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Eclipse. Tar & Nicotine. Welcome to Eclipse.

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Eclipse Offers Page 2 of 2 Questions about your order ... Call 1-800-708-7878 (toll-free) 24 hours a day, 7 days a week. A customer service representative will be happy to help you. 6ttp://www.qrdirect.com/cgi-bin/ncommerce3/ExecMacro/ECL/offer.d2w/report 04/24/2000
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Select Your Flavor ® M C~3C~II~~SC~ Home FeH Flavor Yenthol Customer Ser,•ice IM' -.~z" You have 1 item in your Shopping Cart "W ri a Yiew Cart <M'Za: u'~~i._ Cart Empty Exrt Sile Select Your Style Eclipse Menthol - Carton $25.95 Questions about your order... Call 1-800-708-7878 (toll-free) 24 hours a day, 7 days a week. A customer service representative will be happy to help you. ..Jreport?Krypto=Y2UQY02IIy4kPnLoJyEsNPx%2Fmkw7sdQ9OoYPhgYN6nVnAiYYrm 04/24/2000 Page 1 of I Contect Us ~ -IM Ct,..d .. 11 r rgo' /3S>Cil~ ~
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Customer Service Page 2 of 2 your order continue. Browser Requirements We require that you use a browser that is at least compatible with Netscape Navigator version 4.0, Microsoft's Internet Explorer version 4, or AOL version 4. If you have an older version of these browsers, some sections of the site will not work optimally. You may freely download newer versions of these browsers by following the following links: Neucape httpJ/www.rjrdirect.com/ECL/service.htm 04/24/2000
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Select Your Flavor Tar S 6Lcutme Corn-ra lIN 6; <_:i1~SC3 Home ~~-FuIIFl.vor -~ Yenthoi RU~V,VUY W' _ ~MV ; ` ~ : You have 1 item =ur Shopping O~ffi o >a Yew Cart Empty Cart Custorser Serwe srte Map Select Your Style Eclipse - Carton $25.95 Questions about your order ... Call 1-800-708-7678 (toll-free) 24 hours a day, 7 days a week. A customer service representative will be happy to help you. Contsct Ua Page I of I ..Jreport?Krypto=Y2UQY02IIy4kPnLoJyEsNPx%2Fmkw7sdQ9OoYPhgYN6nVnAiYYrrn 04/24/2000
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Eclipse Offers Tar S WiCOtne rr r.rt Shop Cuetomer SerriCe Contact Us Site A4ap (l~C i~pS> - rull Flavor Ilenthol You have 1 item in your Shopping Cart ~u o 18 View Cart re-l"Ir:~-= tMM Empty Cart SPECIAL INTRODUCTORY OFFER Get a trial kit, which includes a carton, for only $23.95 (plus sales tax) (Free shipping & handling) Satisfaction Guaranteed or your money back. Page 1 of 2 W,, Cherf. . .O.t SURGEON GENfAAL'S WARNING: U atiog Snd.g Now 6remFr Redae hriars Rsks a Yarc NeaRA OFFER RESTRICTED TO SMOKERS 21 YEARS OF AGE OR OLDER FREE CARTON OFFER After your introductory offer, if you buy 2 or more cartons in a single order, you get an additional carton free. (One time only) (Free shipping & handling) FREE CARTON FOR STANDING ORDER Set up a standing order and get a free carton on your third shipment (Shipping & handling is free if you order 3 or more cartons per shipment) m ~ ~ . S httpJ/www.rjrdirect.com/cgi-bin/ncommerce3/ExecMacro/ECL/offer.d2w/report 04/24/2000 ~
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Tar and Nicotine Content a Tsr 8 L'iCa/ne Cantert COrdact U5 Sde Mep -,Mara . . put SUkGEONGM0.ALSWkflN14G OumIgSmakng Naw Grea'Fr R-~ue> Serbut Raln Io Ywr NeaAN Eclipse "Tar" and Nicotine Content EQFSE MEM;NOL 61Umg 'p(. 0 27r, n,~r,ne zv Ppr o}retre by FiC rrejnd. EQIPSE EOX 3 iTi4'ra'. 01 rrg ncxne ac pef riVets br FiC rtyix;. Page 1 of I Custorrce.r Service http://ww-%.~.rjrdirect.cont'F.CL/tnn.htm ii.l~-{ -1iUo
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Eclipse Ter & M1icntcre rArqery - 0 Customar Service Cortact Us Ste b~p Clleck ~ou Ec/pae e rr ext;tkq tr.e;anrra,gh n oo.2ter SUAGEON GfNEflALS WARNING. Uting S,mkrq Now Gemlp Redums Serious i'sla b w Nedh_ de.ipt_ We enceurepa ycu to tsk, your time snd rwisr lhe twa m.n ..cf ims d the .M to fuly .ppr.c ime haw Edipe<wo-ka s. wdlr eeriewmq Hr .n.nuN Kientific das Qta huG..n produc.d. W. V,nk !rt yai r CPrGW A/. Y NM hF/e. Net Ed pee .. Cater wy te .meke f a smoken .RMO h.ve dec ded na to prit The idonmGm bund on 9iis sM1e ia intended (a aurerd sdt/; smokers rnd healihcare professionals uucsested'n sdrntific idornutim and rnedi(al relefentes. P r-k~ I of I .../home.htm?F:rypto°tICXARhqpOc°%2BILcaZdYG},nuTEbBXk8vAIWA6u5Ps46TW°~o2F1i 0-3 ?4'2000
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Customer Service T;r 8 Pd;;;ctine CeN.nt .Ocinieg Smoking Priwcy5tatemenl ~ AeoutRJRT Virtvsl7Aedi. Cecter We understand that good communication is critical to providing you with the best Customer Service. We encourage you to talk with us if you have any issues with your online experience. Please click on the Contact Us button (in the top navigation bar) and select the option that best suits you, or call us toll-free at 1-800-708-7878. Your Privacy We take your privacy seriously, and are committed to ensuring it. To review our Privacy Policy, click here. In addition to your privacy, we are taking the lead in our industry to ensure that tobacco products are never marketed or made available to underage smokers. We have taken extraordinary measures to ensure that only adults (21 years or older) that have been certified can access our site. To read more about our policy on this matter, click here. Shopping Security We use the industry standards to ensure that your shopping session is secure. To that end we employ a method called Secure Sockets Layer (SSL). This method encrypts all of the sensitive information (Customer ID, Password, Email Address, Credit Card Number, etc.) that you provide during the shopping session. To further protect you, The Fair Credit Act specifies that your credit card company can hold you liable for no more than $50 in fraudulent charges to your account. In the unlikely event that you are a victim of fraud, we guarantee to reimburse you for losses up to $50: Should this occur, we ask that you notify your credit card company of any fraudulent charges, and follow their procedures as outlined in your credit card agreement. We provide an additional security feature to ensure that you are transacting with us - a digital certificate (we use Thawte to provide this service). When the Payment page is displayed, your browser ensures that it is communicating with us by examining the digital certificate. Only if this confirmation is made does http://www.rjrdirect.com/ECL/service.htm 04/24/2000 C1+_tumer S-r. ic2 CuntaNd U1- Srte A9ap -jw. cnea. ..Qut SURGtOR GENERAI's wA[NING: OWing L.dcig Novr Grealt/ iiedaes krious Rsks b 1wr Ikahl. Far Sm okvs Page I of 2 . FaHealthcaeRdesgiarcils Customer Service Contact Us
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Privacy Statement Page 2 of 2 Reynolds Tobacco Company's Active Mailing List, please call 1- 800-665-6381. http://www.rjrdirect.com/ECL/privacy.htm 04/24/2000
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Privacy Statement Page 1 of 2 wRGEON GENBUI's waRNMfi adfog SAOtiog tb.sfm* wtm sum " wrm fleaa. Privacy Statement Privacy Overview At RJ Reynolds Tobacco Company we respect the privacy of consumers. We collect information from our consumers in an effort to: • Ensure we are communicating with qualified adult smokers, • Provide the best possible service to our consumers, • Enhance our consumers' on-line experience. We consider the information about our consumers to be confidential and we do not sell or rent or transmit personal information or e-mail addresses to other organizations or entities without the customers specific consent. We limit access to consumer information to only those employees and representatives that need to work with consumer information. Email Address Providing your email address is mandatory and will only be used by RJ Reynolds Tobacco Company to communicate with you. We do not now, or plan to send promotional offers to our customers' email addresses without the customers specific consent Credit Card Information We collect your credit card information during registration and when you place an online order with us. The information is captured and encrypted using the industry standard SSL encryption. If you are concerned about on-line security you can always call our toll free order number at 1-800-708-7878 to place an order. Cookies Cookies are little pieces of information that a website stores on your machine so that it can recognize the same user when he or she returns. We use cookies to streamline the login process and to enable us to communicate with qualified smokers. If you are concerned about cookies please turn on your browsers security feature to "Prompt Before Accepting Cookies" to inspect the information that is being stored. Mailing List Removal If at any time you wish to have your information removed from RJ httpJ/www.rjrdirect.com/ECL/privacy.htm 04/24/2000
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Age Restricted Marketing Guidelines tor the Internet Page 2 of 4 offer easy access to blocking. . Browser Blocking Features . An integral feature of major web browsing software gives parents the ability to set up their web software to block access to certain material on the Internet through three well-established independent rating systems accessible at no charge to all Internet families. In addition to Net Shepard, RSACi, and SafeSurf, the Platform for Internet Content Selection (PICS) provides any interested party with the ability to create additional rating systems to meet the needs and values of his or her own community. In controlling web site access, the challenge for marketers of age-sensitive goods and services is to design a system of safeguards that works in conjunction with the extensive blocking services already available to parents. There are six system design principles: • Empowerment • Disclosure • Certification • Authentication • Age Verification • Password Protection Each of these safeguards is important and necessary. However, as with direct marketing, it is important to keep in mind that they are part of a system of safeguards and that effectiveness is a function of the total system. 1. Empowerment - The first safeguard supports the development and use of Internet blocking services. Using the PICS platform age-sensitive marketers need to label their web sites as containing advertising for goods and services that are inappropriate for children. These sites must be identified as being for adults-only. In addition, by pro-actively working with blocking service providers, age-sensitive marketers can ensure that their web sites have been correctly identified for blocking purposes. This will facilitate parental control over sites that are inappropriate for children. To help enforce this voluntary rating system, age-sensitive marketers should agree to rate all their web sites as part of their regular business practices. 2. Disclosure - The second safeguard supports and expands on the Direct Marketing Association's code of business practices governing Internet marketing. Age- sensitive web sites must clearly identify the marketers sponsoring them. As part of the notice, marketers must provide their e-mail and postal addresses. It is also important and necessary for an age-sensitive marketer to clearly communicate that its web site is restricted to only httpJ/www.Sjrdirect.com/ECUguidetines.htm 04/24/2000
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Age Restricted Marketing Guidelines for the Internet Page 4 of 4 Protecting children on the global Internet while preserving the rights of adults who want to access age-sensitive web sites and ensuring freedom of expression for the publishers of those sites are critical challenges for parents, policy makers, community groups, and the Internet industry. A combination of Internet blocking services that effectively empower parents to control their children's access to sites they consider inappropriate and the system of safeguards for age-sensitive web sites that are outlined above meets the challenges far better than could any censorship law. Questions about your order _. Call 1-888-333-0195 (toll-free) 24 hours a day, 7 days a week A customer service representative will be happy to help you. httpJ/www.rjrdirect.com/ECL/guidelines.htm 04/24/2000
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Age Restricted Marketing Guidelines tor the Internet Page 1 of 4 su*scoe sExeue3wA=s ae(Mgsed;., Naw 6rtalh Rdaes Saiaa raks a ffiw Neik Age Restricted Marketing Guidelines for the Internet There are emerging technologies like the Internet that are being explored by marketers. Some age-sensitive marketers use web sites to advertise and sell their goods and services and they are expected to exercise due diligence in limiting youth exposure to this advertising. The key for age-sensitive marketers is to control access to their web sites. However, with the rapid expansion of the global Intemet, the issue of controlling access to web sites is not confined just to sites advertising age-sensitive goods and services. The broader issue is protecting children who use the Internet from any material that their parents or guardians consider inappropriate for them. Responding to this broader issue, the Intemet industry has developed a wide range of content blocking services to assist parents in their efforts to ensure that their children's Internet experiences are consistent with their own family values. By using the advanced blocking services, parents can control their children's access to material on the global Intemet that they consider inappropriate. There are three categories of blocking services: . Stand-Alone Blocking Software . This inexpensive, easy-to-install software runs with an Internet access program and blocks access to whatever type of content the parents believe is inappropriate for their child. In fact, this software is now being installed on many home PCs at the factoy by hardware manufacturers. Blocking software products include Cyber Patrol, CyberSitter, CyberSnoop, The Internet Filter, Microsoft Plus for Kids, NetNanny, NetRated, Net Shepherd, PlanetWeb, Safe Surf, Specs for Kids, SurfWatch, Times Up!, Triple Exposure, and X-Stop. . Online Blocking Features . All major commercial online services as well as over 145 regional and local Internet Service Providers around the country offer their customers blocking features integrated into their access software. These features are easy-to-use and part of the regular menu of options offered to users; these features are offered for free or for a small fee. Nearly 14 million Internet households have access to online services that http:/fwww.qrdirect.com/ECUguidelines.htm 04/24/2000
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Age Restricted Marketing Guidelines tbr the Internet Page 3 of 4 adult consumers and whether personal information is collected online from individuals. Further, the marketer must disclose its privacy policies and advise parents on the Internet blocking services that are available to them. All visitors must enter an age-restricted web site through the 'Yront door", where all the Disclosure, Certification, and Authentication information is located. All banners or other hotlinks to an age-restricted site should be clearly labeled as such, and they should link to the site's front door. By providing this notice to Internet visitors before they access an age-sensitive web site, marketers can enable the visitors easily and quickly to decide whether or not the site is appropriate for them. The notice also facilitates parents' efforts to control their children's access to inappropriate iveb sites. 3. Certification - The third safeguard is designed to reinforce the notice that an age-sensitive web site is appropriate for only adult consumers. This precaution requires Internet visitors to specifically request access to the web site by certifying that they use the sponsoring good or service, that they are of legal age, and that they want access to the site. Although age-sensitive marketers are fully committed to protecting the privacy of visitors to their web sites, visitors must be willing to accept the sites"Terms of Access". Only adult visitors who certify their acceptance of these terms can enter the site. 4. Authentication - The fourth safeguard authenticates the address on a visitor's certification. There are several ways to do this. One is to collect privileged information like a valid credit card number. Credit cards offer an excellent means of authentication because only the person responsible for the card is authorized to make transactions with it. An underage person who uses someone else's credit card to appear of age, commits a substantial crime. Also, authenticating a visitor by using full name and address information greatly enhances the ability to age verify the visitor. 5. Age Verification - This safeguard is designed to check the age of certified, authenticated adult visitors against third-party information to ensure that visitors meet a site's age restrictions. Visitors can be age verified by checking commercially available databases. There are numerous- vendors available within the Direct Marketing industry providing real-time date of birth information. 6. Password Protection - Once a new certified authenticated visitor has been age verified, a logon and password are assigned for subsequent visits to the web site. http://www.rjrdirect.com/ECL/guidelines.htrn 04/24/2000
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Eclipse - Site Map Cu_tomer CEIY/2P_ COntact Ue Sde Nlati Page 1 of 2 suuM 6txteatswuuN6: aMpq s.AN low 6rod* Aedaas Senaos aeks q Yoa NeohS. Site Map Below is a map to all of the content you'll find on our site. Eclipse Home Tar 6 N:COtine Cpnlent snop' Cuetomer Service CrallaU Us Site Map 4uieurg Smowng priracy Ststemenl About RJ - R[yt»ICi For Smoken 6uy Ecllpxe NCw The Eclip-e Ogorcltc Thc Etlipse Esperferre --`° --~~ For Health Care Profcsaionala Scknl:Gc E>earirve Summary 1e5t4 BW httpJlwww.rjrdirect.com/ECL/sitemap.htm 04/24/2000
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Virtual Media Center Articles GJ C tGlLer s~Fvrc Coraact us Page I of I AnGEON GENEAAI'S MIARNING: qd5np Suokbg No. Grea* Beauces Seious ICslu b Ywr NeaYh. For Heaftheae Adessicrofs Virtual Media tenter Prem Relxs.s I Curtentpdvsrtsinq Selected Articles about Eclipse General Media Articles Only See Scientific Publications for Published Research (No articles published yet) http://www.qrdirect.com/ECUvmcatticles.htm 04/24/2000
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Eclipse - Site Map Page 2 of 2 Yr~mI McCm C.n[e SaGdvallon Guzranleetl .r(:1nlcf.Pi¢I. http://www.rjrdirect.com/ECLJsitemap.htm 04/24/2000
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Virtual Media Center for News Page 1 of 1 conte_-1 u- MaN sEnaarswantas: aasag s.dmy tb.srwk IIeaKes U"as 1116 .xaw xkaaa fv Heafthcae F}dessiomfs Virtual Media tenter Art:ales Pres RaIaae._s Eclipse News CunaN Adrertsinq The Virtual Media Center is the place to turn for the very latest information about Eclipse. The Articles section contains general media reports about Eclipse. The Press Releases section is a listing of the official statements made by Reynolds Tobacco about Eclipse. The Advertising section contains the current campaigns running in print and direct mail. httpJ/www.rjrdirect.com/ECLlvmc news.htm 04/24/2000 a ~ J
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Artifical Smoking Condition Page 2 of 2 other than glycerol and water accounted for approximately 50- 55% of the particle mass from other cigarettes. A second ECLIPSE cigarette with a hollow tube filter design was also investigated, yielding similar results. bttpJ/www.rjrdirect.com/ECL/health/abstracts/refl.htm 04/24/2000
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Scientific Publications Page 2 of 10 Heat Tobacco." Talk and poster presented at the 8 International Congress of Toxicology. Abstract published in Toxicology Letters, 95(Supplement 1):186 Abstract in-vivo (Animal) Studies . Ayres, P.H., M.A. Higuchi, B.G. Brown, D.J. Doolittle and A.T. Mosberg (1998) "Comparison of Histopathology and DNA Adducts in Rats Subchronically Exposed to Smoke from Cigarettes That Bum or Primarily Heat Tobacco." Presentation at Society of Toxicology 38th Annual Meeting, New Orleans, LA. Abstract • Brown, B.G., P. Ayres, K. Boyle, P. Durant, A. Mosberg and D.J. Doolittle (1998) "Comparative Study of DNA Adduct Formation in Mice Following 90 Days of Smoke Inhalation from Cigarettes that Bum or Primarily Heat Tobacco." Presented at the 89th annual meeting of the American Association for Cancer Research. Abstract published in Proceedings of the 89th Annual Meeting of the American Cancer Society, 39:490. Abstract • Meckley, D.R., A.T. Mosberg, J.D. deBethizy and K.R. Van Kampen (1999) "Comparative 30-Week Dermal Tumor Promotion Evaluation of Cigarette Smoke Condensate from a Reference Cigarette and an Eclipse Prototype (7026A) Test Cigarette in Female Sencar Mice." Toxicologist 48[i- S, March]:236. Abstract in-vivo (Human) Studies . Chang, K-M, M. Stiles, R. Davis, D. Edwards, T. Guy, J.H. Robinson and J.D. deBethizy, (1998) "An Improved Method for Estimating Nicotine Absorption as a Biomarker for Smoke Uptake from Cigarette Products." Presented at 37th annual meeting of Society of Toxicology. Abstract . Stiles, Mitchell F., R.A. Davis, T.D. Guy, W.T. Morgan, D.W. Edwards, D.M. Riggs and J.H. Robinson (1997) "Human Smoking Behavior Study: Eclipse Cigarette Compared to Usual Brand and a New Prototype." Presented at the 51 st annual meeting of the Tobacco Chemists' Research Conference. Abstract . Stiles, M.F., T.D. Guy, W.T. Morgan, D.W. Edwards, R.A. Davis and J.H. Robinson Sponsor: K-.M. Chang (1999) "Human Smoking Behavior Study: Eclipse Cigarette Compared to Usual Brand." Presentation at Society of Toxicology 38th Annual Meeting, New Orleans, LA. Abstract http://www.rjrdirect.com/ECL/health/abstract intro.htm 04/24/2000
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Scientific Publications Page 4 of 10 Components from a Cigarette that Primarily Heats Rather than Bums Tobacco and Tobacco Burning Cigarettes Using the Fourier Transform Infrared Spectroscopy Sidestream Smoke Analysis System (FTIR-SSAS)." Presented at 49P annual meeting of the Tobacco Chemists Research Conference. Abstract . McKams, S.C. and D.J. Doolittle (1995) "Comparative Studies of Mainstream Cigarette Smoke Condensate from Cigarettes which Bum or Primarily Heat Tobacco in the Gap Junction Intercellular Communication Assay." Presented at the 7th International Congress of Toxicology. Abstract published in The International Toxicologist, 7:84. Abstraot • Morrison, C.C., D.E. Wingate, K.A. Beard, L.S Winkler, D.F. Simmons, J.C. Rogers and M.F.Borgerding (1995) 'The Effects of Cigarette Design Modifications on Selected Mainstream Vapor Phase Smoke Constituents Yields." Presented at 49P annual meeting of the Tobacco Chemists' Research Conference. Abstraa • Nelson, P.R., F.W. Conrad, S.P. Kelly, C.H. Risner, D.L. Heavner and M.W. Ogden (1995) "A Method for the Comparative Evaluation of ETS Generated by Different Cigarettes and its Application to a New Cigarette that Primarily Heats Tobacco." Presented at the 49P annual meeting of the Tobacco Chemists' Research Conference. Abstract . Nelson, P.R., F.W. Conrad, S.P. Kelly, M.W. Ogden and C.H. Risner (1995) "Comparison of Environmental Tobacco Smoke from a Cigarette that Primarily Heats Tobacco and Cigarettes that Bum Tobacco." Presentation at the annual meeting of the American Association for Aerosol Research (AAAR). Abstraa . Nelson, P.R., S.P. Kelley, F.W. Conrad, D.L. Heavner, C.H. Risner,,D. Taylor. (1996) "Quantitative Comparison of ETS Generated by Different Cigarettes. Part 1: Environmental Chamber Method and its Application to Commercial Cigarettes." Presentation at INDOOR AIR'96. Abstract published in Proceedings of the 7th International Conference on Indoor Air Quality and Climate: Indoor Air '96, 4:21. Abstract . Nelson, P.R., S.P. Kelly, F.W. Conrad and C.H. Risner (1996) "Quantitative Comparison of ETS Generated by Different Cigarettes. Part 2: Effect of Relative Humidity on ETS Composition," Presentation at INDOOR AIR '96. Abstract published in Proceedings of the 7th International Conference on Indoor Air Quality and Climate: Indoor Air '96, 4:21. Abstract . Nelson, P.R_, S.P. Kelly, F.W. Conrad and C.H. Risner htlpJ/www.qrdirect.com/ECL/health/abstract_intro.htm 04/24/2000
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Scientific Publications Page 5 of 10 • Nelson, P.R., S.P. Kelly, F.W. Conrad and C.H. Risner (1996) "Environmental Tobacco Smoke (ETS) Composition at Different Relative Humidities." Presentation at annual meeting of the 50th Tobacco Chemists Research Conference. Abstract . Nelson, P.R., S.P. Kelly and F.W.Conrad. (1998) "Studies of Environmental Tobacco Smoke Generated by Different Cigarettes", Journal of the Air & Waste Management Association, 48:336. Abstract . White, R.T., Jr. and C.B. Rhoades, Jr. (1996) "Mainstream Smoke Collection by Electrostatic Precipitation with the Heinreich Borgwaldt 20-Port Rotary Smoking Machine for Acid Dissolution in a Microwave Digestion System." Presented at 110t' AOAC International annual meeting and EXPO. Abstract . Rhoades, C.B., Jr. and R.T. White, Jr. (1997) "Mainstream Smoke Collection by Electrostatic Precipitation for Acid Dissolution in a Microwave Digestion System Prior to Trace Metal Determination." Journal of AOAC International, 80:1320-1331. Abstract . Rogers, J.C., Winkler, L.S. and Borgerding, M.F. (1995) "Chromatographic Profiling as a Tool in the Development and Evaluation of New Cigarettes." Presented at 49P Tobacco Chemists' Research Conference, Lexington, KY. Abstract . Rogers, J. C., L.S. Winkler and M.F. Borgerding. (1996) "Chromatographic Profiling as a Tool in the Comparison and Evaluation of Complex Mixtures " Journal of Chromatographic Science, 35:5. Abstract . Uhrig, M. and C. Risner (1995) "Primary Aromatic Amines in Mainstream and Sidestream Cigarette Smoke." Presented at the 49th annual meeting of the Tobacco Chemists' Research Conference. Abstract . Wingate, D., K.A. Beard, F.D. Jordan, C.C. Morrison, C.H. Risner, W.S.Smith, III, J.C. Rogers and D.H.Smith (1995) "Utilization of the BAT Fishtail Chimney System for Collection and Quantification of Sidestream Smoke Constituents." Presented at the 49th annual meeting of the Tobacco Chemists' Research Conference. Abstract in-vitro Studies . Bombick, B.R., H. Murli, D.W. Bombick, W. Morgan and D.J. Doolittle (1995) "Comparative Studies on the Genotoxic Potential of Mainstream Smoke Condensate from Cigarettes Which Burn or Primarily Heat Tobacco " Presented at 7*' International Congress of Toxicology. httpJ/www.Sjrdirect.corn/ECL/health/abstract intro.htm 04124/2000
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Scientific Publications sm Ovining Smokng Priurry S:aement About R.R2T Vineal Media Cecter Cu=torner <Prvi7e Page I of 10 .7-f~,Nea~'~cae, c!e'ss oris ` - - I . EXR.il Fwdhedt A ,...Rn.-:-1~~-taaseesd..Sit-, _ Scientific Publications ScierArfic Tests Sciartific Analysis Publiratiars RJR Presentations/Publications 1995 - Present Current Market Prototype Smoke Chemistry Studies . Borgerding, M.F. and W.S. Rickert (1997) "Investigation of Total Smoke Emissions When Cigarettes are Evaluated with an Extreme and Artificial Smoking Condition." Presented at 51 st annual meeting of the Tobacco Chemists Research Conference. Abstract . Higuchi, M.A., W.T. Morgan, J.E. Swauger, P.H. Ayres, J.H. Com, P.A. Deal and A.T. Mosberg (1998) "Continuous Filament Glass (CFG) Insulator Does Not Transfer Into Mainstream Smoke From Eclipse Cigarettes." Presentation at Society of Toxicology 37th Annual Meeting, New Orleans, LA. Abstract in-vitro Studies . Doolittle, D.J., B.G. Brown, J.T. Avalos, D.W. Bombick, C. Smith, S. McKams and B.R. Bombick (1997) "Genetic Toxicology Studies Comparing Cigarettes Which Bum or Primarily Heat Tobacco " Presented at 7th International Conference on Environmental Mutagens. Abstract published in Mutation Research, 379:106. Abstract . Doolittle, D.J., B.G. Brown, J.T. Avalos, C.J. Smith and B.R. Bombick (1998) "Genetic Toxicology Studies Comparing Smoke from Cigarettes which Burn or Primarily Heat Tobacco." Talk and poster presented at the 8th httpJ/www.rjrdirect.comlECL/health/abstract intro.htm 04/24/2000 Contact us Sde Iv1a SORM GE®ndl'S 1MABIING: QWirg Sleokilg Nmr Grea* Redaaa Saious Ireks b Yarc NeaYk Fa Sm okers ScianfYc kfnrmation
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~ v a 00 httpJ/www.rjrdirect.com/ECUhealth/abstractslref5.htm 04/24/2000 J ~ e J co
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Scientific Publications Page 6 of 10 Presented at 7th International Congress of Toxicology. Abstract published in The International Toxicologist, 7:46. Abstract . Bombick, B.R., H. Murli, M. Cifone, J.T. Avalos, K. Putnam, D. Bombick, W.T. Morgan and D.J. Doolittle (1996) "Comparative Studies on the Genotoxic Potential of Mainstream Smoke Condensate from Cigarettes Which Bum or Primarily Heat Tobacco." Presented at 27th annual meeting of the Environmental Mutagen Society. Abstract published in Environmental and Molecular Mutagenesis, 27:9. Abstract Bombick, B.R., J.T. Avalos, P.R. Nelson, F.W. Conrad and D.J. Doolittle (1996) "Comparative Studies of the Mutagenicity of Environmental Tobacco Smoke from Cigarettes which Burn or Primarily Heat Tobacco." Presented at 27*' annual meeting of the Environmental Mutagen Society. Abstract published in Environmental and Molecular Mutagenesis, 27:9. Abstract Bombick, B.R., H. Murli, J.T. Avalos, D.W. Bombick, W.T. Morgan, K.P. Putnam and D.J. Doolittle (1998) "Chemical and Biological Studies of a New Cigarette that Primarily Heats Tobacco Part II. In Vitro Toxicology of Mainstream Smoke Condensate." Food and Chemical Toxicology, 36:183-190. Abstract . Bombick, B.R., J.T. Avalos, P.R. Nelson, F.W. Conrad and D.J. Doolittle (1998) "Comparative Studies of the Mutagenicity of Environmental Tobacco Smoke from Cigarettes that Bum or Primarily Heat Tobacco." Environmental and Molecular Mutagenesis; 31:169-175. Abstract . Bombick, D.W., K. Putnam, B.R. Bombick, W.T. Morgan, P. H. Ayres and D.J. Doolittle (1995) "In Vitro Assessment of Biological Activity of Mainstream Smoke from Cigarettes Which Burn or Primarily Heat Tobacco." Presented at 7tt' IntemationatCongress of Toxicology. Abstract published in The International Toxicologist, 7:73. Abstract • Bombick, D.W., P.H. Ayres, K. Putnam, B.R. Bombick and D.J. Doolittle (1998) "Chemical and Biological Studies of a New Cigarette that Primarily Heats Tobacco. Part 3 In Vitro Toxicology of Whole Smoke." Food and Chemical Toxicology, 36:191-197. Abstract • Bombick, D.W., K. Putnam, B.R. Bombick, W.T. Morgan, P.H. Ayres and D.J. Doolittle (1996) "In Vitro Assessment of Biological Activity of Mainstream Smoke from Cigarettes Which Burn or Primarily Heat Tobacco." Presented at 35th annual meeting of Society of Toxicology. Abstract published in The Toxicologist, 30:129. Abstract bttpJ/www.rjrdirect.com/ECL/health/abstract intro.htm 04/24l2000
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GENETIC TOXICOLOGY STUDIES COMPARING SMOKE FROM CIGARETTES W.. Page 2 of 2 Eclipse cigarettes compared to the smoke or smoke condensate from the I R4F reference cigarette. A study to evaluate urine mutagenicity demonstrated that when smokers switched to the Eclipse cigarette, their urine mutagenicity decreased by approximately 75% (p <0.05) compared to when smoking their usual brand. In conclusion, mainstream smoke and smoke condensate from the Eclipse cigarette was significantly less genotoxic (p <0.05) than smoke and smoke condensate from cigarettes representative of those currently sold in the United States. httpJ/www.qrdinect.com/ECL/health/abstracts/ref3.htm 04/24/2000
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Scientific Publications Page 8 of 10 Smoke Condensates from Cigarettes that Bum or Primarily Heat Tobacco." Presented at the 88th annual meeting of the American Association for Cancer Research. Abstract published in Proceedings of the 88th Annual Meeting of the American Cancer Society, 38:466. abstract . Brown, B.G., J. Kolesar, K. Lindberg, D. Meckley, A. Mosberg and D. J. Doolittle (1998) "Comparative Studies of DNA Adduct Formation in Mice Following Dermal Application of Smoke Condensates from Cigarettes that Bum or Primarily Heat Tobacco." Mutation Research, 414:21-30. Abstract • Lee, C.K., B.G. Brown, B.R. Bombick, P.H. Ayres, A.T. Mosberg and D.J. Doolittle (1995) "In Vivo Genetic Toxicology Studies of Mainstream Smoke from a New Cigarette which Primarily Heats Tobacco." Presented at 7th International Congress of Toxicology. Abstract published in The Intemational Toxicologist, 7:46. Abstract • McKams, S.C. and D.J. Doolittle (1996) "Assessment of Gap Junction Intercellular Communication and Membrane Integrity In Human Cells Following Acute Exposure to Cigarette Smoke Condensates In Vitro " Presented at the 1996 Intemational Conference of the American Thoracic Society. Abstract published in American Journal of Resairatory and Critical Care Medicine, 153:A512. Abstract • Mosberg, A.T., D.R. Meckley and G.T. Burger (1995) "Comparative 30-week Dermal Promotion Assay of Mainstream Smoke Condensate from a Prototype Cigarette which Primarily Heats Tobacco and a Reference Cigarette." Presented at 7th International Congress of Toxicology meeting, Seattle, WA July 2-6, 1995. Abstract • Meckley, D.R., A.T. Mosberg, G.T. Burger and K.R. Van Kampen (1997) "Comparative 30-week Dermal Tumor Promotion Studies of Mainstream Smoke Condensates from Cigarettes Which Primarily Heat Tobacco and a Reference Cigarette." Presented at 36th annual meeting of Society of Toxicology. Abstract • Renne, R.A., R.L. Phelps and A.T. Mosberg (1997) "Comparative Subchronic Inhalation Study of Mainstream Smoke from a Test Cigarette and a Reference Cigarette in Syrian Golden Hamsters." Presentation at 1997 Society of Toxicology Meeting, Cincinnati, OH. Abstract . Renne, R.A., J.W. Sagartz, G.T. Burger, P.H. Ayres and A.T. Mosberg (1995) "Comparative Inhalation Studies in Rats and Hamsters of Mainstream Smoke from a Prototype Cigarette and a Reference Cigarette." Presented at Society of Toxicologic Pathologists 14th International Symposium. Abstract httpJ/www.drdirect.conJECLJhealth/absuact intro.htrn 04/24/2000
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~./V~~Y/YV~~~~ulV-~~Y~.~\{iy~4~YW ~V1tlVl\l~\Vl~1VlIVl\V,AVVAatVI• the mid- and high-dose 7026A CSC groups had statistically fewer dermal tumors and tumor-bearing animals. In this assay, the dermal tumor-promotion potential of the 7026A CSC was, therefore, substantially reduced when compared to the 1 R4F reference CSC. l O~'l. . VI L http•l/www.rjrdirect.com/ECLJhealth/abstracts/ref6.htm 04/24/2000
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I.VMY!'uuJV1VUrYllJ1UYH1riULVl.rr H1V1JL1VAAULUI,IJLVKAIJJUtSI.HKU.. YageLoIL macrophages were absent in the Eclipse exposed rats. All other smoke related histologic changes were reduced in Eclipse exposed rats when compared to the 1 R4F exposed rats. DNA adducts of heart and lungs of Eclipse exposed rats were not different from sham control animals but were reduced compared to 1 R4F responses. The reduction or absence of histologic changes and DNA adducts in lungs and heart of rats exposed to smoke of Eclipse cigarettes indicates a reduction of biological activity compared to the smoke of the tobacco burning 1 R4F cigarette httpJl.vww.rjrdirect.com/F,CL/health/abstracts/ref4.htm 04l24/2000 6 J m
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Artitical Smoking Condition ar 8 raicotine Cont?nt C?Ct/~SC3 Customer $.-rviCB CordaCt Us Site k4ap Page 1 of 2 ~ h I -- ~~~ - SENIGEON GENENAES WARNlNG: Qutf g Srxoing Now GrcA Redutts Saiauc R6ks b Youu Nedlh `-•:-f"ni,~tfesit~ta~e~'t4nP`ess~«ri/s ~.-=~--- ~Oelttleg Smokng - PrivsySitlement -'About RJRT irirtcel nedo center Borgerding M F; Rickert W S INVESTIGATION OF TOTAL SMOKE EMISSIONS WHEN CIGARETTES ARE EVALUATED WITH AN EXTREME AND ARTIFICIAL SMOKING CONDITION Presentation at 51 st TCRC Winston-Salem, NC September, 1997. The smoke chemistry from ECLIPSE, a cigarette which burns a limited amount of tobacco, has been compared with that from five U.S. market cigarettes using an extreme and artificial smoking condition. Cigarettes were evaluated with a 56/26/2 puffing regimen (56 cc puff volume, a puff initiated every 26 s, 2 s puff duration) after taping the filter ventilation holes closed (100% vent blocking). As a result of the extreme condition, some discoloration of the ECLIPSE cigarette rod was observed after smoking. Total smoke emissions were determined for each cigarette sample by individually measuring mainstream and sidestream smoke yields. While the total smoke emissions from other cigarettes were derived from both mainstream and sidestream smoke contributions, ECLIPSE total smoke emissions were derived primarily from mainstream smoke. Analytes investigated in this work included, tar, nicotine, carbon monoxide, eight carbonyl compounds, seven phenolics, two aromatic hydrocarbons and benzo(a)pyrene. By chemical class, ECLIPSE total smoke yields were substantially less than yields for other cigarettes (60 - 95%). Mainstream smoke total particulate matter materials mass balance results suggested that the chemical composition of ECLIPSE tar was different from other cigarettes. ECLIPSE mainstream smoke particles were rich in glycerol and water (85% of the total mass). Materials other than glycerol and water accounted for approximately <r ro 6 http•l/www.rjrdirect.com/ECL/health/abstracts/refl.htm 04/24/2000 co J s s "m. t.Selentiric kdarmation -. I Endl Feedseck 1 Abstracts
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was similar when smoking Eclipse prototype cigarettes compared to usual brands. The PBPK nicotine model provides an alternative tool for estimating nicotine absorption from smoking different cigarette products. hripJ/www.rjrdirect.com/ECL/health/abstracts/ref7.htm 04/24/2000
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Genetic Toxicology Studies Cu_toiner Quitting Smokng RivaoyStaement -_ About RJRT Virtaal Nedu Center ~'untact Llc Em Fa 8mokels a I t : ~a«ssa.:E~.;< DOOLITTLE D; BROWN B; AVALOS J; BOMBICK D; SMITH C; MCKARNS S; REED-BOMBICK B GENETIC TOXICOLOGY STUDIES COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presented at 7th International Conference on Environmental Mutagens, Toulouse, France, September 7- 12, 1997. Mutation Research 379(1SUPPL.1):S106. The genotoxic potential of smoke from Eclipse, a cigarette that primarily heats rather than bums tobacco, was compared with Kentucky reference 1R4F cigarettes, representative of low-tar cigarettes currently sold in the United States. Mainstream smoke condensate from Eclipse cigarettes was negative in the Ames bacterial mutagenicity assays, sister chromatid exchange (SCE) assays and chromosome aberration assays at concentrations where smoke condensate from IR4F reference cigarettes induced a concentration dependent positive response in all assays. Studies on whole mainstream smoke using an in vitro exposure system demonstrated that smoke from the Eclipse cigarette was significantly less active in the SCE assays compared to smoke from an equal number of 1R4F reference cig9rettes. DNA adducts were evaluated in the lungs and hearts of laboratory mice exposed to whole smoke by the inhalation route as well as the dermal route using smoke condensates. DNA adducts, as measured by the P-32 post-labeling assay, were substantially reduced when animals were exposed to smoke or smoke condensate from eclipse cigarettes compared to the smoke or smoke condensate from the I R4F reference cigarette. When smokers switched to the Eclipse cigarette, their urine mutagenicity decreased by approximately 75% compared to when smoking their usual brand. httpJ/www.rjrdirect.com/ECL/hea(th/abstracts/ref2.htm 04/24/2000 Page 1 of 1 h o~----- o ..~~.. ~~ ~ 'e SUNGEON GENENAtS WARMING: QuilNng Smkeg Na Grtm* Aeduces Saiovs fsls b Yoa Bedk
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Scientific Publications Page 3 of 10 Earlier Eclipse Prototypes Smoke Chemistry Studies . Blakley, R.L., M.F. Borgerding, D.D. Henry and L.S. Winkler (1995) "Studies of Mainstream Smoke Vapor Phase Radical Formation Mechanisms." Presented at 49th annual meeting of Tobacco Chemists' Research Conference. Abstract . Borgerding, M.F., R.L. Blakley, L.S. Winkler, D.D. Henry, G.J. Bowman and D.H. Smith (1995) "Methodology for the Quantitative Determination of Free Radicals in Mainstream Vapor Phase Cigarette Smoke " Presented at 49P annual meeting of Tobacco Chemists Research Conference. Abstract . Borgerding, M.F., J.A. Bodnar, L.S. Winkler, H.L. Chung and L.A. Milhous (1995) "Comparison of Two Different Cigarette Designs Which Primarily Heat, Rather Than Bum, Tobacco " Presented at 49P annual meeting of Tobacco Chemists Research Conference. Abstract . Borgerding, M.F. (1995) "Approaches to Characterizing Smoke from New Cigarette Design - A Product Evaluation Strategy." Presented at 49P annual meeting of Tobacco Chemists Research Conference. Abstract . Borgerding, M.F., J.A. Bodnar, H.L. Chung, C.C. Morrison, C.H. Risner, D.F. Simmons, F.N. Wendelboe, D.E. Wingate and L.S. Winkler (1996) "Investigation of a New Cigarette which Primarily Heats Tobacco Using an Alternative Puffing Regimen " Presented at 50th annual meeting of Tobacco Chemists Research Conference. Abstract . Borgerding, M.F., J.A. Bodnar, H.L. Chung, C.C. Morrison, C.H. Risner, D.F. Simmons, F.N. Wendelboe, D.E. Wingate and L.S. Winkler (1996) "Investigation of a New Cigarette which Primarily Heats Tobacco Using an Alternative Puffing Regimen." Presented at 1996 CORESTA Congress. Abstract . Borgerding, M.F., J.A. Bodnar, H.L. Chung, P.P. Mangan, C.C. Morrison, C.H. Risner,J.C. Rogers, D.F. Simmons, M.S. Uhrig, F.N. Wendelboe, D.E. Wingate and LS. Winkler (1998) "Chemical and Biological Studies of a New Cigarette that Primarily Heats Tobacco Part I. Chemical Composition of Mainstream Smoke." Food Chemical Toxicology. 36(3):169-182. Abstract . Cole, S.K. (1995) "Quantitation of Sidestream Smoke Components from a Cigarette that Primarily Heats Rather httpJ/www.rjrdirect.com/ECL/health/abstract intro.htm 04/24/2000
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.... wa.ar a1; t.aVlfl~la I a: t,U1~1rMr,y~ I U V J V/tL DN11V11 tf1V L t11VL. W rnv i v l I r rage L ut L puffs, closer together in time, resulting in significantly greater total puff volume when smoking the E and EHF cigarettes compared to UB. While average absorbed CO measures were higher when smoking E, measures for EHF showed no significant difference from UB. httpJ/www.qrdirect.com/ECLlhealth/abstracts/ret8.htm 04/24/2000
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Scientific Publications Page 9 of 10 . Waldren, C., D. Vannais, M. McGraw, B.R. Bombick, C.J. Smith and D.J. Doolittle (1997) "Lack of Mutagenicity at the S1 Locus of AL Human-Hamster Hybrid Cells of Smoke Condensate from Cigarettes that Bum or Primarily Heat Tobacco." Presented at 4a' annual meeting of the Oxygen Society. Abstract published in Oxyslen, 97:93. Abstract in-vivo (Human) Studies . Avalos, J.T., B.R. Bombick, S.C. McKams, R.A. Davis, W.T. Morgan, S.J. Penn and D.J. Doolittle (1997) "Human Urine Mutagenicity Study Comparing Smokers Using Cigarettes Which Primarily Heat Tobacco With Their Usual Brand." Presented at 28tt' annual meeting of the Environmental Mutagen Society. Abstract published in Environmental and Molecular Mutagenesis, 29:528:4. Abstract . Avalos, J.T., B.R. Bombick, S.C. McKams, R.A. Davis, W.T. Morgan, S.J. Penn and D.J. Doolittle (1997) "Human Urine Mutagenicity Study Comparing Smokers Using Cigarettes Which Primarily Heat Tobacco With Their Usual Brand." Presented at 51st annual meeting of the Tobacco Chemists Research Conference. Abstraa . Doolittle, D.J., S.C. McKams, R.A. Davis, S.D. Livingston, B.R. Bombidc, J.T. Avalos and C.J. Smith (1995) "Human Urine Mutagenicity Study Comparing Cigarettes Which Bum or Primarily Heat Tobacco." Presented at 7tt' International Congress of Toxicology. Abstract published in The International Toxicologist, 7:46. Abstract . Doolittle, D.J., S.C. McKarns, R.A. Davis, S.D. Livingston, B.R. Bombick, J.T. Avalos and C.J. Smith (1996) "Human Urine Mutagenicity Study Comparing Cigarettes Which Burn or Primarily Heat Tobacco." Presented at the 27th annual meeting of Environmental Mutagen Society. Abstract published in Environmental and Molecular Mutagenesis, 27:18. Abstract . Robinson, J.H., M. F.Stiles, R. A. Davis, T.D.Guy, W. T. Morgan, D. W. Edwards, D.M. Riggs and B. J. Ingebrethsen (1996) "Human Smoking Behavior Measures on Two New Cigarettes that Primarily Heat Tobacco." Presentation at 50P annual meeting of the Tobacco Chemists Research Conference. Abstract . Doolittle, D. J., S. C. McKams, R.A. Davis, S.D. Livingston, B.R. Bombick, J. T. Avalos and C. J. Smith (1995) "Human Urine Mutagenicity Study Comparing Cigarettes Which Bum or Primarily Heat Tobacco " Presented at International Congress of Toxicology VII, Seattle, WA. Abstract httpJ/www.qrdirect.conilECL/heatth/abstract intro.htm 04/24/2000
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Scientific Publications Page 10 of 10 Seattle, WA. Abstract • Smith, C.J., S.C. McKams, RA. Davis, S.D. Livingston, B.R. Bombick, J.T. Avalos, W.T. Morgan and D.J. Doolittle (1996). "Human Urine Mutagenicity Study Comparing Cigarettes which Burn or Primarily Heat Tobacco." Mutation Research, 361:1-10. Abstract • Smith, C.J., T.D. Guy, M.F. Stiles, M.J. Morton, B.B. Collie, B.J. Ingebrethsen, and J. H. Robinson (1996) "A Repeatable Method for Determination of Carboxyhemoglobin Levels in Smokers." Presented at 50th annual meeting of the Tobacco Chemists Research Conference. Abstract . Smith, C.J., T.D. Guy, M.F. Stiles, M.J. Morton, B.B. Collie, B.J. Ingebrethsen and J.H. Robinson (1998) "A Repeatable Method for Determination of Carboxyhemoglobin Levels in Smokers." Human & Experimental Toxicology, 17:29-34. Abstra~ Non-RJR PresentationslPublications . Pauly, J. L., Lee, H. J., Hurley, E. L., Cummings, K. M., Lesses, J.D. and Streck, R. J. (1998) "Glass Fiber Contamination of Cigarette Fitters: An Additional Health Risk to the Smoker?" Cancer Epidemiology, Biomarkers & Prevention, 7:967-979. . Stapleton, J. A., Russell, MA.H., Sutherland, G., Feyerabend, C. (1998) "Nicotine Availability from Eclipse Tobacco-Heating Cigarette" Psychopharmacology, 139:288-290 . Rennard S I, Umino T, Millatmal P, Daughton D M, Manouilova L S, Ullrich F. Patil K D, Romberger D J. Floreani A A, University of Nebraska Medical Center. Switching to ECLIPSE is Associated with Reduced Inflammation in the Lower Respiratory Tract of Heavy Smokers. Presentation at the Spring 1999 Meeting of the Society for Research on Nicotine and Tobacco. http://www.drdirecteoni/ECL/healdi/abstract-intro.htm 04/24/2000
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vaporrnase rage 2 oi L hripJ/www.rjrdirect.com/ECL/health/abstractslrefl0.htm 04/24/2000
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J 1 VLIGJ vr MNllvJ i t(r.Hlvi Jmvf~ vHrvn rtlllJL 1CHLn.H1.. rvn1V1H 1 iVlv Nlt.. rS~e t oI L httpJ/www.rjrdirect.comlECLJhealth/abstracts/rei9.htm 04/24/2000
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Scientific Publications Page 7 of 10 . Doolittle, D.J., B.G. Brown, J.T. Avalos, D.W. Bombick and B.R. Bombick (1997) "Genetic Toxicology Studies Comparing Cigarettes Which Bum or Primarily Heat Tobacco." Presented at the 51st Tobacco Chemists Research Conference. Abstract . Doolittle, D.J., B.R. Bombick, R.L. Blakley, P.H_ Ayres, J.S. Gentry, D.W. Bombick and M.F. Borgerding (1997) 'echnologies for Reducing the Toxicity of Cigarette Smoke." Invited symposium presentation at 4th annual meeting of Oxygen Society. Abstract published in Oxygen, 97:25. Abstraa in-vivo (Animal) Studies . Ayres, P.H., MA. Higuchi, D.W. Bombidc, D.J. Doolittle, C.K. Lee, B.G. Brown, G.T. Burger, J.W. Sagartz, E.R. Bombick, A.T. Mosberg, and RA. Renne (1995) "In Vivo and in Vitro Studies of Mainstream Smoke from a New Cigarette Prototype." Presentation given at the 5th International Inhalation Symposium. Abstraot • Ayres, P.H., M.A. Higuchi, J.W. Sagartz, A.T. Mosberg and G.T. Burger (1995) "Subchronic Inhalation Study of Mairistream Smoke from a New Prototype Cigarette." Presented at International Congress of Toxicology. Abstraa • Ayres, P.H., M.A. Higuchi, J.W. Sagartz, A.T. Mosberg and G.T. Burger (1997) "Subchronic Inhalation Study of Mainstream Smoke from a Cigarette that Primarily Heats Tobacco." Presented at 36th annual meeting of the Society of Toxicology. Abstract . Brown, B.G., C.K. Lee, P.H. Ayres, D.R. Meckley, A.T. Mosberg and D.J. Doolittle (1996) "Comparative Studies of DNA Adduct Formation in Mice Following Exposure to Mainstream Smoke from Cigarettes Which Bum or Primarily Heat Tobacco." Presented at the 8741 annual meeting of the American Association for Cancer Research. Abstract published in Proceedings of the 87th Annual Meeting of the American Cancer Society, 37:98. Abstract . Brown, B.G., C.K. Lee, B.R. Bombick, P.H. Ayres, A.T. Mosberg and D.J. Doolittle (1997) "Comparative Study of DNA Adduct Formation in Mice Following Inhalation of Smoke from Cigarettes that Bum or Primarily Heat Tobacco " Environmental and Molecular Mutagenesis, 29:303-311. Absuact . Brown, B.G., JA. Kolesar, D.R. Meckley, A.T. Mosberg and D.J. Doolittle (1997), "Comparative Studies of DNA Adduct Formation in Mice After Dermal Application of Smoke Condensates from Cigarettes that Bum or Primarily httpJ/www.rjrdirect.com/ECL/health/abstract intro.htm 04/24/2000
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T-,r 8 IJoco!ine Ccn,er~ C~C11~5-C; ) Cu:forrier Ser ~dce ® 0 Exd Sd ANtbEON GENENAI'S WANNING: t>,tdfng St.otiy NOw' GrtolFj Aeduas SpcUf raln b TaY kaii `-~W ~'kjate e~ OuHieg Srrakng Prhracy St.tenent About RJRT Yiduel Nedu 6oeta Ayres P H; Higuchi M A; Brown B G; Doolittle D J; Mosberg A T COMPARISON OF I-IISTOPATHOLOGY AND DNA ADDUCTS IN RATS SUBCHRONICALLY EXPOSED TO SMOKE FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO Presentation at Society of Toxicology 38th Annual Meeting, New Orleans, Louisiana March 15, 1998 A subchronic nose-only inhalation study comparing the effects of smoke from a cigarette that primarily heats tobacco (Eclipse), to that of smoke from a Kentucky 1R4F reference cigarette was conducted using Sprague-Dawley rats. Rats of each sex were exposed 1 hour a day, 5 days per week, for 13 weeks to mainstream smoke at 0, 0.16, 0.32, or 0.64 mg/liter of air. Endpoints were carboxyhemoglobin (HbCO), serum nicotine, clinical signs, body and organ weights, serum chemistry, hematology, histopathology, and DNA adducts in heart and lungs using the P32 post-labeling procedure. Neither cigarette produced adverse changes in clinical signs, body and organ weights, serum chemistry, or hematology. HbCO and serum nicotine increased with both cigarettes in an exposure-dependent manner. Smoke related histologic changes were nasal chronic/active inflammation and epithelia] hyperplasia, chronidactive inflammation of the larynx, squamous metaplasia and acute inflammation of the ventral larynx, tracheal epithelial hyperplasia and increased goblet cells, and increased non-pigmented and brown/gold pigmented lung macrophages. Inflammatory changes of the larynx and ventral larynx, and non-pigmented lung macrophages were similar in rats exposed to the 1R4F or Eclipse cigarette. Increased tracheal goblet cells and brown/gold pigmented macrophages were absent in the Eclipse exposed rats. All ~ N B W J httpJ/www.rjrd'uect.com/ECL/health/abstracts/ref4.htm 04/24/2000 ~ a J lP INa.j .:_,-.Sci.ahiriek/armaBen ..~<t_rrnailFesdh.dc..l FM {e§La6tlaYt_. Abstract
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tucernanve runLng category cigarettes. Qualitatively, new cigarette TPM is more volatile and absorbs less UV radiation than TPM from other cigarettes. New cigarette particulate matter is roughly 80% glycerol and water, and 20% nicotine and other. The converse is observed for other cigarettes, a consistent relationship with both puffing regimens. rage t ot t htipJ/www.rjrdirect.com/ECUhealth/abstracts/refl4.hmi 04/24/2000
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neau r uoac:co wnue ru[ung rage t or.4 9 ~ J bripJ/www.rjrdirectcom/ECL/health/abstracts/refl3.htm 04/24/2000 9 ~
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4VMYAL(H I 1 v t; J I UL I Vt UNH HLLUI, l r V!(MA I lUN 1N A111,b T Sr a ~.:i: ;b'1e Con;rrd shop Gu_toRmcr s2rvIC? corrtsct Us Sitc Map ~~10 itps~ Qaittieg SmcAing --_Pri.ocy Statement -About RJ2T YeeellAeCr Ce.ta C rage 1 oI L StlRGEpI 6EEAL'S WA1NniG: podfa9 SmdcM Nor 6tem* Aedutts Setioos ksks b You Nmih Brown B G; Ayres P; Boyle K; Durant P; Mosberg A; Doolittle D COMPARATIVE STUDY OF DNA ADDUCT FORMATION IN MICE FOLLOWING 90 DAYS OF SMOKE INHALATION FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO Presentation at 89th Annual Meeting of the American Association for Cancer Research New Orleans, LA March 31, 1998 The genotoxic potential of mainstream smoke from a cigarette that primarily heats tobacco (Eclipse) and a representative tobacco-burning cigarette (Kentuc reference 1R4F) was compared in male B6C3/Fl mlce and male Sprague-Dawley rats after nose-only inhalation exposure. Animals were exposed 1 hr per day, 5 days/week for 90 days to mainstream smoke at concentrations of 0, 0.16, 0.32 and 0.64 mg total particulate matter/liter of air. In mice, 1 R4F mid- and high-exposure groups exhibited statistically significant (p<0.05) increases in adduct formation in both lung and heart tissues when compared to sham controls. Eclipse mainstream smoke did not induce significant increases in adduct formation at any concentration in either organ as compared to sham controls. In rats, the 1 R4F high exposure induced a significant increase in DNA adducts in lung, but not in heart. Again, mainstream smoke from Eclipse did not induce significant increases in adduct formation at any concentration in either organ as compared to sham controls. Under the conditions of this experiment, mainstream smoke from Eclipse was demonstrated to be less genotoxic in mice and rats than mainstream smoke from the 1 R4F cigarette, which is representative of cigarettes in the current US market. httpJ/www.rjrdirext.com/ECL/health/abstracts/ref5.htm 04/24/2000
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A METHOD FOR THE COMPARATIVE EVALUATION OF ETS GENERATED BY D.. Page 2 of 2 the new cigarette because the aerosol generated by the new cigarette is primarily composed of glycerol and water, not tobacco, combustion products. Most other ETS components analyzed, including ammonia, acetaldehyde, formaldehyde, phenol, oxides of nitrogen, hydroquinone, nicotine and 3- ethenylpyridine, were reduced by 80 - 99+%. httpJ/www.rjrdirect.com/ECL/health/abstracts/refl9.htm 04/24/2000
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btUeJtream JmoKe l;omponen[s Page 1 ot L httpJ/www.rjrdirect.com/ECL/health/abstracts/refl 6.htm 04/24/2000
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Potential Filament Transfer Cu:,torner Sc.INC? r® Guininy Snwkng - Arivsy Statercent About R.RT Yirlual M.edu Center Contact Ua srtvr tan Fw Sm okers Seknfifie MamaDut 1.__ Page 1 of I SUNGEON GENENAI'S WARNING: OudfnB Sod:g No. Grtatk Nedtaes Serima teks b Yuw NaMk. - :=Fi:#Fe.ifSicaePri~Tessitaz~s`~ ~ ~: l:a3aan F.adh.ek ) : _ FAq ce.a~tsa.abt, Abstract CONTINUOUS FILAMENT GLASS (CFG) INSULATOR DOES NOT TRANSFER INTO MAINSTREAM SMOKE FROM ECLIPSETM CIGARETTES. M.A. Higuchi, W.T. Morgan,l.E. Swauger, P.H. Ayres,l.H. Corn, P.A. Deal, and A.T. Mosberg, RJ. Reynolds Tobacco Company, Winston-Salem, NC 27102 A study was conducted to determine if ECLIPSETM cigarettes, which use a special form of continuous filament glass (CFG) as an insulator around the carbon heat source, yielded CFGs in mainstream smoke. After handling cartons of cigarettes using procedures that were designed to simulate commercial shipping conditions, cigarettes were smoked at a volume of 75 ml and a puff duration of 2 seconds, once every 35 seconds. These conditions were employed to maximize the probability that any potential transfer of CFG to ECLIPSETM mainstream smoke would be detected. A 20-port rotary smoking machine with an electrostatic precipitation (EP) smoke trap (Heinrich- Borwaldt, Model RM 20 CS, International Planters Corp., Richmond, VA) was used to collect the smoke from 30 ECLIPSET" cigarettes at 10 puffs per cigarette. CFGs were intentionally added to a series of smoke condensate samples to develop knowledge of the CFG recovery efficiency. Linear regression demonstrated that the recovery efficiency was 84% (C.I.95X, 0.65, 1.04). An analysis of the power provided by this study suggested that a yield of 0.2 filaments per cigarette could be detected with 80% confidence. The number of CFGs collected from ECLIPSETM cigarettes was not statistically distinguishable from background in the regression analysis. In addition, a t-test and a Wilcoxon rank sum test were conducted to compare the centers of the distributions of background samples with ECLIPSETM condensate samples. No statistically significant differences were observed at a level of p<0.05 for both tests. Thus, under the conditions of this experiment, there was no evidence of mainstream smoke CFG transfer from the ECLIPSETM cigarette. A httpJ/www.rjrdirect.corn/ECL/health/abstraacts/higuchOl.htm 04/24/2000 a ~
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. v,.ar ra.w i i v n~w v. r nn i,r uv/ M 1" 1 vmvn ricv,v.v,.v,v c v r.,,v,y l.vlv z w,cot~; e Co trnt C~C11 ~SC, Customer S.rwce Cordad U, rage 1 or z 6:it Sde NRGEON GENENICS 11AqONG: Ouufng Smokiq 1u.' GaO Aeduar Saioat N~eks b Yow Ne& '~ If ~F 3fe~slcSeSrot~ Ocitti.g Snwking Prfroty Sl.tee.ent About RJtT VPrtea111edr Ceeta Hon.:1.:~...-ScQ*ie Ham.COe F#4 ., a _~-~--- Abstract Meckley D R;Mosberg A T;deBethizy J D;Van Kampen K COMPARATIVE 30-WEEK DERMAL TUMOR PROMOTION EVALUATION OF CIGARETTE SMOKE CONDENSATE FROM A REFERENCE CIGARETTE AND AN ECLIPSE PROTOTYPE (7026A) TEST CIGARETTE IN FEMALE SENCAR MICE Toxicologist 48(1-S, March 1999):236 A 30-week dermal tumor promotion assay was conducted to compare the potential dermal tumor promotion activity of mainstream cigarette smoke condensate (CSC) collected from an ECLIPSE prototype cigarette (7026A), which primarily heats tobacco, and a I R4F (University of Kentucky) reference cigarette. Mainstream CSC's were collected by cold trap from smoke generators using the Federal Trade Commission puffing regimen. Female SENCAR mice were "initiated" with a single 75 ug application of DMBA to the shaved dorsal skin. The CSC's were then applied to the skin three times per week for 29 weeks. Each CSC was administered at 10, 20, or 40 mg tar/application to groups of 40 animals. End-points included body weights, clinical observations, organ weights, dermal tumor development data and histopathology. The numbers of dermal tumors and the numbers of dermal tumor-bearing animals for the 1R4F reference CSC were statistically different from the "DMBA-initiated" and "acetone-promoted" control groups, and increased with increasing exposure. The number of dermal tumor-bearing animals for the high-dose 7026A prototype CSC was statistically significantly different from the control groups. The number of dermal tumors for the mid- and high-dose 7026A prototype CSC were statistically different from the control groups and increased with increasing exposure. When corresponding dose levels of reference and 7026A CSC were compared to each other, the mid- and high-dose 7026A CSC groups had statistically httpJ/www.qrdirect.coni/ECIJhealth/abstracts/ref6.htm 04/24/2000
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GENETIC TOXICOLOGY STUDIES COMPARING SMOKE FROM CIGARETTES W.. Page 1 of 2 6cacliP sL Quitting Sniokirg PnvrcyStdernent -- About RJRT Yrnae! Medu Center Custorner S~rYICP_ Contsct Ua ® 0 © `I=a,aie7lt~!S$ICae~r9r~sioiYrfs --=:`-. ScfeMfQc klatMen :'. I Esail F..dk.ck I FM Abstract I cowacc8a..ti.t: Doolittle D J; Brown B; Avalos J; Smith C; Bombick B R; GENETIC TOXICOLOGY STUDIES COMPARING SMOKE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presented at the 8th International Congress of Toxicology Tox Lett 95(Suppl 1):186 A new cigarette (Eclipse) that primarily heats rather than burns tobacco has recently been developed. We have conducted a series of studies to compare the genotoxic potential of whole mainstream smoke and smoke condensate from Eclipse with smoke or smoke condensate from Kentucky reference IR4F cigarettes, which are representative of cigarettes currently sold in the United States. All assays evaluated smoke or smoke condensate from the Eclipse cigarette at concentrations where the smoke or smoke condensate from the I R4F reference cigarettes induced a concentration-dependent positive response. The in vitro genetic toxicology battery consisted of Ames bacterial mutagenicity assays, sister chromatid exchange assays and chromosome aberration assays. In studies on the mainstream smoke condensate, the Eclipse smoke condensate was significantly (p <0.05) less active than smoke condensate from the 1R4F reference cigarettes. Studies on whole mainstream smoke using an in vitro exposure system demonstrated that smoke from the Eclipse cigarette was significantly (p 0.05) less active in the SCE assay compared to smoke from an equal number of 1R4F reference cigarettes. DNA adducts, as measured by the P- 32 post-labeling assay, were substantially reduced (p 0.05) when mice were exposed to smoke (90-day inhalation study) or smoke condensate (30-week dermal study) from Eclipse cigarettes compared to the smoke or smoke h 4.-~---~ C0 ..~~.. ~~ ~ NRGEON GfNtAAI'SWARNING: Gdkng Snnk4 Now Gtwlti Rcduas kriaus laks lo Ywr Nedk httpJ/www.rjrdirect.com/ECL/health/abstracts/ref3.htm 04/24/2000
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....Ll.L1IOLldVH/~L11LVV1vlIHl~LL 1V VJUHLD1V11`1LH1VLHIVLW rRV1Vl lr Yage 1 u1L ~.ir c:IliS~1Ci~ <nn'?rt r_u_tomer 5^r :j(c ® 0 AMGEON GENFNAI'S WAt1NNG: GuA6g Saokig Nw6reallt Aadws Saiwf Ihks p Yar NWk Ouin:.g Smokng PrNay Stdement About RJRT Yirleal ltedr eeaer Stiles M F; Davis R A; Guy T D; Morgan W T; Edwards D W; Riggs D M; Robinson ] H HUMAN SMOKING BEHAVIOR STUDY: ECLIPSE CIGARETfE COMPARED TO USUAL BRAND AND A NEW PROTOTYPE Presentation at 51 st annual Tobacco Chemists' Research Conference Winston-Salem, NC September 15, 1997 Previous work from our laboratory demonstrated significant differences in human smoking behavior measures when smokers smoked Eclipse (a cigarette that primarily heats tobacco) compared to their usual brand (UB) of cigarette. The present study compared puffing profiles, cigarette sensory attribute ratings, expired air carbon monoxide (ECO), serum nicotine and blood carboxyhemoglobin (%COHb) concentrations in smokers smoking their UB of tobacco burning cigarette to the same measures when smoking cigarettes that primarily heat tobacco. Twenty-six smokers participated in three laboratory smoking tests, all between 1:30 and 4:30 p.m. For the first test session, subjects smoked one of their UB cigarettes after reporting the number of cigarettes they had smoked before arriving. Smoking profiles were recorded and samples taken for ECO, %COHb and serum nicotine determinations. Smokers were then sent home with one of two cigarettes that primarily heat tobacco, either Eclipse (E) or a new Eclipse cigarette with a hollow filter design (EHF). The subjects smoked this cigarette type exclusively for 2 weeks and then returned to the lab for testing. Following this second lab visit, subjects were given the E or EHF cigarette they had not smoked, returning to the lab after another 2 weeks for the final test session. Identical procedures were used for all laboratory visits. Consistent with our previous work, puffing and absorbed CO measures varied widely. On average, smokers took significantly more puffs, closer together in time, resulting in significantly ~ ttp://www.rjrdirect.com/ECLJbealth/abstractslref8.htm 4/24/2000 m m 'i ~ m ce w ScpNdic Honmfan EndIF.Nh.et .1:>. FM .;:
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nuec.u ot %,igareue uesign rage z oi L B co U httpJ/www.rjrdirect.com/ECL/bealth/abstracts/refl8.htm p4124/Z000 ~ a ~•
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phase compounds in the ETS of reference and prototype cigarettes was also performed. In all cases, the concentrations were reduced in the prototype relative to the reference cigarettes. Reductions ranged from 25-30% for carbon monoxide to over 99% for phenol. Concentrations of the gas phase bases 3-ethenylpyridine, nicotine and myosamine were reduced by 99%, 95% and 97% respectively. Acetaldehyde in ETS was reduced by 89% and formaldehyde was reduced by 81%. Total oxides of nitrogen were reduced by 94% and N02 was reduced by 90%. Ammonia, if present in the ETS of the prototype, could not be detected above the background ammonia generated by people in the chamber. httpJ/www.qrdirect.com/ECLRhealth/abstracts/ref20.htm 04/24/2000
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JlVLIlW Vl lvlllil.NJIIWly1l Ja4V/\i. •!11 Vl~ l/Il1.N~ I~ll.AL 1 V1~Y{(1/1V1\ 1t11... 1 Qt;G I Vl p I ..cOhne r,_ M.nt CUEtiJiier SEi ci[ e Con15d Uz 52e Ad.ip KFq E(-- lipscD Oaitti.g Smo~ing - -- Prrvncy Staemenf A6out RJR7 Viecal l7edr Ceeter Blakley R L; Borgerding M F; Henry D D; Winkler L S STUDIES OF MAINSTREAM SMOKE VAPOR PHASE RADICAL FORMATION MECHANISMS Presentation at TCRC Lexington, KY 9/24/95 Cigarette free radical yields have been studied since the 1958 publication by M. J. Lyons, et. al. W. A. Pryor from LSU has suggested a mechanism for fomzation of mainstream vapor phase radicals that involves a reaction between N02 and reactive dienes such as isoprene. Experiments have been conducted in our laboratory to systematically explore this proposed mechanism. Included in the experiments were cigarettes from different "tar" categories, cigarettes comprised of new filters and blends, and cigarettes that primarily heat, rather than burn tobacco. Some results indicate that the suggested N02/diene mechanism is viable, while other results do not support the mechanism. For many of the cigarettes studied, vapor phase radical yields increased as either isoprene or NOx smoke yields increased. However, in a series of experimental cigarettes where isoprene yield was constant and NOx levels substantially increased, surprisingly, vapor phase free radicals were dramatically reduced. In addition, preliminary research has suggested that some processed tobaccos yielded diminished radicals as compared to unprocessed tobaccos, while NOx smoke concentrations remained constant. Finally, a "cigarette" constructed from wood shavings produced a substantial free radical response with virtually no isoprene or NOx present in the smoke. Data from these products will be discussed f N 0 htt J/www rjrdirect com/ECUhealth/abstracts/re19 htm 04/24/2000 co J a . p . . ~ s Fw Sm okas SURGEON GENEAAfS WARNING: Caai g Swnk.g Nor Grcdlt Aedaa Saiws Csln b rcur &dh Abstract
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r.tteas ot i-igarene uesigr 1 sr s wI _ oune Contern ® O.itli.g Smokng PrMay Statam.nl - About RJFiT Yrlasl Nsdr Ceala Cu=tomer Service CorQuG1 US ® rage i or z EaH 5 SINlGEON GENEHArS MfhNNING: Guu61g S.ck:g Ib. &A Nedum Saious reks a Yan Neddl. - ForSmokers Abstracts Morrison C C; Wingate D E; Beard K A; Winkler L S; Simmons D F; Rogers J C; Borgerding M F THE EFFECTS OF CIGARETTE DESIGN MODIFICATIONS ON SELECTED MAINSTREAM VAPOR PHASE SMOKE CONSTITUENT YIELDS Presentation at TCRC Lexington, KY September 24, 1995 At this conference in 1989Byrd et al.reported an analysis procedure for the quantitative determination of selected mainstream vapor phase smoke constituents. This procedure has been modified to include the determination of isoprene and 1,3- butadiene in smoke. Briefly, the method consists of smoking cigarettes on a Borgwaldt 20-port rotary smoking machine and collection of vapor phase smoke in a series of four cryogenic traps which contain methanol. After smoking, the individual solvent traps are combined and two perdeuterated internal standards are added. Samples are then analyzed by gas chromatography with selected ion mass spectrometry (GC/SIM). In addition, to isoprene and 1,3-butadiene, the analytes studied in this work include benzene, toluene and acrylonitrile. This method has been applied to Kentucky reference cigarettes, to cigarettes which employ new filter and blend component designs and to a cigarette which primarily heats, rather than bums tobacco. When cigarette design and mainstream smoke yields are based primarily upon filter ventillation and tobacco rod weight, analyte concentrations in smoke parallel mainstream tar yields. Alternative tobacco blends have little effect on smoke yields. However, a new filter design reduces the concentrations of several compounds studied by as much as 69% when compared to yields from other equivalent tar products. A cigarette which primarily heats, rather than bums tobacco, shows even greater reductions in yields of certain compounds by (63% to 98%). httpJ/www.rjrdirect.com/ECLlhealth/abstracts/refl8.htm
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. ajnu a a.a.r. T ir & fdGOtine Cnfl:fflt C3CII~S~ - oaitliag Smoki+g Pr frary Staten errt -A6unt RJtT ViReat l7.dr Ccater ContdCt UL ® For Srrokers :.~ iQa SURGE08 GERAAL'SM'AtNiNG: Guitfig Smkig Yor GreA kdaa Saiooc teks b Tor Nm`h . - . ~. fu~e.-''i fHcaeP.%ntecsta.ii'c :.: --- Borgerding M F; Blakley R L; Winkler L S; Henry D D; Bowman G J; Smith D H METHODOLOGY FOR THE QUANTITATIVE DETERMINATION OF FREE RADICALS IN MAINSTREAM VAPOR PHASE CIGARETTE SMOKE Presentation at TCRC Lexington, KY September 24, 1995 The presence of free radicals in mainstream vapor phase cigarette smoke has been extensively reported in the literature. Most research published to date has been primarily qualitative in nature, often addressing the mechanism of free radical formation, rather than attempting to quantitate radical concentrations in smoke. With few exceptions, all quantitative studies have estimated the free radical concentration in smoke from one cigarette type, the non-filtered University of Kentucky reference cigarette 1R1, and these studies have not attempted to quantitatively compare free radical smoke yields from different cigarettes. In this work, a method for the quantitative determination of vapor phase free radicals will be described. The method is based on trapping free radicals in an N-tert-Butyl-a-phenyl- nitrone (PBN) / benzene solution to form a stable radical species (i.e., spin trapping) followed by detection with an electron spin resonance spectrometer (ESR). Two smoke collection techniques will be discussed which differ in the extent of smoke aging prior to spin trapping. Both techniques are acceptable for the comparison of cigarette smoke yields. Analysis of cigarettes which include a new carbon filter and an experimental tobacoo blend demonstrate a vapor phase free radical reduction on the order of 80% when compared to other equivalent tar cigarettes. Reductions observed for a cigarette which primarily heats, rather than burns,tobacco are even greater (88 - 97%). ~ N 0 0.' J htipJ/www.rjrdirect.com/ECL/health/abstracts/refl0.htm 04/24/2000 e 00 00 aa%.. ava~ l I1FtGrr~rt ~ervi?e
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aiuwucaiu autusc wwyuucuu Tar Fi I lcetm: Conterd c3C~I~SC; Q.in[.g smotng P,Ivecy stateeent Abaut R.RT Vidual M.dr Centr CuKurner Scrvlr_e l.Vntlul Lt$ Em raKciu>.z MUN 6rNERArSxWUNk fIW6g S.nkity Now 6,eedy Aeduas Sxioms teks 6 7oa Ne& Fbs. I .;, ScietriricMamation En.ilFeeA6.ek .N:,FAO :?,4 'Co.tKt6dMisf.:..: Abstracts Cole S K QUANTITATION OF SIDESTREAM SMOKE COMPONENTS FROM A CIGARETTE THAT PRIMARILY HEATS RATHER THAN BURNS TOBACCO AND TOBACCO BURNING CIGARETTES USING THE FOURIER TRANSFORM INFRARED SPECTROSCOPY SIDESTREAM SMOKE ANALYSIS SYSTEM FTIR-SSAS Presentation at 49th Tobacco Chemists Research Conference at Lexington, KY September 25, 1995 Acetaldehyde, acrolein, ammonia, carbon dioxide, carbon monoxide, hydrogen cyanide, and nitric oxide in fresh sidestream smoke from a cigarette that primarily heats rather than burns tobacco and three tobacco burning cigarettes (K1R4F, K1R5F, and a market brand cigarette) have been quantified using the FTIR-SSAS. Briefly, the FTIR-SSAS is a real- time, continuous flow trace gas monitoring system which has been constructed to sample fiRered gas phase sidestream smoke. Average concentrations of the sidestream smoke components are determined approximately every 30 seconds. Component yields are calculated by integrating the concentration versus time curves over the cigarette smoking period with incorporation of sample flow and gas cell pressure data. Uncertainty in the component yields is estimated using a propagation of error technique. The results show that the sidestream smoke yield of carbon dioxide and carbon monoxide from the cigarette that primarily heats tobacco is less than one-half and one-third, respectively, of that for the three tobacco burning cigarettes. The sidestream smoke yield for the remaining analytes of the cigarette that primarily heats tobacco was generally less than 10 % of that for the tobacco burning cigarettes. http•J/www.rjrdirect.eom/ECL/heatth/abstracts/refl6.htm 04/24/2000
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• vw. . .....v...w.. ......w. GyC~7pSL ..ySe..... '~UCi0RiZ1 Service '.OfdaC2 US SEe bAep SURGEEAt GENEAArS N'LRNIpEk Quitirg Sqnkiy Now Grm4r Reduca Saials Caks k Tau Nplh. . ..~ty'~Ca'~Jrcae'F~3ess~6ir3r37c ~: AckH.g 5"nli~g Pr'nrocy St.tem cnt About R.FiT Yidael V.sd'r Ceeter Tcknf7c Normatcn ..._ 1_ _ Ee.R Frdh.ek 1. FAO _ 1_ . Cwf.et6deaYt Borgerding M F; Bodnar J A; Winkler L S; Chung H L; Milhous L A Jr. COMPARISON OF TWO DIFFERENT CIGARETTE DESIGNS WHICH PRIMARILY HEAT, RATHER THAN BURN, TOBACCO Presentation at TCRC Lexington, KY September 24, 1995 A cigarette which heated, rather than burned, tobacco was described at the 42nd TCRC. Application of several chemical and physical measures to mainstream smoke total particulate matter (TPM) from the cigarette demonstrated that heating, rather than burning, tobacco produced an aerosol which was very different from that of "tar." The concept of producing cigarette smoke by primarily heating, rather than burning, tobacco has continued to be refined. A new cigarette has been developed with a 3 mg "tar" yield that burns a small amount of tobacco when smoked. Despite major design differences, TPM yielded by this cigarette is similar to TPM yielded by the PREMIER cigarette reported in 1988. Visual comparison of mainstream TPM collected on Cambridge filters shows minimal discoloration from new cigarette smoke. Elemental analysis reveals new cigarette TPM is reduced in carbon and nitrogen contents when compared to TPM from cigarettes which burn tobacco. Thermogravimetric analysis indicates that new cigarette TPM is much more volatile than that of other cigarettes and a spectrophotometric "tar" determination suggests compounds which absorb UV radiation are also reduced in new cigarette TPM. All results obtained consistently indicate a smoke chemistry which is much simpler than that of cigarettes which bum tobacco. This fact is not surprising, given that the new cigarette TPM is composed of approximately 50% glycerol, 30% water and 3% nicotine. httpJ/www.rjrd'uect.com/ECL/health/abstracts/refll.htm 04/24/2000 't, a m
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Tar S I•L~ t~r~c Cc t-rt G~CII/JSC~ oattf.g smolirg Prtrtcy Statemnnt - -About RJRT Virta sl Aledu Ceater Cuaotrier Ser,Ire Coot ia Us SORGEON GENENAL'S WAtMNIG: Guaing Smkiy Ibr 6mIFj tadaes krioos teks b Tar Mei4. Abstract Nelson P R; Conrad F W; Kelly S P; Ogden M W; Risner C H COMPARISON OF THE ENVIRONMENTAL TOBACCO SMOKE FROM A CIGARETTE THAT PRIMARILY HEATS TOBACCO AND CIGARETTES THAT BURN TOBACCO Presentation at 1995 AAAR Annual Meeting Pittsburgh, PA 10/9/95 A prototype cigarette has been developed that generates smoke primarily by heating, rather than by burning tobacco. The environmental tobacco smoke (ETS) from this cigarette consists mostly of exhaled mainstream smoke. Because very little tobacco is burned in the prototype, its mainstream smoke, and therefore its ETS, has a simpler composition than that from tobacco burning cigarettes. The vapor and particulate phases of the ETS from the prototype and three reference cigarettes were characterized in a controlled-environment test chamber. Compounds in the ETS of the prototype were present at reduced levels relative to the reference cigarettes. The mass concentration of particles from the prototype tested was reduced by 85-90%. Following smoking, the prototypes particulate concentrations dropped rapidly - apparently due to a rapid evaporation of water from the particles. Tobacco combustion products are reduced in the prototype; as a result, markers that traditionally have been used to apportion ETS particles were present at reduced concentration in the particles of the prototype. Ultraviolet particulate matter (UVPM) underestimated the particle mass -- concentration from the prototype by 40% and fluorescent particulate matter (FPM) underestimated it by 70%. Solanesol, which comprised 2.8% of the particles of the reference cigarettes, made up 0.5% of the particles of the prototype cigarette. Hydroquinone, another particulate phase constituent of ETS, was detected in the ETS from the reference but not the prototype cigarettes. Examination of a number of gas phase compounds in the ETS of reference and httpJ/tvww.rjrdira,,t.com/ECUhealth/abstracts/ref20.hmi 04/24l2000
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environmental evaporation chamber (EEC). The EEC provided an ultraclean environment for sample evaporation and predigestion steps that eliminated most of the sample matrix. The remainder was decomposed in a programmable closed vessel microwave digestion system. Digested sample solutions were analyzed by graphite furnace atomic absorption spectrometry and inductively coupled plasma optical emission spectrometry for aluminum, arsenic, cadmium, chromium, nickel, and silicon. httpJ/wwwsjrdirect.com/ECUheakU/abstractslref26.htm 04/24/2000
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---- -------- -5r 8 rlnectyie Cirit.nt SC3 [3C~tP Oa"rtliea Smo\ing ArFvwy Staen ent -:fibout aJFir Vld.el Yd'r Cenla Cuctorr~cr Service C,ontsCt U= SUflGEON 6f NERAL3 YfARMING Gua" S.ok ey Now ircalh Itedues Scious teks to ffir NiaYi Naa. 1,Scinrdc Nermafian .„~. .- 1. Entlt f .eAh.ek Abstract .I Nelson P R; Kelly S P; Conrad F W; Risner C H QUANTITATIVE COMPARISON OF ENVIRONMENTAL TOBACCO SMOKE GENERATED BY DIFFERENT CIGARETTES PART 2 EFFECT OF RELATIVE HUMIDITY ON ETS COMPOSITION Publication in PROCEEDINGS OF INDOOR AIR'96 A method for evaluating differences in ETS composition among different types of cigarettes was applied to the determination of the effect of relative humidity on ETS composition. ETS was generated by human smokers in the chamber at three target relative humidities - 35%, 50%, and 65%. Determinations of 19 ETS constituents were made in the chamber. Relative humidity had little effect on the composition of ETS. For a commercial cigarette, only respirable suspended particles (RSP), NO2 and phenol concentrations were effected by RH. Relative humidity had an impact on concentrations of NOx, NO, nicotine, aldehyde and cresol generation by a prototype cigarette that primarily heats tobacco. In general, effects were small. http•l/www.rjrdirect.com/ECUhealth/abstractslref22.htm 04/2412000
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frequency of one puff every 60 sec. and a puff duration of 2 sec. Extreme conditions are defined as 75 mL puff volumes at a frequency of one puff every 35 sec. and a puff duration of 2 sec. Condensate was extracted from the collection tubes with methanol into Teflon digestion vessels and evaporated in an environmental evaporation chamber (EEC, patent pending). The EEC chamber was custom designed to provide an ultraclean environment to perform sample evaporation and predigestion steps. The major portion of the sample matrix was eliminated in the predigestion step. The remainder of the sample matrix was decomposed in a programmable closed vessel microwave digestion system. bttpJ/www.qrdirect.com/ECUheatth/abstractslret25.btm 04/24/2000
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y/aN1llyya WW+/VJaLLV4 Va a1l~ VWVe~. E- ClipSC~ Quitfleg5rrokng Praterenl .Aboul RJRT Virtael Rtdb Cents cU.tIVfiCr sPI VICp l.ontact U_~ - FaSmokas ® G l 461. I Va l StMEON QBEUL'S NLr111NG: QutlNS S.aFig No. GmAr tedum Saws Kaks q Yeu IIwk Borgerding M F; Bodnar J A; Chung H L; Mangan P P; Morrison C C; Risner C H; Rogers J C; Simmons D F; Uhrig M S; Wendelboe F N; Wingate D E; Winkler L S CHEMICAL AND BIOLOGICAL STUDIES OF A NEW CIGARETTE THAT PRIMARILY HEATS TOBACCO. PART 1. CHEMICAL COMPOSITION OF MAINSTREAM SMOKE. Food Chem. Toxicol. (1998), 36(3), 169-182 A new-technokogy cigarette has been developed. While the new M arette bums some tobacco, it does not use tobacco as the l to sustain combustion and provide heat to the cigarette. Rather, the new cigarette primanly heats tobacco thereby reducing products of smoke formation mechanisms such as tobacco combustion, tobacco pyrolysis and pyrosynthesis. The mainstream smoke composition from a cigarette based on the new design (TOB-HT) has been characterized in comparative chemistry testing with two referenceag arettes using the FTC puffing regimen. Thermal properties, UV absorption charactenstics, elemental composition and materials balance studies all suggest a simplified smoke aerosol. Twenty-five smoke constituents ("target compounds") identified by the scientific community as compounds that may contribute to the diseases statistically associated with snwking have also been measured. Mainstream smoke concentrations of most target compounds are significantly knver with the TOB-HT cigarette when compared with reference cigarettes in the ultra-light "tar" and light "tar" categories. Taken together, chemical analysis results suggest simplified TOB-HT smoke chemistry with marked reductions in specific chemicals reported to be biologically active. bttpJ/www.qrdirect.com/ECL/health/abstractsJrefl5.htm 04/2412000
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& PU: cime Conterd OCIIp SC3 a.itli.g Smol'ng -Prrcsy Sttlrmant About RJRT Virtuel Medu Cetla Cu_torc~er Service COnitaCt Ue ® [qo SWON GENINAfS MANINMG: Curt6rg Slaok:g Nar GrcaM Aeduns Saiars ~ to Yar BwYh Abstract Nelson P; Kelly S; Conrad F; Risner C ENVIRONMENTAL TOBACCO SMOKE (ETS) COMPOSITION AT DIFFERENT RELATIVE HUMIDITIES Presentation at 50th TCRC Richmond, VA. 10/20/96 A method for comparing the ETS generated by different cigarettes was used to determine the effect of relative humidity (RH) on ETS generation. Smokers generated ETS in an environmental charrmber at 72.deg.F and different typical indoor air relative humidities (35-65%). Testing was performed on a commercial full flavor low tar cigarette and a reduced ETS, prototype cigarette. Concentrations of CO, NO, N02, total hydrocarbons, respirable suspended particles (RSP), solanesol, nicotine, 3- ethenylpyridine, myosmine, ammonia, formaldehyde, acetaldehyde, hydroquinone, phenol and cresol were measured. Several small, but statistically significant differences, were observed. Regression showed that the generation of N02 by the commercial cigarette was negatively correlated with RH. ANOVA showed significant (p < 0.05) differences in RSP and phenol concentrations at some relative humidities. No other analytes were affected by RH. For the prototype cigarette, RH was correlated with cresol concentrations. ANOVA showed differences in concentrations of formaldehyde, acetaldehyde, NO, NOx, and nicotine at some relative humidities. Overall, relative humidity in the range of 35-65% appears to have only a minor influence on the composition of ETS. httpJ/www.rjrdirect.com/ECL/heatth/abstracts/ref23.htm 04/24/2000
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CHROMATOGRAPHIC PROFILING AS A TOOL IN THE DEVELOPMENT AND EV.. Page 2 of 2 httpJ/www.rjrdirect.com/ECUhealth/abstracts/ref27.6tm 04/24/2000
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n\\ Y~4 ~\V ~ LL {~1La ~IVY ~ Va~ yY 14Y~(, ~Y \V a~l~.V !~l ~Lr !l/JJVl4 l1Va t(,y n L1V.. 1 V1 L • [LrjY EC1//JSG~ C,~_ti~rriH ~BI Vir a CYo sutstOM GEpERatY waeEAlw: aef q sam6ip Na 6rea~ ledaa Saiws ws b Torr Rwhh. ==~3leaTh'caP ~a sio ~ s ' : Quinieg Srrnling Privecy Stdrnenl A6out RJRT Y rl oe! /Jtd r Cse tr is: ® WR Abstract Chang K-M; Stiles M; Davis R; Edwards D; Guy T; Robinson J H; deBethizy J D AN IMPROVED METHOD FOR ESTIMATING NICOTINE ABSORPTION AS A BIOMARKER FOR SMOKE UPTAKE FROM CIGARETTE PRODUCTS Presentation at Society of Toxicology 1998 Annual Meeting Seattle, Washington March 1-5,1998 Serum nicotine is frequently used as a biomarker for tobacco smoke uptake in smokers. However, it is difficult to relate serum nicotine concentrations to the amount of nicotine absorbed. Application of a validated physiologically-based pharmacokinetic (PBPK) model has been proposed to describe nicotine kinetics and estimate nicotine uptake (Chang et al., 1995). In three separate test sessions, 26 smokers smoked a cigarette of their usual brand or one of two cigarettes that primarily heat tobacco, either Eclipse (E) or a new Eclipse cigarette with a hollow filter design (EHF). Prior to each session, subjects smoked exclusively the test cigarettes ad libitum for two weeks. Blood samples were taken before smoking an 1, 3, 5,7.5, 10, 15, and 30 minutes after smoking. Serum nicotine was quantified by radio immunoassay (RIA). Nicotine uptake was estimated by model simulation to best fit the data with input of individual body weight, smoking behavior profile, and baseline nicotine concentration. Nicotine uptake from the usual brand of cigarettes ranged from 0. 17 to 1.6 mg, with a mean of 0.69 +1- 0.36 mg/cigarette compared to 0.72 +/- 0.38 mg/cigarette for the E cigarette and 0.62 +/- 0.42 mg/cigarette for the EHF cigarette. Our results indicated that while smoking behavior was different, nicotine uptake was similar when smoking Eclipse prototype cigarettes httpJ/www.rjrdirect.corn/ECL/health/abstracts/ref7.htm 04/24/2000
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Tar S IJ cotr~a Ccr,tar~t ~clips~ Oeitling SmnAng~ PrFvecySLtement ~About RJRT Virtua! Wedr Ca.ter Cu.tumer Service Contact U: SAet:4ap Fa Srnokers 191 n 0 E::d 5¢e SORGEON GENEBACS MANMING: Greing Sankny Now Grzok fedurom Saiouc bks b lmr Me& Nelson P R; Kelly S P; Conrad F W; Heavner D L; Risner C H; Taylor W D QUANTITATIVE COMPARISON OF ENVIRONMENTAL TOBACCO SMOKE GENERATED BY DIFFERENT CIGARETTES. PART 1: ENVIRONMENTAL CHAMBER METHOD AND ITS APPLICATION TO COMMERCIAL CIGARETTES Indoor Air'96, 4:21, Proceedings of the 7th International Conference on Indoor Air Quality and Climate 7TH International Conference on Indoor Air Quality and Climate, JULY 21-26, 1996, NAGOYA, JAPAN An environmental chamber method for characterizing and quantitatively comparing the environmental tobacco smoke ETS generated by different cigarettes was developed and applied. The method was used to evaluate the ETS generated by four U.S. and three European commercial brand styles of cigarettes, and one prototype cigarette that primarily heats tobacco (TOH-HT). Significant differences in the generation of ETS components were observed among the commercial and prototype cigarettes. The TOB-HT cigarette generated substantially lower (typically 90% lower) concentrations of most ETS components. A field study was conducted in a restaurant to evaluate the applicability of chamber results to "real world" conditions. The difference between TOB-Ht and commercial cigarettes was comparable to that observed in the chamber studies. httpJ/www.rjrdirect.com/ECL/health/abstracts/ref2l.htm 04/24/2000
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N 0 co J hripJ/www.qrdirect.com/ECUhealth/abstracts/ret29.htm 04/24/2000 ~ m
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r,' 3 7JiCOhfie Cc ~:-M Cuttoliiet cer,i-e ldd1t3c4 u, ® E.:d Sde SUiGEDN 6EN91LLT MfAtNING: Qdiny Sookq Ibr 6mrrly kduca kriouc Eakt b Ta. Beak Ou iC;ag Smoi.ng Privsy Statemern About RJRT VirteetRd. Ceeter - -~Fu~ffei'9~caePrafess~a~'s-'=, He!!..a..:,a Borgerding M F; Bodnar J A; Chung H L; Morrison C C; Risner C H; Simmons D F; Wendelboe F N; Wingate D E; Winkler L S INVESTIGATION OF A NEW CIGARETTE WHICH PRIMARILY HEATS TOBACCO USING AN ALTERNATIVE PUFFING REGIMEN Presentation at 1996 CORESTA Meeting Yokohama, Japan 1113/96 A new technology cigarette which primarily heats tobacco has been investigated using the FTC and an alternative puffing regimen (50 cc puff, 2 s duration, 30 s interval). The relative tar yield ranking for the new technology cigarette was affected by puffing regimen, while the relative nicotine yield ranking is consistent for both puffing regimens studied. New cigarette tar yields are similar to cigarettes from the FTC lights tar category when both are smoked with the alternative regimen. A single spectrophotometric tar ranking of all cigarettes was observed with both puffing regimens. Marked smoke composition differences between the new cigarette and other cigarettes were observed for both puffing regimens. Quantitatively, B(a)P, TSNAs, formaldehyde, acetone and acetaldehyde yields generated with the alternative puffing regimen are substantially less than yields expected from cigarettes with an equivalent tar yield and, in absolute terms, are among the lowest yielding cigarettes. With the alternative puffing regimen, acrolein yield is comparable to other cigarettes with a similar tar yield and carbon monoxide values are typical of FTC full flavor tar category cigarettes. Qualitatively, new cigarette TPM httpJ/www.rjrdirect.com/ECL/health/abstracts/refl4.htm 04/24/2000
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CHEMICAL AND BIOLOGICAL STUDIES OF A NEW CIGARETTE THAT PRIMAR. Page 2 of 2 bttpJ/www.rjrdirect.com/ECUhealth/abstracts/ref34.htm 04/24I2000 i
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t.cw wKd1orw ucs1gu i ot & ( LGC ~unc Crnr'..'rA E-clipsc~ -Ocitlieg SmoAing v~ y si:a.rt.nt ~-About RRT YAosl4ed"u Camter YagelolI Custorner sErvir_e Coritact Uz 0 suet#oN GENERats wuMING: aNiny smokI1g Mo. srtah kduns suws rsks b tar x& Neetr 1-:-.SeietireHormatian ;,,,,,t_Fsa11F..de.ek I Nd -1CoaeetSdMYt , Borgerding M F APPROACHES TO CHARACTERIZING SMOKE FROM NEW CIGARETTE DESIGNS - A PRODUCT EVALUATION STRATEGY Presentation at TCRC Lexington, KY September 26, 1995 New cigarette components and cigarette designs such as new carbon filters, experimental tobacco blends, and cigarettes which primarily heat, rather than bum, tobacco continue to be developed. An extensive chemical analysis program has been applied to evaluate and characterize cigarette smoke from some of these new cigarettes. This paper will review typical chemical analyses which may be applied to mainstream or sidestream smoke to evaluate new cigarette designs. The role of gross measures (measures based upon a chemical or physical property of smoke total particulate matter), aggregate chemical measures (measures based on a summary chemical response from more than one smoke constituent) and specific compound determinations (quantitative measures of individual smoke constituents) within the context of the analysis program will be addressed. Additionally, study designs for comparing smoke from different cigarettes will be presented. Cigarettes from the current US market, control cigarettes pertinent to the study and University of Kentucky reference cigarettes are each useful for assessing smoke from a new cigarette design. Products chosen to study a new carbon filter design, an experimental tobacco blend, and a cigarette that primarily heats, rather than bums, tobacco will be described httpJ/www.rjrdirect.com/ECLhealth/abstracts/refl2.htm 04/24/2000
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cc-'~ C11pS3(- > Oc i^ing Srro~ng P,ivaySt.temant About RJRT VIAoe! Uedu Ce.ter C or~taet U- 91 ARGEfMI GENf1Ai'S frWIING: Gftg Smakiq MOr' 6~ Redata Sqiouc bl{s b 1DYr NlOMt j . ~, Faall Fnl.ek t. Abstracts Borgerding M F; Bodnar J A; Chung H L; Morrison C C; Risner C H; Simmons D F; Wendelboe F N; Wingate D E; Winkler L S INVESTIGATION OF A NEW CIGARETTE WHICH PRIMARILY HEATS TOBACCO USING AN ALTERNATIVE PUFFING REGIMEN Presentation at 50th TCRC Richmond, VA 10/20/96 A new technology cigarette which primanly heats tobacco has been investigated using the FTC and an alternative puffing regimen (50 cc puff, 2 s duration, 30 s interval). Study objectives were' (1) to assess the relative tar and nicotine yield rankings observed for cigarettes under FTC and alternativepuffing regimen conditions, and (2) to determine if the marked malnstream smoke composition differences between the cigarette which primarily heats tobacco and other cigarettes observed under FTC puffing conditions are also observed with an ahemative puffing regimen. Results from the new cigarette, five U. S. ci4arettes, a Kentucky reference cigarette and four European cigarettes are compared. The relative tar yield ranking for the new technology cigarette was affected by puffing regimen, while the relative nicotine yield ranking is consistent for both puffing regimens studied. New cigarette tar yields are similar to cigarettes from the FTC liyhts tar catego!y when both are smoked with the altemative regimen. A si (eng spectrophotometric tar ranking of all cigarettes was observed with both puffing regimens. Marked smoke composition differences between the new cigarette and other cigarettes were observed for both puffing regimens. Quantihatively, B(a)P, TSNAs, formaldehyde, acetone and acetaldehyde yields generated with the altemative puffing regimen are substantially fess than yields expected from cigarettes with an equivalent tar yield and, in absolute terms, are among the lowest yielding cigarettes. Wdh the aftemative puffing regimen, acmleln yleki is comparable to other cigarettes with a similar tar yield and carbon monoxide values are typlcal of FTC full flavor tar category cigarettes. Qualitatively, new cigarette TPM is nare volatile and absorbs less UV radiation than TPM from other cigarettes. New cigarette particulate matter is roughly 80% glycerol and water, and 20% nicotine and other. The converse Is observed for other cigarettes, a consistent relationship with both puffing regimens. http://wwwsjrdirect.com/ECUhealth/abstracts/refl3.htm 04R4/2000 a W Cu_tumet N
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L1 lv~ . uvl/ i'va. 1111.. y l V L L~ ALVAllVI, va L i J V1i1\Li~l~ y l.iL L l L/.. r 6Kc 1 Ul L - Si:=c4 ne ,r_crt--.t eotipsC- Qaitliep Smok:ng PrFrsySLtement -.About RJRT Vinaef Nedu Ceeter Cu_t0ine Service Contact L StRGEON GENENArS YI/NNING: Guit6ig Saokig Ibw Grzak Reduces Saiws kata b rar NWA Ne~~. ~_,t;~-.,SGlI~C Llrppnalion ' ~'.:ei . CraR f..d6.Ck ' ~ Abstract Nelson P R; Conrad F W; Kelly S P; Risner C H; Heavner D L; Ogden M W A METHOD FOR THE COMPARATIVE EVALUATION OF ETS GENERATED BY DIFFERENT CIGARETTES AND ITS APPLICATION TO A NEW CIGARETTE THAT PRIMARILY HEATS TOBACCO Presentation at TCRC Lexington, KY 9/24-27/95 A method of smoke generation and sampling was developed to allow quantitative comparisons of ETS components generated by different cigarettes. The comparison is carried out in a controlled environment test chamber that is minimally ventilated (ventilation rate = 0.12 ACH). Initial temperature and relative humidity are set such that the temperature and relative humidity during ETS sampling average 75 degrees F and 50%, respectively. Following a brief background data collection period, ETS is generated by a group of six smokers. During the smoking period, the smokers each smoke one cigarette to completion (defined as a line 3mm from the overwrap). At twenty minutes, the smokers exit the chamber. The chamber is then resealed and a 120- minute sampling period begins. This method was used to compare the ETS generated by several commerical cigarettes to a new cigarette that primarily heats tobacco. Reductions of ETS- RSP,based on gravimetric measurements, ranged from 86 - 90% for the new cigarette relative to the commercial cigarettes. Other traditional markers of ETS RSP such as UVPM, FPM, and solanesol underestimate the amount of ETS-RSP generated by the new cigarette because the aerosol generated by httpJ/www.rjrdirect.com/ECUhealth/abstracts/refl9.htm 04/24/2000
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'sr 6 I-1~_ct-~e COnlPrd ® ® ~~IlpS@ ~ Ouitlisg Srro\ng Prhmty Stolrmerd Fbout RJF2T - Yrteal lEedu Geeter Cuctcaner ~ en'iCe Contact U: Abstracts F#O w;,1 .Ce.lsctSdutYt. ~ CMcKams S C; Doolittle D J COMPARATIVE STUDIES OF MAINSTREAM CIGARETTE SMOKE CONDENSATE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO IN THE GAP JUNCTION INTERCELLULAR COMMUNICATION ASSAY Presentation at VII International Congress of Toxicology July 6, 1995 In vitro intercellular communication assays are used to evaluate the biological effects of compounds on mammalian cell membrane function. The objective of this study was to quantify and compare the activity of mainstream cigarette smoke condensate from three types of cigarettes on gap junction intercellular communication. The cigarettes tested included: a new cigarette prototype, which primarily heats tobacco, a low tar tobacco burning reference cigarette, and an ultra low tar, tobacco burning reference cigarette. Fluorescence redistribution after photo bleaching was used to assess GJIC in a rat liver oval cell line. Lactate dehydrogenase release was used to assess non-specific membrane cytotoxicity. GJIC was compared at,CSC concentrations which did not influence LDH release. CSC from the new cigarette prototype did not inhibit GJIC at concentrations at which CSC from the 1 R4F and 1 R5F cigarettes inhibited GJIC. In this assay, mainstream cigarette smoke condensate of the new cigarette prototype is less biologically active than mainstream CSC from the 1 R4F and 1 R5F reference cigarettes. httpJ/www.rjrdirectcom/ECL/heatth/abstracts/refl7.htm Srte VAap uo SIN(Gral 6rKEBAI'S M'AiNINU: Quding Snakiq Nov 6m~ Reduas Saiouc faln k Tar Nahh '-=`-Fa"Hea f~`a'et~dess,arsa's ra-:
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cigarettes, a commercial light cigarette and a cigarette which primarily heats, rather than bums, tobacco (new cigarette). YKdh the exception of formaldehyde, analyte concentrations were at least 95% less in new cigarette sidestream smoke when compared with the other cigarettes studied. Formaldehyde was approximately 80% reduced. These findings were consistent with the observed sidestream tar yield for the new cigarette, which was similar to blank levels. hdpJ/wwwajrdirect.com/ECIJhealth/abshacts/raf30.hbn 04/24C2000
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Y/..u///6..Y Va ua~ ~a/\v.\..a/...aaa._. ava...ayvV J..a///v/ Vu.~/.aataaa.{/ Y1 Y4 aY\W~\.. l f4~V 1 Va l rar & iLcotinr Co',.-nt ® ~clipsc: Q.itling Srtn\ng -- A, Fva y Strten ant =About RJRT Vidcal Ued'a Ceeta Customer CFlVire Cordad Us SAe Map ® COa SMON GENEBAI'S INARMfNG: OuOiil; S.nk:g Now Grtodr Redaa faimn R'ela b Taer NmYi. = ~'or:~eq"Trcae#iiessiair's'=-=":-~ Nelson, P R; Kelly, S P; Conrad, F W STUDIES OF ENVIRONMENTAL TOBACCO SMOKE GENERATED BY DIFFERENT CIGARETTES J. Air & Waste Manage. Assoc. (1998) 48:336-344 A method was developed to reproducibly measure environmental tobacco smoke (ETS) components generated by different cigarettes. Measurements were carried out in an unventilated, controlled environment chamber. True ETS (the aged and diluted combination of exhaled mainstream plus sidestream smoke) was generated by human smokers. To retiabty quantitate components normally present at trace levels, the comparisons were carried out at elevated ETS concentrations-greater than 40 times those typically encountered in "real-world" set5ngs. The method was applied to four commercially available cigarettes and a cigarette prototype that primarily heats tobacco. Forty-threeproperties and components of the gas and particulate phases of ETS generated by the different cigarettes were measured. Good precision of measurement was obtained both within and between tests. Statistically significant differences in the concentration of ETS components were observed among the different commercial cigarettes and between the commercial and prototype cigarettes. Most ETS components from the prototype cigarette were reduced by >90% when compared to the commercial cigarettes. The method was used to determine the effect of cigarette design changes on the generation of ETS. httpJ/www.rjrdirect.com/ECL/health/abstracts/ref24.htm
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~+111\V3~1f11 VV1V11111~ I l\V11L1~~V ~J A 1VVL ", 111L. UL . 1,,yV11YLL." I Al\L LV .. 1 CjjG I Vl L TGr S I4iZotre Corrt- C?C1IpSC_- Cu~tomer Sevire lAntaCl Us ANtGEON 6ENOGCS WARNING: Ihifng SonknN Now 6nalii kduca Saiwn tbla a few Neik '-~--~}'iq7{~1Ca'EF'L(8~'IUfY3~6~ ~- Qo'rttiep SrrqAing ~INqy$il1fP.2OI About RJRT Yrl.el ll.du Cseta Abstract Rogers J C; Winkler L S; Borgerding M F CHROMATOGRAPHIC PROFILING AS A TOOL IN THE DEVELOPMENT AND EVALUATION OF NEW CIGARETTES Presentation at TCRC Lexington, KY 9/24/95 Typical chromatographic analyses focus on only a few specific analytes. Chromatographic profiling, an application in which all peaks are examined, is a useful tool for producing a wealth of information regarding sample composition and complexity and for comparing different cigarette designs. In this work, the collection and chromatographic analysis of mainstream cigarette smoke are described. Cigarettes are smoked on a Heinrich Borgwaldt rotary smoking machine and both vapor and particulate phase smoke fractions are collected. Samples are analyzed by gas chromatography with mass selective detection. Profiling data are presented in the form of chromatograms (for visual complexity comparisons) and as bar charts (representing the number of chromatographic peaks, the aggregate chromatographic response for those peaks, and the total chromatographic response). The scope and limitations of chromatographic profiling and its utility in the evaluation of new products are discussed. For cigarettes containing an experimental tobacco blend and incorporating a new filter technology, aggregate chromatographic eak response reductions of approximately 50P /o relative to three commercial Lights products are observed in the vapor phase while particulate phase responses remain comparable. Compared to Kentucky reference cigarettes (1R4F, 1R5F) and a commercial Lights product, cigarettes which primarily heat, rather than burn, tobacco, show aggregate chromatographic peak response reductions ranging from 72% to 95% in the vapor phase and 84% to 99% in the particulate phase. B Wtap http://www.rjrdirect.com/ECUhealth/abstracts/ref27.htm 04/24/2000
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Tar fi ! I -OLrne Cc~nlFr~t C~CIIPS[3 Custiaer Srrvre Curdact U= Sde taap 91NGE0N GENEAArS WdANING: quBitg Smkoy Nor Gmlh Eeduus Saiam fnb b Tagt Neail =-F`LrWb!3*zm-33aTessTam 'c:"s-: Oaitting Smoking - Prtvsy Stdec, nnt About RJRT YrtcelYed'r Ceeter FAO_!r:..t White R T, Jr; Rhoades C B, Jr MAINSTREAM SMOKE COLLECTION BY ELECTROSTATIC PRECIPITATION WITH THE HEINREICH BORGWALDT 20-PORT ROTARY SMOKING MACHINE FOR ACID DISSOLUTION IN A MICROWAVE DIGESTION SYSTEM Presentation at 110th AOAC International Annual Meeting and Exposition Orlando, Florida September 8, 1996 Methodology is described for the collection and preparation of mainstream smoke condensate from cigarettes. The smoke condensate is collected and prepared in a manner which allows the determination of trace metal constituents. A sample is composed of mainstream smoke from as many as 300 cigarettes in a small volume (25 mL) to enhance sensitivity. During each phase of the sample preparation process, extremely clean laboratory conditions are essential to avoid contamination and maintain low limits of detection. The smoke collection and sample preparation equipment was located in dean laboratories that maintain a positive pressure of HEPA filtered air with constant temperature and humidity control. The classification of airborne particles was monitored in all areas 24 hours a day by certified particle counters. Only high purity reagents were used in the preparation of samples and the cleaning of labware. Mainstream cigarette smoke was collected on a modified Heinreich Borgwaldt 20-port rotary smoking machine inside a CORESTA cabinet. Condensate was trapped via electrostatic precipitation (EP) using a high tension generator supplying 17.5 kV to a tungsten electrode and two secondary acid traps placed directly after the EP unit. Samples were collected under two smoking regimens: FTC and Extreme conditions. FTC conditions are defined as 35 mL puff volumes at a frequency of one puff every 60 sec. and a puff httpJ/www.rjrdirect.com/ECL/health/abstracts/ret25.htm 04/24/2000
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Huuivb iISM.vM bmvr.c wLLn,,,1 ivri n r< rr.nf~ ><xVO / ri i i1~ rxn1~ari i.v. iviv r U.. rage i oz .< Cuetame+ S%tltre Conta[t U:, S=ON 6rNrtAt"SIrAtlANG: Quefn9ymoFinD Now G*ledua Saiouc k'ekt b You RWiL =~ Hea'7 i cac Prifess~oiii's:.__ Orn.ng S,rm4ng Prirsy SL'ee en: ~--Ab:wt R.l2i Virtoa! V.edn Ceeta Rhoades C B, Jr, White R T, Jr MAINSTREAM SMOKE COLLECTION BY ELECTROSTATIC PRECIPITATION FOR ACID DISSOLUTION IN A MICROWAVE DIGESTION SYSTEM PRIOR TO TRACE METAL DETERMINATION. J. AOAC Int. (1997), 80(6), 1320-1331 A method is described for collection and preparation of mainstream smoke condensate from cigarettes for the determination of trace metal constituents. A sample of mainstream smoke was collected from 300 cigarettes in a final volume of 25 mL. Extremely dean laboratory conditions during sample preparation were essential to avoid contamination and improve precision and accuracy for trace element determination. The dean laboratories maintained a positive pressure of HEPA-filtered air with constant temperature and humidity control. Mainstream cigarette smoke was collected by electrostatic precipitation (EP) on a modified rotary smoking machine located in a wooden CORESTA cabinet. The EP unit was equipped with a high tension generator supplying 17.5 kV to a tungsten electrode followed by 2 secondary acid traps. Samples were collected under 2 smoking regimens: FTC (35 mL puff vols., one puff every 60 s, and puff duration 2 s) and "Extreme" (75 mL puff vols., one puff every 35 s, puff duration 2 s). Condensate was extracted from collection tubes with methanol into Teflon microwave digestion vessels and evaporated in an environmental evaporation chamber (EEC). The EEC N 0 co J X, ItttpJ/www.rjrdirect.com/ECIJhealth/abstracts/ret26.htm 04/24l2000 N EMw;l :~-,-Seieet7iellamufcn.::,-, :~J. :f~a0F..0.ek -1.. ;.:FIO ...J ~;CwaelSd..tYt
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being significantly less with the prototype cigarette. There were significantly fewer DNA adducts at the low and mid exposures of the prototype cigarette than at the same exposures with the reference cigarette. A similar number of adducts was observed at the high exposure concentration of the two cigarettes. Genotoxicity and cytotoxicity studies in vitro on a similar but not identical prototype indicated significantly reduced biological activity relative to the reference cigarette. Evaluation of the in vivo findings indicated that, in general, the biological activity observed in both rats and hamsters exposed to the prototype cigarette smoke was less than that observed in the animals exposed to the reference cigarette smoke at comparable exposure concentrations. httpJ/www.rjrdirect.com/ECIJhealth/abstracts/ref4l.hlm 04/24/2000
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Cu--tomer ~Enr,'r <,c/ipsc: Oalnieg SnwAng Pr M.~ y St.1 er. ent About R RT V;desl llcdr Ceota C:,rtsct Ui ® For Sm okers ® susrar sr>Irursru=: aa"sMdt4 Ao. srta* teduua saos reks a w. Ilwh =F'u, F1 eu`7r' a eP~d essiam's -. Bombick B R; Murli H; Bombick D; Morgan W; Doolittle D J COMPARATIVE STUDIES ON THE GENOTOXIC POTENTIAL OF MAINSTREAM SMOKE CONDENSATE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at International Congress of Toxicology at Seattle, WA. July 2-6, 1995 The genotoxic potential of mainstream cigarette smoke condensate (CSC) from a new prototype cigarette which primarily heats tobacco was compared to that of CSC from Kentucky reference low tar (1 R4F) and uflra-low tar (1 R5F) cigarettes. The CSCs were evaluated at identical concentrations in an in vitro genetic toxicology test battery which included sister chromatid exchange, chromosome aberration, HGPRT gene mutation, and neutral red cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSCs from 1R4F and 1 R5F were positive in the Ames assay (TA98, TA100, TA1538, and TA1537), SCE, chromosome aberration and neutral red cytotoxicity assays but negative in the HGPRT assay. CSC from the new cigarette prototype yielded negative results in all the above endpoints. These data indicate that in these assays the genotoxic potential of CSC from the new cigarette is significantly less than CSC from Kentucky reference 1R4F and 1R5F cigarettes, which represent low and ultra-low tar cigarettes in the current U.S. market. hUpJ/www.tjrdirect.com/ECL/health/abstracts/ref3l.htm 04/24/2000
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UTILIZATION OF THE BAT FISHTAIL CHIMNEY SYSTEM FOR COLLECTION A.. Page 1 of 2 s u~e~ ~t~nr ~•Er1 Cu_toiner Sef1'tCP Contict U: ARGEON GENEAALTM•AtN916: p tl69 Ldiy No.6IVmFt' tedaa Saion fsla p 1ou YeINL Ouitlieg Smnkng PrMOCy StatemrM About R.l2T Yir1 eat Y,edu Ceeter Fa Sm okas Wingate D E; Beard K A; Jordan F D; Morrison C C; Risner C H; Smith W S 111; Rogers J C; Smith D H UTILIZATION OF THE BAT FISHTAIL CHIMNEY SYSTEM FOR COLLECTION AND QUANTIFICATION OF SIDESTREAM SMOKE CONSTITUENTS Presentation at TCRC Lexington, KY Sept. 24, 1995 Historically, the study of sidestream smoke composition has often employed a Neurath type chamber for collecting sidestream smoke. Since 1988, the BAT fishtail chimney smoke collection system has gained wide acceptance for the determination of sidestream smoke tar. In the first phase of this work, the BAT fishtail chimney design was compared to the Harris Total Smoke Collection Chamber using the 1 R4F reference cigarette. Collection of volatile sidestream smoke components was assessed using benzene as an indicator compound. The two smoke collection systems yielded similar results. Further application of a 20- port linear smoking machine modified to include BAT fishtail chimney collection capabilities has proven to be a flexible; precise and reliable collection system for other selected sidestream smoke constituents. Sidestream collection configurations for quantification of sidestream carbonyl compounds (formaldehyde, acetaldehyde), hydroxybenzenes (hydroquinone, catechol, phenol and p- + m-cresol), and benzo(a) pyrene will be discussed. Results from these determinations and from sidestream tar measurements will be presented for two reference cigarettes, a commercial light cigarette and a httpJ/www.rjrdirect.com/ECL/health/abstracts/ref30.htm 04/24/2000 A •~
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(3C/IP SC3 Cu_tuRmr Servke Contact U-- 0 SI=OB GENERAtS YfAItMING: GuiWg Se kog Mov Grcaiy tetloces Saias aaki b Yuu Ne& ~ ~`=~i*`~1lei`fhcaePFriessiasis:^"~-- Ouittieg SmoAng ^ Pr:vncy SLtemem ,About RJRT Virtuel Y.ed'u Ceeter He.. I. .: . . Scen0e kfermrticn : - :. -l:. Ern.H F..de.ek :1:, : HIG ; Abstract I Uhrig M; Risner C PRIMARY AROMATIC AMINES FROM MAINSTREAM AND SIDESTREAM CIGARETTE SMOKE Presentation at TCRC Lexington, KY September, 1995 A method to quantitate the primary aromatic amines (PAA), 2-aminonaphthalene and 4-, aminobiphenyl, in mainstream (MS) and sidestream (SS) cigarette smoke is described. Wet total particulate matter (WTPM) from either five (MS) or 2(SS) cigarettes is collected onto Cambridge filter pads. The Cambridge filter pads are extracted with hexane containing the perdeutrated internal standards. PAA are isolated from this smoke matrix by solid phase extraction and preparatory, normal phase high performance liquid chromatography (HPLC). The isolated PAA are derivatized to form the stable pentafloropropionamide (PFPA) analogs and identified and quantified using gas chromatography / selected ion monitoring mass spectrometry (GC/SIM). Coefficients of variance for 2- aminonaphthalene and 4-aminobiphenyl are 15 and 21 percent and the recoveries are 88 and 99 percent, respectively. 2-aminonaphthalene response is linear over a 100-fold concentration range and the response for 4-aminobiphenyl is linear over a 50 fold concentration range. The minimum detectable quantity for 2-aminonaphthalene and 4- aminobiphenyl is 50 pglcigt. and 70 pglcigt., respectively. This method was applied to four Kentucky Reference cigarettes, to the investigation of new cigarette component designs and to cigarettes which primarily heat, rather than bum tobacco. PAA concentrations generally increase as MS WTPM increases. PAA concentrations in SS WTPM are 25- to 40-fold greater than that found in MS WTPM, except for the cigarette which primarily heats tobacco where concentrations are similar to blank levels. http://www.qrdirect.com/ECL/health/abstracts/ref29.htm 04/24/2000
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yVa/Vau~Va~aV u~auY.aaaaVa~ yaVUa Va a~YU.~yaaW./Y~a J1~lVIW exposed to Eclipse cigarette smoke. Even though rats exposed to the Eclipse cigarette smoke inhaled more smoke than did the reference cigarette exposed rats, smoke related effects were less in rats exposed to the Eclipse cigarette smoke when compared to rats exposed to reference cigarette smoke at comparable concentrations. a [4aa. L VL L bttp://www.rjrdirect.com/ECLJhealth/abstiacts/ref43.htm 04/24/2000
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WMl'AKA 11 Vb b1 Ull1hJ UN / Hh UhIVU 1 UXU: YU 1 hN 11AL Ur MA1Ns1 KtsAM .. Yage 1 ol 1 GClipsI-- c~aomer cer~;i:e Contacf U:. SIR6E0NGfflIt1CStlAt111MG: ptE6g S.okig Ib.6mO tedaa Saioss Pekt r Yaa kaK Quimeg 9mokng Prirny Stat.cent _- About RJRT YIRCSIR.d'r Cee1s Fa Sm okers ~#lea7t aEr?c7e~oii's'' Hew. 4 seraur~elaanuieon : ,.I. Cy!rti..m.c! 1.~ sIA_~;.~.1... co.rctsd.art Bombick B R; Murli H; Cifone M; Avalos J; Putnam K; Bombick D; Morgan W; Doolittle D COMPARATIVE STUDIES ON THE GENOTOXIC POTENTIAL OF MAINSTREAM SMOKE CONDENSATE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at Environmental Mutagen Society Victoria, British Columbia March 24-28, 1996 The genotoxic potential of mainstream cigarette smoke condensate (CSC) from a new prototype cigarette which primarily heats tobacco was compared with that of CSC from Kentucky reference low tar (1 R4F) and ultra-low tar (1 R5F) cigarettes. The CSCs were evaluated at identical concentrations in an in vitro genetic toxicology test battery which included sister chromatid exchange, chromosome aberration, HGPRT gene mutation, and neutral red cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSCs from 1 R4F and 1 R5F were positive in the Ames assay with TA98, TA100, TA1 538 and TA1537 (negative with TA1 535), SCE, chromosome aberration and neutral red cytotoxicity assays but negative in the HGPRT assay. CSC from the new cigarette prototype yielded negative results in all the above endpoints. These data indicate that in these assays the genotoxic potential of CSC from the new cigarette is significantly less than CSC from Kentucky reference 1 R4F and 1 R5F cigarettes, which represent low and ultra-low tar cigarettes in the current U.S. market .P' hripJ/www.zjrdirect.com/ECL/heatth/abstracts/ref32.htm 04/24/2000 N N
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IN VITRO ASSESSMENT OF BIOLOGICAL ACTIVITY OF MAINSTREAM SMOKE.. Page 1 of 1 c,Clipse- Oslttiea Smnkoq Privnc y State n ent About RJRT Krt.al V.nCr Ceoter Cuctoiner 4-rvi_ro Curda[t Ue e H1.ip Fa Sm okers ., a: 8cierffic Mormatce ® SOQGEON ffl~tll'S wAINil6: Qudin9 %Ai Nor 61* kducec Scras R'sla b 7aer 6Wk .- r6 3lea".Fi `civ !?%dessi'va''s "_'" Ee.R FrBrek I I -'Fna ;;=4 Cwtett6dedN Bombick D W; Putnam K; Bombick B R; Morgan W T; Ayres P H; Doolittle D J IN VITRO ASSESSMENT OF BIOLOGICAL ACTIVITY OF MAINSTREAM SMOKE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at International Congress of Toxicology VII Seattle, Washington July 2-6, 1995 Smoke from Kentucky reference krer'tar' (1R4F) and ultra-low'tar (1R5F) cigarettes and a new prototype cigarette, which primarily heats tobacco was evaluated for cytotoxic and genotoxic potential using cellular smoke exposure technology (CSET). CSET includes a computer controlled 30 port AMESABattelle-Geneva smoke generator which is identical to the system utilized for animal studies and allows cultured mammalian cells (CHO) to be exposed to whole smoke. Cytotoxicity was assessed using the neutral red assay and genotoxicity was assessed using the sister chromatid exchange (SCE) assay. Compared on a per cigarette basis, mainstream smoke from 1 R5F and the new cigarette was significantly less cytotoxic and genotoxic than the smoke from the 1 R4F cigarette. The cytotoxic and genotoxic potential of smoke from the 1 R5F and new cigarettes were similar. In conclusion, in these assays mainstream whole smoke of a new cigarette had similar cytotoxic and genotoxic potential as an ultra-low'tar reference cigarette and significantly less activity compared to the whole mainstream smoke from a low'tar reference cigarette. bttpJ/www.rjrd'uect.com/ECLJhealth/abstrects/ref36.htm 04/24/2000
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Tdr 8 WiCC'Ine Corterd C?C~/j1S@ ooinug snwing Pdvs y SLtem snl --About RJRT YA.e11l.dr 6c.ta Rogers J C; Winkler L S; Borgerding M F CHROMATOGRAPHIC PROFILING AS A TOOL IN THE COMPARISON AND EVALUATION OF COMPLEX MIXTURES. J Chromatographic Sci (May) 35(5):193-200 Chromatography profiling, an application in which all peaks in a chromatogram are examined, is useful as a tool for providing comparative information regarding sample comparison and chemical complexity. The utility of profiling is demonstrated in two studies that involve complex cigarette smoke matrixes. In the first study, profiling reveals that both the vapor phase and particulate phase fractions of mainstream smoke from a cigarette that primarily heats tobacco are reduced in complexity in comparison with control products. Relative to a 1 R4F control product, total chromatographic responses (TCRs) for the tobacco- heating cigarette are reduced by 89% in the vapor phase and 70% (93% if major components are excluded) in the particle phase. The second study focuses on a cigarette that combines two design technologies: an experimental tobacco blend and a new carbon fitter. This study shows that the new filter design is primarily responsible for reducing the complexity of the vapor phase fraction of mainstream smoke while having relatively little effect on the particulate phase fraction. Compared with three commercial products, the mainstream smoke vapor phase TCR is reduced by approximately 60%. http•J/www.rjrdirect.com/ECL/health/abstracts/ref28.htm CuLtomer Service Conta7 Us TM SOAGrON GENEAACS MAiMING: Qieitg Snnk:g Mow " Aedatts Saais Yeks b ruur Mmik ~ - - Noa._1 __,...scmifficFfamatim._~ ,.I.E.WIF..eesel _l .#~4=~i_:.COetectsd.,dl,a..- 04/24/2000 s
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~ CI~pSC~ Cuetomer Service Contact Us Im E>.C Srte =OR 6Ep9GCS lrulullG: Ou+ing S.dq Nor 6m4 kdues Sriais ISela b Yaa NaIE .:.~F,a-Nt1'7tcaeFrore`~la7a's: ~=. Omnmg Srtw/.ng PrNsyStitement --About RJRT ---~ Yidoel4edr Ceeler Be....l.,v..;cISWOc _£wtl1F..A.ek Abstract Bombick Bombick B R; Avalos J; Nelson P; Conrad F; Doolittle D COMPARATIVE STUDIES OF THE MUTAGENICITY OF ENVIRONMENTAL TOBACCO SMOKE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO. Presentation at Environmental Mutagen Society Meeting Victoria, British Columbia, Canada March 24, 1996 The mutagenicity of environmental tobacco smoke (ETS) from a prototype cigarette which primarily heats tobacco was compared to that of four commercially available cigarettes that bum tobacco. ETS was generated by six individuals smoking 1 cigarette each in a 20-minute time period in a 45 m3 environmental chamber operated in the static mode (without ventilation). Respirable suspended particles (RSP) were collected on PTFE fifters at a flow rate of 3 LPM for 120 minutes. Less ETS-RSP (86-90%) was emitted by the prototype tobacco-heating cigarette than by the tobacco-burning cigarettes. To gather sufficient particle mass, five and ten filters respectively were used when the tobacco-burning and the prototype tobacco-heating cigarettes were smoked. RSP was extracted from the filters by sonication in acetone followed by dichloromethane extraction. Mutagenicity was assessed in the microsuspension modification of the Ames Salmonella/microsome assay with strains TA98 and YG1024 in the presence of 5% S9 metabolic activation. The mutagenic activity of RSP from the prototype cigarette was reduced by 75-83% on a per- mg basis when compared to the commercially available cigarettes, and was reduced by 96-98% when calculated as revertants/m3 air. hrip://www.tjrdir+ectcom/ECL/health/abstracts/ref33.htm 04/24/2000
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SUBCHRONIC INHALATION STUDY OF MAINSTREAM SMOKE FROM A NEW P.. Page 2 of 2 metaplasia were noted after exposure to either the reference or prototype cigarette with the degree of change being less in the prototype cigarette than in the reference cigarette. Evaluation of the biological findings indicated, even through rats exposed to the prototype cigarette smoke inhaled more smoke than did the reference cigarette exposed rats, in general, the biological activity of the prototype cigarette smoke was less than the reference cigarette smoke at comparable exposure concentrations. httpl/www.Sjrdirectcom/ECL/heatth/abstractsfref42.htm 04/24/2000
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COMPARING CKiAKl:11'HS WHICH 13UKtV UK PKiMAR1LY HI;AT TOBACCO Tu sr.~„r Cr,rd-'it c~Glipsi~ Custc'mer Srrvice Contact U_ n Page 1 of 1 E;,d ~d-r A/RGF0116ENEBA[S MIA1tlIUS : Uf trg ybkey Ibw 6tearf>• kdas Safarc rajs b 16ar ftaik F r-7ieaificaeri3essiorri's. 6uitting SrrwAng P~i~y st,~eeo~~ About RJRT YiAcat Nledu Centr Mo... 1 ::.:_.£Ceatifie tt Abstract Doolittle D; Brown B; Avalos J; Bombick D; Bombick B R GENETIC TOXICOLOGY STUDIES COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presented at the 51st Tobacco Chemists Research Conference,1997 The genotoxic potential of smoke from Eclipse, a cigarette that primarily heats rather than bums tobacco, was compared with Kentucky reference 1 R4F cigarettes, representative of low-tar cigarettes currently sold in the United States. Mainstream smoke condensate from Eclipse cigarettes was negative in the Ames bacterial mutagenicity assays, sister chromatid exchange (SCE) assays and chromosome aberration assays at concentrations where smoke condensate from 1R4F reference cigarettes induced a concentration dependent positive response in all assays. Studies on whole mainstream smoke using an in vitro exposure system demonstrated that smoke from the Eclipse cigarette was significantly less active in the SCE assays compared to smoke from an equal number of 1 R4F reference cigarettes. DNA adducts were evaluated in the lungs and hearts of laboratory mice exposed to whole smoke by the inhalation route as well as the dermal route using smoke condensates. DNA adducts, as measured by the P-32 post-labeling assay, were substantially reduced when animals were exposed to smoke or smoke condensate from eclipse cigarettes compared to the smoke or smoke condensate from the 1 R4F reference cigarette. when smokers switched to the Eclipse cigarette, their urine mutagenicity decreased by approximately 75% compared to when smoking their usual brand. httpJ/www.rjrdirect.com/ECI.lhealth/abstractslre£i9.hhn 04124/2000
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5 IJv:Jt;'~E L?LI1 PSL CuLtorr~cr ~.e!'JIC? CorAact U: AAtGEON 6r1irRACS 1MARi11NG: U6ig S.oYry Nuv 61M* kdtKC Saiars tskt b Tar Ne& `v: (iei•3rae~'es°s a z3 's •° ~ Ourt:ieg Srral.ing Prirsy Stacnent About RJRT Yirtae! Uedn Ceeler Nar.* t,;i,;,;#defWfficM Abstract Doolittle D J; Bombick B R; Blakley R L; Ayres P H; Gentry J S; Bombick D W; Borgerding M F TECHNOLOGIES FOR REDUCING THE TOXICITY OF CIGARETTE SMOKE Presented at 4th Annual Meeting of Oxygen Society, 1997 Oxygen 97:25 It has been hypothesized that oxidative damage by the free radicals in cigarette smoke may play an important role in the chronic diseases that have been associated with smoking. R J Reynolds Tobacco Company has developed independent technologies which reduce, among other things, the free radicals present in cigarette smoke. One of the technologies (Eclipse) involves primarily heating rather than burning the tobacco while the other technology involves the use of low nitrate tobacco with a novel carbon filter. Both of these technologies substantially reduce the number of free radicals in the vapor phase of cigarette smoke and reduce the concentration of putative free radical generators such as isoprene. These reductions in free radicals are reflected, but not necessarily solely causative in the marked reductions observed in the cytotoxicity and genotoxicity of mainstream smoke as measured in the neutral red and the sister chromatid exchange assays, respectively. httpJ/www.rjrdirect.com/ECLJhealth/abstracts/ref40.htm 04/24/2000
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COMPARAIIVE STUDY OF DNA ADDUCT FORMATION in heart DNA of the animals exposed to the TOB-HT cigarette.Under the conditions of this experiment, the mainstream smoke from the TOB-HT cigarette was demonstrated to be less genotoxic in mice than mainstream smoke from the 1 R4F cigarette, which is representative of cigarettes in the current U.S. market. Page 2 of 2 hdpa/www.rjrdirect.aom/ECUhealth/abstracts/ttf45.htm 04/24/2000
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WMYAlCA11vCJ1uL1YzUr 1r1C,mulAVbrvlt.ilYVrDIVVllCUrvmt'.1VIALlvri.. rageloIl c:cl/ps~ ouftfing smokng Prlwty St~tenent Aboul RJRT Vldael Yediu CectQ C'urjtSCt Ll'• SORGrOM GENEAArS YLUlON6: Miwq Smnkrq Aor 6a* tedaes Saious 6aks k lur Bedth =:-Fu3leq Stcaet'it~FessomTs =z' i;.::' SNetiCC k/wmffim. ~;.: ~.6rtW F.Whdt..J •;-:fJrO :-~.:Gu~tuet6d.aYt': Abstract Bombick B R; Avalos J T; Nelson P R; Conrad F W; Doolittle D J COMPARATIVE STUDIES OF THE MUTAGENICITY OF ENVIRONMENTAL TOBACCO SMOKE FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO. Environ. Mol. Mutagen. (1998), 31(2), 169-175 The mutagenicity of particulate matter concentrated from environmental tobacco smoke (ETS) from a prototype cigarette that primarily heats tobacco was compared to that of four popular commercially available cigarettes that bum tobacco. ETS was generated by six individuals simultaneously smoking 1 cigarette each in a 20-min time period in a 45 m3 environmental chamber operated in the static mode (without ventilation). Respirable suspended particles (RSP) were collected on polytetrafluoroethylene (PTFE) filters at a flow rate of 3 LPM for 120 min. Less ETS-RSP (86-90%) was emitted by the prototype tobacco-heating cigarette than by the tobacco-burning cigarettes. RSP was extracted from the filters by sequential sonication in acetone and dichloromethane. The acetone ext. was dried under nitrogen and the dichloromethane filtrate was added and then dried to obtain ETS-RSP for testing. Mutagenicity was assessed in the microsuspension modification of the Ames Salmonella/microsome assay with strains TA98 and YG 1024 in the presence of 5% S9 metabolic activation. The results show that the mutagenic activity of RSP from the prototype cigarette was reduced by 75-83% on a per- mg basis when compared to the commercially available cigarettes and was reduced by 96-98% when calculated as revertants/m3 air under identical smoking conditions. http://www.rjrdirect.com/ECUhealth/abstracts/ret35.htm l,u$tcnrier ser:Ira HseIt_
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COMPARATIVE STUDIES OF DNA ADDUCT FORMAT'ION adduct formation as compared to the vehicle control group.These results indicate that under the conditions of this experiment, mainstream smoke from the test cigarette has significantly lower genotoxic potential than the 1 R4F reference cigarette, which is representative of cigarettes in the current US market. Page 2 of 2 httpJ/www.rjrdirectcom/ECL/health/abstracts/ref44.6tm 04l24/2000
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tiuman smou.tng Denavior sway at & tneohoe Cr_-n'.nt C<-- (--11}DSC3 UJStORRr Setvice Cufdad U;, ragetort SIRG[ON 6ENEAIPS W4RNING: Quafng Stookep Now 6redlr tedaa Saioas asla b loer RmYh. ... Tearr's =^' <].inieg Srnokng Privecy Statement :About RJRT V rtaetuwi.c.a~ Hsw. HUMAN SMOKING BEHAVIOR STUDY: ECLIPSE CIGARETTE COMPARED TO USUAL BRAND. M F Stiles, T D Guy, W T Morgan, D W Edwards, R A Davis, and ] H Robinson. R J Reynolds Tobacco Company, Winston-Salem, NC, USA. Sponsor: K-M Chan¢. Human smoking behavior measures from several studies conducted'm our laboratory have shown significant differences when smokers smoked Eclipse (a cigarette that primarily heats tobacco) compared to their usual brand (UB) of tobacco burning cigarette. Two studies (conducted about 6 months apart) are presented comparing puffing profiles, cigarette sensory attribute ratings, blood carboxyhemoglobin (Y.COHb), and serum nicotine concentrations in smokers smoking their UB of tobacco burning cigarette to these same measures after smoking Eclipse cigarettes for two weeks. Two groups of smokers (o = 26 for each group) participated in two laboratory smoking tests, each between the hours of 1:30 and 4:30 p.m. Subjects smoked one of their UB cigarettes in the first test session after reporting the number of cigarettes they had already smoked that day. Smoking profiles were recorded and blood samples were collected for measurement of% COHb and serum nicotine concentrations. Smokers were then sent home with a supply of Eclipse cigarettes which had a hollow filter design (EHF). Subjects smoked these cigarettes exclusively and as desired for two weeks, then returned to the laboratory for their next test session. Identical procedures were used for both laboratory visits. Puffmg and absorbed CO measures varied widely as seen in our previous work, indicating a range of smoking behavior. On average, in both groups, smokers took significantly more puffs, closer together in time, resulting in significantly greater total puff volume when smoking Eclipse cigarettes than when smoking their UB. Average "/oCOHb concentrations were: in the first test, UB = 9.6 and EHF = 10.2, and in the second test, UB = 8.3 and EHF = 9.0. Average absorbed CO measures showed no statistically significant difference from UB in either test of the Eclipse cigarette. s 'i a ~ ~ httpJ/www.qrdirect.com/E^L/health/abstracts/stilesOl.httn 04C14/2000 A co
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COMPARATIVE STUDIES OF DNA ADDUCT FORMATION control acetone) and the RAL values were not different than those of solvent controls. The negative results in DNA adduct assays along with the lack of tumors observed in mouse dermal oncogenecity studies and the previous results of in vitro genetic toxicology tests of Eclipse are consistenL Page 2 of 2 httpJlwww.rjrdircet.com/ECLJ6ealth/abstractslref46.htm 04I24/2000
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COMPARATIVE STUDIES OF DNA ADDUCT FORMATION Page 2 of 2 significantly greater (p<0.05) than those of the solvent control animals.No corresponding DRZs were observed at any dose from the DNA of animals treated with CSC from Eclipse or solvent control (acetone) and the RAL values observed following application of Eclipse were not increased relative to the solvent control.These results provide additional evidence that the smokecondensate from the Eclipse cigarette is markedly less genotoxic than smoke condensate from tobaoco-buming cigarettes representative of those currently sold in the U.S. httpJ/www.ryrdirect.com/ECL/health/abstracts/ref47.htm 04/24/2000
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J ~~I~.:C:If1C ~~Cr~~~. srt ® l,u5tN0el cE" ce Cic'f act U= ® SME0I6EIIEtlI'SM1tNOW: p06gSmokig No+&eA ledetn Snious fala 4 rax Redk Ouitlieg Smo/.ing PriwcySt~tement - About RJRT Yirtoallled'u Ce.lm __ .. _ . _ _. _ ._ . :_...._. ~ Fa _ P~-- Hae! SclentifieNmMim _:..-.._l;EntllFwdh.ck_. Abstract :FAG -: ~I Co.tidBdedbl ;` Ayres P H; Higuchi M A; Sagartz J W; Mosberg A T; Burger G T SUBCHRONIC INHALATION STUDY OF MAINSTREAM SMOKE FROM A NEW PROTOTYPE CIGARETTE International Congress of Toxicology VII (1995), 20-P-17 A subchronic nose-only inhalation study comparing the potential biological activity of mainstream smoke from a prototype cigarette, that primarily heats tobacco, to the biological activity of mainstream smoke from a Kentucky 1 R4F reference cigarette was conducted using Sprague-Dawley rats. Animals of each sex were exposed 1 hour a day, 5 days per week, for a thirteen week period to mainstream smoke at concentrations of 0, 0.16, 0.32, or 0.64 mg wet total particulate material / liter of air. The smoke was generated by an AMESA 30 port smoke generator operating at the Federal Trade Commission standard of a single 2-second puff of 35 ml volume once per minute. The smoke was diluted with humidified filtered air and the concentration was maintained by a feedback loop exposure controller. Endpoints evaluated were clinical signs, body and organ weights, carboxyhemoglobin, serum nicotine, plethysmography, and gross and histopathology. Carboxyhemoglobin and serum nicotine were related to the exposure concentration of both cigarettes in an exposure-dependent manner. Plethysmography indicated that the rats exposed to the prototype cigarette inhaled substantially more smoke than rats exposed to smoke from the reference cigarette. Nasal epithelial hyperplasia and laryngeal squamous metaplasia were noted after exposure to either the : He+'ff re:re Ari3essi orii's" http!/www.rjrdirect.com/ECIJhealth/abstracts/ref42.htm 04/24l2000
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sUriI:HKUNll;1NHALA 1 lUN s1 Ull Y Ur MA1NJ 1 HhAM JMUKh . a: b u.:ohne f_ p-~, •rA Ovltlleg Smo4ng P~ivocy Staement -AboutRJRT Virtaalldedu Center Cuetom=~ S_!'dlCe CorGact U= ® - Fa Smokas ® ® E:1 [pi Page 1 02l SIAIGEON 6FAEIAIT M1tMqG: Od69 S^di Ila 6RUM tedaa Sabus 1'ab % Ioor Ntdh ---#a_He~~~JTC~aeArr~essor~'s: -~ Ayres P H; Higuchi M A; Sagartz J W; Mosberg A T; Burger G T SUBCHRONIC INHALATION STUDY OF MAINSTREAM SMOKE FROM A CIGARETTE THAT PRIMARILY HEATS TOBACCO Presentation at Society of Toxicology Meeting Cincinatti, Ohio March 8-13,1997 A subchronic nose-only inhalation study comparing the potential biological activity of mainstream smoke from.a recently developed cigarette (Eclipse), that primarily heats tobacco, to the biological activity of mainstream smoke from a Kentucky 1 R4F reference cigarette was conducted using Sprague-Dawley rats. Animals of each sex were exposed 1 hour a day, 5 days per week, for a thirteen week period to mainstream smoke at 0, 0.16, 0.32, or 0.64 mg wet total particulate materiaUliter of air. There were no exposure related adverse changes in clinical signs, body and organ weights, serum chemistry, or hematology. Carboxyhemoglobin and serum nicotine were related to the exposure concentration of both cigarettes in an exposure-dependent manner. Rats exposed to the Eclipse cigarette inhaled substantially more smoke,than rats exposed to smoke from the reference cigarette. Smoke related histologic changes included nasal chroniclactive inflammation and epithelial hyperplasia, chroniGactive inflammation of the larynx, squamous metaplasia and acute inflammation of the ventral larynx, and an increase of non-pigmented and brown/gold pigmented pulmonay macrophages. Acute inflammation of the ventral larynx was not statistically different in rats exposed to the 1 R4F or Eclipse cigarette. Brown/gold pigmented macrophages were absent in the Eclipse exposed rats. All other smoke related responses were statistically reduced in Eclipse exposed rats when compared to the I R4F exposed rats. Thorough evaluation revealed no unexpected effects in rats exposed to Eclipse cigarette smoke. Even though htlpJ/www.rjrdirect.com/ECL/health/abshacts/ref43.htm 04124/2000
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CHh:M1C:AL ANll 13111LU(il(;AL 51'Ull1EJ OF A N1;W (Y(iAREl-1l; 1HA1 yK1MAR. Yage 1 01 2 7.,, 5 IJ._din2 rr•r'c't Cu_tomer S pi t're a~dsd Ui ® C0o C~CIIpSC3 Qeit:iea Smo1ng Pri.gy Statrrent A6out RJRT Virtael Med'u Ceeta ~~ . FaSmokas SIptGEON 6rAfR1rSWARIBNG:&i7feySakitp Nar 6f* Radms Saiars tda e Yow Xei6. _ '-..+:~Ar.1f-d9rcaeFrdcssiar:'s-~., Bombick B R; Murli H; Avalos J T; Bombick D W; Morgan W T; Putnam K P; Doolittle D J CHEMICAL AND BIOLOGICAL STUDIES OF A NEW CIGARETTE THAT PRIMARILY HEATS TOBACCO. PART 2. IN VITRO TOXICOLOGY OF MAINSTREAM SMOKE CONDENSATE. Food Chem Tox 36(3) (Mar):183-190 The genotoxic and cytotoxic potential of mainstream cigarette smoke condensate (CSC) from a new cigarette that primarily heats tobacco (TOB-HT) was compared with that of CSC from a Kentucky reference low "tar" cigarette (1R4F) representative of the current US cigarette market, and Kentucky reference 1 R5F, representative of ultra-low "tar" cigarettes on the US market. TOB-HT was evaluated at concentrations which induced concentration- dependent positive responses with 1 R4F and I R5F in an in vitro toxicological test battery which included sister chromatid exchange, chromosome aberration, and neutral red cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSC from 1 R4F and 1 R5F was pos. in the Ames assay with Salmonella typhimurium strains TA98, TA100, TA1 538 and TA1 537, and neg. with TA1535, while CSC from TOB-HT was negative in all five strains. CSC from 1 R4F and 1 R5F cigarettes was pos. in sister chromatid exchange (SCE), chromosome aberration (CA) and neutral red cytotoxicity assays, while CSC from the TOB-HT cigarette yielded negative results in all the above endpoints. These data indicate that in these assays the genotoxic and cytotoxic potential of CSC from the new cigarette that primarily heats tobacco is significantly less than CSC from Kentucky ref. 1 R4F and 1 R5F cigarettes, which are representative of cigarettes currently sold in the US. httpJ/www.rjrdiracc.com/ECL/bealth/abstracts/ref34.htm 04/24/2000
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ASSESSMENT OF GAP JUNCTION INTERCELLULAR COMMUNICAIION Page 2 of 2 httpJ/www.rjrdireetcom/ECLlhealth/abstracts/ref49.hmn 04/24/2000
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COMPARATiVE 30-WEEK DERMAL pROMOTION ASSAY Page 2 of 2 condensate at any exposure condition. The tumor- promotion potential of the prototype cigarette condensate was, therefore, substantially reduced when compared to the 1R4F reference cigarette smoke condensate in this model. MtpJ/www.rjrdircei.com/ECUhealth/abshacts/ref50.htm 04/24R000
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U1MCA!(A l l V b J 1 UL1Y.J Vi'LNA AllllUl;1 t`UKMA 11UN ~=ueL_mer c<r.nr_a iArA,iit UL ® Brown B G Kolesar J A Meckley D R Mosberg T Doolittle COMPARATIVE STUDIES OF DNA ADDUCT FORMATION IN MICE AFTER DERMAL APPLICATION OF SMOKE CONDENSATES FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO Presentation at 88th Annual Meeting of the American Association for Cancer Research San Diego, California 4/12/97 Smoke and smoke condensate from R J Reynolds Tobacco Company's Eclipse cigarette yield markedly reduced biological activity in in vitro genetic toxicology tests when compared to the I R4F Kentucky reference cigarette, representative of low tar cigarettes sold in the US today. Eclipse primarily heats tobacco; so, the simplified smoke chemistry (80% glycerol and water) results in expected reduced biological activity. The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin of mice and to compare results with those obtained with CSC from the I R4F reference cigarette. CSC from reference or Eclipse cigar,ettes was applied dermally to SENCAR mice three times a week for 29 weeks. Amounts of CSC applied were 30, 60 and 120 mg tar per animal per week. Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with reference CSC and the relative adduct labeling (RAL) values were significantly greater (p<0.01) than those of the Eclipse-treated animals. No corresponding DRZs were observed from the DNA of animals treated with CSC from Eclipse or solvent control acetone) and the RAL values were not Page 1 of 2 http://www.rjrdirect.com/ECIJhealth/abstracts/ref46.bmn 04/24I2000
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VITRO ASSESSMENT OF BIOLOGICAL ACTIVITY OF MAINSTREAM SMOKE FR. Page 1 of 1 Tar S f{=otine cor,tent Qaittieg Snwking Prlrsy Stiten ent Abaut R.RT YiAeel U.ediu Canta ~ 1 :.ENaFwdewc „~ Abstract Bombick D W; Putnam K; Bombick B R; Morgan W T; Ayres P H; Doolittle D J IN VITRO ASSESSMENT OF BIOLOGICAL ACTIVITY OF MAINSTREAM SMOKE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at 35th Annual Meeting of Society of Toxicology, 1996 Smoke from Kentucky reference low "tar" (1 R4F) and ultra-low'Yar" (1 R5F) cigarettes and a new prototype cigarette, which primarily heats tobacco was evaluated for cytotoxic and genotoxic potential using cellular smoke exposure technology (CSET). CSET includes a computer controlled 30 port AMESABattelle-Geneva smoke generator which is identical to the system utilized for animal studies and allows cultured mammalian cells (CHO) to be exposed to whole smoke. Cytotoxicity was assessed using the neutral red assay and genotoxicity was assessed using the sister chromatid exchange (SCE) assay. Compared on a per cigarette basis, mainstream smoke from 1 R5F and the new cigarette was significantly less cytotoxic and genotoxic potentials of smoke from the 1 R5F and new cigarettes were similar. In conclusion, in these assays, mainstream whole smoke of a new cigarette had similar cytotoxic and penotoxic potential as an ultra-low "tar" reference cigarette and significantly less activity compared to the whole mainstream smoke from a low "tar" reference cigarette. bttpJ/www.rjrdirect.com/ECL/health/abstractslref38.htm iuztorner Ser,;:Z CDrd i M U- SURf,rOM 6rMEAACS Yfu111AG: GuuNg Swo4:y Now 6tadp tatlues Setinut Gsla to Voar Net Hmae J..•, ..Seietrtffiettcrnutin
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•1\ f 1VV fL\1J lll Y i l l\V J 1 11Jr1L.p Vf 1V.flil~u i 1wf11v1 J1elVlw a atVlrl A lqy~ e~ `,1V-. 1 asa: l Vl 6 "- fi IJCOtir~e Cor;znt c~clipsc~ Ouitting Srnnking Privocy Stiter.ent About RJRT YrtealYedu Ceas cuCtoliicr sFrvice Cc,rda[t IJ_ ® rk, wuEOM r,EqElruY rultllw: arwag s.dog Ncre 6m4 tedtlm Saiart kskt b YoM Ikih Sc1Mn7c Hermaticn :.,_ .rl, EeYt F..Ab.et .1 Oaa.cl Sd..fYt Ayres P H; Higuchi M A; Bombick D W; Doolittle D J; Lee C K; Brown B G; Burger G T; Sagartz J W; Bombick E R; Mosberg A T; Renne R A IN VIVO AND IN VITRO STUDIES OF MAINSTREAM SMOKE FROM A NEW CIGARETTE PROTOTYPE Presentation at 5th International Inhalation Symposium Hannover, Germany 2/20/95 Studies comparing the potential biological activity of mainstream smoke from a new cigarette prototype to the biological activity of mainstream smoke from a Kentucky 1 R4F reference cigarette were conducted in Sprague-Dawley rats, Syrian Golden hamsters, and in vitro. The tests used were similar to those used by others to evaluate cigarette smoke. Animals of each sex were exposed 1 hour a day, 5 days per week, for a thirteen week period to mainstream smoke at concentrations of 0, 0.16, 0.32, or 0.64 mg wet total particulate materiaUliter of air. The smoke was generated by an AMESA 30 port smoke generator operating at the Federal Trade Commission standard of a single 2-second puff of 35 mL volume once per minute. The smoke was diluted with humidified filtered air and the concentration was maintained by a feedback loop exposure controller. Endpoints evaluated were clinical signs, body and organ weights, carboxyhemoglobin, serum nicotine, plethysmography, DNA adducts in the lung, and gross and histopathology. In vitro assays conducted included Ames bacterial mutagenicity, sister chromatid exchange, and neutral red cytotoxicity. Carboxyhemoglobin and serum nicotine were related to the exposure concentration of both cigarettes in a dose-dependent manner. Plethysmography indicated that the rats exposed to the prototype cigarette inhaled substantially more smoke than rats exposed to smoke from the reference cigarette. Nasal epithelial hyperplasia and laryngeal squamous metaplasia were observed with the degree of change being significantly less with the prototype cigarette. bttpJ/www.rjrdirectcom/ECL/health/abshacts/ref4l.htm 04/24/2000
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IN VIVO GENETIC TOXICOLOGY STUDIES Page 2 of 2 mainstream smoke from the new cigarette has significantly lower genotoxic potential than the 1 R4F reference cigarette which is representative of cigarettes in the current US market. bttpJ/www.rjrdirect.com/ECLhealthJabstracts/ref48.htm 04/24/2000
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'sr s rJ~~..~xc.e CC= <~lipsc: Cu_,omer S2r, iCe iArd-aCl U: - dc F:1ap MON 6ENERAfS WARNIIIG: Uing Sentnj 16ar 6tcaltr leduca Setiars feks w Yarr RW! eu'~+ca`a~Fiofess±aR;'cr-:-_ -- ~ ---- -- - - - - 0 1 itting Smoing Prrvacy Stileeenl About RJRT Virtasl L1edu Ceeter %k"J . «:..:: SC*WAc Mafmali0n.~:~~ „BeNI Frwhs.C J-'.; i/1Q Abstract Bombick D W; Ayres P H; Putnam K; Bombick B R; Doolittle D J CHEMICAL AND BIOLOGICAL STUDIES OF A NEW CIGARETTE THAT PRIMARILY HEATS TOBACCO. PART 3. IN VITRO TOXICOLOGY OF WHOLE SMOKE. Food Chem. Toxicol. (1998), 36(3), 191-197 Mainstream smoke from Kentucky reference low "tar" (1R4F) and ultra-low"tar" (1R5F) cigarettes and a test cigarette (TOB-HT), that primarily heats tobacco, was compared for cytotoxic and genotoxic potential using cellular smoke exposure technology (CSET). CSET includes a computer controlled 30-port AMESA/Battelle-Geneva smoke generator which exposes cultured mammalian Chinese hamster ovary cells (CHO) to whole smoke. Cytotoxicity was assessed using the neutral red assay and genotoxicity was assessed using the sister chromatid exchange (SCE) assay. Compared on a per cigarette basis, mainstream smoke from 1 R5F and the TOB- HT cigarette was significantly less cytotoxic and genotoxic than the smoke from the 1 R4F cigarette. The cytotoxic and genotoxic activity of smoke from the TOB-HT cigarettes was slightly greater than the smoke from the ultra-low "tar" Kentucky 1R5F reference cigarettes. In conclusion, in these assays mainstream whole smoke of the TOB-HT cigarette had slightly greater cytotoxic and genotoxic potential compared with an ultra-low "tar" 1 R5F Kentucky reference ci~larette and significantly less activity compared with the whole mainstream smoke from a low "tar" 1R4F Kentucky reference cigarette, representative of the US market average cigarette for FTC yields of'Yar", CO and nicotine. httpJ/www.qrdirect.com/ECI,/healt}Jabstracts/ref37.htm 04/24/2000
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~ z L G--dine Ci. r,te~nt C i NS--Z-~) oukting smoLng PrivnCyStdemrrrt-- About RJRT- Yidca'A!edi. Ceeter "a Brown B G; Lee C K; Ayres P H; Meckley D R; Mosberg A T; Doolittle D J COMPARATIVE STUDIES OF DNA ADDUCT FORMATION IN MICE FOLLOWING EXPOSURE TO MAINSTREAM SMOKE FROM CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presented at the 87th Annual Meeting of the American Cancer SocietyProceedings of the American Association for Cancer Research 37:98 (1996) The -genotoxic potential of smoke from a test cigarette which primarily heats tobacco and a reference cigarette (Kentucky reference 1 R4F) were compared in mice following two different routes of exposure.In the first study, B6C3/F1 mice were exposed by nose-only inhalation for 1 hour a day, 5 days/week for a 4 week period to mainstream smoke at concentrations of 0, 0.16, 0.32, and 0.64 mg wet total particulate matterlliter of air.DNA adduct measurement by the P-postlabeling method indicated an exposure-dependent increase in lung adducts of B6C3IF1 mice exposed to the reference cigarette smoke but not in mice exposed to the test cigarette smoke.An exposure-dependent formation of DNA adducts was•also observed in the heart tissues of B6C3/F1 mice exposed to the reference cigarette, but not in the animals exposed to the test cigarette. In a second study, cigarette smoke condensate (CSC) from the test and reference cigarette was dermally applied to SENCAR mice three times a week for 4 weeks. The amount of CSC per dermal application was 10, 20, or 40 mg/animal.SENCAR mice exposed to reference CSC exhibited a dose-dependent increase in lung and heart DNA adducts.However, animals treated with test CSC showed no increase in adduct formation as compared to the vehicle control bttpJlwww.rjrdirectcom/ECUhealth/abstracts/ref44.htm 04/24/2000 iuaomer ~21\i[e ® ® WtGrON 6ENEAAfS NIAWINU: qmf g 5.dig IbW 6raby tedas Seisws fda lo Yomr Ilelidi 'F..ah.ck 1
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COMPARATIVE 30-WEEK DERMAL TUMOR PROMOTION STUDIES Page 2 of 2 were observed in mice exposed to the Eclipse or Eclipse prototype cigarette condensate at any exposure condition in any of the studies.In this assay, the dermal tumor-promotion potential of the Eclipse cigarette condensate was, therefore, substantially reduced when compared to the I R4F reference CSC. httpJ/www.rjrd'uect.oom/ECL/health/abstracts/ref5l.htm 04/24/2000
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LACK OF MUTAGENICITY AT THE Si LOCUS Page 2 of 2 detectable (2).Sponsored by contract #95773059 from the RJR Tobacco Co.(1) Bombick et al., Environ Molec Mut 27 (9) 1996, (2) Hei et al., Cancer Res 52 (1992). LttpJ/www.cjrdirect.com/ECUhealth/abs~actslref54.htm 0424I2000
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COMPARpTIVE SUBCHRONIC INHAI,p1ION STUDY OF MAINSTREAM SMOKE Page 2 of 2 of these lesions were related to exposure concentration in all exposed groups, but there was clearly less degree of change in hamsters exposed to the test cigarette compared with the response to the reference cigarette. Biological evaluation indicated that although hamsters exposed to the test cigarette smoke inhaled more smoke than did the reference- cigarette-exposed hamsters, the biological activity of the test cigarette smoke was reduced compared to the reference cigarette smoke at comparable exposure concentrations. httpJ/www.tjrdirectcom/ECLJhealth/abstracts/ref52.htm
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IN VIVO GENETIC TOXICOLOGY STUDIES T; ~. ta,Co:ne fP't?-t ~.clipsC~ ~u'rtlleg Smotng~ PrMsy Stitement Abeut RJRT--~ - YdualYled"a 6ente Cu_torr~er SprVi-iP Cor¢sa Ua ® For Sr.lokers 17 Page 1 of 2 J od waaNs[N[urswunmw: a+~ss.ioy Nor srealh tedaca Safaa Llu a row xedk `'FAiH6Y7icaeP.-ofEt-ziorr.ts-'-=--- Lee C K; Brown B G; Bombick B R; Ayres P H; Mosberg A T; Doolittle D J IN VIVO GENETIC TOXICOLOGY STUDIES OF MAINSTREAM SMOKE FROM A NEW CIGARETTE WHICH PRIMARILY HEATS TOBACCO Presentation at International Congress of Toxicology, VII Seattle, WA July 2-7, 1995 Mainstream smoke from a new cigarette and a reference cigarette (Kentucky reference 1 R4F) were compared in B6C3/F1 mice by examining DNA adducts and micronuclei formation after four-week nose-only inhalation exposures. Mice were exposed 1 hour a day, 5 days/week for a 4 week period to mainstream smoke at concentrations of 0, 0.16, 0.32, and 0.64 mg wet total particulate matter/liter of air. DNA adduct measurement by P-postlabeling method indicated an exposure dependent increase in lung adducts with both types of cigarettes. However, the concentration of DNA adducts was significantly lower in the lungs of animals exposed to the new cigarette compared to the reference cigarette. An exposure- dependent formation of DNA adducts was also observed in the heart tissues of animals exposed to the reference cigarette, but heart tissues of animals exposed to the new cigarette did not exhibit DNA adducts at any of the smoke concentrations tested. The results of micronuclei assays in both bone marrow and peripheral blood were negative with both types of cigarettes, while the positive control, cyclophosphamide, elicited positive responses. Under the conditions of this experiment, the mainstream smoke from the new cigarette has httpJ/www.rjrdirect.com/ECUheatth/abstracts/ref48.htm 04/24/2000
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COMPARATIVE INHALATION STUDIES IN RATS AND HAMSTERS Page 2 of 2 hamsters necropsied at the 13-week recovery period.Evaluation of these data indicated that although rats and hamsters exposed to the prototype cigarette smoke inhaled more smoke than did the reference-cigarette-exposed animals, the biological activity of the prototype cigarette smoke was less than the reference cigarette smoke at comparable exposure concentrations. 18tpJ/.vwwsjrdirect.comlECUhealth/absaacts/ref53.htm 04/24/2000
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%.vMrtfiW 11 V D J t vL1LJ Ur u1vA HUUUU t r ViCN1A 11 Vtv ;r & I eccur~e Ccr:cM ® EC :II~S(3 Ourtling Smnling~ P~WSCy Stacement About RJRT Virtael uedu Ceeer iuctWer cFr•: ire ® ® rage I oi t St1RGE0N rENER,U'S WdAMING: Coit6g Sndcog Ma Grcu* kduns Saas feks b losr Mwllh. ~-~~~=~~A~E~J~ffIC;lrP-PfL~CbSIQa 6..:~~ Abstract Brown B; Kolesar J; Lindberg K; Meckley D; Mosberg A; Doolittle D COMPARATIVE STUDIES OF DNA ADDUCT FORMATION IN MICE FOLLOWING DERMAL APPLICATION OF SMOKE CONDENSATES FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO. Mutat. Res. 414, 21-30 A new cigarette (Eclipse) that primarily heats rather than.bums tobacco has been developed.Since Eclipse primarily heats tobacco, the smoke chemistry is much simplified, consisting of 80% glycerol and water.With the simplified smoke chemistry, it would be expected that toxicological activity would be reduced.Smoke and smoke condensate from Eclipse have consistently yielded markedly reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke and smoke condensate from the 1 R4F Kentucky ref. cigarette, which is representative of typical low'tar' cigarettes sold in the U.S. today.The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin tissue of demially- exposed mice and to compare the results with those obtained with CSC from the 1 R4F Kentucky ref. cigarette.CSC from Eclipse or 1 R4F cigarettes was applied dermally to SENCAR mice three times a week for 30 wk.The amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per wk.Tissues were collected after 1, 4, 14 and 29 wk of CSC application.DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method with P1 nuclease modification.Distinct time and dose- dependent diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with 1 R4F CSC.The relative adduct labeling (RAL) values of lung, heart and skin DNA from ref. CSC-treated animals were significantly greater (p<0.05) than those of the solvent httpJ/www.rjrdirect.coaJECLhealth/abstracrs/ref47.htm 04/24/2000
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WMl'AliA11Vt; SU-WN:KK llKKMAL yKUMU1IUN ASSAY ;t 8 r~I,_u;tne Cont~rd cclipsc; Ouitling5mokng . Yriwcy SLtement About RJRT Vi tt aat lled ia Ce. ter Cu_tomer SFr~ ice Contict ll_ Fa Srnokae IJ rpo Page 1 ot2 wMa srM1w,uauw: U4 sM&jj Notr sraar bdwn sem reln r raw emlk .-..=: -fu.NeT:fTcaePrdmz~fo Mosberg A T; Meckley D R; Burger G T COMPARATIVE 30-WEEK DERMAL PROMOTION ASSAY OF MAINSTREAM SMOKE CONDENSATE FROM A PROTOTYPE CIGARETTE WHICH PRIMARILY HEATS TOBACCO AND A REFERENCE CIGARETTE Presentation at International Congress of Toxicology VII Seattle WA July 2-6, 1995 A 30-week dermal promotion assay in mice was conducted to compare the potential tumor promotion activity of mainstream cigarette smoke condensates (CSC) collected from a prototypical cigarette, which primarily heats tobacco, and a 1 R4F (Univ. of Kentucky) reference cigarette. The smoke was generated by an AMESA 30 port smoke generator operating at the Federal Trade Commission standard of a single 2-second puff of 35 ml volume once per minute. Mainstream CSC's were collected by cold trap. Female SENCAR mice were initiated with a single 75 ug application of DMBA to the shaved dorsal skin. The CSC's were then applied to the skin three times per week for 30 weeks. Each CSC was administered at 10, 20 or 40 mg tar/application to groups of 40 animals. End-points included body weights, clinical observations, organ weights, tumor development data and histopathology. The numbers of tumors, the percentages of tumor-bearing animals and the median times-to-tumor for the 1R4F reference cigarette condensate were statistically different from the DMBA-initiated and acetone- promoted control group and increased with increasing exposure to the 1 R4F condensate. No statistically or biologically significant tumor formation data were observed in mice exposed to the prototype cigarette condensate at any exposure condition. The tumor- httpJ/www.rjrd'uect.com/ECL/health/abstracts/ref50.htm 04/24/2000
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HUMAN URINE MUTAGENICITY Page 2 of 2 compared to the weeks they smoked their usual brand. These results indicate that smokers of tobacco-heating cigarettes voided urine that was significantly less mutagenic than that voided when they smoked tobacco-burning cigarettes. ttp:Uwww.rjrdirect.comlECL/bealth/abstracts/ref58.btm 4/24r2000 (n N B CO v k~ m o,
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COMPARATIVE 30-WEEK DERMAL'NMOR PROMOTION STUDIES .'i ~hl;>ullr~e ' ce.rae.~l ~CII~SC~ Quittiag Smo~i+g Primcy Statement A6cut RJRT--- Vi9ual Yled'u Centx ru[iorr~er sern:ice ,~ordsct us am For Sm okers ® ~t~"r7lei'9icasPniessTorti!s :." Meckley D R; Mosberg A T; Burger G T; Van Kampen K R COMPARATIVE 30-WEEK DERMAL TUMOR PROMOTION STUDIES OF MAINSTREAM SMOKE CONDENSATES FROM CIGARETTES WHICH PRIMARILY HEAT TOBACCO AND A REFERENCE CIGARETTE Presentation at 1997 Society of Toxicology Cincinnati, OH March 9-13, 1997 Three 30-week dermal promotion assays were conducted to compare the potential dermal tumor promotion activity of main-stream cigarette smoke condensates (CSC) collected from the Eclipse cigarette and two Eclipse prototype cigarettes, all of which primarily heats tobacco, to that of the 1 R4F (Univ. of Kentucky) reference cigarette.All three studies were conducted using a standardized study design. Mainstream CSC's were collected by cold trap from smoke generators using the Federal Trade Commission puffing regimen. Female SENCAR mice were initiated with a single 75 ug application of DMBA to the shaved dorsal skin.The CSC's were then applied to the skin three times per week for 30 weeks.Each'CSC was administered at 10, 20, or 40 mg tar/application to groups of 40 animals. End- points included body weights, clinical observations, organ weights, dermal tumor development data and histopathology.The numbers of dermal tumors, the numbers of dermal tumor-bearing animals, and the median times-to-tumor for the 1 R4F reference cigarette condensate were statistically different from the DMBA-initiated and acetone-promoted control groups, increased with increasing exposure and were similar for all three studies.No statistically or biologically significant dermal tumor formation data were observed in mice exposed to the Eclipse or COD Page 1 of 2 SOflGE0116ENEAOI'S MeRMING: aiaNg SLdig Mo.6rcaAr telum Saious teks b 1ar MnMk hripJ/www.rjrdirect.com/ECLhealth/absUacts/ref3I.htm 04/24l2000
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COMPARATIVE STUDY OF DNA ADDUCT FORMATION sI; ,r CCnta n Cu:tome! Ser4'IC!' Contatl U_ Page 1 of 2 sJVroN srNIMs waaraG: ctlaft s.dl:q Na &ea~ kdtaa Suian ~slls b You Ne~ QaiT.ieg Snwkng Pttrsy State¢ent~--~ Aboul RJRT Vi rt ual 1R.d u Cae la Brown B G; Lee C K; Bombick B R; Ayres P H; Mosberg A T; Doolittle D J COMPARATIVE STUDY OF DNA ADDUCT FORMATION IN MICE FOLLOWING INHALATION OF SMOKE FROM CIGARETTES THAT BURN OR PRIMARILY HEAT TOBACCO. Environ. Mol. Mutagen. (1997), 29(3), 303-311 The genotoxic potential of mainstream smoke from a test cigarette (TOB-HT) that primarily heats tobacco and a representative tobacco-burning cigarette (Kentucky ref. 1 R4F) was compared in male B6C3/F1 mice after nose-only inhalation exposure.Mice were exposed I h per day, 5 dayslwk for a 4 wk period to mainstream smoke at concentrations of 0, 0.16, 0.32, and 0.64 mg total particulate mattedL of air.Micronuclei formation in bone marrow and peripheral blood polychromatic erythrocytes (PCE) of animals exposed to either the TOB-HT or 1 R4Fcigarette was not significantly different compared with control animals exposed nose-only to filtered and humidified air (sham controls).DNA adduct measurement by the 32P-post labeling method indicated an exposure-dependent increase in lung adducts of animals exposed to 1 R4F cigarette smoke at all three concentrations with the mid and . high exposure groups exhibiting statistically significant increases in adduct formation compared to sham-exposed animals.The concentration of DNA adducts in the lungs of animals exposed to the TOB- HT cigarette was not significantly increased at any concentration compared to sham-exposed controlsA statistically significant concentration-dependent formation of DNA adducts was also observed in the heart tissues of animals exposed to smoke from the 1 R4F cigarette at all three concentrations, but no significant increase in adduct formation was observed in heart DNA of the animals exposed to the TOB-HT httpJ/www.rjrdirect.com/ECIAhealth/abstracts/ref45.htm 04/24I2000
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HUMAN URINE MUTAGENICITY STUDy Page 2 of 2 cigarettes to Eclipse, a reduction in urine mutagenicity was observed. Urine mutagenicity declined 731 14% (Mean 1 SD) and 78 ? 13% (Mean ? SD) as measured in the Ames assay using the YG1024 and TA98 strains, respectively (p = 0.0001). These results indicate that smokers of Eclipse cigarettes (which primarily heats tobacco) voided unne that was significantly less mutagenic than that voided when they smoked their usual brand of cigarettes. httpJ/www.rjrdirect.com/ECUhealth/abstracts/ref35.htm 04/24l2000 m r
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VVL~Y tuV LLL 1L+NVLIVLLl~V1\L~... L\LYfy/'111V1~ ULVL 1 VL 1/LAl1~U1L\Li/"1lyl JlY1Vl1(' (Qgc I Ul l. ® ID ~CII}7SG Ouitting Smo\ing PlFVacy Stateoant About RJRT Vlrt.el4.ed1. Centa CUnGtLer =ClVIc? CofAaCt U: For Srn okss K~I SURGEON GEN= WAtMIKG: Gefn9 S°nkn9 Nor &wdl' tedaa Saions &ks b YaK Reallh ~:Fwu.Hea`.3icaPPrr~es~i'ar,!s.=:--, - Renne R A; Phelps R L; Mosberg A T COMPARATIVE SUBCHRONIC INHALATION STUDY OF MAINSTREAM SMOKE FROM A TEST CIGARETTE AND A REFERENCE CIGARETTE IN SYRIAN GOLDEN HAMSTERS Presentation at 1997 Society of Toxicology Meeting Cincinnati, Ohio March 10, 1997 A subchronic nose-only inhalation study comparing the potential biological activities of mainstream smoke from a test cigarette with that of mainstream smoke from a Kentucky 1 R4F reference cigarette was conducted using Syrian Golden hamsters.Groups of 30 hamsters of each sex were exposed 1 hour/day, 5 days/week, for a 13-week period to mainstream smoke at target concentrations of 0, 0.16, 0.32, or 0.64 mg wet total particulate materiaUliter of air.The smoke was generated by an AMESA 30-port smoke generator operating at the Federal Trade Commission standard of a single 2-second/35-ml volume puff once/minute.The smoke was diluted with humidified filtered air and the concentration was maintained by a feedback loop exposure controller.Endpoints evaluated were clinical signs, body and organ weights, carboxyhemoglobin, serum nicotine, plethysmography, and gross and histopathology.Carboxyhemoglobin and serum nicotine were related to the exposure concentration of both cigarettes in an exposure-dependent manner.Plethysmography indicated that hamsters exposed to the test cigarette inhaled substantially more smoke than animals exposed to smoke from the reference cigarette.Squamous metaplasia, hyperplasia, and hyperkeratosis of laryngeal epithelium were noted in hamsters exposed to smoke from the reference cigarette.Squamous metaplasia, hyperplasia, and hyperkeratosis of laryngeal epithelium were noted in hamsters exposed to either the reference or test cigarettes.Incidence and severity of these lesions were related to exposure httpJ/www.rjrdirectcom/ECI:./6eatth/abstracts/ref52.htm 04/24/2000
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HUMAN JMUKiN(i l3t:HAV1Utt Mt;AsUKES the UB and TOB-HT ciga.rettes.Average absorbed % COHb increased when smoking the TOB-HT cigarettes (8.5 vs 10.4, UB vs TOB-HT-FF and 9.6 vs 12.9 UB vs TOB-HT-LT).Serum nicotine concentrations were qude variable and did not differ statistically at any time point comparing usual brand to either tobacco-heating cigarette. Page 2 of2 hripJ/www.qrdirect.com/ECIAheatth/abstracts/ref59.htm 04/24/2000
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HUIvIAp URINE MUTAGENICITY S1UDY Page 2 of 2 the smoker subjects switched from their usual brand cigarettes to Eclipse, a reduction in urine mutagenicity was observed. Urine mutagenicily declined 73 +1-14% and 78 +/- 13% as measured in the Ames assay using the YG1024 and TA98 strains, respectively (p = 0.0001). These results indicate that smokers of Eclipse cigarettes (which primarily heats tobacco) voided urine that was significantly less mutagenic than that voided when they smoked their usual brand of cigarettes. httpJhvww.ijrdirectcom/ECL/heatth/abshacts/ref56.htm 04/24/2000
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LACK OF MUTAGENICITY AT THE Sl LOCUS T r H 1:_i~n'ie fnr!2~d m CU`tORiFr S.1.:'Ice Contact U> HEM Page 1 of 2 SUlGEON 6rNElUCS N'ANNING: Cuefig Smakiq Na 6rto* Nedws Srriars fela b Yw Ik& Qaittieg Srtakng P~FwcyStutnment Abwl RJRT YiM1.dlpadu 6sdr Waidren C., Vannais D., McGraw M., Bombick B., Smith C., Doolittle D. Lack of mutagenicity at the S1 locus of AL Human Hamster hybrid cells of smoke condensate from cigarettes that bum or primarily heat tobacco Presented at the 4th Annual Meeting of the Oxygen Society, Oxygen, 97: 93. We compared lethal and mutagenic effects on cultured mammalian AL cells of mainstream smoke condensate (CSC) from cigarettes that bum (B-CSC) or primarily heat (H-CSC) tobacco.Mutation was detected by loss of expression of the S1 human cell surface antigen encoded by the gene MiC1 = cd59 on human chromosome 11, the sole human chromosome in the AL humarn-hamster hybrid cell line.Mutations ranging from intragenic to chromosomal deletions of > 140 million base pairs are detectable at this iocus.ln two separate trials, B- CSC was about - 1 0-fold more lethal per mg/ml than H-CSC: LD50S for B-CSC were 15 and 35 mg/ml; 150 and 300 mg/ml for H-CSC.At its highest dose (300 mg/ml) H-CSC reduced survival by about 35% but induced no S1 mutants.B-CSC, 60 mglml, reduced survival by 90 - 99% and gave a slight but not statistically significant increase in the yield of mutants.Thus, at the hprt locus of CHO cells (1), neither B-CSC nor H-CSC induced mutants in ALlS1 assay in which low levels of classical mutagens, e.g., (aikylating agents, UV, X-ray) and so-called non- mutagenic carcinogens such as asbestos were detectable (2).Sponsored by contract #95773059 s N 0 ttpJ/www com/ECL/heatth/abstractsJref54 rjrdirect htm p J A 04/24/2000 . . . „ ~ Fw 3m oicas CFvfieaT B~cafaFYires~s fN.. l.w. ., Sci.nwic Mlannatloe -: _ -1. FsaRF..dh.eY „a -.;,..fAO „_1_ ~ Coaiet6datYt -' . Abstract
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FIIIMAr1 UBINE MUTAGENICITY STUDY COMPARING CIGARETTES Page 2 of 2 httpJ/www.cjrdiroctcorolECL/health/abstracts/ref6o.htrn 04/24/2000
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riUMAN UKllVb MU 1AlitIVll;11 Y A' 1 UUY I:UMYAKllVIi l-1CiAKE1-1!•;J W17ju(;g gU.. PBgC 2 ot 2 resin and tested in Ames strains TA98 and YG1024 with metabolic activation.Tobacco-buming cigarette smokers experienced a 79% reduction in urinary mutagenicity as measured in strain YG1024 and a 72% reduction as measured in strain TA98 during the week that they smoked the tobacco-heating cigarette while maintaining a fixed dietary regimen.The results of this study indicate that smokers of tobacco-heating cigarettes void urine which is significantly less mutagenic than urine voided by smokers of tobacco- burning cigarettes. httpJ/www.ryrdinctcomJECllhealth/abstracts/re%1.htm 04124l2000
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ASSY:JSMEN"1 OF CiAP JUNC7ION INTERCELLULAR COMMUNICATION T~'a S N.LOan~ ~'r.rte~it c cl/psc: Qa"rtt•:eg Smol.ing Privacy Staem ent About RJRT V{M.edle Ceeta Cuamner `::P.irP Abstract McKams, S C; Doolittle, D J ASSESSMENT OF GAP JUNCTION INTERCELLULAR COMMUNICATION AND MEMBRANE INTEGRITY IN HUMAN CELLS FOLLOWING ACUTE EXPOSURE TO CIGARETTE SMOKE CONDENSATES IN VITRO American Journal of Respiratory and Critical Care Medicine, 153:A512 The cellular plasma membrane is one of the critical target sites for chemical toxicity.Gap junctions are intercellular channels between cell membranes from adjacent cells. Quantification of gap junction intercellular communication (GJIC) provides a sensitive method to quantity the potential toxicity of chemicals and complex mixtures.Aggregate cellular injury following chemical exposure is routinely measured using LDH release as an indicator of plasma membrane integrity.Thus, quantification of both membrane integrity and GJIC assures a more reliable assessment for potential cell toxiary.Furthermore, a lack of LDH release can be used to verify that results obtained from the GJIC assay are not compounded by general plasma membrane toxicity.The objective of this study was to quantify and compare GJIC and LDH release following exposure to cigarette smoke condensates in a battery of secondary cells obtained from normal human tissue.The cell types tested included: bronchialltracheal epithelial cells, coronary artery smooth muscle cells, coronary artery endothelial cells, and foreskin keratinocytes.All assays were conducted following a one hour exposure to mainstream cigarette smoke condensate from three different types of cigarettes, including: Kentucky Reference 1 R4F low "tar" tobacco burning cigarettes, Kentucky Reference 1 R5F ultra low "tar cigarettes, and cigarettes which primarily heat rather than bum tobacco. Our results indicate, in all cell types tested, that mainstream cigarette smoke condensate from cigarettes that primarily heat tobacco is less cytotoxic than mainstream smoke from low "tar' and ultra kn v"tar"cg arettes that bum tobacco, as determined by in vitro GJIC and LDH release. Cordact U: KM Page I of 2 SIRIGtON GENr1Al'S WAItlRNG QuAfng S.nk1y Now " tedun Saiwt R~e6 ta Tow Iko1k sckttfie Harn.Asm..x-4.:f._Fauu.F.ean.er A httpJ/www.rjrdirectcotn/ECL/health/abstractslref49.htm 04/24/2000
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HUMAN URINE MUfAGENICITY a T5r °. IJ.coSne O,, .:nt cZ' ;IiP 5c Qultlieg Srno\i+g . Prirsy SLfemenl -About R.F2T ----Vidasf N.du Ceoter Cordact Uc "ie I:~13p F Page 1 of 2 SIR6EOA riE11B11'S MltYtlIG: Gm9 smkil7 Nor 6taAh kdam Saioi fsla e yow 11wi ~ ~ FaSmokes ~LSccnVAc Hmmalim Ewa9 F..db.ck BdNtYt~y Abstract Doolittle D J; McKams S C; Davis R A; Livingston S D; Bombick B R; Avalos J T; Smith C J HUMAN URINE MUTAGENICITY STUDY COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at Environmental Mutagen Society Victoria, British Columbia March 24-28, 1996 Cigarette smokers have been reported to void urine which is more mutagenic, as measured by the Ames assay, than urine voided by non-smokers. Mainstream condensate from a cigarette which primarily heats tobacco (test cigarette) has shown significantly reduced mutagenicity in in vitro genotoxicity assays compared with tobacco-burning cigarettes. The objective of this study was to determine whether the reduction in mutagenic activity observed in vitro would be reflected in the urine of test cigarette smokers. Twenty smokers were enrolled in a 4 week crossover study. Each smoker consumed test cigarettes ad libitum for a week and their usual brand of tobacco-burning cigarettes the other 3 weeks. The strictly controlled diet excluded broiled and pan-fried meat to minimize ingestion of mutagenic protein pyrolysis products. There was no statistically significant difference in consumption of tobacco-heating and tobacco-burning cigarettes and smokers mean salivary cotinine concentrations did not significantly change while smoking the test cigarette. Twenty-four hour urine samples were collected twice weekly, concentrated using XAD-2 resin and tested in Ames strains TA98 and YG1024 with S9. Smokers experienced a 79% reduction in urinary mutagenicity as measured in strain YG1024 and a 72% reduction as measured in strain TA98 during the week that they smoked the test cigarette compared to the weeks they smoked their usual v a ~ ~ rjrdirectcom/ECIJhealth/abstracts/ref58.htm ://www htt 04/24/2000 ~ . p m s Cu norr cr Servire J
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expired breath CO values for an individual are reproducible when using this protocol.Carboxyhemoglobin and expired breath CO levels were elevated by 24.4 and 30.6%, respectivey, after switching to the TOB-HT cigarette.This increase was not due to an increase in the number of cigarettes consumed since the subjects smoked an average of 21 cigarettes prior to the measurement session when smoking either their "usual brand" or the TOB-HT cigarette. httpJ/www.rjrdirect.com/ECUheatth/abstracts/refK3.htm 04/24/2000
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COMPARATIVE INHALATION STUDIES IN RATS AND HAMSTERS cu-toiuer _ F,•lcp ® Page I of 2 L R+Sn.F~.E: ~ °A.ysJa~ ~ TMtK~ Abstract Renne R A; Sagartz J W; Burger G T; Ayres P H; Mosberg A T COMPARATIVE INHALATION STUDIES IN RATS AND HAMSTERS OF MAINSTREAM SMOKE FROM A PROTOTYPE CIGARETTE AND A REFERENCE CIGARETTE Presentation at Society of Toxicologic Pathologists 14th International Symposium San Diego June 11-15, 1995 Subchronic nose-only inhalation studies comparing the potential biological activities of mainstream smoke from a prototypical cigarette with that of mainstream smoke from a Kentucky 1 R4F reference cigarette were conducted in Sprague-Dawley rats and Syrian golden hamsters.Animals of each sex were exposed 1 hour/day, 5 days/week, for a,13-week period to mainstream smoke at concentrations of 0, 0.16, 0.32, or 0.64 mg wet total particulate material/liter of air.Smoke was generated by an AMESA 30-port smoke generator operating at the Federal Trade commission standard of a single 2-secondl35-ml volume puff once/minute.Endpoints evaluated included clinical signs, body and organ weights, graphy, and gross and plethysmo histopathology.Groups of animals were sacrificed and necropsied immediately following 13 weeks of exposure or following a 13-week recovery period.Plethysmography indicated that rats and hamsters exposed to the prototype cigarette inhaled substantially more smoke than animals exposed to smoke from the reference cigarette.Hyperplasia of nasal and laryngeal epithelium, laryngeal squamous metaplasia, and increased numbers of macrophages in pulmonary alveoli were observed after exposure to smoke from either the reference or prototype cigarettes, with a less degree of change observed in response to smoke from the prototype cigarette.Changes related to prototype cigarette smoke exposure were not observed in rats or hamsters necropsied afthe 13-week recovery htlpJ/www.rjrdirect.com/ECUheatth/abstracts/ref53_htm 04/2412000
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HUIvIAN URINE MUTAGENICITY S'NDY COMPARING CIGARET'TES T.,r 3 W,ro4ne C~ r.~nt C~CII~SL. Ourttleg SmoFing -Privs y SLtemeut - AboutRJRT Vldual uedu Cesta Contact Us Sde R4ap FaSmokas J Pagelof2 SIRGr016rNFRIrS N! AMING: GuiG9 SmAnD Nor.6leo leduoes Sitiaxf Gekt b YaYr Ik& -- - -- _.~FcT 3iea`tFlcaeA'rJessiorrFits ~.T. Doolittle D J; McKams S C; Davis R A; Livingston S D; Bombick B R; Avalos J T; Smith C J HUMAN URINE MUTAGENICITY STUDY COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presentation at tntemational Congress of Toxicology VII Seattle, WA July 2-6, 1995 Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames assay, than urine voided by non-smokers. Condensate from the mainstream smoke of a cigarette which primarily heats tobacco (test cigarette) showed significantly reduced mutagenicity in a battery of in vitro genotoxicity assays compared with tobacco-burning cigarettes. The objective of this study was to determine whether the reduction in mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette. Twenty smokers were enrolled in a double crossover study, with each smoker consuming test cigarettes ad libitum for a week. Diet was strictly controlled throughout the study. Smokers' mean salivary cotinine concentrations did not significantly change while smoking the test cigarette. Twenty-four hr urine samples were collected twice weekly, concentrated using XAD-2 resin and tested in Ames strains TA98 and YG1024 with metabolic activation. Individuals who smoked the test cigarette voided urine which was significantly less mutagenic than that voided when they smoked their usual brand of cigarettes. ~ v s 00 J ;~ httpJ/www.prdirect.com/ECLhealth/absttacts/ref60.htm 04/24/2000 ~ 10 l,U;t0lTier Ser:ir_e
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HUMAN SMOKING BEHAVIOR MEASURES 7 ::r & PL,COtme Content ® lU lUILE1 'ervice Contad U:. Srte Map Foi Smokes ScWafflc Mormatim Page t of 2 1111 C Cq°go SIAGEON GflHNdrS 1NAIMING: Gog Smokq Now Gaff tedoca Safaa tda M Ya. NnMh 0 ---'~ Fcr-7fe~iG~caeP,=ifessiar3fs: - rff,w t..a.ck a Hb Co.bd "ONtYl :; Abstract Robinson J H; Stiles M F; Davis R A; Guy T D; Morgan W T; Edwards D W; Riggs D M; Ingebrethsen B J HUMAN SMOKING BEHAVIOR MEASURES ON TWO NEW CIGARETTES THAT PRIMARILY HEAT TOBACCO Presentation at 50th TCRC Meeting Richmond, VA October, 1996 Previous work from several laboratories, including ours, has indicated wide variations in human smoking behavior measures on cigarettes that heat tobacco (TOB-HT) compared to those that burn tobacoo.The present study compared puffing profiles, cigarette attribute ratings, expired air carbon monoxide (ECO), and serum nicotine and blood carboxyhemoglobin concentrations (%COHb) in smokers smoking their usual brand (UB) of tobacco burning cigarette and again after 2-3 weeks of exclusively smoking cigarettes that primarily heat tobacco.Two groups of smokers (n=23 and n=24) participated in two laboratory smoking tests between 1:30 and 4:30 p.m.For the first test session, subjects smoked one of their usual brand cigarettes after reporting the number of cigarettes they had smoked before arriving.Smoking profiles were measured, and samples taken for ECO, %COHB and serum nicotine determinations.Smokers were then sent home with one of two styles of new cigarettes that primarily heat tobacco (full-flavor {FF} or milds (LT), instructed to smoke these exclusively for the next 2-3 weeks.The same procedures were used for the2nd laboratory visit, except subjects smoked the TOB-HT cigarette they had been smoking for the previous 2-3 weeks.Puffing measures varied widely, but on average, smokers took significantly more puffs, closer together in time, resulting in more than twice the total puffing volume when smoking the TOB-HT cigarettes compared to UB.Consistent with the literature, there was wide variation in absorbed CO measures for both the UB and TOB-HT cigarettes.Average absorbed % http://www.rjrdirect.com/ECL/health/abstractsJref59.htm 04/24/2000
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AK);1'1:A1A13LGMh1riVU1'VKUb1tsKM1NAl1V1VVCl.AK13V.iYlYl;MVhLV13llV.. YagOLOIL 14 subjects, the R2 for %COHb versus expired breath CO is 0.84. The 8.2% group mean COHb value measured in this study is similar to COHb values F reviousl~ reported in the literature by several other boratones. >atp:uwWw.I;rai:tacoro/ECraneattb/abstraddref62altm 04/24/2000
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HUMAN URINE MUTAGENICITY STUDY T:a- S Ni:ofir~, r.or:errt GC1IpSC_ Qaittieg Snaking P~ivncy StAenent --_-Rbout RJRT YReaI Nedie Cents Gu:.toiner Service Contact US Fn-ile~'tficaeArn(~sfor.~,s ~- Hsn. 1. :., . SderNRC Hcrmatlon ..:... 1-, Eeal F..dEek. ~.1 t-~ iA0 ::-_ 1 Avalos J T; Bombick B, R; McKams S C; Davis R A; Morgan W T; Penn S J; Doolittle D J HUMAN URINE MUTAGENICITY STUDY COMPARING SMOKERS USING CIGARETTES WHICH PRIMARILY HEAT TOBACCO WITH THEIR USUAL BRANDS Publication in 51st Tobacco Chemist's Research Conference, Benton Convention Center, Winston- Salem, NC September 14, 1997 The R J Reynolds Tobacco company has developed and is test marketing a cigarette prototype (Eclipse) which primarily heats tobacco. Smokers of cigarettes which bum tobacco void urine which is more mutagenic, as measured by the Ames assay, than urine voided by non-smokers. . Mainstream smoke condensate from Eclipse cigarettes has significantly reduced mutagenicity in in-vitro genotoxicity assays compared with the reference cigarettes tested. The objective of this study was to determine whether the reduction in mutagenic activity observed in-vitro would be reflected in the urine of Eclipse cigarette smokers. Twenty-three smokers were enrolled in a 4 week single crossover study and assigned to one of two groups. Twelve non-smokers served as the Control group. Each smoker smoked Eclipse cigarettes ad libitum for a week and their usual brand of cigarettes the other 3 weeks. A strictly controlled diet was administered during the study which excluded broiled and pan-fried meat to minimize ingestion of mutagenic protein pyrolysis products. There was no statistically significant difference (p > 0.05) observed in smoking of cigarettes when subjects changed from their usual brand to Eclipse cigarettes. Similarly, smokers mean salivary cotinine did not significantly change (p = 0.12) when subjects changed from their usual brand to Eclipse cigarettes. Twenty-four hour urine samples were collected twice weekly, concentrated using XAD-2 resin, and tested in Ames strains TA98 and YG1024 with S9. When the smoker subjects switched from their usual brand Page 1 of 2 ARGEOB fiEMBAY 1MAd8N6: IAeim Smke! Ao.6aa* teducm Sria/s LICS f. ffir 14aYk httpJ/www.rjrdirect.ecm/ECL/health/abstractshef56.htm 04124/2000
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Page 2 of 2 http://www.rjrdirect.com/ECL/images/eclipsenewspaperad.jpg 07/18/2000
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HUMAN URINE MUTAGENICITY STUDY C?CILpSN cuacmel =e-r :~i: e Comtar-1 Ue Page I of I SUA4E0116tIta1CS wd9N6: Oumiag S.Kq Mor GA tedums Seio.L feb M Yorr IlKW Fu N~'_:hcaePr'r~ressia~'s_ . ~ Ovitting $moL.ng Pt rv:r y St.tem ent - About RJRT Vrlaa!L"edia Lenta Ne.~ 7:=,:;,:: Soe~7ie Mamries ~,;~KI, FsdlFrde.ek Abstract -;.Cot„et5d*lb:_s Doolittle, D J; McKams, S C; Davis, R A; Livingston, S D; Bombick, B R; Avalos, J A; Smith, C J HUMAN URINE MUTAGENICITY STUDY COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO Presented at the 7th International Congress of Toxicology International Toxicologist, 7:46 (1995) Cigarette smokers have been reported to void urine which is more rnutagenic, as measured in the Ames bacterial mutation assay, than urine voided by non-smokers.Condensate from fhe mainstream smoke of a cigarette which primarily heats tobacco (new cigarette) showed significantly reduced mutagenicity in a battery of in vitro genotoxicity assays compared with tobacco- burning cigarettes.The objective of this study was to determine whether the reduction in mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette.Thirty-four subjects (20 smokers and 14 non-smokers) were enrolled in a 4-week study, with the smokers randomly divided into 2 groups.The study was designed as a double crossover, with each smoker smoking both the new cigarette and their usual brand of cigarettes.This design allowed each smoker to serve as his or her own control, while at the same time allowing comparisons between groups of non-smokers and smokers of both new and usual brand cigarettes.Salivary cotinine concentrations clearly differentiated smokers and non- smokers.Smokers' mean salivary cotinine concentrations did not signifcanty change while smoking the test cigarette.Twenty-four hour urine samples were collected twice a week and concentrated using XAD-2 resin. Urine concentrates were tested in Ames bacterial strains TA98 and YG1024 with metabolic activation.lndividuals who smoked the new cigarette voided urine which was significantly less mutagenic than that voided when they smoked their usual brand of cigarettes. httpJ/www.rjrdirect.com/ECL/health/abstracts/ref57.htm 04/2412000 ~ T A
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HUIvtAIV URINE MUTAGENICITY STUDy COMPARING CIGARETTES WHICH BU.. Page I of 2 'ar & IteiSir~e Cnntent Cu=loiner Serrice COnltact Us Fa Sn okes =de l:7a ~C1~~7SC; Qultting Smol.i.g PrhrsySt.tenent ~~ ; About RJR7 Virtaal Ued'u Centa 10 SII&GEON GENERiCS MARBAUi 669 Smkn Nor 6tnd~tadutes Saious fala le Yow Ne~k ~Fa H~i'7~caeProTe~sfan's- Smith C J; McKams S C; Davis R A; Livingston S D; Bombick B R; Avalos J T; Morgan W T; Doolittle D J: HUMAN URINE MUTAGENICITY STUDY COMPARING CIGARETTES WHICH BURN OR PRIMARILY HEAT TOBACCO. Mutat. Res. 361(1), 1- Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames assay, than urine voided by non- smokers.Condensate from the mainstream smoke of a cigarette which primarily heats tobacco (test cigarette) has shown significantly reduced mutagenicity in a battery of in vitro genotoxicity assays compared with tobacco-burning cigarettes.The objective of this study was to determine whether the reduction in mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarettes.Twenty smokers were enrolled in a 4-wk crossover study, with each smoker consuming test cigarettes ad libitum for a week and their usual brand of tobacco- burning cigarettes the other 3 wk.Diet was strictly controlled throughout the study, and broiled and pan- fried meat was not served to minimize ingestion of mutagenic protein pyrolysis products.There was no statistically significant difference in consumption of tobacco-heating and tobacco-burning cigarettes.There were no statistically significant differences in salivary cotinine concentrations for smokers when smoking either tobacco-burning or tobacco-heating cigarettes.Urinary nicotine (ng/mg creatinine) was not different for smokers when smoking either tobacco-burning or tobacco-heating cigarettes.Urinary cotinine (ng/mg creatinine) was 32% lower when smoking tobacco-heating cigarettes as compared with smoking tobacco-burning cigarettes.Twenty-four-hour urine samples were collected twice weekly, concentrated using XAD-2 resin and tested in Ames strains TA98 and YG1024 httpJ/.vww.rjrdiract.com/ECLJheatth/abstracts/ref6l.htm 04/24/2000
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HIJMAN URINE MUTAGENICITY STUDy T3 5I lccllfic Co_tr-I ® --~ C3C~I~SC; ~ Deinieg SuwAing~A~'rwcyStalemertt ~~ RcwiRJF2T YACalNedu Centa Cu:tomer Sgr9ca_ COrS.S[t LI: NEW Fa Smokers Sderaffic ttmmafion. Page 1 of 2 h r-% CrD Ma SOAGEOM r>E1191ArSNARMING: Ufm9 ydq N" 6roodr tdue Strioui R'eln 10 Taar Aeaik Eetll F..dE.ek. Abstract F`s.rAca`dicaePrrTe>~i6in's; :::'. ,i/iq A CW.LCt6d..[Yt ._ Avalos J T; Bombick B R; McKarns S C; Davis R A; Morgan W T; Penn S J; Doolittle D J HUMAN URINE MUTAGENICITY STUDY COMPARING SMOKERS USING CIGARETTES WHICH PRIMARILY HEAT TOBACCO WITH THEIR USUAL BRANDS Presentation at Environmental and Mutagen Society in Minneapolis, Minnesota April 23, 1997 The R J Reynolds Tobacco company has developed and is test marketing a cigarette prototype (Eclipse) which primarily heats tobacco. Smokers of cigarettes which bum tobacco void urine which is more mutagenic, as measured by the Ames assay, than urine voided by non-smokers. Mainstream smoke condensate from Eclipse cigarettes has significantly reduced mutagenicity in in-vitro genotoxicity assays compared with the reference cigarettes tested. The objective of this study was to determine whether the reduction in mutagenic activity observed in-vitro would be reflected in the urine of Eclipse cigarette smokers. Twenty-three smokers were enrolled in a 4 week single crossover study and assigned to one of two groups. Twelve non-smokers served as the Control group. Each smoker smoked Eclipse cigarettes ad libitum for a week and their usual brand of cigarettes the other 3 weeks. A strictly controlled diet was administered during the study which excluded broiled and pan-fried meat to minimize ingestion of mutagenic protein pyrolysis products. There was no statistically significant difference (p > 0.05) observed in smoking of cigarettes when subjects changed from their usual brand to Eclipse cigarettes. Similarly, smokers mean salivary cotinine did not significantly change (p = 0.12) when subjects changed from their usual brand to Eclipse cigarettes. Twenty-four hour urine samples were collected twice weekly, concentrated using XAD-2 resin, and tested in Ames strains TA98 and YG1024 with S9. When the smoker subjects switched from their usual brand cigarettes to Eclipse, a reduction in urine http:/lwww.prdirectcom/ECL/health/abshacts/ref55.htm 04/24/2000
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A REPEATABLE METHOD FOR DETERMINATION OF CARBOXYfEIvtOGLOBIN.. Page 1 of 2 T ar & I1:;:cUr,c Coct-r,t (3CI/PS(:~ CuLtOrnier Ser V6Ce CorNSd U_ NEW ® 4AlGEOM 6ENFIGLYIr/AIpMG: rbAq Smoi+i Nor C.eA kducn Saiom b6 b Yo.lbdl4. -"`~nr'HAa':F7caeFrnFessicr.,ts '-:.: 4.iHieg Smok u~g -- PrMocyStatement . About Rhi7 Yirtaat /J.eWu Center Nar•~;r.~:.sSckun7icHpmath~',..::_l_Ee.OF..®.dr Abstract Smith C J; Guy T D; Stiles M F; Morton M J; Collie B B; Ingebrethsen B J; Robinson J H A REPEATABLE METHOD FOR DETERMINATION OF CARBOXYHEMOGLOBIN LEVELS IN SMOKERS Presentation at TCRC Conference Richmond, VA; Publication in TCRC Fourteen male smokers participated in 5 afternoon test sessions to determine the daily variation in expired breath carbon monoxide (CO), percent carboxyhemoglobin (%COHb), hemoglobin and hematocrit levels. Each individuals sessions were conducted in the afternoon at approximately the same time each day, in an attempt to estimate CO- related measures under conditions approaching relative stability. Subjects smoked ad libitum prior to the testing penod. For each subject, the usual brand of commercial cigarette was smoked during the measurement week on Monday through Friday. Expired breath CO samples were collected during all five sessions while blood samples for %COHb, hemoglobin and hematocrit concentrations were collected in sessions 1, 3 and 5. The data indicate that daily measurements of aftemoon %COHb and expired breath CO values for an individual are reproducible when using this protocol. The sample day-to-day pooled %COHb standard deviation is 0.94 %COHb units for the usual brand. Similarly, the sample day-to-day pooled standard deviation for expired breath CO is 4.7 ppm. After smoking their--- usual cigarette, the average %COHb value among the smokers was 8.2% with a range of 1.4% to 14.5% for the individual readings. The average expired breath CO was 23.5 ppm after smoking with a range for the individual readings of 4.1 - 41.2 ppm. For the 14 subjects, the R2 for %COHb versus expired breath httpJ/www.rjrdirect.com/ECL/health/abstracts/ref62.htm 04/24/2000
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~ N B W J hupJ/www.ry'rdirect.com/ECUsmokecs/eclipexp.htrn oananooo ~ ~ to w
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?Sr e Idei4m2 Cor.rrt [9C11(JS(3 auln~nq Srrol\ng Prirsy Statement ADOUt R,1RT - ViA uaI Med u Center ou_toRer S~rci_e Contad Us c htap F1 SORGEON 6EN6GC51r1R19MG: WMfag kok:il Ibr 6rem* Aedum Seiors Wn r Yow IfWL Fa Sm okers c N,avulim I Frau c«ae.ct Abstract 1W Smith C J; Guy T D; Stiles M F; Morton M J; Collie B B; Ingebrethsen B J; Robinson J H A REPEATABLE METHOD FOR DETERMINATION OF CARBOXYHEMOGLOBIN LEVELS IN SMOKERS. Human Exp Toxicol (Jan) 17(1):29-34 Fourteen male smokers participated in ten afternoon test sessions to determine the daily variation in expired breath carbon monoxide (CO), and whole blood percent carboxyhemoglobin (%COHb), hemoglobin (Hb) and hematocrit levels.Each individual's test session was conducted at approximately the same time of day to est. CO- related measures under relatively stable conditions. Subjects smoked ad libitum prior to testing.The "usual brand" cigarette was smoked during the first measurement week (sessions 1-5 held on Monday through Friday) and a research cigarette prototype which primarily heats rather than bums tobacco (TOB-HT) was smoked by 12 of the 14 subjects for 3 wk prior to and during the second measurement week (sessions 6-9 held on Tuesday through Frtday).Following the last "usual brand" measurement session, subjects completed 21 days of ad libitum smoking of the TOB-HT cigarette before starting sessions 6-9 to allow acclimation to the TOB-HT research cigarette.Following session 9, 11 of the 14 subjects continued to smoke the TOB-HT cigarette for an additional. 3 wk and then participated in an additional test session (session 10).The data indicate that daily measurements of afternoon %COHb and expired breath CO values for an individual are httpJ/www.rjrdirectcom/ECLJhealttJabstracts/ref63.htm 04/24/2000
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www.Eclipse.RJRT.com Purpose, Content and Age-Verification Controls R.J. Reynolds Tobacco Company (RJRT) has developed a website (www.Eclinse.RJRT.com) to provide adult smokers (21 and older), and scientists, researchers, health-care professionals and members of the media (who must also be 21 or older), with information about Eclipse, including: . how Eclipse works; . how it differs from other cigarettes; . how the company is test-marketing the brand; and . the science that forms the foundation for Reynolds Tobacco's claims that, compared to other cigarettes, Eclipse may present smokers with less risk of certain smoking- related diseases. In addition, the website allows age-verified smokers who are 21 and older to order Eclipse on-line. They can also order Eclipse through our toll-free number - 1-800-708-7878. Since this website contains cigarette advertising and the ability to order cigarettes, we have put a system of controls and safeguards in place to ensure that access is strictly limited to adult members of the audiences mentioned above. Only age-verified smokers 21 years of age or older can order cigarettes through the website. Scientists, researchers, health-care professionals and• members of the news media can, however, access the site to review the information it contains. All access is controlled by passwords and personal identification numbers. No one can order cigarettes through the site unless the person certifies he or she is a smoker and RJRT can verify that the person is 21 years of age or older. Who qualifies for access to the website Adult smoker access: . Individual must certify that he/she is already a smoker, age 21 or older. We will verify age using the methods and safeguards described below. Other appropriate adult access (for scientists, health-care professionals, etc.): . Individual must certify his or her occupationfinterest and age (21 or older). RJRT will verify the individual's age and will deny access to anyone who cannot be verified as 21 or older. People who register this way wili have access to the information on the site, but will not be able to purchase cigarettes on-line. If they wish to purchase Eclipse, they must go through the smoker-certification process outlined below, and RJRT must verify that they are at least 21 years of age. There are six types of safeguards buiit into our website. 1. Disclosure - On the opening page of the website, we clearly indicate that this site is intended only for smokers age 21 or older. Anyone who visits the website the first time must register and then meet our strict eligibility controls before they can access the rest of the website. Therefore, no one can "accidentally" gain access to the full LttpJ/www.rjrdirect.com/ECUpressreleases/ageid.htm a4/24n000
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? ir S Fdiit~~ iz Co-.enl ~CIIpSC, Custaner ".rdi9? Contad U;: ARGE011891fAAL'S MA11WI& Ouai°D S.ok.g Ilo.6trO Ideas Saiars Rda b Your IkiE Fa Healthcae Ptdessio~fs Oui,vng Srnokng Privrcy Stafeeent ^ A6out RJRT V{R usl LAed u Cee ts Virtual Media Center I PressPal~.s I CurtenlAdrerfsing Eclipse Press Releases 4/19I00 Reynokls Tobadco's Risk-Reduction Methodo" Demonstrates Eclipse Cigarettes May Present Less Risk 4/19/00 Aoe•Verification Controls Fact Sheet 4/19/00 Ediose Science Fact Sheet nnp•r/T>vww.drairect.com/ECr.rn,TcPress.btm 04/24/2000
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and now 1 oouklnY go back to the other ones. If you're going to try them you need to stick with them, because it you just try one you wont like fhem.l6ke how they don't make your house or car smell, and you don't smep like cigarettes.' Jil! K, Tennessee http://www.rjrdirectcom/ECIJsmokers/what.h>m 04/24/2000
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completey adjusted. But all smokers smoke differently, so for you the ad~usfinent may be shorter or longer. The best way to adjust is to put aside your regular brand and smoke Eclipse exdusroey. Th~s is also the best way to a all that Edipse has to oTler. Most smokers who sw Eclipse smoke about the same number ofag arettes as they did before - and say that they'd never go back to their old brand again. httpJJwww.ry'rdirect.com/ECLlsmokerslinst.btm 04/24/2000
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~ N 0 04/24/2000 ~ Ac~ N N O
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Eclipse Science Fact Sheet An extensive battery of scientific tests, along with independent scientific verification, demonstrates that, compared to other cigarettes, RJ. Reynolds Tobacco Company's Eclipse may present smokers with less risk of cancer and certain other diseases, such as chronic bronchitis and possibly emphysema. How It Works The concept is simple. While most cigarettes primarily burn, rather than heat, tobacco to produce smoke, Eclipse is just the opposite. Eclipse primarily heats, rather than bums the tobacco, using heated air to produce smoke. When a smoker lights Eclipse, he or she ignites a highly refined carbon heat source at the tip of the cigarette. This heat source continues to bum as the cigarette is smoked, transferring heat and heated air through the cigarette as the smoker puffs. As the heat passes across the tobacco, it forms smoke by releasing glycerin' and natural and added flavors from the tobacco, much the same way that hot water passing through coffee grounds releases the flavor and aroma of the coffee. ' Figure 1 Eclipse Cigarette ' GlyeaK a dyaud, occws Wdnsivdy in'uooe and is a nnmd, eoWeA ryfupy rpad tlut has a n.¢a hAe.4lycaie is nuu.lly fwmd'm the - _.-_. etas o(plab, mwWs and 6mru.1[ is ined m baked goods, /Ydoil; milk produas, e6ase.jms and jdiia, medicinal dtup. cossmeba and m6r.co pe~eA r i: aaa o aprm~ ~., hu~um-,o agent a~ ndp retain moisture to keep ur ayu~ e~n. In Fd~, mee n a e~.mnw uf dr~: e~ee me e~r~,er i...o«md iry me bmvame w WgbtM me.~o rod rcrus the emn far m: make There is a small amount of tobacco in the heat source itself and in a special tobacco paper that is sandwiched between two layers of a glass-mat insulator surrounding the heat source. This tobacco (a total of about 15 mg) does bum, to provide initial and additional tobacco flavor to the smoke of Eclipse. httpJlwwwsjrdirect.com/ECUpressreleases/sciencefactsheet.htm 04/2412000
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website. Until someone passes through our system of eligibility controls, they can't get past the'Yront door" of the website - and we do not have advertising messages or brand information on that opening page. Once inside the website, only smokers (age 21 and older) can order Eclipse. 2. Smoker Certification - With the exception of scientists, researchers, health-care professionals and members of the news media, everyone who gains access to our site must certify that they are a smoker. Everyone must certify that they are 21 years of age or older. 3. Authentication - We require that new website visitors provide a valid credit-card number to authenticate their identity. (We do not charge the credit card, but we do conduct an authorization transaction to confirm that the credit card is valid and that the address for the card matches the address we are given by the person on-line.) 4. Age Verification - When someone requests access to the website and certifies that he or she is a smoker and age 21 or older, we obtain age-verification using third-party databases. This is done BEFORE we grant access to the information on the site and the ability to order cigarettes through the site. (We also verify the age of any scientists, researchers, health-care professionals and members of the media to ensure that they are 21 or okier, but we do not allow them to purchase Eclipse.) Five databases are used in the age-verification process. They contain information our suppliers have derived from driver's license data, public directory databases, credit information and warranty registration. Our suppliers are nationally recognized by the Direct Marketing Association (DMA) for providing reliable demographic information. These databases are maintained by our suppliers and provided to us solely to verify that anyone who wants to receive marketing information from RJRT is at least 21 years of age. 5. Password Protection - For subsequent visits to the website, we assign a Personal Identification (PID) number and password to facilitate access to smokers 21 and older. 6. Parental Empowerment Tools - These can help parents prevent children from accessing age-restricted sites. RJRT supports parental empowerment, and is registering this site with all major filtering software programs. We wilt also mail a registration card to all qualified smokers, 21 and older, who register for access to our website. The wallet-size registration card contains the smoker's PID and password, and the mailing includes clear instructions on how to remove access to the website, if desired. httpJlwww.cjrdinect.com/ECUpressreleases/ageid.htm 04/24/2000
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By clicking on the folbwing highlighted links, you can view: . A summary of the scientific tests that have been conducted on Eclipse. . The scientific literature that has been published on Eclipse (and its predecessors and prototypes) in peer- reviewed scientific journals and abstracts that have been presented at national and intemational scientific conferences. . A scientific analysis of the data on Eclipse. httpJ/www.rjrdirect-com/ECL/health/ses.htm N 04/24/2000 0 -4 00
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. -L.f ~ J V l J things you should know. We don't claim that Eclipse presents less risk of cardiovascular disease or complications with pregnancy. There is some evidence suggestin$ that compared to other cigarettes, Eclipse may pose less risk to smokers of developing cardiovascular disease. However, other evidence suggests that smokers who already have this disease may further increase their health risk by switching to Eclipse. As everyone knows, atldgarettes pose heatth risks, including Eclipse. Consult your doctor with questions about your health. Eclipse Is Not An Aftemative To Quitting Eclipse is not for people who want to avoid the risks of smoking. No cigarette is without risk. And it is not for smokers who want to quit httpJ/www.qrdirect.com/ECUsmokers/consu.htm 04r14/2000
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• Produces 90 percent fewer skin tumors in mice; • Produces 70 percent less exposure to mutagens (chemicals that may damage DNA) as measured in smokers; and • Produces 46 percent less bronchial inflammation, and 36 percent less inflammation of the lower lung in smokers who have switched to Eclipse. An expert panel of prominent doctors and scientists reviewed and confirmed the scientific results on Eclipse. The panel is chaired by Dr. Bernard M. Wagner, an emeritus research professor of pathology at New York University Medical Center, who has served as a member of the Committee on Toxicology of the National Academy of Sciences. The tests also determined that the potential effect of Eclipse on the cardiovascular system is inconclusive. The company will not be making any claims in that area. David N. lauco, Reynolds Tobacco's senior vice president of marketing, says that the company will market Eclipse through advertising in newspapers and magazines, and direct- mail to smokers in the Dallas/Fort Worth area, along with information about Eclipse at www.Ec1iM.RJRT.com. "Smokers have consistently told us they want a cigarette with less risk, and Eclipse may present less risk of certain smoking-related diseases," lauco says. "It's important to understand that it takes about a week to become used to Eclipse. But many smokers who have switched to Eclipse say they'd never go back to their old brand." The first carton a smoker purchases will include a brochure that describes how Eclipse works, the adjustments smokers have to be aware of when switching to Eclipse, and information about the scientific test results, lauco says. "Eclipse is not an alternative to quitting," he says. "But for smokers who are concerned about their health and won't quit smoking, Eclipse may be the next best thing." Gary T. Burger, RJRTs executive vice president of research and development, says that Eclipse burns only about 3 percent as much tobacco as other cigarettes. This results in a much simpler smoke chemistry, consisting primarily of glycerin and water, with only 20 percent of the smoke being "tar" (minus glycerin) and nicotine. "That's almost the exact opposite of other cigarettes," Burger says. Burger adds, "The smoke from Eclipse contains far less of many of the compounds linked to smoking-related diseases, which translates into substantially lower levels of smoke toxicity. The results of an extensive battery of tests on Eclipse are striking." Schindler says, "Given the test results on Eclipse, we believe that smokers should know about the potential benefits of Eclipse. It is time to see whether this type of cigarette is acceptable to smokers." He adds, "The introduction of Eclipse should be helpful in framing the important elements of any government policy and standards for cigarettes with reduced-risk potential. Any policy must encourage competition in the private sector to develop and market these types of cigarettes to smokers." httpa/www.rjrdirectcom/ECIJpressreleaseshestmarket.htm 04/24/2000
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T ir 3 1, C.-:- d SG~ C3~iI1P Cu_tart~er Corrtact Lle ® ® ® 17 'J SOWlHl GENEIACS wAtNI11G: Odstug Smin laeGtedi Ik1~m Se~on Irels ataer NeiE For Hea!:hcaePrdessiornk OciT.irg Semkiig Privacy St~!ement About RJRT Virtcal Vedu Cssta b S VnIes.oaMay;I Overview for Smokers Feedback FAQ Satisfadlon Guaranteetl The Eclipse Experience raMe _I 11w rrcNpN..01pmta.13he EMpit El¢raNwe ra_ j 3. Smoke you can see, flavor you can taste in.weueee -, Eclipse is just like anything new that youYe tried. It takes a short time to get used to (about a week). But like most new things, once you get used to it, you wouldn't consider going back to the old way. Many smokers who first hear about Eclipse assume ifs a smokeless cigarette and won't have any taste or smoke. Not so. Eclipse produces smoke that you can see and flavor that you can taste. Eclipse does taste somewhat different than what you're used to and takes a little longer to light Most smokers tell us that it usually takes about a week of smoking Eclipse exclusively to get completely used to - but that the benefits are well worth the initial effort Most smokers who switch to Eclipse tell us they wouldn't go back to their old brand. After the first couple a packs you'll begin to notice that you no longer smell like a smoker and aren't hassled with a lot of ashes and second-hand smoke. Please take the time before ordering your trial kit to read the "Instructions" page to fully appreciate how to best enjoy smoking an Edipse. _ httpJ/www.rjrdirect.com/ECUsmokers/eclipexp.htm 04/24C2000
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-ar o rj,.otire Cprd~nt ® cclips(l _.__. -_- Qurtlieg Smoking Privacy StLtem.nt ~AboutRJRT YirlaalMedie Leota OJetomet SEt`d[e CC~re,act us :=rVrs-rb&v-r ® a J wRGEOII s[IkRU'S rllnmtk otAfag Sod:t Ib. 6nadr tedaa saiorc rsks w Tar Neik -Far Healthcae Rdessiornls FMw. 1Th. EeHp. C4n.tla. I 7L. Eetlpc. E.p.rWc. I. Mti! S.oken Say -) 1oelucliau u U fHerviewforSmokan =- FtedDadt --: FAQ Satisfaction Guarant.a - How to light an Eclipse . Use a good flame (a car lighter won't work). . Take 3 or 4 puffs while holding the Bame to the tip - it's much like lighting a cigar. • A glowing red tip means Eclipse is lit. • It takes a little longer to light After it is lit an Eclipse lasts about 6-7 minutes, about as long as a typical IGng-S¢e cigarette. How to smoke an Eclipse . Smoke and enjoy d like your usual brand. . Eclipse may seem milder at first, but avoid taking too strong a puff. That can cause the paper to scorch and turn brown. - and change the taste. Eclipse doesn't bum down. . A lighter draw gives you a smoother taste. A harder draw gives you a stronger taste. Try to make sure you are taking gentle, even puffs. . You'll know you're done when you get less taste and smoke. . You can't re-light it, because the carbon tip will only work-once __ __- How to adjust to Eclipse Like anything new, Eclipse may take some time to get used to. Most smokers have said it took about a carton before they were completely adjusted. But all smokers smoke differently, so for httpJ/www.rjrdirect.^.om/ECL/smokersl'mst.htm 04/24/2000
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C! ctorr~er cPrVirF ~clip5c- OciCtng Smokng - - Prirecy Statement About RJRT Yidcnt V ed'u Centw i.ontsd Us ~ A BETiER WAY TO SMOKE N.w. =Fvr S^oi:-s _ M SIRGEON 6rNQACS MGdml& 0~9 ~~C No. B~ kduca saioac IWn r toa Medk For Healthca e Prdessicfmis Th.aEetlpKCiOanlla_'.I.iM6eUl+~~•ea ! WIdS.obn6.7.~ _)n!tnreUeu HbN Ec1iPE2 N/Crl-- A Better Wayto SmUe 0 ~..: Oyafy;aw ror ShcokYf ~ Feedback FlW = Satialanfon Guaramead This section describes'in detail how Eclipse is made and how it works, its many benefits compared to other cigarettes, and comments from smokers who have switched to the brand. httpJ/www.rjrdirect.comBCUsmokers/ectip.htm 04/24/2000
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l',uLt6tileJ Ser vice CufSad U, e I^l.ip ECLIPSE IS THE NEXT BEST CHOICE. SURGE011 GENERAIS NAItlMG: Mng S.ok.g Noe Greak teilats Serian fsla k Toa HeA _~. THE BEST CHOICE FOR SMOKERS WHO WORRY ABOUT THEIR HEALTH IS TO QUIT. Eclipse is a new cigarette from R.J. Reynolds Tobacco Company that may present less risk of certain smoking related diseases. Extensive scientific studies show that compared to other cigarettes: e Eclipse may present less risk of cancer. e Eclipse produces less inflammation in the respiratory system, which suggests lowerrisk of chronic bronchitis and possibly even emphysema. WHY THERE'S NO CIGARETTE LIKE ECLIPSE Tobacco Burned COMPARN(i SMOfO: COkVOrBdTS TeN and ticu6te rs. Nfta end Gycain (snpLamWitwnpawesl Certingms" Secandwtd smdee"' Cerbon MOnopde ~ lYicCf. . Ou! Overview (or Smokera Feedback FAQ Satisfaet[on Guannteetl 0.18 mryM' 5.4 mg Eclipse 15 mg 0.3 mg 3.3 mg /0.17mg ' 0.07 mghn'- 6.] mg Difference 97% less 63 Y% less 313% mor 80% less 22% less 177G more A M.rk uAight wu tested as the opie>V Wa9yht. ' FTC'tY mi.u Opetrt 9idx FTC oon6tions, R RT meawrM 14 eodrooMs n careNte smcke Mr amer en ar n ma. d tlw fda.Yte httpJ/www.qrdirect.com/ECLJsmokers/consu.htm 04/24/2000
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Beesuse the only part of Eclipse that bums is the heat source and the tobacco sandwich paper, Eclipse does not "burn down" the way other cigarettes do. When a smoker finishes smoking an Eclipse, the cigarette is the same length it was before it was lit Smoke Chemistry Since Eclipse produces smoke by primarily heating tobacco, rather than burning it, only a very small amount of tobacco is actually burned (about 3 percent as much as other cigarettes). As a result, the smoke from Eclipse is chemically much simpler than that from other cigarettes, and its composition is very different For example, the smoke from tobacco-buming cigarettes is generally about 20 percent water and glycerin, and 80 percent tar (FTC "tar" minus glycerin) and nicotine. In sharp contrast, the smoke from Eclipse is about 75 percent water and glycerin, and only 25 percent tar and nicofm Figure 2 Smoke Composition Comparison of an Eclipse with a Reference Light Cigarette Ec6pse •F7L "Ym"mixus Glycerin Reference Light Cigarette Because of its simpler smoke chemistry, Eclipse contains far lower levels of many of the chemicals that are believed to be associated with smoking-related diseases. Tests show that those reductions translate into substantially lower levels of smoke toxicity and biological adivity. Scientific Test Results Reynolds Tobacco has performed an extensive battery of tests on Eclipse, both in-house and through outside laboratories. In addition, studies with actual smokers of Eclipse have been performed by major medical schools in the United States. The weight of the scientific evidence from chemical tests, cell and animal tests, and htunan studies, demonstrates that Eclipse may present less risk of certain smoking-related diseases than other cigarettes. The differences in test results comparing Eclipse with cigarettes that primarily burn tobacco are dramatic and striking. bttpJ/wwwsjrdirect.com/ECUpressreleases/sciencefactsheet.htm 04/24/2000
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i ir S I L80Lrrc Cr -~1 c- C11P sC-- Cuttomer SEfvire CorSact Ut ® ® ARGE0116iM6tAl"S WAAM11N'i: pi66g Smofoy Now eMaGFt kdem Saian IWa a Vow xedb <::~FiY7iea'9 icaPFrafes'siora's .-" Ouinfng Smo4ng Privncy Stater. ent AboutRJRT Virtuat Nedu Ceeta This section presents, in detail, the science behind 6cipse, scientific tes6np, as well as the research findinps ptblished in various saentiic periodicals regarding the Eclipse ciparefte. ~ ~. httpJ/www.qrdirectcom/ECL/healthrndex.html 04/24/2000 m m J ~ N B U, Hsa*A........:SCkeMicMermat:mr.~;,:../ :E]eanFrAhI eYK.•.aFAC ~";tro!teClfidrtYt Healthcare Prof essionals
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Page 1 of 2 THE BEST (HOICE fOR SMOKERS WHO WORRY ABOUT THEIR HEALTH IS TO QUIt `t~ +NERE'SiNENEMiB[Ji(N01(f" tiuJ: A w.~ alla..a..A.. M Ywaa It•. A... 4~bM.. Mw.t iM M M.....V ad.w al+t -iYMwr~.r.YMa.ns • aai.wl..a.e.r.r.rr r r...p+~r rr.alrr ~.. ~.....L.Id..a r.. W. rp.w....w11'..a TUa a.aap b .M.l4. Motl.t IatpN .t WrNw.. t~w...Yr..Lr..JwaY'r.MM~MMtv M..w r.. Mwl TL.Ltt~t.arya FNw/wry.w..mrr..w L.r. .d. a.a t.,t.. M.. Y.r rrt a r L... MM1 +i. M.~i4 L/+.. 1./.awlry.awr~4.J.w.e11MwY.. .wM W Mrw-vlVn ^yY~w.pVwrLr A/rr~a M.~u~ . .w.Y..'t li/. ...t... wriMa~rw.A..Mryt.rdw.w Np...a.w..uW....r•M ML - W M.M1~... Y IM.rRtlMua....w r w..~r.a c<nr.. t.. ~ an.a- G~..+/l..~w rr. w. v.'ra:y /w r..M Y.e w.~.rear ~.r. « w.~ytu..r.rlwp.c~ t~+ruw.~r.r++...r..r W+.~ sasra..r. Mu......r....4.ea..«e~. .r....fw~L..rr.....r.M..a.n Y..M.M. M!".dM. LAr .LL~'~ f4ta Ca.Y. Mw~t~ wil wew. Mww Mrt~a 4/MtaWrr.r)i \W.NY...7WY+ ~~wri.'Mr MY.rs Y.pl Yl IryY.Y rtwYr.r~...rM.+arwr.l~.aYt rM< G....k 4a~ ..n...Md MG.IlV-.ACIi GW.AMTE. Ltiw~ Wrr..al...rM~tru.raYV. twMtaW w.sw.~arYlw.a.a.r avdasTMa 'i..l .4ar r. av~ ^.T1.0. D.us Nw.reY~../al+.raK Wll W... aY '-'BACK CUAR7RM! I Ava1LABLI BY MA1L OMV GFT1WaM1117 CAROM WROaYi11Kd..aMwl f.11NMCTWM GMMMf W OlqlN MpM[Y UiK •rrsr•..nMw.Y.a.twpMw 1 a 500-708-7078 .r.rw..P.e.t www.ocllpte.r)rt.com t Et1AL INTROpUtTORY OffER;> ~ I~ ;. r;C-- cliUs, c-O, A BETTER YTAY TO SMORE AmOM GNmS,Ma<Bl& U, S.dat http://www.qrdirect.com/ECL/images/eclipsenewspaperad.j pg 07/ 18/2000
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aaba.cvaa biologically significant exposure to the smoker will not occur. An independent, external panel of inhalation toxioologists, pathologists and pulmonologists has determined that,'under the conditions of intended use, glass filaments in the Edipse cigarette pose no toxic or carcinogenic potential to humans.' httpJ/www.rjrdirect.com/ECLhealttJglass.htm 05/24/2000
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19s «kno.q prab.Ge «pnssEle Mm.n cacnogwu: Ywmatiuny Ayewq r« rieseuchme.nw.. nwiaw roMcdbXProg+in.ra Enwioamn.aiPHoa.ainn Agenes Wrden ws ne A/Men. a un eonmaf eempcnds memr.d'nFaps. snwk..an (h.hr+IJ shors rNOr.x..-exw msmow p.xcrs. , The concept is simple. Heating instead of burning. The smoke from Eclipse contains far less of many of the compounds found inag arette smoke that are believed to contribute to the risk of cancer and certain other illnesses. How? The concept is simple. Eclipse primarily heats tobacco rather than burning it Heated air then releases the smoke and flavor as you puff. Smoke you can see, and flavor you can taste. • FTC t: mk~ qyc«m Eclipse Makes A Smokers Life Easier With Eclipse you can enjoy smoking without a lot of the hassle. • Edipse reduces second-hand smoke by 80%. • No lingering odor on your hair, clothes, home or car. • No messy ashes. • No visible stains on walls, glass, or draperies. Eclipse Isn't Perfect Eclipse isn't perfect - irs still a cigarette, so there are a few more things you should know. bttpJ/wwwrjrdica;t.com/ECUsmokers/consu.htm 04r24C1000
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Because of its unique design, Eclipse produces: . 80 percent less secondhand smoke than other cigarettes; . no ashes; . no visibk staining; and . no lingering odor. Additional Information Reynolds Tobacco has developed a website (www.Eclipse.RJRT.com) that contains a detailed summary of the science behind Eclipse, as well as dozens of scientific papers that have been published in peer-reviewed scientific journals or presented at international scientific oonferenors. The company is also mailing a letter and scientific brochure to health-care providers in the Da11aslFort Worth area, and in other parts of Texas, so they can be informed about the science behind Eclipse and can answer questions that their smoking patients might have about the cigarette. Reynolds Tobacco is making every effort we can to present the public, the medical community and the scientific community with all the information that forms the basis for our claim that, compared to other cigarettes, Eclipse may present less risk of cancer, chronic bronchitis and possibly emphysema. We believe that smokers have a right to know that a cigarette that may present less risk of cancer and certain other diseases is now available. 1#IpJlwww.qrditect.com/ECUpressreleases/sciencefactsheet.htm 04/24/2000
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?at 8 fJicotrtle corrtent ~clipsc. Ouitting Srtnkng Pifvscy Statenent ~ About RJRT ViRaal Med'o 6eete Cordact Uz Srte F,19p --- - ~ `~~.-£cr~oF:~s SURGEON 6ENFAArS NfUAM& Gulfoy kck:y Nor tiaafk 14duces Sniars Ifaks r Yoar Ikolk For Healthcae Rdessiants 711eECllp.a ciyaf.lh"1_The.Eplipe Esp.r(Ne* .:1:YVN1,5ao,61n 6.y :.'PS; 4 InaNelfow I Overview for Smokers Feedback FAO Satisfaction Guaranteed MONEY-BACK GUARANTEE* Give Eclipse a good, fair try - at least a week or so - and if it's not right for you, just give us a call at 1-800-708-7878. We'll send you a full refund right away. No strings attached. 'Money-Back Guarantee available for the fust-time purchasers of Eclipse only. Purchaser will be requested to answer a short series of questions to receive refund. httpJ/www.rjrdirect.com/ECUsmokerslsatis.htm 04/24/2000 Cuetoiner Setvlce
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. 6. Would my doctor endorse Eclipse? No. Your doctor would no doubt advise you to quit smoking entirely to avoid risks associated with smoking. Back . 7. Can I switch between Eclipse and other cigarettes? The best way to benefit from Eclipse is to smoke it exclusively. You'q also find it much easier to get used to - and you'll see advantages that muoh sooner. Back . 8. Are there more details on how Eclipse may present less risk of smoking-related Illnesses? Yes. Visit the "For Healthcare Professionals" section of this web site. There you'll find an extended summary of the scientific tests conducted on Eclipse, as well as dozens of pubiished scientific papers and articles. Back . 9. What If Pm not happy with Eclipse? You have our Money-Badc Guarantee. All we ask is that you give it a fair try - at ieast a week or so. If ifs not right for you, we'll send you a full refund on your first carton. Back . 10. So... Is Eclipse just as good as quitting? Absolutely not. If you decide to - or want to - give up cigarettes, ug itting is sti71 the best choice. 6ttp•l/www.rjrdirect.com/ECUsmokerslfaq2.htm 04/24/2000
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LripJ/www.zjrdirectcom/ECL/healthJtestl.htm 04/24/2000
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-~ "'..-1•,,•-: y 1, ` ;;; F.; Vej P.O. Box 2959 Winston-Salem, NC 27102 RJRT 2000-19 Reynolds Tobacco's Risk-Reduction Methodology Demonstrates Eclipse Cigarettes May Present Less Risk Dallas/Fort Worth Test-Market to Begin This Week WINSTON-SALEM, N.C. - April 19, 2000 - Using a four-step scientific methodology, RJ. Reynolds Tobacco Company (RJRT) has concluded that Eclipse, a cigarette that primarily heats tobacco, may present smokers with less risk of cancer, chronic bronchitis and possibly emphysema, when compared to other cigarettes. Eclipse will be test-marketed in the Dallas/Fort Worth area beginning this week through direct mail and internet sales to age-verified, adult smokers 21 and older. The company plans to follow with retail distribution of Eclipse in selected retail outlets in the Dallas/Fort Worth area Today's announcement was made at the annual shareholders' meeting of R.J. Reynolds Tobacco Holdings, Inc. (RJR), the parent company of Reynolds Tobacco. RJR Chairman and Chief Executive Officer Andrew J. Schindler says: "To assess whether new products or processes may provide the potential for risk reduction, Reynolds Tobacco established and uses a four-step scientific methodology. "Before we make any claim that a new cigarette may present less risk compared to other cigarettes, it must be substantiated by extensive scientific testing and verified by independent experts." Schindler says the four steps of the methodology are: • chemical testing and analysis; • biological and toxicological testing; • human testing; and • independent scientific verification. "The public is well informed of the risks of smoking, as they should be," Schindler notes. "Reynolds Tobacco is committed to developing new cigarettes or processes that may present less risk to smokers, and, if successful, we will communicate our efforts in a clear and ethical mannec" The scientific methodology used by Reynolds Tobacco demonstrated that, compared to other cigarettes, the smoke or "tar" from Eclipse: . Contains 80 percent lower levels of many carcinogens in smoke; httpJ/www.rjrdirec.t.com/ECUpressreleases/testmarket.htm 04/24/2000
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present less risk of cancer, chronic txonchi6s, and possdily emphysema than other cigarettes. Eclipse isn't perfect. It hasn't been shown to present less risk of all smoking-related diseases, including cardiovascular disease or compbcations with pregnancy. Of course, the best way to reduce the health risks assoaated with smoking is to quit And, as everyone knows pregnant women and people with cardwvascutar disease shouki not smoke Eclipse or any other cigarette. httpJ/www.rjrdirect.com/ECUhealth/test.htm 04/24/2000
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For example, compared to other cigarettes, Eclipse produces: . 80 percent lower levels of many known or suspected human carcinogens in smoke. This is based on chemical measurements (under FfC conditions) of 14 compounds that are listed as known, probable or possible human carcinogens by the Surgeon General, the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP) or the Environmental Protection Agency (EPA). These tests showed an 80 percent reduction in the amount of these compounds in the smoke from Eclipse, compared to that in the smoke from a leading ultra-light cigarette. The level of acrolein was no different. Of the 25 compounds measured in Eclipse smoke, one (furfural) showed an increase. . Dramatically fewer effects than other (burn-down) cigarettes in smoke inhalation and "tar" skin-painting studies in rodents. Eclipse produced 90 percent fewer tumors in mouse skin-painting studies, and 80 percent fewer tumor-bearing animals, compared to the group of mice treated with the "tar" from a tobacco-burning cigarette. Inhalation studies showed significantly fewer smoke-related effects (e.g., inflammation) in the rodents exposed to Eclipse smoke, compared to those exposed to the smoke from reference cigarettes. . 70 percent less exposure to mutagens (chemicals that may damage DNA). This is based on the results of a human urine mutageiiicity test comparing the mutagenicity of smokers' urine when they were smoking their usual brands versus when they were smoking Eclipse (while on a controlled diet throughout the test). . 46 percent less bronchial (upper lung) inflammation, and 36 percent less inflammation of the lower lung. These results are from a University of Nebraska Medical Center study conducted with smokers who switched to Eclipse. These results are supported by the results from another study at another medical school, and by rodent studies at RJRT indicating that Eclipse produces less respiratory inflammation than other cigarettes. These results, in conjunction with additional results from chemical, and biological and toxicological tests, suggest that Eclipse may present smokers with less risk of chronic bronchitis and possibly emphysema, compared to other cigarettes An expert panel of prominent doctors and scientists (in the fields of oncology, pulmonology, pathology, toxicology, pharmacology and hematology) has reviewed the scientific results on Eclipse. The panel reached conclusions consistent with those of RJRT - that Eclipse may present smokers with less risk of cancer, chronic bronchitis and possibly emphysema The chairman of that expert panel is Dr. Bernard M. Wagner, an emeritus research professor of pathology at New York University Medical Center, who has served as a member of the Committee on Toxicology of the National Academy of Sciences. Reynolds Tobacco does not claim that Eclipse presents less risk of cardiovascular disease or complications with pregnancy. There is some evidence suggesting that, compared to other cigarettes, Eclipse may pose less risk to smokers of developing cardiovascular disease. However, other evidence suggests that smokers who already have this disease may further increase their health risk by switching to Eclipse. As everybody knows, all cigarettes pose health risks, including Eclipse. RJRT advises smokers to consult their doctors with questions about their health. RJRT also believes that, as everyone knows, the best way to reduce the risks of smoking is to not start in the first place, or to quit. Eclipse is not an alternative to quitting. But for those smokers who are concerned about their health and won't quit, we believe Eclipse may be the next best thing. Other Benefits httpJ/www.rjrdirect.com/ECUpressreleases/sciencefactsheet.htm 04/24/2000
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W11HOLESMOKE ASSAYS Cells were exposed to whole smoke from Eclipse or from reference cigarettes in the sister chromatid exchange and the neutral red assays (described above). SUMMARY OF RESULTS The results of all of the in vifro tests conducted on Eclipse indicate that the smoke from Edipse is less likely to produce genetic damage and to reduce cellular growth rate than the smoke from tobacco-buming cigarettes. « BACK htip!/www.rjrdirecLcom/ECUhealth/test2.htm 04/24/2000
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GCilPS(3 OaiCicg SrrokFg Prirs y St.:em ent -AbonIRJRT vircel /ded'u Centa` Cuetomer Service Cuntad U_ A BETTER WAY TO SMOKE _._ .- _.- __~.-~~-o!~ - _ SIRGtt!N 661EIAL31tafJNN& Ou1f~g Snolui No. finaar !bruas kriors!Csks b!ta r tbilk For Heafthcae Rdessiernls How. I 7h.EeGp.q0aw1l...I ThoEdip.Ezp.ri..e. I WYrS.obqCry l...lntmctioa...:_ What Eclipse Smokers Say "1 like that Eclipse has no ashes and is less messy. I also like the Navor and the fact that there's 80% less second-hand smoke. It seems like iCs lighter, iPs not a heavy smoke " Wayne 0, IVorth Carolina "I enjoy the fact that with Eo!ipse, it doesn't smeN like cigarettes in your house or your car. The smoke doesn't bum your eyes either. tPs a moist cigarette instead of dry and scratchy." Timi V, California "I switched to Eclipse because they are lower in tar and nicotine. Overall, they are cleaner and less offensive to people who don't smoke. Be patient whi!e you learn how to smoke them. The majority of my family want me to quit smoking, but they are glad that I am smoking Eclipse." Stephen S, Tennessee "The main reason I switched to Eclipse is that they don't stink up the house and they really aren't a bad cigarette." Shirley R, Tennessee "I've chosen to switch to Eclipse because of the smell mostly. NAy husband does not enjoy the sme!l of cigarettes and will kiss me notv." FJI S, Tennessee "Peop!e don't mind me smoking around them because they can't smell the smoke. They teN me that other cigarettes have a bad smell, but that Eclipse doesn't." Gennie G, Tennessee "A friend recently discovered that I smoked and couldn't believe it! She said, 'But you don't smell bad. You always smell c!ean.'" Markay L, Noath Carolina 'I was more or less a guinea pig once I started smoking them and now Icouk1nY go back to the other ones. If you're going to try httpJ/www.rjrdirect.com/ECL/smokers/what.htm 04/24/2000
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T;r 8 I-li[u;ind Ccr:rnt GC t1~SCi waomEr S~rVlce Corrtsct U-- M1e Iclip A BETTER WAY TO SMOKE Q :94 wtcto N sfNrtu s wumatc: oA4 s.ok:g No. smmlf teduus Scae Ifda r roa SeihA r Fa Healthcae Prdessianle . Oeittieg Smokng P~ivscyStdement -AbouLRJRT ViAeal ll.sd"n C.otw~ Howe i'Th.Fstip.C(an.ea 1.7A.t:dipaeE>aeria.c..l YrilSook.nSeya.IndrucWaa~ Overriewfor Smokers Feedback FAQ Satisfaction Guaranteed Questions About The Product 1. How long does It take to get used to Eclipse? 2. Is Eclipse a "smokeless" cinarette? 3. Does Eclipse last as long as other ciaarettes? 4. If Eclipse doesnY bum down, how can I tell when It's done? 5. Will I smoke more Eclipse than I currently do with my usual brand? 6. Would my doctor endorse Eclipse? 7. Can I switch between Eclipse and other ciaarettes? 8. Are there more details on how Eclipse may present less risk of smoking-related illnesses? 9. What if rm not happy with Eclipse? 10. So... Is Eclipse just as good as guitting? httpJ/www.rjrdirect.com/ECUsmokerslfaq.htm 04/24/2000
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coverpage Page 1 of 1 ECLIPSE A CIGARETTE THAT PRIMARILY HEATS, RATHER THAN BURNS, TOBACCO SUMMARY OF SCIENTIFIC TESTS R. J. REYNOLDS TOBACCO COMPANY APRIL, 2000 hltpJ/www.rjrdirect.com/ECLJsci/coverpage.htm 05/24/2000
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mid and high dose (20 and 40 mg/application) produced a total number of tumors that was statistically greater than the DMBA/Acetone control group. For the low-tar reference, all dose levels produced total numbers of tumors that were statisticaly greater than the DMBNAcetone control group. AII dose levels of Eclipse condensate produced statistically fewer tumors as compared to the low-tar reference groups. Except for the low- dose groups (where few tumors were produced by either Eclipse prototypes or the low-tar reference cigarette), the activity of Edipse was dramatically less than the activity of the low-tar reference cigarette. In addition, the animals painted with the smoke condensate from Eclipse had greatly reduced DNA adducts in their lungs, compared to those animals painted with the smoke condensate from the tobacco-buming reference cigarette. DNA adducts from tobacco-burning cigarettes have been reported in the scientific literature. « BACK Ln N httpJ/www.rjrdirect.com/ECUhealtWtest3.htm a 04/24/2000 ~ ~ N N 0
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Table of Contents B. Huaun SmoldnQ Behavior Studies Page 2 of 2 httpJ/www.rjrdirect.com/ECLlscihableofcontents.htm 05/24/2000
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T.,r S thCOLr~e !r,i._nt GCII(75C3 CL,tomet serviCe i.imtsct U'_ SAe hliri W7 SORGEON 6ENEBAfS MAtN04i: Ou" Snnkiy No+6nmtr /rdum Saiws tda b 1aa Nedtk =frr Hi'afiFica'eFiorp~sf ~oiz31"s -= '~~ Quittiag SmoAing PifvsyStatemenl About RJRT - Virtual lladi. Center ti.y: Seleniffic HotmaOm /.'_Fitdt F..dO.eU , { ~.~.; I raa.elsa.lYf_, Introduction for Medical and Scientific Professionals SciaRRc Tests StiertificAnays's Publiqtiors The best way for smokers to reduce their health risks is to quit smoking. But many smokers who are concerned about the health risks have decided not to quit Eclipse was developed to provide these smokers with aag arette that, compared to other cigarettes, may present less risk for certain diseases, including cancer, chronic bronchitis and possibly emphysema. Since the early 1950s, R.J. Reynolds has been a leader in developing a number of new technologies for cigarette design, including the use of filters; air dilution to lower tar and nicotine levels; blends that lower the concentration of nitrogenous smoke compounds; and the use of tobacco sheets. The use of each of these technologies might contribute to risk reduction. But none of them can produce the dramatic reductions (in the overall delivery of tar components and toxic, gas-phase smoke constituents) that can be achieved through the use of an entirely new approach to cigarette design - primarily heating tobacco rather than burning it This concept has led to the development of Eclipse, a new cigarette that has been extensively tested during the past several years using a tiered scientific testing approach that is based on the current understanding of disease processes. Because Eclipse primarily heats tobacco rather than burning it, its smoke chemistry and the biological activity of its smoke and its tar are dramatically lower when compared to other cigarettes. For example, compared to other cigarettes, Eclipse produces: . 90% fewer skin tumors in animal studies. . 70% less mutagens in the urine of smokers. . 46% less human bronchial inflammation (based on httpJhvww.rjrdirect.com/ECUhea)th/ses.htm V N 6 04/24/2000 `~ ~ N 6 U.
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controned. When smoking Eclipse, smokers showed substantial reductions (averaging 70% to 72%, depending on the test) in urine m iaty, compared to when they were smoking their usual bra s of tobacco-burning cigarettes. This result indicates that the smokers were exposed to dramatically fewer mutagens when they were smoking EGipse, compared to when Ciey were smoking their usual brands of lobacco-buming cigarettes. « gqCK hripJ/www.rjrdirecLcom/ECUhealthJtest4.htm N o4a4/2oo0 ~m J ~ N N N
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';r s u;coti.~ Conl-r,t EM CCiIiJSG~ l]u'rtlicg Srrokng Privecy Strtemerd ~--Abwt RJRT Yirtaal LICd'u Ceeter CuE20Rie1 SFI'':YC? Gontact Uz e bAap ® Technology Issues Ca6 wtstor sWuswaias: aMIys.A4 Nur 6rteal1lr kluttl SCioui &ks M toer IIwIE _ - Fv Healthcae Prdessianls . 1. How long does It take to get used to Eclipse? For most people, usually about a week. Back . 2. Is Eclipse a "smokeless" cigarette? No. The smoke you exhale from an Eclipse is clearly visible - but disappears quickly because it is largely moisture. On the other hand, the burning 6p on an Eclipse gives off virtually no smoke at all. Back . 3. Does Eclipse last as long as other cigarettes? Yes. About as long as a regular fi@er king. Back . 4. If Eclipse doesn't bum down, how can I tell when It's done? The taste. The flavor of Eclipse gets weak - even thought you still may see some smoke. Especially striking is that, though you ve finished an Eclipse, it remains the same length as when it was first fit. Back . 5. Will I smoke more Eclipse than I currently do with my usual brand? No. Smokers in our product trials say that, compared with their usual brand, they smoke about the same number of cigarettes as they did before. Back . 6. Would my doctor endorse Eclipse? http://www.rjrdirect.com/ECLJsmokers/faq2.htm 04/24/2000
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"3r S Nieotme t`; •n!.r't ® ci clipsc- ouRting Srtotng . Privsy Statement .About RJRT V{e1el V.edu Centa ru:toRie7 Semce ® See r:•t-sp Fa Smokers Sciertrric Tests SUAGEOX 6ENEIt4l's yfAANING: tAEfrcg Smdcig No.6,emtr Aeduoes Seouc ICaks a Yoar Mmu =-:17THiItBOiaT4or'-r~svzi`s StivAificAnatysis Publicalips Four main types of comparative tests were conducted to determine whether Eclipse may present less risk for diseases associated with smoking: Smoke Comoosition tests to determine smoke constituents and their concentratbns. Test-tube studies to determine the effect of smoke and tar on animal and human cells. Rodent studies to determine the effect of smoke and tar on various rodent organs (inhalation and skin tumor studies). Studies with smokers to characterize various changes in smokers after switching to Eclipse from their usual brand of tobacco-burning cigarettes. The results of the tests conducted on Eclipse indicate that the smoke and smoke condensate (tar) from Eclipse generally produce demonstrably less bioWCical activity (fewer biological effects, less intense e~ects, or no effects whatsoever) than the smoke and smoke condensate of cigarettes that primarily bum tobacco. Since Eclipse primarily heats rather than bums tobacco, the smoke from Eclipse is very different Many of the compounds in cigarette smoke that are suspected of contributing to the risk of cancer, emphysema and chronic bronchitis are substantially reduced in Eclipse compared to other cigarettes. Further, the weight of evidence from extensive biological testing indicates that Eclipse may present less risk of cancer, chronic bronchitis, and httpJ/www.rjrdirect.com/ECUhealth/testhtm ~ 04/24/2000 e m ~ ~ ~ w
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T ar 8 hkcc{inc Ccnt~rrt G~Ct/~S(3 Qeittieg Smokng Privmy Staam ent Aba,t R.Rr Wrles161edr Ceeter SMOKE-CONDENSATE (TAR) ASSAYS Reynolds Tobacco compared the smoke condensate (tar) from Edipse with that of a low-tar reference cigarette in the folknving in viho (test tube) studies, which measure the potential of the test substance to cause changes in genes, chromosomes or other parts of cells. At concentrations where the smoke condensate from tobacco- buming dsarettes produced strong, statistically significant increases in response, the smoke condensate from Edipse produced negative results (no changes), or marginally positive responses in the following in vitro assays (genetic toxicology assays and cytotoxicity assays). Genetic Toxzokx7y Assays • Ames Test - which uses special strains of bacteria to determine whether the test substance has the potential to cause genetic mutations. • Sister Chromatid Exchange (SCE) - which evaluates the potential of the test substance to increase the incidence of genetic material changing places within the chromosome. • Chromosome Aberration (CA) - which evaluates whether the test substance has the ability to produce changes in the structure of mammalian chromosomes. Cytotoxicity Assays • Neutral Red - which evaluates the potential of the test substance to after energy-dependent growth processes in mammalian cells. • Lactate Dehydrogenase Release - which tests the potential of the test substance to cause leakage in the cell membrane of mammalian cells. WHOLE-SMOKE ASSAYS r ~ httpJ/www.rjrdirect.com/ECUhealth/test2.htm 04/24/2000 ~ J Cuctomer Cord'act Us SAeldip SUAGEON GEN[tAfSwARNING: Qr:Ifrg Sonkiq Now Gna* tedues Saias " b ras Ned k Types of Tests: Test-Tube Studies WN a N J
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. ..b.. . v... KW Eclipse Glass Filament Insulator The heat source assembly utilized in Edipse consists of carbon, glass mat insulator, tobacco sandwich paper, and an insulator paper overwrap. The glass mat insulator functions to insulate the heat source, reduce propensity for the ignition of other nlaterials, and enhance cigarette performance by directing heat flow to the substrate materials of the cigarette. The glass mat insulator is composed of continuous filament glass fiber and a binder. Glass fibers are ubiquitous and are commonly observed In ambient air in both an occupational and non-occupational setting (homes, schools, other public places). Continuous filament glass is commonly used In consumer products such as firefighters' clothing, carpet backing, drapery fabrics, Christmas ornaments, hairdryers, and air filters. Survey data demonstrates that consumers are exposed to literally thousands of glass fibers daily as a result of non-occupational environmental exposure. The potential transfer of continuous filament glass to Eclipse mainstream smoke has been evaluated. The results of these studies consistently demonstrate that, relative to background, biologically significant transfer of continuous filament glass to Eclipse mainstream smoke does not occur. Further, the continuous filament glass used in Eclipse was designed to be non-respirable. The continuous filament glass mat insulator is made from continuous glass filaments of a size that prevents them from reaching the pulmonary region of the respiratory tract. In addition, the chemical composition of the filament used in Eclipse is similar to glass fiber compositions that have failed to produce either tumors or fibrosis in chronic inhalation studies conducted in rats. Further, fn vitro dissolution data demonstrate that the filament used in Eclipse is more soluble than biologically active fibers such as asbestos and rock wool. In short, the transfer data and the unique physical characteristics of the filaments (controlled physical dimensions, chemical composition and dissolution characteristics (biological solubility)) demonstrate that httpJ/www.rjrdirect.com/ECL/health/glass.htm 05/24/2000
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au.ww.UW .aauw nuawc.a ra8c -f U. Y provide a source of heat for Eclipse. tt allows warm air to flow over the tobacco, providing the flavor. Back . 17. This looks pretty simple. Why wasn't It developed or introduced earlier? It may look simple, but it wasn't easy getting here. We, and others, have experimented with the concept of heating rather than burning tobacco for many years. But it wasn't until the mid-1980s that RJRT was able to produce a tobacco-heating cigarette that actually worked. it's taken us the years since then to design a cigarette that's acceptable to smokers. Back . 18. Why canY you use a car lighter to light Eclipse? Conventional car lighter coils are ineffective at transferring heat to the Eclipse cigarette. Back httpJ/wwwsjrdiroct.com/ECUhealth/faq2.htm 04/24/2000
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Tar b I-leotine Cr,r +:~rt c~clipsc_ WCtO?et ~-/vlCe COfd-act U, J SUlGEON GENtAACS WAtNING: Guufng Seak4 Nmr GrtuAl ledom Seiom Aaks p'bar NpNh .:_ _7Ta-Fie~ ficaBpiCii~mars _~: Ocitlleg Smokng PrivxyStdenent About RJRT Vi&.-I IAed"uCenta - HsraC.1,L`. 'SeieeOTieklamaLon. Types of Tests: Smoke Composition Cmtpoatim of 6leinstream Smoke TPM UndQ FTC Smolicz- Cm~tiom EeEy: (rM(-39 a.Sleg) COL (SP!<1-U aajh%) . BKNie.tl.e-~M ® 4r.NinH.e-tSY -21% .. vucr~'~t• laWa4t-3S7Y 1RSF (rPlrt-i,.qdet) ®uNlNa.a-a% N %Watr-1®%  %Watr-12M. 1 R4F = a full-flavor low tar cigarette (approximately 85 mm in length) with FTC smoke yields of 9.2 mg tar and 0.80 mg nicotine, which was developed and is made available by the University of Kentucky as a highly consistent reference cigarette. Cigarettes in the 8-12 mg tar range represent approximately 44% of total U.S. sales. I R5F = an ultra low tar cigarette (approximately 85 mm in length) with FTC smoke yields of 1.7 mg tar and 0.16 mg nicotine, which was developed and is made available by the University of Kentucky as a highly consistent reference cigarette. Cigarettes in the 0-3 mg 'Yar' range represent approximately 2% of total U.S. sales. CUL = a U.S. commercial cigarette (approximately 85 mm in length) which was chosen from the ultra low tar segment with FTC smoke yields of 5 mg "tar" and 0.5 mg nicotine. Cg arettes in the 3-8 mg tar range represent approximately 13% of total U.S. sales. I&/F (rYM-l15 aq/etj) ° Y. Nkatlne-7% httpJ/www.rjrdirect.com/ECLhealth/testl.htm 04/24/2000
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glycerin and natural tobacco taste. That is why the smoke dissipates so quickly, like warm breath evaporating on a cold morning or steam produced by a pot of boiling water. In fact, the smoke particles of Eclipse are about 75 percent water and glycerin, as opposed to 20 to 25 percent in the smoke of other cigarettes. After 6 to 7 minutes, the heat source self-extinguishes and the cigarette stops producing smoke. Back . 5. What's in It? The main ingredient is tobacco, like any other cigarette. Immediately behind the heat source is a processed tobacco blend to which glycerin (a common food ingredient found in most cigarettes) has been applied. At the mouth-end of the cigarette is a hollow cigarette fiQer. Back . 6. What's on the tip? A heat source made primarily of high-purity carbon, surrounded by a twoJayer glass-mat insulator that has tobacco paper in between. Back . 7. How much and what kind of tobacco is inside Eclipse? Eclipse has about the same amount of tobacco as some ultra-low-tar cigarettes on the market today (e.g. Now 85 or Merit Ultima 85). Most of the tobacco in Eclipse is domesticaly grown flue-cured and burley tobacco. Eclipse also contains some Oriental tobacco. Back . 8. Does Eclipse contain any reconstituted tobacco? Yes, as do most cigarettes. We use a variety of tobaccos, including flue-cured, burley and Oriental, which are all processed into tobacco sheets to make Eclipse. Back . 9. How does It tastelsmeii compared to other cigarettes? Smokers tell us they Gke the taste and that it is similar to that of low-tar cigarettes. Eclipse has a mild aroma that leaves no lingering odor. Back . 10. Does It need tobacco? Absolutely. As in any other cigarette, the tobacco in Eclipse provides smokers with the taste and smoking enjoyment that they want Back . 11. How is the smoke from Eclipse different from httpJ/www.rjrdirectcom/ECUhealth/faq2.htm 04l24/2000
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':,r S 1LcCCne Ccntert ME ~Clipsc~ Ooitfieg Smo\ing Privsy Statenent Aboul RJRT virtCat uldY CfiEtY Cuetomer Serv4ce CCd7tact US 0 SORGEOB 6EN6Gl'SMGp8N6: quaing Smokig Ibw Geatk tetluoes Saiars feb b Yur 6caitt For Sm okers $cklAHic t/CMAipl t "'"~r=R.He~rvicaeFiu a s.~-` Endl FrdA.ck A AC, CeiAr.l6d.aH~:: I Types of Tests: Rodent Studies INHALATION STUDIES Four-week and 13-week subchronic inhalation studies in rodents (mice and rats) were conducted to assess various biological end- points in animals, comparing the smoke from Eclipse with that from a low-tar reference cigarette. Mice were exposed to three different concentrations of the smoke from Eclipse or the smoke from a reference cigarette one hour a day, five days a week, for four weeks. The mice exposed to smoke from the Eclipse prototype showed significantly fewer changes (fewer DNA adducts) in the respiratory tract and the heart (fewer DNA adducts) compared to a reference cigarette. Thirteen-week inhalation studies were conducted in rats, using the same three exposure concentrations as those used in the mouse study. In general, the changes seen in animals exposed to the reference cigarette were greatly reduced, or entirely absent, in the animals exposed to the smoke from Eclipse. SKIN PAINTING STUDIES An eight-month skin painting study was conducted with a sensitive mouse strain to compare the skin-tumor-prornoting ability of the smoke condensate from Eclipse with that from a low-tar reference cigarette. In this test the backs of mice are shaved and the bare skin is painted once with a tumor initiator called DMBA (dimethylbenzanthracene). After that the mice are divided into three groups. One group receives no further treatment A second group receives daily paintings of tar from the low-tar reference cigarette. A third group is painted with the tar from Eclipse. At the end of the study, the number of mice that have tumors and the total number of tumors in each group are compared among the three groups. Reynolds Tobacco subjected Eclipse to the mouse skin-painting test since it has been commonly used by various organizations for several decades to study cigarettes. Tumors were produced at all dose levels of Eclipse but only the mid and high dose (20 and 40 nmg/application) produced a total httpJ/tvww.rjrdirectcom/ECL/healttJtest3.htm 04/24/2000
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Table of Contents Table of Contents TLe Evolution of Tobacco-Heating Cigarettes The (baraacteristics of Ecliox How Eclipse Wocks Scien6tic Studies L Component Review Il. Chemical Studies Mainstream Smoke A. Detumination of Mainstream Smoke Yields by the FTC Metbod B. Gross Measures of Smoke Total Particulate Mattcr (TPM) 1. TPM Materials Mass Balance 2. Spectrophotometric Determination of "Tar" 3. Thetmoi:ravimettic Analysis 4. Elemental Analysis C. Ane¢ate Chemical Measures by GC/MS D. Quan6tative Analyses of Target Compounds/Classes of Compounds Sidesheam Smoke Enviroomental Tobacco Smoke Continuous Filament Glass III. Bioloeical Studies Genedc Toxicolo¢y-Smoke Condensate A. Ames Test B. Sister Chromatid Exchange (SCE) in Smoke Condensate C. Chromosome Aberrations in Smoke Condensate CVtotoxieitv-Smoke Condensate Genotie Toxicology and Cytotoxicity-Whole Mainstrea"+ Smoke Animal Studies A. [nhalation Studies B. Dermsl Tumor Promotion Studv DNA Adducts 1V. Human Studies A. Human Urine Mutacenicity Study httpJ/www.rjrdirect.com/ECLlsciftableofcontents.htm Page l of 2 05/24/2000 N N D
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Elemental Analysis Page 2 of 2 multiplied by 100. b The computed % change value is not statistically significantly different from zero (p 5 0.05). bttp:l/www.rjrdirect.com/ECUsci/elemental_analysis.htm 05/24/2000
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' ~r ;i r.:utirie Cpnterrt Cu£tuttler Service Contact Us ® SUAGEON 6tYBGL'S INAIMNW: Oiid6Mq Sonkop No.6RaAr tadue Stioas tksks N Tau NraYh. = Fn He~?~tcaet~roTa~siaz 's .- Qultling Srrokng Privs y $Ltement About RJR7 Yiilcel Nedu Centa Hew../_itl~5q4row' gMatvoM ;"_,:;.4 En.nF"dh" l,t~r;~It[t,c.: t- Go.,retBd..11a:V Answers Technology Issues . 1. What exactly Is Eclipse? Eclipse is a cigarette that produces smoke by primarily hearing tobacco, rather than burning it It is an ultra-low tar and nicotine cigarette (by the FTC method) ahat produces 80 percent less second-hand smoke, no lingering odor, no visible stains and no ashes. Back • 2. Is this a real cigarette? It certainly is. Eclipse is a cigarette that contains tobacco rolled in paper. When it is iit, it produces smoke that a smoker inhales and exhales. Back . 3. How does it work? Eclipse looks like any other cigarette, with one exception. At the lit end, Eclipse has a small tip made primarily of high-purity carbon that bums and sends warm air through the tobacco inside the cigarette. With this design, Eclipse primarily heats rather than bums, tobacco. As the heated air passes through the cigarette, it creates smoke by releasing glycerin (a common food ingredient that is found in most cigarettes), flavorants, and aroma, taste and flavor components from the tobacco. Eclipse's heating process produces smoke in much the same way that coffee is produced by pouring hot water through coffee grounds. Back . 4. B the tobacco doesn't bum, what creates the smoke? Eclipse does bum a small amount of tobacco in and around the heat source, which is important to provide tobacco flavor to the smoker. The remainder of the tobacco inside Eclipse does not bum, but is heated, to provide the smoke and the tobacco flavor. The smoke is generated primarily from warm air releasing water, glycerin and natural tobacco taste. That is why the smoke httpJ/www.rjrdirect.com/ECL/health/faq2.htm 04/24/2000
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? ]r :i ri~~•rrt aaZvLne C~CII~SC, Cuctcmer cer;ir_v Contact U<, SMON 6EM9GCT 11'ARIGNG: Wifn9 Seqkq Ibr 6nmk Aedem Strious R'eb lo bM NmYh. ---Fnr Hea,'6tcaeFii3'e'ssicr~'s -v.~:. ~uinieg SrrwMng Priwcy s,,,eneM About RRtT Virtlat Ved'u Ceete How._-t„i:.:. Sdn~ifc Harmatloa,;.':.,::t. FadlF..dh.ci.a'1 ~;~ Ei Types of Tests:Studies with Smokers BEHAVIORAL AND PHYSIOLOGICAL END-POINTS Since Eclipse represents a new cigarette design that primarily heats rather than bums tobacco, studies were conducted to compare a number of behavioral and physiological end-points in smokers when they were smoking Eclipse compared to when they were smoking their usual brands. These end- points included puffing patterns and carbon monoxide concentrations. When smoking Eclipse prototypes, smokers tended to take larger, more frequent puffs than when smoking their usual brands of tobacco-buming cigarettes. They did not, however, smoke more cigarettes per day. There was wide variation in measures of blood nicotine and absorbed carbon monoxide (CO) for both the usual brand and Eclipse prototypes. For Eclipse - in general, smokers had slightly lower nicotine levels than when they were smoking their usual brands. Average blood carboxyhemoglobin levels were somewhat higher when smokers were smoking Eclipse than when they were smoking their usual brands. Also see the Human Smoking Behavior Studies of the scientific analysis. URINE MUTAGENICITY Some scientists believe that urine mutagenicity is an indicator of how much a person has been exposed to mutagenic material. A number of published studies have shown that the urine from smokers is more mutagenic than the urine from nonsmokers, as measured by the Ames assay. (Increases in urine mutagenicity have also been reported in workers exposed to combustion products, e.g., foundry workers, and in people who consume fried, broiled or grilled meats.) A three- week study was conducted to compare the urine mutagenicity in smokers when they were smoking Eclipse prototypes with that of the same smokers when they were smoking their usual tobacco-burning cigarettes. Diet was strictly controlled. httpJ/www.rjrdirect.conilECL/healthftest4.htm 04/24/2000
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11. How is the smoke from Eclipse different from other cigarette smoke? Smoke particles from other cigarettes are typica0y about 75 to 80 percent tar (excluding glycerin) and nicotine, and 20 to 25 percent water and glycerin. Eclipse is almost the exact opposite. Its smoke particles are only about 25 percent tar (excluding glycerin) and nicotine, and 75 percent water and glycerin. Glycerin is a common food ingredient that is found in most cigarettes. Back . 12. How much tar, nicotine and carbon monoxide does Eclipse have? Eclipse's tar and nicotine yields, by FTC method, are in the ultra-low category compared to other brands. Both styles of Eclipse yield just 3 mg of tar. The regular style yields 0.1 mg of nicotine and the menthol style has 0.2 mg of nicotine. The carbon monoxide yield is 6 mg for the regular style and 7 mg for the menthol style (by the FTC method). These levels are similar to those from low-tar cigarettes. Back . 13. If you can reduce tar and nicotine, why coutdn't you do something about the carbon monoxide? We're trying to reduce the carbon monoxide yields from Eclipse. Whenever anything bums, carbon monoxide is produced. The carbon monoxide in Eclipse comes from the burning heat source. The carbon monoxide yield is 6 mg for the regular style and 7 mg for the menthol style (by the FTC method). These levels are similar to those from low-tar cigarettes. Back . 14. After an Eclipse Is smoked can It be re-Iit and smoked again? No. Once the heat source has burned out, it would be very difficult to re-light And even if one could, the tobacco flavor that smokers enjoy would have been depleted, in much the same way that the flavor of coffee grounds or a tea bag is used up once it is brewed. Back . 15. Can someone cut oft the heat source and smoke the cigarette? That would be very ditficult if not impossible, given the des'g n. It wouldn't stay lit, it wouldn't bum down, and it wouldn't taste very good. First, the tobacco is very moist, and second, the Eclipse cigarette paper is lined with a thin layer of aluminum foil, so it wouldn't bum down like ordinary cigaret6e paper. Back . 16. Does the carbon tip add anything different to the smoke? Based on the chemical analysis, the carbon tip adds nothing to the smoke of Eclipse that isn't reported in the smoke of other cigarettes. The carbon ti is there to provide a source of heat for Eclipse. It aPows warm air to httpJ/www.rjrdirectcom/ECLJhealth/faq2.htm 04/24l2000
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46% less human bronchial inflammation (based on standard, visual bronchitis indices conducted at a major medical school). • 36% less k>weraung inflammation in humans (based on inflammatory cell counts in the above referenced medical sctrool study). • 80% lower concentrations of many known, probable and f ossibie carcinogenic smoke compounds, as listed by the ntemational Agency for Research on Cancer, the National Toxicology Program and the Environmental Protection Agency. In addition: . Condensates (TPM) from Eclipse display significantly decreased cytotoxicity and genotoxicity in bacteria and cell cultures. Whole smoke from Eclipse typically displays reduced genotoxicity and similar or reduced cytotoxicity in cell cultures. . Animal inhalation assays demonstrate a decreased pulmonary inflammatory potential in Eclipse. When the Eclipse data set is examined as a whole, the decreases in cellular damaging chemicals and the resulting reduction in inflammation/profrferation processes that have been observed indicate that Eclipse may present less risk of cancer compared to other cigarettes. The fact that Eclipse produces less respiratory inflammation in animals and humans suggests a lower risk of developing such smoking related diseases as chronic bronchitis and possibly emphysema. Information concerning whether Eclipse presents less risk for cardiovascular disease is inconclusive. There is some evidence suggesting that, compared to other cigarettes, Eclipse may pose less risk to smokers of developing cardiovascular disease. However, other evidence suggests that smokers who already have this disease may further increase their health risk by switching to Eclipse. Click here for more information. Eclipse isn't perfect. But overall it's clearly a step in the right direction. Of course, the best way to avoid the health risks associated with smoking is to quit And, as everyone knows, pregnant women and people who have cardiovascular disease should not smoke any cigarette, including Eclipse. There has been discussion in the scientific community regarding the Ectipse glass-mat insulator. An independent, external panel of inhalation toxicologists, Qatho ists and pulmonologists has determined that, under e conditions of intended use, glass filaments in the Eclipse cigarette pose no toxic or carcinogenic potential to humans.' For more information about the glass filament insulator click here. ~ httpJ/www.rjrdirect.com/ECL/health/ses.htm e 04/2a/2o00 w J ~ N m J
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Dotetnunation of Mainstream Smoke Yields by the FTC Method Page 2 of 2 Eclipse 1R4F 1R5F CUL TPM 4.8 12.0 2.2 6.3 (mg/cig) Wco e 0.18a 0.82 0.47 (mg/cip~ 0.17 a er 1.5 1.4 0.2 0.6 (mglcip) 3 2a 9.8 1.8 5.3 (mg/cig) a on Monoxide 7.5 12.4 2.9 6.5 (mg/cipJ u 15.0 9.2 7.0 7.9 (per cig) ' The nicotine, "tar" and carbon monoxide results presented in this table were generated for the express purpose of comparing Eclipse with three tobacco burning cigarettes in a single study. In this study, the number of each cigarette smoked was not sufficient to meet FTC reporting requirements for nicotine and `ltar" and carbon monoxide httpJ/www.rjrdirect.com/ECIJsci/detemiination_of mainstream.htm 05/24/2000
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Spechophotometric Detecmination of Tar Page 2 of 2 httpJ/www.rjrdirect.com/ECllsci/spect determination.htm 05/24/2000
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7' i NicO'ne Contenl M -EC ItPSG outving Smokng Prinwy Stdemcnt About RJRT 14rluallled"r Ceeler Cu_torner Service Contad us •_ae I"l3p Fa Sm okers ca.+K+_sa.Kr.t;` Science Book Information Sciertific Tests ScientrfieAnaYysis Publicatiors RJR has demonstrated that a cigarette that primarily heats rather than bums tobacco provides substantial reductions in terms of mainstream smoke constituents, second-hand smoke, and mainstream smoke biological activity when compared to cigarettes that primarily bum tobacco. RJR has continued efforts to improve Eclipse. These efforts have focused on qualities or characteristics related to taste, lightability, and ease of puffing. As a result of these ongoing efforts, RJR has developed a new version of Eclipse that addresses the issues of taste, lightability, and ease of puffing. The new Eclipse prototype has been designed with a focus on improved lightability and taste. The differences between the current Eclipse market product(Eclipse 7-026) and the new prototype (Eclipse 9-014) are subtle. The specific differences between these two prototypes are primarily in the heat source assembly and are described in detail in the Eclipse Science Summary. As described in the Eclipse Science Summary, the scientific results of the testing performed to date on both Eclipse prototype 7-026 and Eclipse prototype 9-014 indicate that the smoke they Eroduce is very similar in both chemical composition and iotogical activity. Further testing based on the 9-014 prototype is currently underway. No claims will be made about the level of relative health risk presented by 9-014 prototype un61 such tests have been completed and analyzed. For the science on current Eclipse market product (7-026) clidc here. httpJ/www.rjrdirect.corn/ECIJhealth/book.htm \ E7 CIOD ~ SU9GEON 6ENtiU[S WWII NG: IhWg Srrok.q /b.6nd* Nadues Saioes Nela a bo Neclh. ~' ~r~ai-fi'-ea?[F7caeFaresstorr3rs`"° n ro 9 04/24/2000 ~ ~r- U
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The Evolution of Tobacco-Heating Cigarettes Page 2 of 2 of Eclipse, a new cigarette that primarily heated, rather than burned, tobacco. While it was based on the same concept as Premier - producing smoke by heating tobacco - the basic design of the Eclipse prototypes was significantly different from that of Premier. Although all of the Eclipse prototypes do burn a small amount of tobacco, their smoke chemistry is much simpler and the biological activity of the smoke (as assessed by a battery of toxicological assays) is greatly reduced compared to that of commercial cigarettes. The scientific results from all prototypes tested to date indicate that there are significant differences between Eclipse prototypes (which primarily heat, rather than bum, tobacco) and cigarettes that are currently on the market (which primarily bum, rather than heat, tobacco). There were some differences in test results among prototypes, but all differences observed between different prototypes were small. This report summarizes the scientific testing performed using the current Eclipse U.S. market prototypel. Although smokers have found the Eclipse prototypes much more acceptable than Premier, the company is continuing to develop additional Eclipse prototypes (focusing on issues concerning taste, lightability and ease of puffmg) to enhance consumer acceptability. (11 The development of the Eclipse cigarette has resulted in the generation of a number of Eclipse prototypes. Prototypes are numbered sequentially beginning with a single-digit designation of the year in which they were developed. The current U.S. market prototype, developed in 1997, has been designated Eclipse 7-026. httpJ/www.rjrdirect.com/ECL/sci/evolution of tobacco.htm 05/24/2000
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1he Characteristics of Eclipse Page 1 of 1 The Characteristics of Ecliese In response to growing demands for a cigarette that produces significantly less environmental tobacco smoke (ETS or second-hand smoke) than cigarettes currently on the market, RJR has developed a number of prototype cigarettes that produce smoke by primarily heating, rather than burning, tobacco. Compared to cigarettes presently on the market, laboratory tests conducted on the current U.S. market Eclipse prototype indicate that: • Eclipse reduces second-hand smoke by 82% to 87%. • Eclipse produces virtually no lingering odor and almost no ashes. • Eclipse reduces staining on fabrics, such as curtains, drapes and wall coverings. • The smoke exhaled by the smoker dissipates very quickly. • Eclipse is low in "tar"[1] and nicotine, with carbon monoxide levels similar to the yields from low "taz" tobacco-buming cigarettes.j21 In addition, the results of a battery of scientific tests that have commonly been used to study cigarettes and cigarette smoke indicate that: • The chemical composition of the smoke from Eclipse prototypes is much simpler (i.e., contains fewer compounds and smaller quantities of compounds) than that of cigarettes that produce smoke primarily by burning tobacco.M • The smoke and smoke condensate ("tar", nicotine and water) from Eclipse prototypes generally produce demonstrably less biological activity than those from cigarettes that produce smoke primarily by burning tobacco, when compared in a variety of toxicological tests, as summarized in this report. • The information and data contained in this report refer to, and have been collected, using the current U.S. market prototype. [11 "Tar" is the total particulate matter in cigarette smoke (minus the nicotine and water) that is retained on a Cambridge filter pad when smoke passes through it. M Based on U.S. Federal Trade Commission (FTC) method tests, Eclipse yields 3.2 mg "tar" and 0.18 mg nicotine. The carbon monoxide yield is 7.5 mg, a level within the range of tobacco-burning cigarettes. (The U.S. FTC method is a standardized testing method designed to provide reliable and reproducible results that make possible the comparison of smoke yields among various cigarette brands.) httpJ/www.rjrdirect.com/ECIlsci/characteristics of eclipse.htm 05/24/2000
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How Eclipse Works Page2of2 As a simplistic analogy for purposes of illustration, the process Eclipse uses to produce smoke can be thought of as similar to the process used to make drip coffee. In the coffee maker, water is heated and then passed through coffee grounds to release the aroma, taste and flavor components. In the Eclipse, air is heated and then passed through tobacco to release components that produce smoke, taste and flavor. [I) Non-respirable filaments are those considered too large to reach the small airways in the pulmonary (or alveolar) region of the lung.Scientists generally agree that filaments greater than 3 microns in diameter are too large to enter the small airways of the lung. [2) Glycerin, or glycerol, is a colorless liquid that occurs extensively in nature and is naturally found in cells of plants, animals and humans. It is used in baked goods, fats/oils, milk products, cheese, jams and jellies, medicines, cosmetics and cigarettes. Glycerin is widely used in tobacco products as a humectant - a substance used to promote the retention of moisture in tobacco. Because the smoke aerosol of the Eclipse cigarette is comprised predominantly of glycerin and water, glycerin was tested in a genetic toxicology battery and in inhalation studies. The results of these studies, in conjunction with the results of biological and chemical studies performed using the Eclipse cigarette, provide evidence that the use of glycerin is consistent with the product development objectives of reduced biological activity and simplified chemical composition in the smoke of Eclipse. httpJ/www.qrdirect.cont/ECIlsci/how eclipse works.htm 05/24/2000
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Aggregate Chemical Measures by Gas Chromatography and Mass Spectrometry t ,I Iy r,cttpse Page 2 of 2 http://www.cjrdirect.com/ECLlsci/aggregate chemicals.htm 05/24/2000
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Elemental Analysis Page 1 of 2 4. Elemental Analysis The elemental composition (C, H, & N) of the mainstream smoke from Eclipse compared to that of 1R4F, 1R5F and CUL cigarettes is presented in Table 2 Eclipse TPM contains similar amounts of hydrogen and substantially less carbon and nitrogen than the TPM of the other cigarettes studied. This is consistent with the fact that Eclipse burns considerably less tobacco than the other cigarettes. TABLE 2. Elemental Analysis of Mainstream Smoke Total Particulate Matter (TPM) in Eclipse % TPM Eclipse 1R4F 1RSF CUL cadwn 29.2 58.1 60.6 60.9 Hydracm 7.6 7.7 8.1 7.9 NtIcen 1.8 4.2 4.5 5.0 % Reduction-a Eclipse Compared To: 1R4F 1RSF CUL Carbon -.50 - 52 - 52 Hydrogen nSb nSb nSb Nitrogen - 57 - 60 -64 % Reduction = [(Eclipse value - reference cigarette value) divided by (reference cigarette value)] ~^ N 0 OD a httpJ/www.rjrdirect.com/ECUsci/elemental_analysis.htm 05/24/2000 N A A
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Mainsiream Smoke Mainstream Smoke Page 1 of 1 Mainstream smoke is the smoke that comes through the filter of the cigarette when it is puffed. The mainstream smoke of Eclipse was characterized and compared to that of other cigarettes by means of the following approaches:(1) standard FTC measures; (2) gross measures of smoke total particulate matter (mass balance analysis by electrostatic precipitation; spectrophotometric determination of "tar"; thermogravimetric analysis; and elemental analysis); (3) aggregate chemical measures by gas chromatography and mass spectrometry; and, (4) quantitative evaluation of specific chemical constituentsfl,], or classes of compounds, in smoke. Except where noted, one or more of the following cigarettes were used for comparative purposes in these studies: [2] IR4F = a full-flavor low "tar" cigarette (approximately 85 nun in length) with FTC smoke yields of 9.2 mg "tar" and 0.80 mg nicotine, which was developed and is made available by the University of Kentucky as a highly consistent reference cigarette. Cigarettes in the 8-12 mg 'tar•' range represent approximately 44% of total U.S. sales. 1RSF = an ultra low "tat" cigarette (approximately 85 mm in length) with FTC smoke yields of 1.7 mg "tar" and 0.16 mg nicotine, which was developed and is made available by the University of Kentucky as a highly consistent reference cigarette. Cigarettes in the 0-3 mg "tar" range represent approximately 2% of total U.S. sales. CUL =a U.S. commercial cigarette (approximately 85 mm in length), which was chosen from the ultra low "tar" segment with FTC smoke yields of 5 mg "tar" and 0.5 mg nicotine. Cigarettes in the 3-8 mg "tar" range represent approximately 13% of total U.S. sales. jD RJR measured smoke concentrations of approximately 25 specific smoke constituents identified by many in the scientific community as compounds associated with the diseases that have been statistically linkedwith smoking. L2] Except where noted, the Eclipse, lR4F, 1RSF and CUL cigarettes were analyzed together in one study. httpJ/www.rjrdirect.com/ECIJsci/mainstream smoke.htm 05/24/2000
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Thernrogravimetric analysis Page 1 of 1 THERMOGRAVIMETRIC ANALYSIS Thermogravimetric analysis (TGA) was used to assess the volatility and thermal stability of the TPM from Eclipse compared to the TPM of two reference cigarettes (1R4F and IRSF) and the CUL cigarette. As presented in Figure 4. Eclipse TPM typically contains a larger proportion of volatile compounds (and, therefore, shows greater weight loss) compared to the TPM of the reference cigarettes. This is consistent with the fact that Eclipse TPM is 75% water and glycerin, compared to about 20-25% water and glycerin in cigarettes that bum down. FIGURE 4. Thermogravimetric Analvsis htap•1/www.rjrdirect.eom/ECUsci/thermogravimetric analysis.htm 05/24/2000
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•'dr $ fJiCitlne !'r,rd•:nI C3Ci/pSC. Oaitl7sg Smeking P,ivucy Statement --About RJRT -- Vlrlaalllau Centa A number of studies have reported that cigarette smoking increases the risk of cardiovascular diseases such as myocardial infarction (heart attack), ischemic stroke, abdominal aortic aneurysm and peripheral• vascular disease. There is ongoing scientific debate over the role carbon monoxide may play in cardiovascular disease. Some scientists believe that exposure to carbon monoxide increases the risk of angina and myocardial infarction. In general, smokers have significantly hi~;her levels of COHb than nonsmokers. The level of COHb in individual smokers will vary and is dependent upon how he or she smokes. Reynolds Tobacco has performed a number of short-term studies on smokers switching from their usual brand of cigarettes to Eclipse. These studies have shown that, on average, COHb levels in smokers of Eclipse are somewhat higher than the levels when they are smoking their usual brand (8.66% COHb for Eclipse, versus 8.10% COHb for their usual brand). In some cases, individual smokers have shown relatively large COHb increases. However, the levels were within the range (2.5 - 16.8%) observed among smokers of other cigarettes. There is little reason to believe that COHb elevations of this magnitude would increase the risk of cardiovascular diseases in otherwise healthy smokers. Although there is no direct evidence to show that individuals who have ischemic heart disease would be at increased risk, these individuals could conceivably be at increased risk for myocardial infarction (heart attack) because of these COHb elevations. Since half of all heart attacks occur without any prior waming symptoms, any smoker who is already at risk for heart disease (including people with diabetes, high blood pressure, high cholesterol or a family history of heart disease) is already at increased risk from smoking and may or may not increase that risk by switching to Eclipse. Because Eclipse has significant reductions in vapor phase free radicals, carcinogens and cytotoxins some scientists believe Eclipse may present less risk for cardiovascular disease. Similarly, a pregnant woman who switches to Eclipse mey or may not increase the risk of pregnancy complications. http://www.rjrdirect.com/ECL/health/cohb.htm Cu_torner Service Contact Uz StNlGEON GFN9tICSY'IAMING: quAfng Smokiy No.61radr kdnce Saiwc Neka a Yax Wk Hae* j , . .. Sdendfie Mormativl . --..-1 ;Eedi F..dO.et J FnG t Co.1~ot6d.slYt;-q: Potential Cardiovascular Effects Carbon Monoxide I Carboxyhemoglobin (COHb) `~Re t••4.ip ~ e 04/24/2000 -j ~ N a ~
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Gross Measures of Smoke Total Particulate Matter (TPM) Page 1 of I B) Gross Measures of Smoke Total Particulate Matter (TPM) A variety of complementary, gross analytical measures were used to characterize the chemical and physical properties of the TPM in the mainstream smoke from Eclipse: 1. TPM Materials Mass Balance For cigarettes that bum down, TPM is principally made up of tobacco pyrolysis, distillation and combustion products. Glycerin is released from cigarettes as a constituent of mainstream smoke TPM. A relatively small amount of glycerin (6%-19%) is found in TPM from cigarettes that bum down. Mass balance analysis of electrostatically precipitated TPM shows that glycerin constitutes a significantly higher proportion (40%) of TPM from Eclipse. Cmo.it10 t M.4mas 6mdce TPM Ueda FTC 6moldo= Cmddw. [dr.(l}Y.S).gkk) 0%lqe.m.-4% . %'OM~'ANL/ %W.er-b% laA (r}aAl.LW ®%mr.a-t%  %W.v-u% %Cbs..l- 1K. %•oe.r-n%  %Wa-12% %Gban1-!%  %ro6n°-72% Figure 2 compares Eclipse values with those of 1 R4F and 1 R5F reference cigarettes and a commercial ultra low "tar" cigarette (CiJL) based on mass balance analysis of mainstream smoke TPM by the electrostatic precipitation method. The composition of the TPM from Eclipse is 75% water and glycerin, and 25 % "tar" (excluding glycerin) and nicotine. The TPM of the other cigarettes studied is roughly the reverse - approximately 75-80% "tar" and nicotine, and 20-25% water and glycerin. httpJ/www.qrdirect.com/ECUsci/gross measure_of smoke.htm 05/24/2000 lroL (ttHi] xiASiLI O %Nk.b-8% JM%Walr-d% %Cben1-7% IQAi (RY.IIS.49kW ° % nkd6lr-Ti
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Quantitative Analyses of Target Compounds/Classes of Compounds NAT (ng/cig) Page 2 of 2 NNN (ng/cig)` 20 115 47 148 -83 -57 -87 NNK (ng/cig)° 23 97 27 63 -77 ns -64 ec µ cig 0. 45.3 8.4 26.0 -99 -93 -98 umone µ cjg 1.1 42.9 6.5 24.6 -97 -83 -9 µ cIg 0.2 8.9 1.2 4.8 -98 -86 -97 m µ cig 0.1 7.6 1.0 4.1 -99 -90 -98 a pyrene n cig 0. 5.4 1.5 4.0 -9 3 -86 nap ene n cig 1.4 10.9 3.6 8.2 -87 -61 -8 1P ~Y n m8 0.8 4.0 1.1 2.4 80 ns -68 ca (vapor p ase P ~g 2.22z10 4.85x10 1.02x10 2.25x10 -95 -78 -90 '`/e Change = [(Eclipse value - reference cigarette value) divided by (reference cigarette value)] multiplied by 100. b The computed % change value is not statistically significantly different from zero (p 5 0.05). ` NNN = N-Nitrosonomicotine, NAT = N-Nitrosoanatabine, NNK = 4-Methylnitrosoamino-1{3- pyridyl}1-butanone. httpJ/www.rjrdirect.com/ECUsci/quantitative analyses.htm 05/24/2000
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Environmental Tobacco Smoke Page 2 of 2 y e Wghn3) 45 307 300 303 210 78-85 y utnone 4 3 0.01 3.6 3.4 4.0 2.4 100 G18 m ) Phenol (µg/m ) 0.5 13.0 12.9 16.7 12.5 96-97 Ctesol (µg/m ) 0.10 3.2 3.1 3.9 2.9 97-98 o y ns 0.5 2.5 2.6 2.7 2.5 79-81 (mg/M3) Nitric oxide (µg/m ) 19 190 181 214 179 89-91 Nitrogen dioxide 5.6 44 42 49 40 86-89 (1+8IM) = respirable suspended particulates. detected above blank level. httpJ/www.ijrdirect.com/ECLlsci/environmental tobacco_smoke.htm 05/24/2000
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III Biological Studies Page 1 of 1 III. Biological Studies A comprehensive toxicological testing program using in vitro cellular test systems and rodents was developed to assess the potential biological activity of the smoke from Eclipse compared to the smoke of a variety of cigarettes that primarily bum tobacco (the Kentucky 1R4F or 1R5F reference cigarettes or commercially available cigarettes). A regimen of genetic toxicology and cytotoxicity assays - Ames; sister chromatid exchange (SCE); chromosome aberration; neutral red assay; and lactate dehydrogenase release - were conducted on smoke condensates ("ta2', nicotine and water) from Eclipse. This condensate was collected using FTC smoking conditions. The Ames assays were conducted in bacteria (Salmonella typhimurium), while both the SCE and chromosomal aberration assays were conducted in mammalian cells (Chinese Hamster Ovary (CHO) cells). The Ames, SCE and chromosome aberration assays are genetic toxicology tests that are used as screens to measure the potential for DNA damage in cells. The neutral red and lactate dehydrogenase assays (conducted in CHO cells) are cytotoxicity tests that measure cellular toxicity that does not involve genetic (or DNA) damage. To provide a broad characterization of the potential effect of particulate-phase smoke components, all of these assays were conducted on cigarette smoke condensate ("tar", nicotine and water) from Eclipse. To evaluate the potential effect of vapor-phase components, the neutral red and SCE assays also were conducted on whole mainstream smoke from Eclipse. httpJlwww.rjrdirect.com/ECUsci/biological studies.htm 05/24/2000
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Ddermination of Mainstream Smoke Yields by the FTC Method Page 1 of 2 A) Determination of Mainstream Smoke Yields by the FTC Method The FTC method was developed by the U.S. government to compare mainstream smoke yields from cigarettes that burned down when being smoked. The U.S. government specifies both the equipment and the smoking parameters for this method in detail (e.g., a puffing regimen that consists of a 35 cc puit 2 seconds in duration every 60 seconds). The Eclipse cigarette required a key modification to the FTC method. The FTC method specifies that filtered cigarettes should be smoked to a butt length of the tipping paper (f.e., the paper that connects the filter to the tobacco rod of a filtered cigarette) plus 3 millimeters.However, since the Eclipse does not bum down and is not reduced in length during smoking, butt length is not a feasible parameter for determining the smoke yields of Eclipse. Therefore, an approach was developed to standardize the smoking of Eclipse under conditions comparable to those specified by the FTC Method. It was established that smoking Eclipse for 15 puffs was appropriate to ensure the capture of all the smoke yielded by an Eclipse cigarette under FTC conditions. In addition, to ensure complete ignition of the Eclipse heat source during the lighting process, the Eclipse cigarettes were exposed to the hot electric lighter on the automated smoking machine for a greater length of time than other cigarettes. The basic constituents of mainstream smoke determined by the FTC method are: • total particulate matter (TPM) • nicotine • water • "tar" (as a calculated value) • carbon monoxide Total particulate matter (TPM or cigarette smoke condensate) is the particulate-phase portion of mainstream smoke aerosol, which, in the course of machine smoking, is collected on a glass-fiber filter of defined pore size (i.e., the Cambridge filter).As described earlier, "tar" is the TPM minus the nicotine and water. (See, note 2, supra.) Gaseous compounds, which form the vapor phase of mainstream smoke, are not retained by the Cambridge filter. Table 1 compares Eclipse to IR4F, 1R5F and commercial ultra low `Yar" cigarettes (CUL) in terms of TPM, nicotine, water, "tar," carbon monoxide and puffs per cigarette. . TABLE 1. Comparison of FTC "Tar" of Eclpse,lR4F and 1R5F Reference Cigarettes and a Commercial Ultra Low Tar Cigarette (CUL) httpJ/www.rjrdirect.oom/ECUsci/determination of mainstream.htm 05/24/2000
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The Evolution of Tobacco-Heating Cigarettes Page 1 of 2 The Evolution of Tobacco-Heating Cigarettes For the past several years, RJ. Reynolds Tobacco Co. (RJR) has been test-marketing various prototypes of Eclipse, a new cigarette that produces smoke by primarily heating, rather than burning, tobacco. Eclipse represents the latest innovation in a long search for additional types of cigarettes that goes back at least until 1839, when a U.S. patent suggested the use of sunflower and rhubarb leaves as tobacco substitutes. During the past several decades, cigarette design innovations have focused largely on "tar" and nicotine reductions using such techniques and tools as filtration, reconstituted tobacco, more porous cigarette papers, expanded tobacco and filter ventilation. Reynolds Tobacco pioneered many of these innovations and continues to develop other product improvements. In 1988, RJR test marketed a new cigarette called Premier, which heated, rather than burned, tobacco. Premier significantly reduced second-hand smoke compared to tobacco-burning cigarettes. Because of Premier's unique design, many of the compounds commonly found in cigarette smoke were dramatically reduced in (or eliminated from) the smoke from Premier. In addition, a comprehensive battery of toxicological tests indicated that the smoke from Premier had significantly reduced biological activity compared to that from tobacco-burning cigarettes. RJR took Premier off the market after several months, primarily for two reasons: • Smokers found the taste and aroma unacceptable. • Premier was criticized by anti-smokers, who perceived Premier (or any other alternative cigarette) as an obstacle to their stated goal of achieving a smoke-free society. RJR researchers went back to their laboratories to address the taste and aroma problems that prevented the commercial viability of Premier. Three facts quickly became apparent: • First, the simplified smoke chemistry and the reductions in second-hand smoke and biological activity associated with Premier would be irrelevant if smokers would not smoke the new cigarette. • Second, to provide taste and aroma that were acceptable to smokers, a cigarette needed to bum some tobacco. • Third, a balance had to be achieved between providing acceptable taste and aroma, and maintaining the significant reductions in mainstream smoke chemistry, second- hand smoke and biological activity that were associated with Premier. In 1996, following several years of intense development efforts, RJR began to test market a prototype htapJ/www.rjrdirect.com/ECIlsci/evolution of tobacco.htm 05/24/2000
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How Eclipse Works Page I of 2 How Eclipse Works Eclipse looks like, and is smoked, much the same way as any other cigarette. The smoker lights the tip of the cigarette and puffs on the mouth-end to draw smoke through the cigarette rod and filter, and into the smoker's mouth. As with other cigarettes, the smoke produced by Eclipse provides tobacco taste and smoking enjoyment. But because Eclipse primarily heats, rather than bums, tobacco, there are some important design differences that distinguish it from other cigarettes (Figure 1). ncuse I e.~ ck...m At the tip of Eclipse is a heat source made primarily of high purity carbon. The heat source also contains binders and a small amount of tobacco. The heat source is surrounded by a specially designed continuous-filament glass-mat insulator that reduces heat loss to the surrounding air. The glass-mat insulator is made from continuous-filament glass with an average diameter of 8.5 microns (ranging from 5.5 microns to 14 microns) and a length of 9500 microns. The type and size of these filaments were specifically engineered to be non-respirable.fll A thin layer of tobacco paper is sandwiched between two layers of the glass insulator. The tobacco paper and the tobacco in the heat source burn when Eclipse is lit to provide tobacco taste when the cigarette is first lit and while it is being smoked. Immediately behind the heat source is a tobacco roll that contains two segments. The first segment is a roll of processed cut tobacco that is impregnated with glycerinL2] (a common food ingredient that is found in most or almost all cigarettes). The second segment of the tobacco roll contains another processed tobacco blend. At the mouth-end of the cigarette is a cigarette filter made from cellulose acetate (the filter material used in most cigarettes). Holding the cigarette together are cigarette papers and laminates of cigarette paper and food-grade aluminum foil.The foil helps to retain the heat and conduct it through the cigarette. The smoker lights an Eclipse by puffmg on the filter while the heat source is exposed to a flame. As the smoker puffs on an Eclipse, heated air flows through the dual segment tobacco roll and the filter.As the heated air passes through the cigarette, it produces smoke by vaporizing the glycerin and by releasing flavorants, aroma, taste and flavor components (including nicotine) from the tobacco. After about 6 or 7 minutes, the heat source self-extinguishes and the cigarette stops producing smoke. The carbon heat source and a few other components of the heat source assembly are the only parts of the cigarette that bum. Therefore, an Eclipse is the same size when it is finished as it was before it was http:Hwww.rjrdirect.com/ECLsci/how eclipse works.htm 05/24/2t100
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Aggregate Chemical Measures by Gas Chromatography and Mass Spectrometry Page 1 of 2 C. Aggregate Chemical Measures by Gas Chromatography and Mass Spectrometry The particulate and vapor phases of Eclipse mainstream smoke are chemically simpler (contain fewer compounds and/or smaller concentrations of compounds) than those of the other cigarettes studied. Figures 5 and 6 illustrate and compare typical GC/MS chromatograms for mainstream smoke particulate and vapor phases of Eclipse with those of the iR4F and IR5F reference cigarettes and a commercial ultra low "tar" cigarette (CUL). The studies were designed to compare numbers of components as well as their relative amounts (for components present in smoke at a concentration of 0.5 pg per cigarette or greater). Chromatograms are scaled to an internal standard, and thereby make possible direct visual comparisons on a per- cigarette basis. The use of an internal standard corrects for absolute instrument response differences due to variations in mass spectrometer tuning and chromatographic injection volumes. Figure 5-Vapor Phase GC/MS Chromatograms IRSF tl.,. lh ltt ,- J~ ,. _,t k I ,.I Eclipse Jt. 1 fi1 &~,l-I ..,_ ~ 1 Wbt~i~i~~~~i Figure 6-Particulate Phase GC/MS Chromatograms ` -1 L,JUJWAJSJ L1R4F L 1RSF i =1r - - -1a :. =I httpJ/www.rjrdireat.com/ECIJsci/aggregate chen,icals.htm 05/24J2000
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Genetic Toxicology and Cytotoxicity Page 2 of 2 ' Slope Value: a measure of the increase in the number of SCEs per unit of smoke concentration. b Eclipse statistically significantly lower (p 5 0.05) than 1R4F and iRSF. httpJ/www.rJrdiroot.conJECUsci/genetiic toxicology_and cytotoxic.htm 05/24/2000
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Chromosome Aberrations C. Chromosome Aberrations in Smoke Condensate Page 1 of I Chromosome aberrations are structural changes in chromosomes (which may include breaks or rearrangements in one or both chromatids) that result in an alteration of genetic material. Sister chromatid exchange and chromosome aberration assays are often conducted in mammalian cells, such as Chinese hamster ovary (CHO) cells. As shown in Table 8, the condensate from Eclipse produced negative results (no changes) under all conditions (with and without metabolic activation) in the chromosome aberration assay. In contrast, condensate from the 1R4F and 1R5F induced chromosome aberrations under all test conditions. TABLE 8. Smoke Condensate - Chromosomal Aberration Assay t Without Activation Activation Eclipse Negative Negative 1R4F Positive Positive IRSF Positive Positive http:l/www.rjrdirect.com/ECL/sci/chromosome aberrations.htm 05/24/2000
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Animal Studies Page 1 of 1 Animal Studies Two types of animal studies - inhalation studies (13-week subchronic studies in B6C3/Fl mice and Sprague - Dawley rats); and a dermal tumor promotion study in female SENCAR mice - were conducted to compare the biological activities of Eclipse to those of the 1R4F reference cigarette. The Eclipse cigarette demonstrated a profile of significantly reduced biological activities when compared to the 1R4F reference cigarette in these comparative toxicology assessments. httpJ/wunv.rjrdirect.com/ECIJsci/animal studies.htm 05/24/2000
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Environmental Tobacco Smoke Page 1 of 2 Environmental Tobacco Smoke Environmental tobacco smoke (ETS) is the aged and diluted mixture of sidestream smoke and exhaled mainstream smoke. A specially designed and equipped 45 m3 environmental chamber was used to characterize the ETS generated by Eclipse and compare it to the ETS from various market cigarettes. During testing, six smokers entered the unventilated ETS chamber, and each person smoked one cigarette ad libidum to a line 3 mm from the overwrap or until completion (Eclipse). After 20 minutes, the smokers exited the chamber, which was then resealed. Real-time monitoring and sampling of discrete analytes were continued for an additional 120 minutes. The analyte concentrations from the types of cigarette were then compared. Table 5 presents the results of ETS chamber tests comparing Eclipse with the leading style of the leading market brand in each of four categories: full flavor (FF), full flavor low "tar" (FFLT) 85 mm, full flavor low "tar" (FFLT) 100mm, and ultra-low "tar." (ULT). TABLE 5. ETS Component Reduction Ranges for Eclipse Analyte Analyte Analyte Analyte Analyte Reduction Conc. Conc. Conc. Cone. Conc. in Eclipse Eclipse FF ` FFLT FFLT ULT (85mm) (100 mm) artic es 192 1510 1402 1460 1057 82-87 Carbon monoxi e (mg(M3) 5.0 6.8 6.5 >7.9 5.7 13-37 Nicotine (pglm3) 4 92 86 131 92 95-97 e°y yn . e 3 0.6 33 34 41 41 98 (lig/m ) Myosmine (µglm ) 0.07 5.2 5.2 7.3 6.6 99 Ammonia (µg/m ) ND 440 410 603 520 100 orm e y (F+8im3) 16 107 104 117 77 85-87 http!/www.rjrdirect.com/ECL/sci/environmental_tobacco smoke.htm 05/24/2000
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Genetic Toxicology Page 2 of 2 5/16/97 +116 +1075 negativeb +494 6/8/97 +161 +1589 negativet' +816 6/18/97 +129 +1340 negativeb +773 6/25/97 +233 +1770 negativeb +668 'rev/mg TPM is revertants/ milligram Total Particulate Matter. b A response is characterized as negative when revertant counts per treated plate do not reach double the number of revertants observed in background (i.e., solvent control) plates. FIGURE 7. Ames Assays of Eclipse TA98 5% S9 100. i5 90 OS BO 7S 70 65 80 SS 50 45 40 35 30 25 20 15 10 5 0 0 http://wnvw.qrdirect.coro/ECUsci/genetic toxicology.htm 05/24/2000
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Inhalation Studies Page 2 of 2 (p0.05) from the sham exposed group. <_ d Changes denoted as Similar or Reduced indicate the response of the Eclipse-exposed animals relative to the 1R4F response. ° Changes denoted as "Absent" were not statistically significantly (p 5 0.05) or biologically significantly different from those in the sham exposed control group. FIGUREB. NASAL SECTION 1 EPITHELIAL HYPERPLASIA FEMALE RATS 70 4 10 ! r-~a.v ~•ECLPSE ! u 0.1 0.2 0.3 0.4 0.5 ConceMrelun of Smok e ptOitJ 0.6 0.7 http•l/www.rjrdirect.com/ECL/sci/inhalation smoke.htm 05/24/2000
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Cytotoxicity Page 2 of 2 e 1R4F and iRSF exhibited statistically significant cytotoxicity at concentrations of 50 µg/ml and above. d Concentrations tested were 50, 75, 100, 150, 200, and 250 µg/ml. Eclipse did not exhibit statistically significant cytotoxicity at any concentration tested. ° 1R4F exhibited statistically significant cytotoxicity at concentrations of 200 µg/ml and above. f1R5F exhibited statistically significant cytotoxicity at concentrations of 75 µg/ml and above. httpJhvww.rjrdirect.com/ECIJsci/cytotoxicity_smoke.htm 05/24/2000
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.<b3>Scientific StudiesVh3> Page 1 of 1 Scientific Studies Eclipse has undergone a variety of chemical and toxicological tests (including smoke chemistry analyses, in vitro and in vivo tests) that are frequently used by the scientific community to study and compare cigarettes and cigarette smoke. All tests presented in this document were conducted using the U.S. Federal Trade Commission (FTC) smoking method puffing regimen, with the exception of those tests which involved human smoking. Unless otherwise noted all statistical analysis was performed at a 95% confidence interval. L Component Review Material and component review began with acquiring a detailed description of the material from the supplier followed by a comprehensive scientific literature review of ingredients or components. Whenever possible, food-grade materials or materials commonly used in or around food (e.g., food ingredients and packaging) were employed. For components not used in foods, stringent standards and specifications were established, based on toxicological standards and principles generally applied to food-grade components. II. Chemical Studies Based on tests using the FTC method, Eclipse is low in "tar" and nicotine, with carbon monoxide levels in the range of low "tar" tobacco-burning cigarettes. In addition, the composition of the smoke from Eclipse is much simpler (i.e., contains fewer compounds[j] and smaller quantities of chemical compounds) than that of tobacco-burning cigarettes when cigarettes are compared by smoking them using the FTC method puffing regimen. V] Based on measurements of smoke constituents present at concentrations of 0.5 µgJcigarette or greater. httpJ/www.rjrdirect.conJECL/sci/scientific studies.htm 05/24/2000
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Spectrophotometric Determination of Tar Page 1 of 2 i Spectrophotornetric Determination of "Tar" Spectrophotometric detemunations assess the relative amount of compounds in TPM that absorb ultraviolet radiation (such as carbonyls, aldehydes, phenolics, and aromatics). Spectrophotometric determinations also reveal marked differences in the TPM of Eclipse compared to that of cigarettes that burn down. Spectrophotometric analyses of the TPM from cigarettes that bum down (with a wide range of "tal" yields - from 1 to 17 mg per cigarette) yield values that correlate well with the FTC method measurements, while this is not the case with Eclipse (Figure 3). Although the FTC method produces "tar" yields of 3 mg to 4 mg per cigarette for Eclipse, the spectrophotometric values are much lower, at levels of - 0.5-1.0 mg per cigarette. FIGURE 3. Comosison o[FTC and %!ectrophotomNric "TW" Measm-es ~ .., 4 16 ~~ 14 ]i s.kdrdw a MoaetRCueRs : 6 4- 2- f® 0 ~ 0 2 4 6 8 10 12 14 16 18 F7C'Yt'(u8ldg) This difference can largely be explained by the fact that glycerin - the largest component of Eclipse mainstream smoke - is picked up at its full weight by the gravimetric method (employed in the FTC protocol). However, since glycerin is transparent to UV, it is not registered spectrophotometrically. Consequently, the TPM from Eclipse cigarettes contains proportionately less UV-absorbing material than does TPM from the other cigarettes studied. This is consistent with the fact that Eclipse cigarettes burn a smaller amount of tobacco (which produces many compounds that are detected spectrophotometrically). It is also consistent with chemical analyses of the smoke from Eclipse cigarettes, which indicate that Eclipse smoke contains fewer and smaller concentrations of tobacco pyrolysis, distillation and combustion products than the smoke from other cigarettes. 3.Thermogravimetric Analysis Thermogravimetric analysis (TGA) was used to assess the volatility and thermal stability of the TPM from Eclipse compared to the TPM of two reference cigarettes (1R4F and 1R5F) and the CUL cigarette. As presented in Figure 4, Eclipse TPM typically contains a larger proportion of volatile compounds (and, therefore, shows greater weight loss) compared to the TPM of the reference cigarettes. This is consistent with the fact that Eclipse TPM is 75% water and glycerin, compared to about 20-25% water and glycerin in cigarettes that burn down. httpJ/www.rjrdirect.eom/ECIlsci/spect determination.htm 05/24/2000
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Continuous Filament Glass Page 2 of 2 susceptible to chemical leaching processes within the lung. It has been hypothesized that this characteristic of the glass fibers accounts for their observed inactivity in animal models. In vitio biopersistence in the lung is frequently assessed by in vftro fiber dissolution studies using simulated biological solutions and flow past techniques . Comparative studies have been conducted which include IvIMVF 10, MMVF 11, MMVF 21, and crocidolite asbestos as controls. Dissolution rates were calculated from weight loss data assuming that the rate is proportional to the reaction surface area. The results of these studies indicate that the continuous filament glass used by RJR in Eclipse is significantly more soluble than either rock wool or crocidolite. In summary, transfer data and the unique physical characteristics of the filaments demonstrate that significant exposure of the smoker will not occur. The available environmental survey data clearly demonstrate that Eclipse smokers are extremely unlikely to be exposed to continuous filament glass at a level representing an increase relative to background exposure levels. Further, the chemical composition and dissolution characteristics of the filament used in Eclipse demonstrate similarity to glass fiber compositions that have failed to produce either tumors or fibrosis in chronic inhalation studies conducted in rats. In short, exposure of Eclipse smokers to continuous filament glass is extremely unlikely to occur at a level that may be construed to be of biological significance. http://www.rjrdirect.com/ECUsci/continuous_filament_glass.htm 05124/2000
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Quantitative Analyses of Target Compounds/Classes of Compounds Page I of 2 D. Quantitative Analyses of Target Compounds/Classes of Compounds A variety of analytical methods were used to obtain quantitative data for selected smoke constituents from both the particulate and vapor phases of the mainstream smoke from Eclipse, as well as the concentration of free radicals in the vapor phase. All are "state-of-the-art" methods, and many were improved by applying a variety of instrumental techniques to increase specificity, accuracy and precision. - Table 3 shows the concentrations of mainstream smoke target compounds and vapor-phase free radicals for Eclipse in comparison to the reference cigarettes 1R4F and 1R5F, and a commercial ultra- low'Yar" cigarette (CUL). Quantitative analyses of selected smoke constituents indicate that the yields of the specific compounds analyzed in the smoke from Eclipse were reduced compared to those in the smoke from the reference cigarettes, with the exception of (1) an elevation in the level of acrolein compared to the IR5F, and (2) an elevation in the level of furfural compared to all three tobacco-burning cigarettes tested. It is important to note that although these constituents were not reduced, their levels measured in the smoke from Eclipse were in the range of other cigarettes currently in the market. Furthermore, results of biological studies performed using Eclipse indicated that the presence of these constituents did not result in an increase in biological activity. These studies included genetic toxicology tests (Ames, sister chromatid exchange, and chromosomal aberration assays), a cytotoxicity test (the neutral red assay), and animal tests using rodents (inhalation and dermal tumor promotion assays). TABLE 3. Comparison of the Concentrations of Selected Mainstream Smoke Compounds and Free Radicals in Eclipse vs. 1R4F and 1R5F Reference Cigarettes and a Commercial Ultra Low `°Tar"CiAarette (CUL) veraEe ~e s % ChanQe'- c ipse Compared to: c ipse arge ompoun s cet e y e µ cig 75 640 134 311 -44 -76 Isoprene µ cig 14 366 109 248 -96 -88 -95 Nitrogen oxides µ cig 41 258 146 -84 -49 -72 Acetone µ cig 27 284 65 138 -90 -58 -80 y ogen cyam e µ cig 165 18 79 -95 -57 -90 o uene µ cig 5.9 73.3 16. 39.4 -92 -64 -85 cro em µ ag 33 65 11 35 -50 +197 ns u tene µ cig 2.0 36.5 11.0 24.0 -95 - 2 92 Benzene µ cig 4.9 44.2 13.1 27.5 -89 -62 - 2 oma µ cig 5.4 16.0 5.3 14.2 -66 ns -62 cry omtn e µ cig 1.2 13.9 3.0 7.8 1 -59 -84 orm e y e µ cig 0.8 8.5 1.4 3.6 -91 ns -78 µ cig 4.1 1.4 0.4 0.7 ; +187 + 98 +533 o me n ag 8 230 40 121 -97 -80 -93 AT (ng/cig)° 17 126 45 110 -86 -62 -84 bttpJ/www.tjrdirect.cont/ECL/sci/quantitative analyses.htm 05/24C1000
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DNA Adducts httpJ/www.rjrdirecLcomIECIJscl/dna adducts.htm Page 4 of 4 osn4nooo
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Dermal Tumor Promotion Study 0 -+-1R4F -f• Eclpee 10 20 30 CSC (mg condensatdapp6cation) 40 Page 2 of 2 N N m OD J A httpJ/www.rjrdirectcom/ECUsci/derma)_tumor-promotion.htm 05/24/2000 N co
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Sidestream Smoke Sidestream Smoke Sidestream smoke is the smoke that is emitted from the lit end of a cigarette. Page 1 of I To perform chemical analyses, sidestream smoke is generated and collected under somewhat artificial conditions (which might cause the formation of artifacts). Several smoke-collection systems have been described in the literature. The most widely used system employs the "fishtail chimney," where single cigarettes (one or several in sequence) are smoked with the lit end placed in a tube-like, vertically positioned glass "fishtail chimney." Fresh sidestream smoke is collected at the top outlet of the "fishtail chimney.,,[O Table 4 compares the sidestream smoke "tar," nicotine and carbon monoxide from Eclipse with those from three other cigarettes: iR4F,1R5F, and CUL. TABLE 4. Concentrations of Sidestream Smoke Components from Eclipse Compared to the 1R4F and 1R5F Reference Cigarettes and a Commercial Ultra Low Tar Cigarette (CUL) c pse O.Oa 26.8 18.0 20.4 (mglcig) Nicotine a O.l 5.6 3.2 4.0 (mg/cig) Carbon onoxt e 27.6 84.8 47.6 39.1 (mg/cig) a'Ihe value is not statistically significantly different from a blank evaluation (p 5 0.05 [1] Proctor, C.J., Martin, C., Beven, J.L. and Diamond, H.F. (1988) Evaluation of an apparatus designed for the collection of sidestream tobacco smoke. Analyst 113(10), 1509-13. httpJ/www.rjrdirect.com/ECIlsci/sidestream smoke.htm 05/24/2000
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Human Studies S Ecp~secipanetla weekl week 2 vRek3 Page 2 of 2 httpJ/www.rjrdirect.com/ECUsci/human studies.htm 05/24/2000
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DNA Adduots Page 2 of 4 25 -~ 20-:. 15 -~ 10-I 5 -I 0 20 40 * • I 60 80 100 Concentration (mg CSC/Week) •- 7htWkdy splt'ceitly lets tlrn IR1P Figure 11. Rat Inhalation Studies/DNA Adducts Eclipse vs 1R4F -0-1 R 4I -.-Eal4ee I -.-1RlF -o-E t 11p Ot HEART 13 W..ks Eaas.te 1 13 W eeYs Expetere >TT- LVNe 1 httpJ/www.rjrdirect.conm/ECUsci/dna adducts.htm 05/24/2000
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Human Smoldng Behavior Studies Usual Brand Product Ecipse Table 16. %Carboxyhemoglobin (25 minute measurement) Page 3 of 3 tu y um er o Subjects Mean Range c ipse Mean c ipse Range 30 7.05 2.5-12.9 3.4- 4 7.77 Vet'd 8.10a ' 8.66' • ' Overall mean weighted per number of subjects. tpJ/www.rjrdirect.com/ECIJsci/human smoking behavior.htm /24/2000 cn N O OD J A N _ J J
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Genetic Toxicology and Cytotoxicity Page 1 of 2 Genetic Toxicology and Cytotoxicity - Whole Mainstream Smoke Whole mainstream smoke (which contains particulate and vapor phases) is collected after it passes through the cigarette rod and the cigarette filter. Scientists at RJR have developed a methodology (cellular smoke exposure technology, or CSET) to expose mammalian (CHO) cells to whole cigarette smoke. Two of the assays that were conducted with cigarette smoke condensate (the neutral red and the sister chromatid exchange assays) were also conducted with whole smoke, using this new technology. - As measured by these assays, Table 10 and Table 11 show that the whole smoke from Eclipse has less cytotoxic and genotoxic potential, respectively, than the whole smoke from a low "tar" (1R4F) reference cigarette. Under the conditions of these assays, the cytotoxic potential (Table 10) of the whole smoke from the Eclipse is similar to that of an ultra-low= `tar" (iRSF) cigarette, while its genotoxic potential (Table 11) is significantly lower. In the neutral red assay, a higher concentration of whole mainstream cigarette smoke (measured as the number of cigarettes smoked per cubic meter of air) from Eclipse was required to reduce the cell population by 50%. Eclipse required approximately 22 cigarettes per cubic meter of air to affect these cells while the 1 R4F low "tar" cigarette required only 4 cigarettes per cubic meter of air.ln the SCE assay, a lower slope value is indicative of lower mutagenic potential. The slope value for Eclipse was statistically significantly lower than that for both 1R4F and 1R5F. TABLE 10. w.Me s..ke (CSEq-IVe." xed Awr eutra e Assay EC50 Value' Eclipse 21 Jb 4.2` 22.1 ' Concenttation of mainstream smoke (cigarettes per cubic meter of air) to cause 50% reduction in growth of cell population. 61R5F mainstream smoke and the Eclipse cigarette were not statistically different from each other (p 20.05)in cytotoxicity. e Statistieally different from Eclipse and IR5F (p <_ 0.05). TABLE 11. Waws..rM tcsert-scE Ana Slope Value' (average of five separate assays) cupse i1114ai«~ 0.055 b 1 0.295 1 0.065 httpJ/www.rjrdirect.com/ECUsci/genetic toxicology_and cytotoxic.htm 05/24/2000
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DNA Adducts Page 3 of 4 0 , 0 . x a . 2  y u a 1 1 1 11 ~ ~ ... < ~ 0 1 1 1 T - rT~Ts T ~T~TI T~'1 0.0 0.1 0.2 0.3 0A 0.6 0.6 0.7 Concentratfon (mg TPMlL) -*. Sutktka0y tiqn8undy l.at tk a. IReF Figure 12. Mouse Inhalation Studies/DNA Adducts Eclipse vs 1R4F 10 HEART 13 Weeks Exposure --1R4F -o-Ecllpso  0 10 0 I I --1R4 F -*-E clipse I I ~~ i I LUNG 13 Weeks Exposure I I I I s ___----' 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Concentration (mg TPMIL) •w 4.eseullr sbdiunlN Lss tMn lesF bttp://wwwajrdirect.com/ECIlsci/dna adducts.htm 05/24/2000
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Gytotoxicity Page 1 of 2 Cytotoxicity- Smoke Condensate In vitro assays are widely used to evaluate the biological effects of chemicals on mammalian cells. The cellular toxicity of cigarette smoke and cigarette smoke condensate from Eclipse and standard reference cigarettes has been measured in two assays: • -neutral red • lactate dehydrogenase (LDH) release The neutral red assay measures the growth rate of a population of cultured mammalian (CHO) cells. Viable cells take up the neutral red dye and transport it to a specific cellular compartment, the lysosome. The uptake, transport, and storage of neutral red dye occurs via active biological processes that require energy, as well as intact cellular and lysosomal membranes. Damage to any of the systems involved in the process (or a reduction in cell number due to cell death), would result in decreased uptake of the neutral red dye in a given number of cells. Lactate dehydrogenase (LDH) leakage through the cell membrane is routinely used as an indicator of damage to plasma membrane integrity. An increase in LDH leakage into the extracellular environment indicates a loss of membrane integrity, and is interpreted as a cytotoxic effect. As measured by these two assays, smoke condensate from Eclipse had virtually no cytotoxic potential under the conditions tested, whereas smoke condensate from a low tar (iR4F) or an ultra-low tar (IR5F) reference cigarette did induce cytotoxicity under the same conditions (Table 9). In the neutral red assay, a higher concentration of-cigarette smoke condensate required to reduce the cell population by 50% is indicative of lower cytotoxicity. Eclipse required more than 150 µg/ml condensate to affect these cells. For LDH release, the lower concentration of condensate required to damage a cell is indicative of greater cytotoxicity than higher doses.For Eclipse, LDH release did not occur when more than 250 µg/ml of smoke condensate was added to the cell media, while less condensate caused LDH release for the 1R4F and 1R5F. TABLE 9. Cigarette Smoke Condensate - Neutral Red Assay and LDH Release Neutral Red e ease Assay Lowest Concentration Exhibiting Cytotoxicity EC50 Value Eclipse >150b >250d 73.0` - - 200e - _ IRM 73.3e 75 ' Concentration of cigarette smoke condensate (µg/ml) required to cause a 50% reduction (ECS0) in growth of cell population. b Conoentrations tested were 10, 25 ,50 ,75 , 100, and 150 µg/mI. In three trials, Eclipse exhibited statistically significant cytotoxicity only once at the high dose of 150 µg/ml. httpJ/www.rjrdirect.com/ECLJsci/cytotoxicity-smoke.htm 05/24/2000
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Sister Chromatid Exchange (SCE) in Smoke Condensate Page 1 of I Sister Chromatid Exchange (SCE) in Smoke Condensate A chromatid is one of the paired chromosome strands which make up a metaphase chromosome.Sister chromatids are two identical chromatids of a chromosome held together by a centromere. Sister chromatids exchange pieces of DNA with each other even under normal circumstances, but when cells (CHO) are exposed to genetic toxicants, more exchanges (SCEs) are likely to occur. By comparing the tiequency of SCEs in exposed cells to the frequency in unexposed cells, a measure of the potential genotoxicity of tobacco smoke or smoke condensate can be obtained. As shown in Table 7, the condensate from Eclipse produced negative or marginally positive responses that were statistically significantly lower than the iR4F and 1R5F responses in the sister chromatid exchange assay. In contrast, condensate from the 1R4F and 1R5F induced sister chromosome exchanges under all test conditions (with and without metabolic activation). In the SCE assay, a lower slope value is indicative of lower mutagenic potential. TABLE 7. EdOSe snotce Condensste- scE Assay blmmus &Np.e SYiy &.dY Ao 4ebe•d6s9at'vAa Filipe _ Lon¢ laAW IQSF mm ]{ I C1 p!'{/~OJYiW~~ ~y.. nra~ ! uZSr GI}n S~tjl~.~iY .R.~." ID12 D297 a Slope Value: a measure of the inctease in the number of SCEs per unit of smoke concentration. b Eclipse statistically significantly lower (p <_0.05) than IR4F and 1R5F. httpJ/www.rjrdirect.conJECL/sci/sister chromatid.htm 05/24/2000
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Human Smoking Behavior Studies Page 2 of 3 Figure 15. Puffing Behavior (Normalized to Usual Brandr I ~ Nonnalization is a graphical technique used to display widely divergent numbers on a common scalc.Normalization is accomplished by dividing the test paruneter by the corresponding control parameter and then assigning the control parameter the value of 1. For example, if the test parameter is 15 and the control parameter is 10, then the control would be assigned the value 1, and the test would be 1.5 (15 divided by 10). Plotting there data, as above, provides a visual representation of percent differences. Puffs = Number of Puffs, Puff Vo1= Puff Volume, Dur = Puff Duration, IPI = Inter-Puff Interval, Lit = Time Lit, Smldr= Smolder Time, T Vo1= Total Puff Volume, T Dur= Total PutfDuradon. Figure 16. %Carboxyhemoglobin Eclipse Change in %COHb from UB By Subject (N=109) With Overall Mean and Standard Error Bars httpJhvww.qrdirect.com/ECI/sci/human_smolcing_behavior.htm 05/24/2000
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Human Studies Page 1 of 2 Human Studies A. Human Urine Mutagenicity Study Urinary mutagenicity has been widely used as a non-invasive quantitative measurement of recent human exposure to potentially genotoxic agents. Several studies have reported that the urine from smokers is more mutagenic than the urine from non-smokers, as measured by the Ames assay. Eclipse was compared with commercially available cigarettes in the human smoking studies. A three-week study was performed to compare the urinary mutagenicity in smokers when they were smoking Eclipse cigarettes with that of the same smokers when they were smoking their usual cigarette brands. The study incorporated a cross-over design that allows smokers to act as their own controls. Smokers smoked either their usual brand or Eclipse ad libitum during the study. After one week on their usual brand, smokers smoked Eclipse for the second week, and their usual brand for the third week of the study. All smokers were on the same strictly controlled low-mutagenicity diet throughout the study, resulting in a low and stable diet-related urinary mutagenicity baseline for all study participants. Non- smokers served as negative controls. Urine samples were tested by Ames assay with two Salmonella strains: the traditional TA98 and the new, much more sensitive YG1024 (a derivative of TA98 that overexpresses the O-acetyl transferase enzyme), both with rat liver homogenate metabolic activation. Urinary mutagenicity as measured with TA98 and YG1024 in Eclipse smokers was reduced 70°/r72% compared with smokers' urine mutagenicity when smoking their usual brands of tobacco-burning cigarettes (Figure 13 and Figure 14). The observed decrease in mutagenicity was not due to reduced cigarette consumption (Table 14). TABLE 14. Urine Mutagenicity Study - Daily Cigarette Consumption ee Igare es onsum (mean SD) su ran (30 t 9) Eclipse (26 t 7) sua ran (29 ± 8) http://www.rjrdireet.com/ECUsci/human_studies.htm 05/24/2000
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Genetic Toxicology Page 1 of 2 Genetic Toxicology - Smoke Condensate A. Ames Test The Ames test (a widely used first step in characterizing the potential of a substance to induce mutagenic changes) uses different strains of Salmonella to determine whether a chemical produces point mutations in vitro. Because bacteria lack many of the metabolic capabilities of intact mammals, the Ames test usually is conducted under two conditions - with and without the presence of a mammalian metabolic activation system. The mammalian metabolic activation system utilized in these assays is referred to as the S9 system. It is a liver homogenate fraction from rats which were administered a chemical (Aroclor 1254) to induce metabolizing enzymes in their livers. Ames data are interpreted in terms of the number of "revertants per milligram of Total Particulate Mattet" (rev/mg TPM) observed. The larger the number, the greater the potential mutagenic effect. The mutagenicity of cigarette smoke condensate (CSC) is greatest in strains TA98 and TA100 with S9 metabolic activation. As detailed in Table 6, at concentrations where the smoke condensate from tobacco-burning cigarettes produced strong, statistically significant increases in response, the smoke condensate from Eclipse produced negative results (no changes), or positive responses that were significantly lower than the 1R4F responses. Figure 7 contains plots of Eclipse results in the Ames assay. The results presented in Table 6 and Figure 7 are from repeated assays performed on different dates. TABLE 6. Summary of Ames Assay Results for Eclipse and 1R4F 5Yo S9 Date rev mg TPMa rev mg TPMa c lpse c lpse 4/15/97 negativeb +1408 negativeb +553 httpJ/www.rjrdirect.com/ECIJsci/genetic toxicology.htm 05/24/2000
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Continuous Filament Glass Page 1 of 2 Continuous Filament Glass As indicated in the introduction, in Eclipse, smoke is formed by hot air generated by a carbon heat source that passes through a glycerin-rich substrate, volatilizing glycerin, nicotine, other natural tobacco flavors, and added flavorants. The heat source assembly utilized in Eclipse consists of carbon, glass mat insulator, tobacco sandwich paper, and an insulator paper overwrap. The glass mat insulator functions to insolate the heat source, reduce propensity for the ignition of other materials, and enhance cigarette performance by directing heat flow to the substrate materials of the cigarette. The glass mat insulator is composed of continuous filament glass fiber and a binder. It should be noted that glass filaments are ubiquitous and are commonly observed in ambient air in both occupational and non-occupational settings. Continuous filament glass is commonly used in consumer products such as firefighters' clothing, carpet backing, drapery fabrics, Christmas ornaments, hairdryers, and air filters. Survey data demonstrate that consumers are exposed to literally thousands of glass filaments daily as a result of non-occupational environmental exposure. The potential transfer of continuous filament glass to Eclipse mainstream smoke has been evaluated. The results of these studies have been presented at scientific meetings and are currently being prepared for publication. In brief, methodology was developed that allowed the capture of any filaments that might be transferred to Eclipse mainstream smoke. Subsequent to handling procedures that were designed to simulate commercial shipping conditions, cigarettes were machine smoked using exaggerated conditions (ten 75 ml puffs, 2 second duration, taken every 35 seconds). These conditions were employed specifically to maximize the probability that any potential transfer of continuous filament glass to Eclipse mainstream smoke would be detected. The results of these studies consistently demonstrate that, relative to background, biologically significant transfer of continuous filament glass to Eclipse mainstream smoke does not occur. The continuous filament glass used in Eclipse was designed to be non-respirable. The continuous filament glass mat insulator is made from continuous glass filaments having an average diameter of 8.5 µm (range = 5.5 - 12 µm). These filaments are chopped to a length of 9500 µm and subsequently converted into a mat. The calculated aerodynamic diameter (parallel) of these filaments would be approximately 53 pm (range 35 - 73 pm). It is generally accepted that structures with aerodynamic diameters greater than 7 pm are unlikely to reach the pulmonary region of the respiratory trac-t. There are epidemiological data that specifically focus on the potential impact of occupational exposure to continuous filament glass. In the studies where the potential impact of occupational exposure to continuous filament glass has been specifically addressed, long-term health consequences have not been associated with occupational exposure to continuous filament glass. Further, chronic inhalation studies have been conducted with rat respirable fractions of representative glass fibers. In these studies, rats were exposed by nose-only to a rat respirable (size selected) fraction of two representative glass fibers (MMVF 10 and MIvIVF 11). Although crocidolite asbestos (the positive control) was demonstrably carcinogenic to rat lung in these studies, no statistically significant increase in fibrosis or lung tumors was observed subsequent to exposure to either MMVF 10 or MMVF 11. It has been hypothesized that biopersistence plays a significant role in determining the potential bioactivity of a fiber. The relationship between in vivo biopersistence and chemical composition has been evaluated. The toxicological potential of fibers appears to inversely correlate with the rate at which specific fibers disappear from the lung. By example, asbestos fibers and refractory ceramic fibers, which are relatively durable in the lung, do produce significant increases in lung tumors, mesothelioma, and/or fibrosis in the lung. Rock wool (MMVF 21), which is less durable than asbestos fibers or refractory ceramic fibers in the lung, produced fibrosis in rat lung but not lung tumors. Glass fibers such as MMVF 10 and MMVF 11 have been shown to be significantly more http:l/www.rjrdirect.com/ECLlsci/continuous_filament_glass.htm 05/24/2000
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DNA Adducts DNA Adducts Page 1 of 4 DNA adducts are formed when compounds attach themselves to DNA molecules. DNA adducts are most often used as molecular dosimeters of exposure. The biological significance of DNA adducts depends upon the type of adduct formed as well as other factors (e.g., cell replication and DNA repair rates). Scientists believe that the formation of DNA adducts can lead to mutagenesis and in certain circumstances play a role in carcinogenesis. It is important to note that, because of natural repair mechanisms, the types of changes seen in these tests often reversed after exposure to the test substance ended. Mice exposed dermally to cigarette smoke condensate from Eclipse for up to 29 weeks had no statistically significant (p <_ 0.05) increase in DNA adducts in their lungs compared to solvent control exposed animals, with the singular exception of the highest dose (40 mg CSC, 3 times per week). However, compared to the IR4F, animals exposed to the smoke condensate from Eclipse had a statistically significant (p <_ 0.05) decrease in lung DNA adducts at all doses tested at 29 weeks (Figure 10). Inhalation studies were performed to evaluate the amounts of DNA adducts in lung and heart tissue of both rats and mice. Inhalation exposures of mice for 13 weeks, for the evaluation of DNA adduct formation, were conducted using the same conditions as the rat inhalation studies. Results indicate that the amount of DNA adduct formation in heart and lung tissues of both mice and rats exposed to the smoke of Eclipse was not statistically significantly (p 5 0.05) different from that in the sham exposed animals. However, compared to the 1R4F, rats exposed to Eclipse showed statistically significant (p 5 0.05) decreases in the amount of DNA adduct formation in lung tissues at all three exposure concentrations (Figure 11): Compared to mice exposed to the 1R4F, mice exposed to Eclipse displayed statistically significant (p <_ 0.05) decreases in the amount of DNA adduct formation in heart tissue at the two highest concentrations tested. In lung tissue, mice exposed to Eclipse displayed decreases in the amount of DNA adduct formation at all three concentrations tested compared to 1R4F. However, only the mid-concentration was statistically significantly (p <_ 0.05) different (Figure 12). Figure 10. Mouse Dermal Studies/Lung DNA Adducts Eclipse vs 1R4F 50 45-a 29 Week Exposure 40-I -m-1 R4F -*-Eclipse 35-I 30-I ~n N 0 ttp:// wwsjrdiract.com/ECUsci/dna adducts.htm OD J A 05/24/2000 N T ~D
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Human Smoking Behavior Studies Page 1 of 3 B. Human Smoking Behavior Studies Human smoking behavior studies of Eclipse were conducted to compare a number of behavioral and physiological end-points in smokers when they were smoking Eclipse compared to when they were smoking their usual brands. These end-points included puffing patterns, cigarette attribute and acceptance ratings, and blood carboxyhemoglobin measurements. During the initial session, subjects smoked one of their usual brand cigarettes after reporting the number of cigarettes they had smoked before arriving. Smoking profiles were measured, and samples taken for blood carboxyhemoglobin determinations. Smokers were then sent home with a supply of Eclipse, and were instructed to smoke these exclusively for the next two weeks. The second test session was conducted (as nearly as possible) at the same time of day and the same day of the week for each subject. The same procedures were used for the second laboratory visit, except subjects smoked Eclipse, which they had been smoking for the previous two weeks. On average, smokers took significantly more puffs, closer together in time, resulting in significantly greater total puff volume when smoking Eclipse compared to when they were smoking their usual brand (see Table 15 and Figure 15). Subjects took, on average, approximately 75 seconds longer to complete the smoking of Eclipse compared to their usual brand. They did not, however, smoke more cigarettes per day. There was wide variation in carboxyhemoglobin levels when subjects smoked both their usual brand and Eclipse. Mean carboxyhemoglobin levels were statistically different (p<_ 0.05) when smokers were smoking Eclipse (8.66 %COHb) than when they were smoking their usual brands (8.10 % COHb). However, in these studies, the range of blood carboxyhemoglobin concentrations observed when smokers were smoking Eclipse was consistent with the range observed when they were smoking their usual brands of tobacco-burning cigarettes (see Figure 16 and Table 16). There was also wide variation in measures of serum nicotine for both the usual brand and Eclipse. For Eclipse, smokers had somewhat lower serum nicotine levels compared to when they were smoking their usual brand. The average peak serum nicotine concentration achieved during smoking was 36.8 ± 10.Ing/ml for usual brand and 31.8 ± 14.7 ng/ml for Eclipse. Average peak serum nicotine "rise" (change from baseline) was 14.3 ± 8.1 ng/nil for usual brand and 12.1 ± 7.7 ng/ml for Eclipse. Table 15. Puffing Behavior (Group Means) Usual Brand Eclipse umero us 12.3 21.2 a o ume m 53.1 67.0 Duration sec 1.9 1.9 n er- u n erva sec 29.2 19.7 me sec 328 405 o u o ume 640 1371 ota u ura on sec 23.3 38.0 httpJ/www.rjrdirectcom/ECLsci/human_smoking_behavior.htm 05/24/2000
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Inbslation Studies A. Inhalation Studies Page 1 of 2 In the subchronic inhalation studies, animals (mice and rats) were exposed by nose-only techniques to mainstream smoke of Eclipse or the 1R4F cigarette at concentrations of 0.16, 0.32, or 0.64 mg Wet Total Particulate Matter (WTPM) per liter for 1 hour per day for 5 days per week for 13 weeks. A third group of animals (sham-exposed) was treated identically, but with no smoke exposure. Biological endpoints included in-life observations (respiratory patterns, clinical observations, body weights) and pathology (gross changes, organ weights, organ weight ratios, and histopathology). Smoke-related changes were initially defined by comparing the changes observed in the 1R4F- and Eclipse-smoke exposed animals with the sham-exposed animals. Comparisons were then made between the two smoke-exposed groups, to quantify the incidence and severity of the changes. In general, effects observed among the animals exposed to smoke from Eclipse were fewer and less severe (in some cases, entirely absent) compared to those observed among the animals exposed to smoke from the IR4F. As shown in Table 12, rats exposed to smoke from Eclipse generally showed fewer and less severe smoke-related changes than those observed in rats exposed to smoke from the reference low "tar" cigarette. A specific example of smoke-related changes (decreased nasal epithelial hyperplasia) is in Figure 8. TABLE 12. Histopathology - Rat16 '- 1e Eclipse 1R4F as ammation, c mc active u + YPerP asra, epi e u + Goblypertrop Y sent +/- as et ce ypertroP Y Absent arynz ammatron, c omc active ~mr ar + eo ra larynx ; quamous metap asia u + Inflammation, acute um ar +/- rac ea Yperp asia, epi ei u +/- o etce s Absent +/- uug on-pigment macrop ages rmr ar + ro go pigment macrop ages sent * + • The smoke-related changes noted in this table in the animals exposed to the Eclipse cigarette or 1R4F reference cigarette were statistically significantly different (p < 0.05) from those in the sham- exposed animals (except for the changes denoted as Absent, which were not observed in the Eclipse exposed rats). a Changes denoted as + were statistically significantly different (p S 0.05) from the sham exposed group. ` Changes denoted as "+ /-" were not always observed to be statistically significantly different httpJ/www.rjrdirect.com/ECUsci/'mhalation smoke.htm 05/24/2000
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Dermal Tumor Promotion Study Page I of 2 B. Dermal Tumor Promotion Studv A dermal tumor promotion study (30-week) with the SENCAR mouse strain (a strain specifically bred for sensitivity to dermal carcinogenesis), was used to compare the tumor promoting activity of smoke condensates from Eclipse with that of a tobacco-burning reference cigarette (1 R4F). The dermal route of condensate administration was selected because it has been reported in the scientific literature (National Cancer Institute and others) to show positive results for cigarette smoke condensate, and can differentiate the tumor promoting potential of different tobacco products. Biological endpoints included survival, clinical observations, body and organ weights, tumor tracking data and histopathology. In the dennal tumor promotion studies, dorsal skin was first painted with DMBA (7,12-dimethylbenz [a]anthracene, a known tumor initiator) and then painted with 10, 20 or 40 mg applications of cigarette smoke condensate (CSC) from Eclipse or from IR4F, three times per week for 29 weeks. (There was a one week rest period between DMBA initiation and CSC dosing.) Tumor Bearing Animals The number of tumor-bearing animals (Table 13) was increased with increasing exposures to the iR4F CSC. Except for the low-dose groups (where few tumors were produced by either Eclipse or the 1R4F reference), the activity of CSC from Eclipse was significantly less than the activity of the IR4F CSC. Total Tumors Total dennal tumors (Table 13) were increased with increasing exposures to the 1R4F CSC. At all dose levels the activity of CSC from Eclipse was significantly less than the activity of 1R4F CSC. Total dermal tumors for the 3 dose groups are also represented in Figure 9. Table 13. Dermal Tumor Promotion Dose Tumor Bearing rma ota Tumors e iau Time to Onset (weeks) c pse c ipse c rpse a 1/40 6/40° 1 11'-b 27 21 M 2/40 28/40'0 11° 184°b 13 14 F1 12/40' 36/40a6 31a 244'~b 22 15 ' Statistically significantly different (p _<0.05) from DMBA initiated/Acetone promoted Control. b Statistically significantly different (p _<0.05) from DMBA initiated/Eclipse promoted group. Figure 9. Tumor Data from ECLIPSE Prototypes: Comparison of Total Tumors >ti httpJ/www.rjrdirect.com/ECUsci/dermal tumor_promotion.htm 05/24/2000
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Glossary Page l of 2 Glossary Acrolein: A volatile acrid liquid formed during incomplete combustion or pyrolysis of organic materials such as fuels, wood, synthetic polymers, food and tobacco. Acrolcin is listed as a Class C substance (possible carcinogen) by the Environmental Protection Agency (EPA). Ames Test: A study where bacteria are exposed to a substance to determine if that substance may cause genetic mutations. Positive results in an Ames Test (i.e. an increase in mutations) are an indicator of the potential for the material to cause genetic damage and possibly cancer. Analyte Concentrations: The concentration of a substance in media such as cigarette smoke. Carbon Monoxide (CO): An odorless, colorless and tasteless gas. CO is formed by incomplete combustion of carbon or organic compounds. It binds, with high affinity, to blood hemoglobin, forming carboxyhemoglobin which cannot transport oxygen. Carboxyhemoglobin (COHb): Hemoglobin in combination with carbon monoxide. COHb can not transport azygen. Cardiovascular Disease: Disease of the heart or blood vessels. Chronic bronchitis: Long-continued inflammation of one or more bronchi, often with a more or less marked tendency to recur after stages of no symptoms. It is due to repeated attacks of acute bronchitis or to chronic general diseases. Cytotozicity: Cellular injury or cellular death. DNA: Deoxydbonucleic acid. DNA is the primary base material that makes up the genetic information in cells. DNA Adducts: The resulting compound formed when a substance binds to DNA. DNA adducts are often used as an indicator of exposure to mutagens/carcinogens. Emphysema: A disease in which the walls of the air sacs (alveoli) are weakened or destroyed. Emphysema results in lungs that are bigger than normal, cannot empty air normally and are unable to transfer oxygen efficiently into the bloodstream. Environmental Tobacco Smoke: The aged and diluted smoke that comes off the lit end of the cigarette plus the smoke exhaled by the smoker. Exhaled Mainstream Smoke: The smoke that a smoker exhales. FTC: Federal Trade Commission. The FTC enforces a variety of federdl antitrust and consumer protection laws including those governing the regulation of cigarettes. Furfaral: A colorless, transparent, oily liquid with the characteristic odor of bitter almonds. Furfiaral is formed from the acid hydrolysis or heating of polysaccharides which contain pentose and hexose ~ ents and has been detected in a broad range of fruits and fruit juices, wines, whiskeys, coffee Gas Chromatography: An analytical method that separates components of a vaporized solution by passing the vapor along an absorbent column. The separation allows for the determination what N components make up the solution and how much of each is present. a CO `2 ~ httpJ/www.rjrdirect.conJEClJsci/glossary.htm 05/24/2000 ~ co
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(ilossary Page 2 of 2 Glycerin: A clear, colorless, syrupy liquid that occurs extensively in nature and is naturally found in the cells of plants, animals and humans. It is obtained as a by-product of soap, by carbohydrate fermentation, and by propylene synthesis. Glycerin is used as a solvent, humectant and vehicle in various pharmaceutical, cosmetic and food products. Mass Spectrometry: An analytical technique method that allows for the identification of components of a mixture by separating the molecules by their mass. Mntagen: Material capable of capable of causing a change in the genetic information stored in the DNA of living cells. Nicotine: A colorless, soluble, fluid organic base with a bitter odor and a burning taste obtained from tobacco or produced synthetically. Respiratory Tract: The organs that are involved in breathing. These include the nose, throat, larynx, trachea, bronchi, and lungs. RSP: Respirable suspended particles - particles of sufficiently small size that they can be inhaled into the deep lung. Sidestream Smoke: The aged and diluted smoke that comes off the ht end of the cigarette Snbcbronic Inhalation Studies: Studies of the toxicity of chemicals administered via the respiratory tract that lasts for an extended period of time. Subchronic studies involve exposure to quantities of a toxicant that do not usually cause any evident acute toxiciryA 90-day period is typical and considered appropriate in mammalian inhalatioi7 studies. Tar. The total particulate matter in cigarette smoke, minus the nicotine and water, that is retained on a Cambridge filter pad when smoke passes through it. Toxicity: The quality of being poisonous, especially related to the dose of toxicant at which the adverse effects occur. Urine Mutagenicity: A method by which human urine is evaluated in an Ames assay (see above).The presence of mutagenic material, as indicated by in bacteria mutations, can be used as an indicator for recent exposures to mutagenic compounds. httpJ/www.rjrdirect.com/ECI/sci/glossary.htm 05/24/2000
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things you should know. We don't claim that Eclipse presents less risk of cardiovascular disease or complications with pregnancy. There is some evidence suggesting that, compared to other cigarettes, Eclipse may pose less nsk to smokers of developing cardiovaseular disease. However, other evidence suggests that smokers who already have this disease may further increase the'v health risk by switching to Eclipse. As everyone knows, allpg arettes pose health risks, induding Eclipse. Consult your doctor with questions about your heaAh. Eclipse Is Not An Altemative To Quitting Eclipse is not tor people who want to avoid the risks of smoking. No cigarette is without risk. And it is not for smokers who want to quiL htlpJ/www.rjrdirect.com/ECUsmokers/coasu.htm 04n4/200o
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~xs a inw~ aoe+m. n possw h.na oraiwy~nc K«namiw +y«~ rcr rkpych m Cuar, N~ionY Ta.ioob~J progaR aM FiwFmmnwN maeuien Ay ene} Aad.n ws no BMeK p IM doaead cumpands m.nv.d h ENp» aeokS. ane pu W aq shora an Yia.au.-BmA ae anoke oatld.a The concept is simple. Heating instead of burning. The smoke from Eclipse contains far less of many of the compounds found in cigarette smoke that are believed to contn'bute to the risk of cancer and certain other illnesses. HoMI1 The concept is simpte. Eclipse primanly heats tobacco rather than twrning iL Heated air then releases the smoke and flavor as you puff. Smoke you can see. and flavor you can taste. The smoke irom Ecipse • FTC tu m:ws alycerin Eclipse Makes A Smoker's Life Easier Wdh Eclipse you can enjoy smoking without a lot of the hassle. • Eclipse reduces second-hand smoke by 80%. • No ingering odor on your hair, obthes, home or car. • No rnessy ashes. • No visible stains on wa9s. glass, or draperies. Eclipse Isn't Perfect Eclipse isn't perfect - irs s6A a cigarette, so there are a few more things you should know. WJ/www.rjrdirect.com/ECLsmokers/consahtm o4/24121X)0
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'3r 817iCi4ifi? CO-r~^t hop GCI/PSC3 Quittieg Snwking Privacy St.temmt About RJRT Virtnsl Medu Center Cuetorner se(Y0.0 Contact U-- ~ .-- .:Fu.Srnok~s ~a-mc I. . Out Q :J SORGEOM 6EAEIGCS N'1AMIX& Gl.lfaa Smi:, Ib.6remit SelhRes Saiaa A'do b Ta. Maa Far Heanhcae PRdessiorols Fl.e.l Th.FeYp.Cloareltv I TA.fsnp.e.F..p}rl..e.! 1riRS.elanSsy._L~Indluelbr.: THE BEST CHOICE FOR SMOKERS WHO WORRY ABOUT THEIR HEALTH IS TO QUIT. OraniewforSmok.rs < Feedbxt FAO .$illif7ct(orl (`itNr7111qd .a ECLIPSE IS THE NEXT BEST CHOICE. Eclipse is a new cigarette from R.J. Reynolds Tobacco Company that may present less risk of certain smoking related diseases. Extensive scientific studies show that compared to other cigarettes: . Eclipse may present less risk of cancer. . Eclipse produces less inflammation in the respiratory system, which suggests lower risk of chronic bronchitis and possibly even emphysema. WHY THERE'S NO GIGARETTE LIKE ECLIPSE Tobacco Burned CObPARtdO SM110KE COhPOrfNf4 Ter• erd Kcdine 47 mg M wder Ird Gyarit 0.8 mp (swroM smoko comporwnKS) Cercinogern° 0.68 m 0./8 m SecorWheM mrokC" Carbon hbnoride 5.4 mg Eclipse 15 mg 0.8 mg 3.3 mg - 0.13 mg 10.03 mOhnz 6.7mg Difference !T%tess i] !G less 313% more M'A~ less 82% tess 17% more A Ment Iluafght rIU tested as the qpical Jo+igM- ' FTC 1r' mirws yyc.n~ 'Skdw FTC cmdmms, R.IRT meaurM 14 connorC in tiuaW4 tmo4. Mat am.ar an ar a met* d tlu /nla.iw httpJhvww.rjrdirect.com/ECllsmokers/consahtm g/m' o4a4nooo 41 m 00

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