBtT. .}. . ~le_ ~ 6Dri BTIAEWALT wr. Dr. C. R. t} ~sY~n ~Dr. L. H. !!s . !!. R. 71nsit(r.. R. G. 4,Mr. W. S. Mr. 8. 8. . 71. E . .. .. AT AEPOAT C R D E OU r; kes~t A~ I r.tand . S. E. C"Or , ~.~ Hs. G. L. YrA~. H. D. nlo~ ^,Ns. 3lWA. ywJby = ar...Mr. JM . okbur~ Mr. +7~A. r 44rs!!r. R. Z. tisks. L. E. ~' !i. D. J. Mr. D. N. ~ ' .Va.,alt., w. D. 8~ ke h ,~lr. 1~. J. a,mMr. G. E. CIANOr ; p „~~. M. G. tar; . F. M. Ii~y . C. A. Coras~ ~tr. J. 8. Threatt ir. T. L. giokoan l~ir. D. It. Boeson A+lbkl-. D. A. Poindext:r ~" . R. 8. Laureac.; Mr. E. L. williams Mr. X. w. Smith Ms. T. C. DeLuca Mr. A. D. Siauaons E. Curtis V. Sardin J. Porter L. Suber E. Gu.ss L. Potter J. Dryden L. Stanley L. Bass R..Puqh 8. Normats W. Lawson E. Townsend L. Davis C. Martin E. Robinson R. Stewart W. Siaea S. Fa94 s R~• Mr. C. 11: lixt Dr. T. A. Pert.tti Mr. T. w. Brown Mr. R. 0. Shore Ms. C. C. Davis Ms. C. R. Carpenter Mr. N. P. Rndr.sen Hr. 0. R. Andersen Mr. P. D. Phillips Ms.' P. Z. Woods Xr. M. L. Smith Mr. W. C. Luffman Ms. J. A. Davis Ms • K. J. Wright -Mr. C. D. MaGee Mr. A. C. Marsh Hr. Thi.n Phan Ms. J. P. Slater Dr. H. M. Lawrence 8. 'Sarnett Mr. R. E. Earper Mr. 8. L. Smith hr. S. W. Jacob Mr. • D. E. Wilhelm Ma. 1C. K. Sandep Ms. L. A. Crumpler MS.-T. R. Young Ma. S. W. D.vin. L" ~ NOTE: Exercise aonlidentiialliLy-in sharing procdased-tobacco Ztem Id. Guide _ ., m ~.. V CO ;
Page 635: raj82d00
f "~•tnl,:~l:~tioa 10.~ tt~ ,, , WO-31+r•+ea3z in thF+vr plaee tti 1ht lrrel or c:postNe tor a Stie-ti.ak.a-Ory CAl•aL fi uAr ~#ittDket. ~ P=W !nr'~`+s . +n~'- !w .~:cor,;3nt Nittsl131 1.a3!! r}epcxrd«tlrrns, the !lres?tp10 L1slt Viluc i7LV) 'ar r,, iMP*l*sor,3t• !s tat" ot a3rVwh is esttaattW the1r thr svernec Porseri Snsalis 1n .•r-of AonanLi Si i ttip3rstoty 'itr3t:t++t tina inbtrlstlon in r1LA tonetnatalonK Wy et:As .~ .~ tatos of th4 reso3ratory trae4, ftt ot ylett3s Vntl tuttessattan. The lctrwl 01,, , oonethttat3on in eets tLw titsvdetsrti3nes to #+s %01~0 ppm for onti hovr. ;; . . . - - _ _ . . M SaaMrlIon ot Nar.er I-Ropaure; f`hrsASld J.Satit Vilw .tYee:urc i ~ r.. _.. ......~.. ~ .. ~ ,.~ _. r . .: ~ t'•teaust ot thc cstensivthise-ot wo:3s -tn oo*sreiatl Oroessscs suoh aa in ~~ ju.nutr,oturt of t.rt3fiser, niLrie aoid,•toysrat3n; hy9ra3t, Mtrld3.: or .tral, r~v r ~,the sefe e:aosure levels tar "r;;tri 4n indvstrr have been tlqroujhly investt,;a!•:: , ~. As a result or tMse inv.st3,Wons, Ttreshole i.3a1t Yulvet tor tc4,Kia u:pou+rexvc• , ; .. fa~ to~ean tary) ia~A It is or fpterest to san"yaro tht lwel of t:popvre penAitted - j ,.. . + i~ M~ ~ + ~aommet t:s ffiroup 6fttortnoe llait, lorjs.on Press). our3ni en e3 jht•1our.'work day, ~ n wkin ' r t~as lM e ssnt inln it n~ t + s t t ki t ... . .~. - t . .~ ; t.,~a3r ln~rse3jr~ttovr per3o0 ~~ntoni~titnal toa~atsslo:+ on ltisielo~y i•roLCa3w,: f:Pr: j t, ~ r rsa a t a r.on r aL s. o J yvt eu v :e o r- . , - ~ d tQula it,hale 1'L7L-X of aeaon3ir, 71t3i is 1?S ji~es thr estl"tte aaily dose for f;:. tipLw•W~K.e-3~~~, FS1Lar'~kCr, , .. ~4pi Tr.csr t.dsM: of enpoixr eeay net *4 eo*psr=ele becauir :Ae o::+va,tionil '~ %w~.t>rposire is :t'Ve:ls over an e3,•bAt-Aew Oty, ind. ~ht r3larrKt espasurc cfseurs aurs7,`r r . tir%rrcfrr•,trl, sW.ael Sntervilt<;tnrotrshdut, the gay.'- Slesot0inj to AG?':at rcZul:~:ionl,;;, eNk - str~s.~• tt~~ s•:!n.:rr}• liAit tlrsn a~tr, 1f afnvLe:~)`to suw.~t:+ rt 2t N,;r»= ;~cr:eil~tit~)r. A perw!: rorY.i% in an a:vS;Aa•rr con::sn:t•r P1 :«t e,r :.woaw ye' eM: ~`~Ltr 4.I' iQr Wlld tlt:Nl17 s.j ~~ .Cf -;r1*E.:. jE 1'• ~,r1Yl'?!•. :L7s 1s 0v.Y, I.• rrAte+: tf :.~aant:. a in e4tr vhi);• Is2t.r:.• :F t,r o' a'it sj+,a.•' oll:' C''~! F:;tt* e1; r`;• ~ w , . ..j ..,.. .~ ~ tJ1 H J G J tJl N
Page 636: raj82d00
Dr. A,a••d has also 4av-tlopr4 :an azbtidine aneloq of niaotir,* whi.:h is. 5 times rrtura potent then ni4otirie itself,- as judqed by rrcrK.t~~r L-inJinq atsayi (;fi). Th: struatyr* is shown beiowi MPA ~ : ( (R,S)•3~pyridyl-l•~n.thyl-2- ~9-pyridyl)-azetidin , - - Msre recently, pri Abqod has had some -limit.d succes* t carbamatt esters of chojin*..s'pot.nt nicotinio i9onists (39).: ~h onty other analog thaf, has bi.n shown to be aquipotent with nfi'ao• ne i tse i f i s E-methyl nic.ottine,- whicn was synth.sized and tested d~tv al yeers ago by Rondahi~ et al; ($) ds part of the Swedish synt'ht' analoq program. Howevfr, potency wes'=sttsessed using a n~u~a1• aontractility assay. The struoture is shown below: RJFT ANALOG PROGRAM STRUCTURE (PML) A. In vi tro icre.ninq~ of-potintial compounds using receptor b fn,~i`:nq assays in con]uncti6p with structure-sattvity •nniysos. F. in vitro funotional testing of compounds for phormacoloq4oa=1F, . alrctraphysioloqical;, arndF;:biolo9icsl .ctivities. .. , . _. ~ : ~. : . . _ . ..... C. in vivo testinq o:f •'conipoundi.- to aas.ss biological activity, pharmecohinatics rnd: meteboti*m, and bdhaviotat -eff.ots. ThR flow chart shr,wn;on tho foa.lowinq page summorites the specific R J R2 1762
Page 637: raj82d00
, Ii PItCCtsSLD \_RECQ31iTZTDT'T0811CC0 ~tZVISl.fl l~Ob11~ 10, 1991_ Papar Shast Prooasss ; :: G7-1 R~ular 07ii Rst~ipa, : C Ritt/lB,L~i.T G7-1 TI Isolated 0I-1 _aor RalTZ C Jt,idt/tF,LT;tiLT G7-2 RsQnlas 0741 AMOhiRtod C itidt/l7,WTLT G7-2 TZ Isolatsd 07411xxoliiatdd C Rm/!'t,LI 1~Ti.T T~c7-3 tr~tsssdiati. t Mater l~olabl.s C. R /!t, ~L '~fG7-4 2ntsxssdiatii"~OV. :Artai~iat.a C. R J!'l,1~•~ r G7-s ~dditi.~ li, +Ca~4iirt:.Msrka C v.7RTx . ~» 1~..WG7-6 Add. !sN ni4~d~ -adian NOct. C, F.TRTI L :G7-7 G7-1 Ateaoll itid EEt.titot C iticH/!!,L'AtiTLT ~ G7-8 Rpulti a'tl7 DsO,~C~t~niid4 , ; E Itilt/ L'MJLT ~jc7-9 ntsaed. #" ~1,0. .J~ia~l,atod ~hct.ract C R J!!,L'~ G7-XOC iqh 8t.a# .~bootsn~, ~Aist . C ~ i: ipb Stes ~a®oniat;Aid 8bayt C 3tmi .~ ~ ~~'c7-SC ~ 00% !3 st- i~! . $tsm ~, Svrop Shs.t C • - Jt.?RTI -~ ~~'" G7-10 AP ''tili ~7~1 + ~ ~ R M, ~ 0 G7-11 3it~rMd.' ~ = G7-12 A ~„G7-12 8 a ~17-12 C ~ c~~i+lW ~ c7-la G7-19 ~ G7-20 • G7-21 ~ G7-23 rMi 07-24 /~ G7-25 ~ C7-26 •6Mt 4;df1Et ~i ' A~P l ~ pani~d Tobaooo proalss~~ ~ G13-23 G13-24 W13-26 G14-1 G18-1 G19 019 C ,G7 7 Shsfit v th o.iluloss axtandsr E .~;G7 EhN/t ~I~ttt ~t1s'~ Z '`-"'~09 8h.ut -# j dust .. +r°-Caliuloss - - E ~G7 dib.nt +; $~ f asolidloss +'T8! _ 8 + ~1' 8 t ' 11 7 1 .d tut "pi11er • lr.oR ftwp~.d Vut liilsr IPs~4 =~t+':R1~r,d lr.oa ~d C'~+' ~sirnd + Cus RcpaAdad liit- kollsd staals ca aa.°-Q"t R.7RTI ~ ~t / '"~ vLT RiH/PF.L ~GLT RiN/Fl,L ,'iJLT RiK/!!~, ~!~r t1LT it81t/1~',L oLT Rir1~/!!.L ~ ;OLT RilV!'l,L T.,ILT ` JEiY/7~1'~S ~:Dld dom C RURTI ~ C _ RiN/!!, pLT C ;iliK/FF, ULT s ,;RiM/!t. ~ cLT Propatla niaridod, ptooass (PZp) E RiK/!lOId' Casbos 3fio~iQe bcpdhdsd -cut lillts E Ri~1t/!`l,Z.T~1vLT C0, aqaaltidd4 Cut x~liiMr •!or canada C i4TRTI _ soonstittit : Tob. °#h8at ( Ca001) E- R / LTotTLT E R J L9~tJLT Ts (C&rbo~iaod Cratt) T8 (DaCp3~ Carbbn,issd.Cl'att) L. 7t / LS„OLT .avy -E~ctr Ot ;RooonitUtuled E RiK/!!',MtJLT 7-7 Y6lh1~dd8d sum E 1ti!(/!!, L797Z.T ~i7-3!C WitK ~ Mi+ "1`rastlunt E G' sh.ot : with -tobacno salts -addsd E ' ~,4R8 1A G7 . ahMl ~ ~#D 1~ 07 Hsa: S~irit~d EXt~aQt .+ t~71p + N8, E
Page 638: raj82d00
Niptri4inv analr,gs, basod on in vitro niaotina receptor bindiog assays Unfurtunat:ly,; thf assay methadul,oqiet b eing uted are rnut c%;,nsidrr•d t~y rr,any in the fieltl to represent the state-of-the-art. ir„d •rd, Martin's pastu1p ticn ,of Ms many as fiva separate clasies of nicotir,e recept., rs 4 ri • t!•,o brain is not qyneratly accepted, particutarlV ir, liqht of niord,- rectnt d.v.lopn-sents in both pharrne.oloyicat and moiecular-bioloqiQal (26,27) laboratories. (F~:% r some up-to-date r+views of present thinkinq reqardinc) :;cNS r,icutins recapto rs, see; refs. A ro uml- er c+f Japanoset qroups have be4ome intereP td in niao iA e arnatc.qs. Some of th.sr 4re fynded by -Japan Totaooo k,v., whioh as ot, tair,ed petents or, oktieally active nioatine derivatives ar,d ,O:r; he addition of d-nicotine to'"tobace-o as a-llovor-Qomponent (see App• ;ix E). . Gthorr isolated at,t#rnpts by -acod.mio laboratories to syn<^*eW-te novel nicotine analogs have been mede, but few of these compounds re tested for physi.oloqical :.lotivity ' (31-3=). Fortunately; me laboratories have beqyn to 'ineorporste CNS pharmeeotoqical.nd behaviorat testing of nic,otine analogs into their research pro:~:r~s. F o r eRarn .1 e,. Rosecrarns it al . (3_4) . and Ztolerman .t e1 .(35 y ~v• tasted of thy rnorit o~omrnon 'a n.lo9s, such as toxins .( 1.Q. ar,atoxin d pl+r,t ~lkaloi.ds (e.g. cytislne, tobeline), u nq Jiscrima stimulusi pare`diqms (see `Phsfe 111 Planninq" is ~ -a rr kind of .pproach shsruld be9in to ol.rify the CNS p ey of` v•i ourds es th r d 1 d ~ ~ t a . p y . e ere ape . a . ldentifi tent Analogs -.Of a11' .,the analogs developed and tet date, sev have shown partigular prZ~~~iseo For er.emple, muctr .;ws,rk has beth donp or, bridged nicotine ane qs since it has been suqqested by anumber of investigators that.- ..,:.he spatial relationship,'of _thd pyri'dirre snd pyrrolidin.-rinqs in nioo (,e is critical to physiological pot.noy•(i6,36,37). The most potent ;:af these compounds was reaen'tly devtloptd by itsuffor Chemie.l Co. in cc~llat.oration with Or, le~ ~Abo;od (U. of Rocheit.r). It has qh patency in CNS nicotinan reeeptor binding assays, being rou w!ly t,;uip,,tent with nicotine. 'fihe strw~u`cttlre is thown below: u, ~ - PyFJdo j3,4-bl homo,tropine m ~ ~ rv R,! RrL1V ~
Page 639: raj82d00
H pLAINTIFFSO OATE . RIGHAAb IG. 4fi1REWALt pEa. PROF. -C©UAT REPORTER r ~1dllN~aHNO~ 1 WA - PolYsstss v.o ooat.d :vithan orgatlic acid solatioa via rato~rav~. ~rsss. ~1ib/i~id rods are aada ~, t#~¢ ad vsb tiltsr_a~csr ard oasl~n+d -with avA tiltaY' sodr srqy..At sft a t#~.ad. .~s ~i3ter s.Q~os~ -vapor ..eks ooapot~t.1~ tbat aitiot asobthnsss, s~iAlYpvMr phass nicoti*s F" .00 CPF - A spsOi+sl ?i4tar tror M It ooasi.sts.+o! a•Cd srs r surrourdsd ' aiat.d 0ap.r sleeve. Thi. li~sr : pzessws dtop. ~,. ~ yields b iqb!l0~ade~jr_ at lov, ~ ,.., KsF - a spscial 3i ta~r lroi~ J1rt. This tiltak is rtata Wd.d i Ca vitb qzootss~ - r.s: This lilteY gioes tiq~ W xasssr4 dsop c a~ isr tli p . Y c ~ s . ~ XS-60 4 -7l oast t h4et; 'GT 1ikk matierial vhioh contaitis up to 60= Meaw. " .~00~. c7-2S O~ s2~tat pie>duo*d ~r~,th i.ss aiasaio~iw~. Pbosphat~ M.er OJ~P) , ai~d haoted a~ctsaot (=00'~ tar 1 hout). , .,, . - , HFCS - iqh lt+iotos* Cora • syrrr~ps Car bs utsd to, tspiae~l2 ~ Vr Corn ~3;~p ~ t atd ss ~ d hfYSSt stiiqar ~: ie1 ltox'7~ ~- nq ~l!`~t oontairis~r: ixtra~sous sa~ra.rials an ~ s~sandou!lsr~s ~srraatsr aadiorilltr and biohst suqa .w... : I . ~:. `r E-60 -~sprov.~Iants to produas a tiitsr ot aqwl qaality~nd ~ ~partominco pt ° s ~dif. end •tow veiqbt. ~ ~„~ sx TscihtvZpQy ~ fl wsivp a' v6ty_,1ov oost' sub+q.rario ziqara~ . "W ~ NOWiW1iG4 % i•1 • . -, ~ -. ~ . . _. G7-Z6 ~7 vith -e%kr*qt° trdatad Vitb 371 M at1d hsAt prlqC*v to sappli satiq* :t6#ba ~ss wb 1 f uniqUe TDR's - Top drspsLn.sirbiaM btvs nniWs properties latch ~ as ~ sspr~rinq tb. paro.ptiao o! alt.:tast.. ~ ~q =v Altarnative - N.v $iro¢o~ -~l~slopa~s:tt which stittitisss ~! end s.oks and bi , letqidal 4stf~r-~ty and sis~pliti.s .ai sam ssolc. . etietii . ~b.Ya ~ril ous=.ntly ~vo t~ps ~ 7~D0 - toba~epeinq aad tob.ooo hsatin. z G7-KDV - Procesi by tifiioh -biaotisa lroa the i0D1i proosss i~%idded to07. ~. v ~ ~~IDENTikI ; : for. RJR Use Only
Page 640: raj82d00
in vitro screariinq assaY s far ass4s•inq the.bioloqieel activity of c :,1 ina ane.1:. Tha t hird an d iinel phase will irlvulve a .•;rr~r.•ination of in vitro arna in vi-v:o 'appraeches to further charect«ri-t con,`•~•ur,J: of iroterest. Ttiete -L tucJiti; wi11 utiii:f both acutt arnd ch rornic testinq to det ine ` tht bet,avioral effiets and toxi~;vl~:yiqel proptrties of the eorr.poundt, riletivt to nicotint, end.to assess tht pharmakokin-rtics and metabolliswe of-selfctad vomp4unds. or thrt testinqamethrodoloqies in phass$ one, two, and tKrra': .. are presently aveitablb either in-house or in ex•hou=o`` cuntract/colleborative lat-oretories. ln particular, the utili;atioa.: ',r •.or a.iatinq cr.-hause rtsoufices `will teeilitatt the rapid proqresst; . ~P f the overel 1 proqr4rn, ; The .present report detai 1 s the over*' f structure o the aneloq rasesrch program and iumntariYes the proq:rt ~' rrmade to date. I ~ O.STATUS: Approximetely 100 ot the n.erty 300 potenti.l_ n iootine ane:to identified by the Committty on Nicotine Analog Reseireh (CONAR) 6i. Ok een purchesed or synthefi3ed to date. A contract d9reernent to bliq' h l les« 1 pharmeco W aqicel ;cre*ninq has tatR n initiettld with ero eead*fnt - Alal'•vretur An in- ho s ;d i s d % ,:. y, u e ata ~rs e of i ent fied structures has t~!. . ~. e: ~~cornpt ated. . ical data, in -tfia f;qrro _ of hydrophobici ty peremete ' tlavr elrra! been obtair..~bd for a mejority of the oompounds fro ,, e~-hcuse r~ch laboratory.. ~ ~ K EYW ica ine, nir,otine analogs, tobacco alkaloids, nicotine • ~~ol t~i co t receptor = struv~ture. - s~ , eetivity relationships (SAF) : iNTRODUCTZON (pMl) ~ Frseereh in the area of nioatint n l s fi hi f ir t a oq stv a aa ory o s . a 10~dacedes and during that timt more then 200 con~pounds heve be ~contidered ats potentiel an4loqs. Most of thete ere synthetic compouei g~hich were d.rveloped in eeodemio .laboretories. Some ert nature:l 'AIN o.:currinq alkaloids, meny:of which or* known to be present in tabta AM*•.d/or •ciqaritte, smoke end=var.ious,plsnt sources. A-1iat of nicoti analoys, includinq itruct>;rfi, itprestnted 'in-'Apptndix A. This incllides thc,se which have qerrr discussed in the liter.eture as we11' as^ thaooz e identified by CONAR as potentie9 analoqs, sueh es salt+~af'W roicetine and nicotine m.tabolitts. Appror.imattly helf of ; tht cermpounds listed in Appendix Aa r•W synth,etir, cornpounds whieh w.r+' ;:;preparsd' and tested in Swedish laboratories (1--10). Most of the Swedish:analoqs were tested fc-r physioloqical activity. Th.ir rsl`.tive poteneies -wfre oharact-eri,ed RJR21758
Page 641: raj82d00
L i t t 1 e i s present'1 y kr, own about the pot,6nt ia1 physi ol oqi cal or pharmacc-lc.gical activitr ot niceitine's metabc•lites. :ame researchers hav? post1.lat•td that;ootinint; for exempl6, may be pharmacoloqically active. Hawever, there~is f+r.tt.nntly v_ery little, if ar,y, evidence to support this idea. Th,erel'ora,:o litt of over E0 nicotine m*tabolites (in rr,osL t cases both atereoiaomer,ti) was compiled and a contrast hes t- aen initiate-i with Dr.. f'*ter Crooks (U. of Kentucky) to syn,t-host;e 9 ran, cluantities Of tho'aie -,.ompounds fos irncorporation into phss.e. 1 pharrna:ologicat i*oret6 inq' •'studits (see below), Twenty-fiva comfraunds wi 11 t-e synthesi;ed, ct;aracter°i t*d and forwarded to RJRT over #toe showr, irn the appropriat_e saotion of Appendix A. first year. A11 of the,r,tiftat.ol.ites to be synthesized and testedVire STATUS: A contract ~with. flr. P.ter A. Crooks (Associate Prorrs University of Kentucky ;Collsge of Pharmacy) was executed on Augui;t 1988 f or the synthesi's of 25 mito_bo1 i tes of nicotine over the e:o of a year. The metaboll.te: include the` mcjor* human metebolit4t nicotine and are listed in -Appendix A. Or. Crooks has'hired Or. Chinyl, a synthetic or.qa~r+ic'chtmist,,to perform the syntheses of ::.t cornpounds. Tha initi~l :,rnetabolites -to= be synthesized are:'t 3-hydroxycotinine, cis-lend trans- nicotine 1'-_N-oxide, r,ornioo.t and cot ~ N-axi de.i . The metabol i tes approxirn~L,.ijate of two: Fer month. se of so ie ns s, will be synthesized se.*n . As thiry b`qcsme availbbie these metabolites 1A a 60~ l on, the available: `~ fc•~in' laylical ac~tiviti,ts: 4 ~, ng in the nicotine receptor ~. 4enieity in=the Ames assay. Octanal:weter partition Dr. Corwir, Hanech. 2 's. Purity will t:eiqu.r'ant*od as end anel yti cai ;methode. A ,omplete rnesi' spectrum will reference. & ssaY (A.C. 'Co 1lirns) . qreater than 99s• by ehemicel determined for future ~ _ _- ln addition to be(n_g useful for ider,tifyir,q ~ this infvrniation wi11''b. invelueble to thf ~~ bioloqical activity of 6ieotiitie. analogs of eisessment . : Tobacco and Plant Alkaloids nicoti~., oi he At least 70 tobeato an4/_or tobacco smoke specific alkaloids have baen id3ntified over tb6 yfart. A recent review by leete (40) lists the struatures of 4f• of; the4f.: These striretureu fiave been compiled in Appendi,x C for easy refe'rence. Sorne=.of' the more-common alkaloids., such RJR21767
Page 642: raj82d00
~ - - . ; f.perim!nr,al tndp.•ints to:tr util`i~frJ and thh er.-l,puse laturat that wi i l support the arrel•c•v F-rogr'am. PROGRAM PERSONNEL / RESPON:SIBILII'tES The .f ol l owi ng RJRT per analoq rFsaarah program: s4r~n e 1 a r# prfstrntly partieipetinq in th3 Program Coordinator (P.M. ~ipF•i;*-laca he coordinator i s rt=p~nsibte.' ' for '' orqani=inq artd inte9ratinq' t various components of the onal*q pro'qram and : for reportinq qerF..r 'v.r rogress, includinq retv'Its, Conolu4.iont -and r.commendations. 'T boordinator is also responoibte for itit* rf.oinq with the t.boretorp'' r. Allan C. Collins, whfte:pha4_.:-I pharmaooloqioil sar*eninq wi1t': r,nducted, and for arnaly.tihq the t,eault,a obtiined. 041-014naloq Chemistry Coordinator (T,A, P*rfetti) W 0.>..~~~~thi i prrsan i s rtt;•ons~blt= for adv.i tinq CONAR on the ph,ysical„ hen-ical pr ties ot pottr,tial a`rna logs and tvaiuating the potent J,; or proposa : novel anajogs, ir;oluding various bridqed niaoti:n cornp;,urnda. as coordinat6d Vhe acquisition of niootin. salts a:c ! t~"st1, q end - is=inttr(aeir,q with RJ~tT k&D library perso ~~R.W•~li 1 1' ) to implem4nt a domFr`hensive'.in-house data base ~a~,icoti~ ena •a. UWAcqui si tion thesi s Coordindtor •=(W.S. Celdwell ) ` 14MV ' .34 h i¢ F•ersv 1 s coordinati the id.ntification and •cquisitiOn a hh j . :41, V ei 1 at.le ni~tine eneloQs : and patent`ie1 •nsloqs and has b.• esponsit.te for initid.tinq controoL: syntheses of those not presere_t:l W-'j tet,te, such as thost or:ipinal.ly-:deveioped in £wedish l.boratorf.a ja wi 11 aI sU be responsititi fuf the ideni,ifioation dnd •valuation:,o MM.Aribacco and plant alkaloids"-4S ;poibntial analogs, including ths.i ~cqvisition and/ar italat~i~on. This person is also; intdrfacinq w{t ibrery p«rsonnei to m.inta'.i_n an up•to-date •n.loq data base. ~~tructure-Activity Coordina'tor -$ .ars).ars) :Pv'lr,hij p•.•rson wi11 coordinete and fvaluate the ttructure-activi>t. ;~:ail~tEa1 ysasy of arnataqs, t•assd1 on - data 4oquirfd f rom phase g.harmaaoloqi+sal testing f~d -physi4o-ahemical. propefties meetured .in tha laboratory of Or. Corwih H,nsch. tie will also psrticipate in tFi. eY a1•uatior, of analoq-reeeptcrr, _ st~ucturdl interactions -based on ds:t.a wr~icr~' wi11 be generated at the U. of Iath, usinq thr.e-dimensioetel c e>niputer madei inq. Biological Activity Coordin'tor jJ:D.'de8ethi3y)
Page 643: raj82d00
Tt,i s psrsvr, wi il formu:lett an in vitro/in vivo t.bltinq pr4yren, f4r t.hr bivlc•ci ical activity of; ~otar,taal an,alogs. Thas wil~l include in vi tro icuJi+, t, b astd - onidantii' iad cardiovascular .end mutaqer,ici ty er,dpcuint•,; in vivo stu•lirs' af'car'dic.veaoulor phy=iu.l;6qy and overall city, and studiws tc, aevalud,ta t•ha-pt,ermac4kinet;ici ar,d rnttat•ulisrr, of r,icotinic carnFuunds. Su'i-Labl.,;~xwhouse laboratoraes- for pe,L•. 1e fundirny in these araet arb"'presen't;] y being i.dentif'ied. Behavioral Testing Coordin'ator (J.H. R.obinson) Thi s pers.:n wi 1 i ftyrrriIj tate an in vi tro/in vivo t*sting prr,4iranr: to ~esstss the phy:iological ar,4 behavioral tffects of potential analoq. tilizing er•-house ov1la'bGrat'ivt taboratori`is. Informal discuisiarg, ` ave already begun with `se~erel i~,vas4iqators. tructure-Activity Consult»ant (W.;£..Simmona) s This person is servin:)._as li~iaan io tht l.boratory-of Cr. Carwi~ ansch. He witt aid in t~he -4os04ment of struotura•aotivity ds ok~tai ned f rom . that l~boratory, '' i n col labo,rtti on wi th otructure-ectivity cooroinAtor,° ~`~'~ PHASE 't.PROGRESS. .4 ' I ~ . COMPOUND;S (M%TAP/WSC) Foter~ti i c o tinic c~urnpounds fiave bean tantativety as`iqne :ktour gen•ra :categories,, inoludin9 synthetic org.nic cornFou "nic0tir,e sa nicotine m'etcbal itea, •anti tobacco/Flent alketoids. ., ` Vvfallowir,g ieLw.,jans summari~i proi~ri't 1~yin..cquiririg compounds from ts ~rf thes~t ca+.«goriea for in;itiol;in vitro pharmseological testing. ~ ~ Synthetic '0r9.nic Compounds ~ Mure - than 120 ni06ti "iC coniis ounds were s ntheti:ed and tasted - , y - ~Swedi sh 1at•cratories over ;the iitt' two dtoades (e.q. L. R:nds ~(f:ayal tnstitute, of Technology ) and F. Haqlid (Nerolin4 lr~:ti tute)). Therefore, a'tttmpts were madE to contact these gr~tiu~~:= dtt+r,r~ine the status of; their work in the a rea, to exNlorr-t 004W•ssi bi 1 i t y of accessing t;hiir"J6ta.-l;roses pn .Ki sting compounds and` ' J iscuts the availability of eompounds. Some pr,tli,n,inary inquir-i were made through Dr, Qika;r $tui•ii. ~.t was diot~ove.red that two of prijnary Swedish reserrch'ers ir~ r<fie-fi.1d,,Drs. Haqlid and von £uTsr,: wera; dtceated. R: a resui t`.;.,ieotine analoq work in these laboratorie.s t,a,s bearn Jisr,or,tinued ar,d't#,eir onmyouridi `ira no long.r available. Corntact wa's made wi th,:'Or. Lara _;Aondaht, wf,o• i s,presentl y en,ployed by IVL, a£wedith institut'e involvod -in onvironmerital tor•icolsgical
Page 644: raj82d00
I ATTACWW 111 . ~'• .. . • ,~ .. •., `~...•. . u,., .,. i :% ootober Z0, 1988 Dr. 0. R. DiZtaroo Dr. W. N. Hildebolt AZ s Intercepted Pbil i~ 3torris _.lroftots 41b ` Niootin./hlavor,E~hano4Xant Tsohnoloqy R.c.ntly, two. Philip H4rrjs =oduqts (oodea:N4-and 93) were intercepted from a oonOum~r ~ast panal and th~ ahalyted by RiD.' The results from the ar~alysa_;tav. ;providsd -miyni9ioant inteiliq.noe regarding ,1a~ new Ahl~1~~ Morris t.ofino~oqy; and' may indicate a potential pxoduct applioation tor that teohnoloqy. Incr.aseMlavor and i0paat at low tar seems to be the development ~' T':~ obf.ativd" !br the int.roooted tost 'broduots:' - Most reviewers o! 'l .. , ~~ very sim ~t to Projsot~ xQf in :#~at ~WR ~~s preparin4 low 'tar' an '"J niootins bl.nds which ~ra .,an =~at~o~ by . ~, =t is im ant to not •th-at fixas~l ~rodnots rsbrssent teohnoloqy' a~a~iive sl.~sq nioo in./txavor .nhanoemsnt t*ohnoloQy. Ttiat Y..: >~hypotha;la~s support. b#bi f~turrt~al-blsnd oomppsittons, high of th! , test products d low ita 'oot~ns ~atios ~~ niootines, .7• ;"` °^•'•ac th~~Prod ata aoa a~raca~ti ~iishea rh-iitp xorris sorop.an ~ r~}~ paL~Fi~t ap oation bal~.va :ths 1*se ;.d*xlvsriss tiavb been ~ niootin.. = , ~~W the addition or natura?~ tobaooo axtra oontaininq biqh leveis o `an-4 Products such as tbosa ~~ntarosptl4 o~dld• be impitrtant~intr~es itr A v. o w t h k a.rna s~noe t s~ prov th. oiqaratt. ~aar a ._ s a Rs .....~..~..F *..1t *l.v~.o iw 00,21 h# ivar 1ev ~*~r! armuets that oombiiia thi bin*- tits 4! bat.h Q4teiqorl~es. Th! .produoks may also be impostant baoaus. : they ~~tsill a~ ~tsv ~taohnol _ ~n what will bs:; perc.iv.d by oonsnmers1as a oobvihtional oiqar~ t~ (which burns : tobacoo). ~ . . . , Phx.ioai. Qbamje_aXeL'aa1'bait. , aoth products were sim~las ko Marit 86 in appearano., physical data, and FTC 'tar' -di~iv+rtc,last hotraveri the remaining an)lysss revealed that -these prpduQts vsTo` =ad$+~ally, di!lorent from Merit SS as well as other Philip sorris proasots., The outstandinq analytical l.atures of 1thaUit.ppoducts wsr. lowhr total ciqarette weiqhts, siyfi3,tioantl~-Aiqhar tobaooo and smoke nicotinss, and lower ~,artvto-n ostloe ratios than Kerit 85 .
Page 645: raj82d00
f+vth":rbk F'atriCt M. LiF.E.ie1'1v f,F`ML ) (•'I Wi 11 i arn S. .'.aldwfl,l (kt^•C) (+) J. ~~r~a1i daBetti=y ~JGLi) (•) Thomas, A. F'erfetti (TAf)` (~•) JQhn H. Fot-insore (:JHR) (•) stephern f..Sear• (SFs) (~~) wi 1 1 i a rn S. S i mmo n s (w Sw ) ( s••• ) F;ich:arJ W. 1v'illianIs '(fiWW) (•••) r40 ups: Bioe.heinical/E-ic,teekievirrrel`--:`F;E.b (•) Applied RSO (•4) ' RGO Admin. & Servioes (s4+,) Smcrkinp & Health (t•••) &fir•1, 13E8, No. 265 *" :. af Faqei: Oate: October 7, 1:ES Nptlfbook Pages: N/A . ~`rGjact3: f "f 1 ~ . ~ Bicbe_ha _i,lrql ~ 011; - Ars~ 1• • 'r •h Ar4 tNTE*0E_G F e AF~i iKr~~ M-TKE STUOY-Q1 biCOTiNE AN OW4 r ~ 1ai .UA - U,- lows. _V4W . 06JL~~itE: • a divelopnifnt ond initiation of an , inteqr n-h~use/e>; tt program ~r, incroast dur s~nderstandin9 of the b :: •• ~,hysir,al, cfi iical, pharr,~ecOloqical, arnd toxicoloqical propertie! ~,icvtina ar ts arnaioga. MK_ _ UMMARY: An analog reseerch proqr,am has been initiated in arde:E: M idanl,ify, acqtjire wnd oharo9tirize Oorfopoundi thet_ are sirriilar„ ,icatine. The primary 'op1 of this program is to'obtain a det.ti: ndar:tandinQ of the unfqve atrtietyral properti.s of nicat.i;a •ompr,unds which determine their bioloqieal function. In particu_l!a ,4Wthe relationship of niCOt±ine-likrt *. truct u r * t 1.0 nicotine recept '~structure arnd function wi?I1`be eraluetfd and this information wil:i>;. ~turr, t,t currtiated with F•hirrrr.ooltqioai and behavioral end points.. ~ Th,e teatinq of potential cr', mpounds wi11 Frocesd in three phssr *e first phase will involavt the proaurenvent of identified czmp ou.r, and ini ti el screening c,,Y the'te`' compoundt f or relative pharmacstbg, potency, using receptor bi.riding ass.ays. This work will be supF,,rt:ed by • quanti tative structur;r•eotivi3,y ; jinalys.s. Th.:_aeeond phase wi11:; invo'1ve in vitro bioloqlicel testing of appropriate eampaundt;; iderntifi*d in phase one;. This wilt include the deterntinatiGn aV pharmacoloqical properties-, using apprqpri+te ilectr;ophysioloaical and neurvchemi cal assaya. Ir,; addi tion, a program to oharaettri ze the bioloqic..l ectivity of nic:dti_ne will• oe ireitisted in order to develop _! CID
Page 646: raj82d00
whiCh C4rr.;lates t. i-,to~'iq4 l ac.Livity of riicVtint•like cornp0unds wif,f, fund aonintal propart:ies.. . 1t.wkuld be surprising if "1oqlF')" were the cnly variable necessary~-tc1 ,ri6a16-tt+e earretation. ' Mvre' tikrly, vne or mare variat;les frorre additi,Gna1 -~cattqories:-(-aee +bc+ve) will be required to produca a suocesaful Q;,AR, Thf chr,ict of additional variables dapends upon several iactort. ft,remost among these is the selectian of a sp-ci f ic biutoqica' acti,r,ity ,to ~m4de'1 : The binding assay data to l•-e provided by Profestc+.t A. ' C', • Collins (U. of, Colorado) is e log:i'aal C hO 1 v d. .Tha ne..t s tep rfouirtd, for the QrSAR por`tion sf the pro consists of salectir,g: end systematically cate9c•rizing poten analogs into famil_ies;_of compounds. The original compila,tio already partially structtirtd a,lonq these lints (s.• Appendik ~). Collaboration among -Oty's f.rfstti, Caldwell, tear; and Simmo11668 y then identify those terniii.s toba pasied on to P[of.ssor Hansah or preliminary QSAR work~ -__Thia woriC- will consist of selectirq he general form c,f the GSAA equationwhich varidbles to inelu ), and sul>sequerntly, acquiririg the voriable values for the core eompo ds " chosen. results The actual detfrminati olt af::the QsAR equstiore must await he of t-inding e>:perimsnts frorn- Dr. Collins' laboratory. Structuft,tivity Rel'tionsh-ips r 4 ligand-r.ceptor lnteractions;j(194L) p e ir ry arnino ei.cid sequenC:es of a nurr~ber of nicotine rt ~or s., qV*i ts ~m marnrnal ier~ rcin=havi _been determined. Drs. Georqt nt ea9~:us onnacott tiave r*q,tntty inccrrparet4d atudi•i af tht wn receF~tur, `enoes iroto ithair RJRT-fun"ded research pro9rarn in vr te take aclvent e of the st'ati-of-th7-art molecular modeling oapabi `es availaGi •tha .Liniversity of-6ath. They presently have the ebi :ty t4) model 'lr'4re nicotinR tinding':sts.es of the various receptor sub-t es in three dimensions, usi,ng oomputir software ("1NStGHT") developt:oci,.by Dr. E.A. Osguthorpe of t;t,tir mol#pulat +nodelinq te,am, The suitabi .ty of a given compound as j rfc+ptor ligand can be assessed by `u energy rninimiiation apFroOqhis ihd.applying them;to both receptor campound structures. It -i s.trrev#sioned that this approach could at_ ~ed tc, seleet high probab'ility .as.t~uotures from a group of pottn al r,icotiroe analogs es w.1L -at• t0;pr~diCt novel strueturos. • '~ Phase ! t teatir,g_wi 1:1_ be beted t,"re in vitro fun;ctional astays:._a.imed at defining pharmacolo'pieal pot4 noy and biolaqica) activity of poterltiai analogs, as w.lt ~as,-understanding the effeets of chronic nicotina exposure' in marntnals. Tht.1at,ter program.'wi.11 be necessary for the dev4luprnent of tebhniquts 'ta ~Gssesi'tho bi'ol'ogieal activity of nicotine and its analoaf'. RJR21771
Page 647: raj82d00
n'~tthQdi f~f thtr pl'!/iirOCi 4_n ¢f-I, iAGtine inalG9 s, rbceiving patents for Sfvrral (swe Appendi,: fiheir inethods eriat.lel the prak.aratiorn of a, ic~~tin.sids titirinq ill.yl ;ar,d ,try1 subttitusrits o1'4 the pyridine and pyrrdiry a rinqs in high iohen, ical end optical yields. They have also J nk vrl oped a rwrthod for the° pr,eparation of anaioqs whieh eorntairn carbon cf~ains of varyinq lenqtfis- conrstqtinq`the two rinqs of nicotir,e and havd r.yi:vi•te'd the syntheii,`f of several such bridqed ; nicatine af, iioqs (t..). rei. 10). (n conjunction with th'eir-=synthstio work, these investiq.ators Etiv*:° drveloped a liquid chrop.,ato9raphio method for ihe enantiamsr:i esulution of nicotine an~ nigvtinc. analogs which uset a-eyclodexi;at onded pha ses ( 19 ) . A qr..a;t ~dfo1 - c, f ph.rmaool oqi a.1 -and physi ot oylfa r t.estiriq h•as also b~orri*d out in 1•boratori.es funded by~R! ncludinq Martir, at al, (MCV). Ro=eorans et 0. (MCV3, and Abood? -i , _ (U of Rochester) to Rostorans .nd Ai~o^ ` iio rdin vfr o c , : q we , c o uersonal corrrrnunications) inuch oT `-this was blind testino and few ~,~~,..~ . .-..-. .... ~ ~... r...., .,..~. .~ Many of the potentiol anal,oqs developtd by Philip Morris •ttov 1 ready been sut+jecttd to aensory,.tes,tinq. For exantipie, work in 'lt of strctu a-activity;rel,rtionshi_ps in odor and flivor percep;iljj:. f alkyl su uted benteiles . end pyridints was pr.sented by .%~ S* err,an at a.. > . J8o (20) . y,. ~`4 . W_1V1 Th~fac ~ ; ' S hi .... .tef. vt makes 1't 1 tructure-a atabase th h e desired ;~ f r,he 'vefreparati ~ r2nd Tobecka,Ch.misti' Research.Confertnoe in Octo at PM sciei+tists '4.r `their collaborators have subje nal;,qs ts. ilindinq, sensory and bic-activity atu ,.,y thet they'heve been:able t•a compite a databate on ti"ity rtlati4nships for nicotine. Utiti:inq 6ght be ebl;, to r&tiqnelly design nicotine analoQs wVt *W~oqical sctivity,, end`sinsory attributes. Applicati.o . synth:tic me+.ho4oloqy disoussed sbyvt would enable on of these nicatine anel;pqz_. wedi sh Research - A numt~et of Swfdish groups, fund.d pri~narily by 1;! ~wrdi sh Tot>acco Co., devel.4ptd nov,tl;,-synihetia anaoques of nioottn ov%urinq the decades 'of theA60't',nd 74'•s. These compounds were stu~A;o' `~xtensively by Erdtmpn, aHaqiid, y i!+'n fuler, ond° Rondaht (1-t4~) . ~p~:~rc,xi~nicely 1:6 ~iottn~i_+1 a,naloqs4 were devsloped and te4ttd o vwrver, this work was l.discontinued, with the last pu4liciti peariitiy in 1980 (10). t'eCY few C4MpGunds :showed .Fpr.ciable actir ;A . ~ ,n' assays desiqned to measure -nturon'outcular- nicotinic rtspons:itt .; Hawtver, at that tirner it wos, n.di realited that the CNi nic-:,tini-C receptors were tubstantially _cliffeftnt, an both ttructure and functlon,: Thare,fora, CNS potency iemdlr,s unctiarao.tcri=ed for nwst of tbes. oorr~pounds. . Misceltantous - Dr. Wil_1,tim-.Me rtin`(Ut of Ktntucky) has bequn to cornpile s'tructura-aotivity:4.to on sbme pyridine,"' pyrrolidine, and
Page 648: raj82d00
(c1,,;l ir,+r;io) receptGr syst~mi' ir• the brain. One clettc of si tes hir,ds nicctinr, whigh affinity ar~d eppbar= t~• LlrYve i neurGnocdulatcary r,l,e athtr tir,di elpt,e-iiur,yarotOxin w.ithi hiqh" affinity (ar,d r.icc, tir,e with, 1aw effin'ityl an.1 ii tAr~u4ht tG noediate ntvr6l treyrr;r111LtiGn in the t,rain (;a). :ince it is likely that both sytlerrrs are irnportar,t in tha produttign of pt,arrnaeola9ieal`` yffects, `atentiel ar,al-;oqs wi 11 be scr..erned usi rrg tiindiriq assoys for both. Th,r capat:ilities for dosinq so a te presently'available ir, the: latt~:ratGry of 6r. A.r,. Cv11-i.ns (lt.' of Colorado), who already has s: cc•ntract/cc, llat.arative eqreerfrartt with RJRT irn the .araa of nicotine~ : ~. r e.searchr. A. separate cantraot ;wai drawn'up,: covsrir,q the screeninq pf' ~ ni~cotinic corrnE. Gunds thqt wI tl be setos tcr. Qr. Colli'ns #+y FJRT. ThF3s: r aement provi des f or bl ind testin;c of: at 1i.st 30 s'tl ect.d eompoundli. , ~ Gv..rr the first year, usIn9:.teeap;'rir binding assays for both of t.hi jGr nicotine receptor subimammalian brein. 'The end point t` ypss in o~ . . t~ measured for structur}-.ectivi_ty stu~d.ifs wiil be the inhibitiort n•dinq constant (Ki), the oono.ntfiition of a compound that inhibils49:. •a of the bindinq of redlolabeled niQotine-or alpha-bunqarotoKin t:o: receptors. es The phase I criteria for the suikability of a given compound as a#t fi'rective an wi11't-a thi a`bi_litj~ to block nicotine bindinq irn the~ : 1:,w nanan~ol~anoe and ;bu'r.rearot•oxin' bindine in the .liow micromolrr•d ,ranye. These W eria were bated on- the known affinities of t '*4<8"rp e c t i v e 1 i:fq a rr ' F h dow I s for the teesptors (t3•i5,?E).` tirny will , t•eqin with -spprqximatel,y 60 compound ir,clu0hi*M r+t~ ntacive struaturet from Che four Frimar.y cateqari 'iti;,ned ae ' , i.e. iyrr4hitiQ ina104s, ni0otine =s1 ts, tobacco a i~~nt sll.alr,ida nd nicotini rndtabolite.s. MK~ ~tructure-ACtivity Anelyses . Phy°Sioo6hemical. Parameters (S6S/WSS) ~ Phase I of the CONAR prcoQram consists of thF identifieatian:,:- .rdictic,rn ar,d screeninq a( pas"sibl,e: mql.cutar analogs of nicotintc rnction. The relation4hip Letwfen the thret activities i# ~:es:eril y strongly cc-uple4. 6eqinninq the cyole with ider,tificatior~: ,~ e..i sti n,~ rrrotecular -- carididates, .6 _ verification , of hyp~~thesi:Rd ifiorict iGn i s made orr the besias: sf a-stsr,derdited soretnirnq procedure;.: nq then form the ~a}e spe3ief showing posi(ivt retultj in the soretni . ;'s for prediction of "new" carc didite; for testinq. Amoncj tha: predi cted eompounds, scrs#nirrq ;wi11 typically reveal suceesses 664 reilures. The •uccesses ser;ve to updat. and extend'the di0tionary of:. prav ejr cGmpaurnds, strenqther,inq . eonfidence - in , future predictions..t lGqice•lly, the eycie iteratit. !o a ielisfsetory 'endpaint, at whi oh predicti.:-n of positive r,i,eotirnio funotion is stati'stically robust. F;«ali:ticblly, such e prac~eas rarel,y eonverqes to an exhaustive dictionary Gf compounds. ~ 3:nst-eadr the endpoint is rnore often a dittribution of compounds ;useful for -prediotin9``species function RJ ~21769
Page 649: raj82d00
end the numeric.l prrametfrs iittinq to Lnown activity dst~. : 00*A~r ~ P~: , dn_d o" •r• determin.d by reqr.ssion ; I
Page 650: raj82d00
STRATE6IES/PROGRAMS: 1. BY ADVANCING OUR UNDERSTANDING OF NICOTINE AND RELATSD TECHNOLOOIES. MEET EXISTINQ AND EMERGINO CON=UMER Dck"D! WITH THE TIMELY DEVELOPMENT OF SUPERIOR PRODUCTS. PR~rs~# 1. Low TAR/HIGH FlJ1VOR (GT) 2. Low NYCOTINz PRODUCTS (LN'!) CONTINGENCY 3. XGT' 4. Low NICOTINE PRODUCTS (LN'f) DEViLOPMENT S. BETA 90 6. PREMZER NN ATTACHMENT 1: PRZOR:TtZATYON CRYTERIA
Page 651: raj82d00
A brainstorminq ssssion oonduotsd witb-Ri0 experts from various disciplines generated t;h4__followb9Aypothssaa and discussions regarding the tsahnoloqy'and .dav~~il6paant objootivas tor`thss• Philip Morris oould~hava,obiar-Mdthi bi niootinss and subsaquant•low ftarl"to-n~ootibs-ratios. bls~nd: olsiiion alonst howavsr, thio hypothesis is vu~ik ysino Phi p Morris would bavs dlkf! ou y4nstailpi anationai brand o! . this tY9s bioauss "ot tobaooo_ ativailobii ty isovos. ~-lso, ths ..: - llavor and aooaptab l~ty o~ the ?~i sst biootins--proauot would be di!lioulti o iohLovo by blend solootion alone. deliveries by addiny nivotiAs/tiavors to the blend in a mannor. It is mors likely that Philip-Morris aohiovsd thos• niootina Korri oonsl: similar , ni ti th oot vol o R7R Proj oot %GT.tiohr~oloQy+ This hypothesis is t with ot~i~-',.r. int~alli10noa r~qardinq the now Philip niootinisst~ion proasps and ~savy swphasis on llavor rassaroh.~ i~ Aiootino, low ~tart-to•nioot duots may be tho ~~ se~~iva~t tbat=1roosss and rass ay rsparasanilt a,dpv_~o~i st-t ittost to ttilit• the llavors -ox~.raot+d 1 durinq low -fliootins produot to The .linatb of the tost=:.produots suoQSsts that these produots~would be so d i.n4ox ~-tbsr, tthan solt 'paoX versions Howsvor, the atypS. blin4t'~o .sdsst a-diro line extension but Usta~- ~~ow ,p~ with uniquo deliveries ii =l~t ~s +osphasis in tbs bo~C oat~ orias consistent with Ph or that is markstsd o~ box e~rodnot. '~his bypothssis to as well as the potsn ~il ,t#-rQ*t markets .tor produots with thos ;~, asi~vsrsos. _ ,-"4w produots. The biqb, added stoas tway, i:r4ioats A -cost reduction :-stratoqy but the lack oi bast' -vhsst;4 oontradiots: that_.hyps~thssis. It more liksly that t~is' stsr~t -Ar~1 ~=cost--oltsotivi vehicle for adding tlavors/nioot1no, totha.blsnd. RJR224a7, ~
Page 652: raj82d00
~ t,,,,,, a givcrn chernical fa/Tf i1`y. 1 r, corder f ur the i terat iv,a -schtrne outl ined at.ove to succt4d tti«rF rt. v :! t~ a rel ibt- ie method to~yF~othesi=t rr~oltcular speeies wto ich n~ey as nicotint analr,qs, ':~ This ~ask its.addressed by Qu.nt'itative :truc+.ure Activity Relatiorr SAR) -ttiaar.y, In brief, Q;AF ects a: a b r i d c) e between rnicroLropic ; orid ma'crosc4pic descrif•tit,ns of oh«rroical carlipou1*1 d runction, wro i 1# -t to er -o~re no~w n,eny varie'tlori s of str~,cture-activity thearies- in'the litiratvre, all Fievi trne objectivw ;n comrnar,. Thfy seek to cort.l'ate soin4 mfesurt of biolaqical sr t•iechenlical ectivity with; ttlscted charnica l propertitss ar.d/4r prc•perties of riwlecular structur*. FcF r the purposes of Phase I of ,thi CONAR pro jeot we have e4optaRd 4T1. The H.n:eh mtthadoloqy: ~e Hansch spproach to QSAR m~idelinq (iil , i tecome a standard tool of thf"pharmee.uticat industry, and hes` ~,betn applied successfully to •en #normous varietr of bioloqicet' ~~iviti.s and ehemicel fies. 1n addition, Proftssor Hansch i eady carryinq out QSAR research under : a dr•nt_ with RJRT A maco: '91 ai l•d description of .the;Hensoh- a pproact+ is presonted in Appendi>r. ,.. ~ifWh The basic conoceF,t of the pproech is i;iased or, the h,ydrophot~icit ::. X,,' r,r~ti 1 s:- 1 ut, i 1 i ty, of compounQs . ' POZO The ir~~po'Ojwt r.ole of i hydropfiobiaity in det;rrmininq bioloqiuals es activity has cornfirrntd i~ Q;AR ;tudies on many div;erse famili ' nf~ chamical unds. Hyfipthtticeily,'the inforniationr imparted by it0fd.i&ophot+icit pe arneter ec-rr.40lat:es with the affinity of a' pertioula ca#WW1spe for the fatt;y pha4ts of nerve cells. Thus, a highl F- hdV* c sF~ cic s might t~e fk.und .3o pet+etret* sc~rne o-.11 mamt,rarno wi th ~~ii~cul jficieney. .:,W6i1e (t' ha: not be'en conelusivel'y prova 'OW~:~1t the "#)ct#w.ter" perti:tion -rotio is the optimum - indicator o 't*$logical hydr~'hobicity; it has -nev4rtheless become a standard i: ;44,': f i al d_ F werL ear ri.d 6ut 6v Wa nteh st el .. _ -- 44) under eh RJRTprent;.rsveils< the importance:bf_,,octanol/wateF.e titior coefficients in' o;orrel,et`inp Ames muteqenicity withi'>3;, rerent classes of organic oompounds. nificant:< drophobioit se h E«ca ;i h p ihesi=•d to b• . si q y s y y u y -jk&.jperty for t.pecies displ.yir~q nicotine-1iw• activity, the first sta~p'.. - ~ the CONAR QSAR program het, bten a dettrminetion (or tstimation) " ' " ' " preliminary ) l(F param4ter for; vorios s•peci.s in the oy,..-u' ' re presentsd in: ilati.,n t. f nieatine arne'1.o9sA "These values a . *"endi+, A along with the acs0npenyinq Chemicall namis. The n-.oriberu .... ,~~or r.ed are ei ther the r•tu1 ts of experin'oental meesturemtnt s or art; 04*4-n. at«s calculat.d by means yof a c-t,mputer alqorithm in Frofes ' Hanrcto 's laboratory. Eoth;- computer estimates end .xperimentst: cr,,ff iciants art included whent possible in'order to qi"ve' an indication ; cf the atqorithm's ecsureoy., l,t CA.n be e*tn that the quality of th.; tstir..e't'es varies, but tht velu4r= ars °=in general sufficient to qive rou..)h idta of the species' lip546phificity. The hy,lrophobicity varietrte is expected to;eppear in any Q'sAR. R J R2'I 770
Page 653: raj82d00
pletelet and vasculerii<uri-ct_ions,:heva besrn reported in healthy im4kirs F. r i o r to any rroarnifatta{io.C oardiovoseulsr 'israse Ires bern used to emphasite th s irnportonot' trf the `srAOkinq-inductd augrnented pletelet eqylregatic-n in vasCu.1ef dis+r4so 'i4cjj. Flowivefi tFie' role, if any, that nicotinf pleys in `Lhlsotivi t;.irt_40bsorved in smoh'srs is stil l unolear, 6efor+ trying to chare4trrite this biological •otivity for nicotine aneloqt, it ' must ba !, +lrt.rrnined what role nicotine itself pttys;: if any, in thi s sJi feat•a pr'octss. The chronic eff,eots_ o(, niootin. _ exposure are not we11 cheractarixed, but havo; been ~r.ported to include efrtots on,'', ~o.cd vessel intimal pe~iro oa;b{1ity, impoirment of ondothtlial fVitc. on, effects on platelets on'd on ihtt0s4tion betwoen platelets aAd the vessel wall, effects o'n 'plasma lipoprot.in profiles":a on other atheroqenio evtrtiis, on fibrinogen lsvels and blood f_T ul:ity (49). Long term studi os wi th ni ootine In exporim.ntal animsi's~svo been limited.' ::. ( In one seri.s of studieo, is was found that nicotine kq edministered twice a day intramuscularly) sdmini~f.etod for 22 ths to beeqles produCed sim~l•"r oordiovoscular,-chinqes as wert prodv0>in a group of beaqles -smoMirtq 1 oi9sr.ttes p.r day. These oh ges inctude evat.d meat+ aortic pressure and deeroasts in th:+r 'oft ventric , ejection fraction iir,d tht -, first d.rivative of sft ;Q ventric*lar~ pressure 164). Tfissir'dosss of nieotine are reason if ~con ide that a s~nak-ir_ .a~bnsuming 40 oiqarettes per d and a~~rbir~ 1.5 mq/ciqWotte: would~ have a dos"of--approximatr 1P.85 q/d Howevtr, th}r`a -was -no -conf i rmsti on thot, equi vat ent ses wtre used;in the-smok'in9 studios sif10e the eoncen. .. ion of nico na:in blood wa; not dotormined. There wsr• no ai qn ,o.nt chenyes heart r4tet strok* volumo, left ven,trioular end di'ds sic pre:sure pd volume, and intravontrieular eor,duetion timr{ rrar t i l i h l id eorp o oqy -a~1d strum rnyocard ip a s ~. The 1onq-term_ osrdiovascu'lsr effeots rilpor.ted to be •ssoa ',ted with srnotinq can not be~ssoribod to nicotine with:th. date cutr. tly he available. Because '.or th o ...out:., .ft.ot,a ` of niootine en :.t cerdiovasoular endPoinC 4.*ot~fbi~d_abovo, niootina has bten idsAt a'td as the ltadinq oan-di %~t, in , oi9sritte omoke responsible fo the cardi ov.seul ar di se.oe ; r"or tyd to, be assooi ated wi th s,no Nowever, in sc~me .thnij~ qroups` o r in the :abseno. -of hyperlipidlta .>!in the western populatton, snookiAqk is Aot ' associated 3th atherosclerosis. In tdditi,9,n, thpr, is a fair, amount of tale e~ot inductd with rtqard to sympot#~otio'ootivdtion by ~smokin9 or oh nic nieotint administration.' 4Toxicity Tsstinq itrdte4.y„-(J,pO)" 1. A basic research program sti-dttermine the role of nicotine, if any, ir, the etiology of peripharsl votioular disease , or coronary heart di skase would be ini tiat;e4.-Th_is_ i; ourr.ntly envision.d as a two year proqram, in a l.bariVor,y. -to' b.. dstsrmined, beqinninq in 1989. 51>70 1$05
Page 654: raj82d00
f.F•trir„rrnl,dl ar, in,dls h,es t>ten dticriht,i. Srin,e of th,t effects rep?rt!r in •:hroa•,i c t•tuJiaa ir,cludal qrowth retardation c,r . wfiQb t ivts; ddr±nel sr,larqemtnt; ch,drc q e5 in tr,e e4n)ur4 ..tiVe, retine and GF't14 ntrvt~ de.) rr,erdtive chanyet in tr,t ;•itlilta ry, th y r o i,, arid Otrier F.arts h.; nt r vGus syStern. Hr.wtrv«a' a in tt,t a_'i_6d Rep_or t of tht FJv i.SOry Coi t tee to the 5urqeon Gtn* rat af~ tha 'F•ubl ic -Htetth *.ervict (47) i t wd:• cc,ncivdo.J that "mott Gf 'the r.hraonic :tudiaa ' on nieotine were p~.r.,r1 y d.,tiqr,ed era d controlled ;~ end were o f littlt value fa.,r POp,ilar, to n•,an." Vne o:f the'Ri,Aj0 r'profllems with ever, the rratti ar' th ete stuclits wes that th,e dai1 y'rdcd se of ni'cotir,e wet clase to the:t me<irrmum tol+tr.attd dose which .~is fer _in ;ixceS! to thQ - hunfan smoking' e.~.csu re. lt was cornclude;d that even • thouqh the 1t11diei wrrt•. deq uate the data suyges,t; that 'ohror# ic systerni.c toxicity of, ;smokinQ-dosd* (4$).-Ttierffore, it will t,e: rnicotine is quite law at ~~essary to characterize the; ehrbhio toxicity of niootine employir,I N,doses relevant to smoking. 00 ry iooEi~e ~ The reported elevation #R ' •rdiovasculer Activity of .N qa ~..n~., ddiovescular mortelitr of sn•,okers has been attributed by sarne pecpl • L; rl 1. V 4 1 fl7 • .1 VwC v v,, O i V I• . _{.. DYT iW.IV• me7 VY 1r 0 . v Y sI. • v v.•. i. W••vW nic.tint "th,e case fr,r n~iCotime es the miin cutprit #s vi 1 y deba In fect, ;i tstens. prematurt to asstrss the retativ! ~; r0 les of ni ':ne, carbor, ; morioxide and other testimated 4,000j: `"a.,.r~..stituents sn~oke in (he cavfetion of cefdiovasculer disesses."~ Sa dr rat re on tobac++t th i : svi h ld l