Tobacco Documents Online

CURRENT AWARENESS BULLETIN Y ~./TOBACCO COMPANY RESEARCH LIBRARY Vol. 24, No. 6, June 3, 1994

TABLE OF CONTENTS I. NEWS BRIEFS .................................. 619-646 II. ABSTRACTS FROM CURRENT LITERATURE ........... 647-649 III. BOOKS RECENTLY RECEIVED ..................... 650-651 IV. RECENTLY PUBLISHED .............................. 652 V. ANALYSIS OF PAPER OR FIBER .................... 653-654 VI. ANALYSIS OF PESTICIDES ........................ 655-656 VII. ANALYSIS OF TOBACCO ............................. 657 Vlii. ANALYTICAL CHEMISTRY GENERAL ................. 658-665 IX. BIOLOGICAL EFFECT OF ADDITIVES .................... 666 X. ENVIRONMENTAL TOBACCO SMOKE ................ 667-670 XI. FLAVORS ...................................... 671-675 XII. FOOD ADDITIVES ............................... 676-679 XIII. MEDICAL ARTICLES ON TOBACCO .................. 680-689 , XIV. NITROSAMINES ................................. 690-696 XV. STORED PRODUCTS ................................ 697 XVI. TOBACCO AND TOBACCO SMOKE .................. 698-707 XVII. TOBACCO PHARMACOLOGY ....................... 708-709 EDITORIAL STAFF: LARRY SKLADANOWSKI Library Supervisor Ext. 6896 STARR PENNINGTON Library Assistant Ext 6894 MARIA MILLER Research Librarian Ext. 6895 ANN STRINGFIELD Information Specialist Ext. 6913 GENNIE GREENE Information Specialist Ext 6897 FOR COMPANY USE ONLY Vol. 24, No. 6, June 3, 1994

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NEWSBRIIEFS Tobacco International Apr 15, 1994, p. 11 WHERE THERE'S SMOKE.. ATLANTA, GEORGIA - Indoor air pollution may be the buzzword in some circles, but baseball fans in Atlanta are at a loss to explain a new ban on smoking at the open-air Atianta-Fulton County Stadium, one of numerous arenas that have adopted similar measures. Spectators will now have to go nine innings smoke-free or find one of a few designated smoking zones, thanks to the new policy. "It's an outdoor stadium, so I don't see what the big deal is," said one fan. -"The no smoking policy applies to seating areas, rest rooms, and concourses, but not to the team clubhouse or dugouts: The city's baseball team surveyed fans and found that 62% preferred restrictions on smoking in seating areas. But the survey found fans did not want an outright ban. Despite the tobacco restrictions, two MARLBORO billboards are inside the stadium:'This makes paying customers more uncomfortab(e-and feel unwelcome," said Tom. Lauria of the Tobacco Institute°''Espeitally with the outdoor stadiums, there is no logical explan_ationfortW'' Science News Vol.145,1994, p. 314 THE GREAT NICOTINE DEBATE: ARE CIGARETTE RECIPES 'COOKED' TO KEEP SMOKERS HOOKED? F ood and Drug Administration Commissioner David A. Kessler is- sued what amounted to a battle cr~- in February when he reported indica- tions that cigarette manufacturers fortih• low-tar brands with nicotine. Why would they do this? To ensure that all the nation's 50 million smokers maintain their addiction to tobacco. he said. If true. it means that the tobacco indus- try is deliberately fostering a physical need for a product that kills 434.000 Americans each year, according to the U.S. Surgeon General's latest estimates. Indeed, smoking-related illnesses ac- counted for nearfy one in five U.S. deaths in 1990-most of them from heart disease and cancer-states a report in the March 31 NEW ENGLAND JOURNAL OF MEDICINE (NEJM). An April 7 follow-up on ci,aa- rettes' economic toll by the same Univer- sity of Colorado School of Medicine tean-. estimated that a smoker's average life- time medical costs exceed a nonsmoker's by $6.000. ln response. the House Subcommittee on Health and the Environment cor:- vened a trio of hearings in March anz April. and more are planned. Kessler an _ Vol. 24, No. 6, June 3, 1994 several congressmen also have renewec calls for greater regulation of tobacco - perhaps as a drug - or for nicotinefre= cigarettes. Arguing that it does not add nicotine tr cigarettes, the tobacco industry mair.- tains that these recent salvos constitute nothing less than a move to prohibit th= sale and use of cigarettes. S ince cigarette companies have the technical know-how to eliminate nicotine, why don't they? It pro- vides "an important flavor to me:' ex- plains Alexander W. Spears. chief operat- ing officer of the New York City-based Lorillard. But other. nonaddictive compounds could provide the same biting. acrid flavor. so whv not use a substitute and "take the nicotine out of the product." w_ nar asked. "W hv should we take the nicotine out?" Spears responded. "It is integral to the Droduct" Waxman proposes either requiring manufacturers to take nicotine out or 1vEWSBRIEFs putting a label on cigarette packs warning against nicotine's addictive properties - something he says the industrv has suc- cessfully lobbied against in the past. New legislation would also step up policing of cigarette sales to minors. Figures from the Centers for Disease Control and Prevention indicate that about 75 percent of smokers become addicted by age 18- before it is even legal for most of them to buy tobacco products. Contending that cigarettes are "the single most dangerous consumer product ever sold:' Waxman argues that such moves would constitute pretty tame med- icine. _ s19

NEWSBRIEFS Science News Val.145,1994, p. 308 NICOTINE - CHEWING ON IT During the past few months. events have focused a spotlight on the nicotine in cigarettes (see p. 314). But this poten- tially addictive drug natilrally laces smokeless tobaccos. too. Moreover. un- like cigarettes, snuff and chewing to- bacco labels do not disclose the amount of nicotine these products contain. Arguing that consumers have a right to such information, three researchers with the University of Alabama at Bir- mingham have just analyzed and pub- lished for the first time the nicotine content - by brand - of 11 of these smokeless products. They include the most popular moist snuffs as well as loose-leaf chewing and "plug" tobaccos. From a health perspective. nicotine intake is important because "it drives tobacco usage patterns," says oral pa- thologist Brad Rodu, who headed the study. And research has linked smoke- less tobacco not only to leukoplakia - oral calfouses-but also to the develop- ment of oral cancers. Five of the six analyzed snuffs led the list - carrying between 2.1 and 3.35 percent nicotine by weight. Manufac- turers tend to sweeten chewing to- baccos with sugar, which can dilute their nicotine content. notes Rodu. In- deed, the two plug tobaccos weighed in with a little more than 1.6 percent nicotineeach; thethree loose-leaf prod- ucts had 0.77 to 1.1 percent. Ironically, the product with the least amount of nicotine was a moist snuff: Conwood Co.'s Hawken brand pos- sessed just 0.59 percent of the drug by weight, the Birmingham team reports in the May.IOURNAL OF THE AMERICAN DEN- TAL ASSOCIATION. Studies show that smokeless-tobacco users subconsciously modulate how they use these products - such as by holding one wad in the cheek for 4 hours instead of replacing it every 30 min- utes - to achieve a relatively constant concentration of nicotine in the blood. In fact, Rodu notes. these tobacco users often obtain as much nicotine from their "habit" as do cigarette smokers. -J. Raloff Vol. 24, No. 6, June 3. 1994 Chemical & Engineering News May 16,1994, p. 40 PESTICIDE MAKERS MAKING HEADWAY WITH RISK ASSESSMENT ARGUMENT F or several years, representatives of agricultural chemical makers who tried to explain the intricacies of risk assessment to members of Congress met with blank stares. Persistence seems to have paid off, however, because Con- gress is beginning to give serious consid- eration to the usefulness of risk assess- ment in setting regulatory priorities and formulating final regulations on use of chemicals. More acceptance of risk assessment will help pesticide makers, whose prod- ucts for years have been the focus of legislative and regulatory activity. At a meeting of the National Agricultural Chemicals Assoaatfon (NACA) in Wash- ington, D.C, late last month, representa- tives from companies all over the coun- try were told how this shift in policy and how other pesticide issues will be han- dled by the government in the foresee- able future. Overall, there seems to be some movement toward softening the previ- ous hard-line stance on the toxicity of agricultural chemicals. The Adminis- tration's recent proposals to i'evise the Federal Insecticide, Fungicide & Ro- denticide Act (FIFRA) include provi- sions that would slightly modify the Delaney amendment, which bans from processed food any substance shown to be carcinogenic to humans or animals (C&EN, May 2, page 6). Legislation that would give the Environmental Protection Agency Cabinet-level status is tied up in the House because of insis- tence that the agency be required to perform cost-benefit analyses on its regulations. And EPA is at least talking about changing its guidelines on carci- nogecucity to allow wider use of avail- able scientific information. The result of this interest is that sev- eral bills have been introduced in the House and Senate that would put risk assessments done by EPA and the Oc- cupational Safety & Health Adminis- tration and other agencies on a more formal legal basis. But the confusion surrounding risk assessment is likely to keep any of these from being passed during this Congress.

NEWSBRIEFS Chemical & Engineering News May 16,1994, p. 47 COMPLEX REMOVES NITRIC OXIDE FROM COMBUSTION FLUE GAS Researchers at Lawrence Berkelev Laboratory have found that nitric oxide can be removed from flue gases by absorp- tion to an iron complex and subsequent reduction to ammo- nia. Combustion of fossil fuels generates sulfur dioxide and nitrogen oxide pollutants, which cause acid rain and urban smog. Existing flue-gas desulturization scrubbers use wet limestone processes that are effective at controlling sulfur dioxide emissions but incapable of removing water- insoluble nitric oxide. Hence, nitric oxide emissions current- ly are controlled in a separate postcombustion process. In an effort to side-step the need for this separate step, Eric K. Pham and Shih-Ger Chang of the Energy & Environment Division of LBL have developed an iron(II) thiochelate com- plex that absorbs nitric oxide and forms water-soluble iron ritrosyl complexes [Nature, 369,139 (1994)]. The bound nitric oxide can then be converted to ammonia by electrochemical reduction, regenerating the active iron(II) catalyst for contin- ued nitric oxide capture. ''Cur results suggest that this pro- cess can be readily integrated into existing wet limestone scrubbers for the simultaneous removal of sulfur dioxide and [nitric oxide]; ' the researchers say. Chemical & Engineering News May 16,1994, p. 41 PUBLIC PERCEPTION MAY NOT BE AN ACCURATE GAUGE OF RISKS "As a nation, we suffer from a syn- drome of paranoia and of neglect. We are frightened of every tiny concentra- tion of chemicals in our food, but tol- erant of major killers in our society." This was the message John D. Gra- ham, director of the Harvard Center for Risk Analysis, had for the partici- pants at the spring conference of the National Agricultural Chemicals As- sociation last month. Graham's center has done many in-depth surveys of public opinion as it relates to risk. Graham's studies tell him that the U.S. public wants the government to do more risk assessments and more comparisons of costs and benefits. Survevs of U.S. citizens find 83% agreeing that the government should use risk assessments to identify seri- ous problems. "The only town [in which] I meet resistance to risk based priority setting is in Washington, D.C.," he says. Still, people believe that the num- ber of unseen environmental risks is increasing. "Public perception of envi- ronmental risk is particularly impor- tant Asked if environmental quality has gotten worse over the past 20 years, most respondents will say'yes; " Graham says. "If they are asked what the source of their most serious health risk is, most think that chemicals in the envinanment are more of a risk than are personal habits." This is de- spite research that shows that 85% of premature deaths are caused by life- style situations. Graham makes his point by ana- lyzing deaths and injuries from trau- ma-accidents and violence. "All of the deaths due to trauma injury cost the economy as much as cancer and heart disease," " Graham says. Yet al- most no research funds are directed toward reducing trauma injuries. He thinks that a little money invested in this area would reap bigger gains in health than spending in areas that AtEWSPRiEFs the public considers more important. Rather than requiring municipali- ties and companies to spend millions of dollars for marginal environmen- tal benefits, Graham advocates that communities be given money to spend on more pressing problems. Some 'of the investments these com- munities might choose include home- less shelters, drug and alcohol treat- ment facilities, cancer screening pro- grams, prenatal care programs, violence reduction seminars, even painting clearer lines down the centers of roads to reduce the number of traffic accidents. While not saying that real environ- mental risks don't still exist, Graham urges the U.S. to change its percep- tions and move on to other problems. "This country cannot continue to spend big money on very marginal risks while ignoring other enonnous health risks in our society," he concludes. Vol. 24. No. 6. June 3. 1994

NEWSBRIEFS New York Times May 16,1994, p. A1, A12 PHILIP MORRIS ON OFFENSIVE IN CALIFORNIA LOS ANGELES. May I i - For the last five years, California has been the national leader in the fight against smoking. using a combination of restrictions, taxes and advertising campaigns to reduce cigarette con- sumption by almost 30 percent. Now, with smoking higher than ever on the nation's health agenda and other states beginning to look to California as the model for ways to combat it, the country's largest to- bacco company, Philip Morris, has begun an all-out counterattack in- tended to slow and then roll back the nationwide drive toward more strin- gent smoking laws. Through the help of a political con- sulting firm and at a cost of more than $500,000, the company has used street canvassers and phone banks to gather enough petition signatures throughout the state to place a strong proposal favoring smoking on the bal- lot in November. Generally speaking, the proposal would replace some 270 stringent lo- cally enacted smoking laws in Calf- fornia with a single, less stringent statewide law. More to the point, it would let business and building own- ers rather than government officials decide where to permit smoking, so long as it was in specifically designat- ea. weli-ventilated areas. -Philip Morris's campaign is be- lieved to be the first time that any area of the cigarette industry ha= taken a proposal in favor of smokinr to voters statewide. And the compamts prepared to spend a much more on its-efforts, but it will not disclose how r>Auch. -:`All we seek is uniformity and to provide fairness for both smokers and nonsmokers," said Lee Stitzen- lierger. the consultant hired by Philip Morns to run its campaign in Califor- nia. "We sav let businesses and build- ing owners decide whether they want to~allow smoking and whether that will bring in or run off customers. - "A lot of people, especially restau- rant owners, tell us smoking bans have cost them 20 percent or more of t#teir business if they're in a locality that forbids smoking and the next iown over doesn't forbid.it." bpponents of smoking contend the effort has nothing to do with fairness and uniformity and everything to do with selling cigarettes and rolling back the anti-smoking movement. Vol. 24, No. 6, June 3. 1994 Tl+ey also contend that the cam- p'aisn's supporters misled many, of ttte 607.000 people who signed the petttton sheets necessary to qualify the proposal for the November ballot. : ="Philip Morris has decided to make California the front line of the stnoktng war," said Julia Carol, a director of Americans For Non- Smokers' Rights, a national group based in Berkle,y, Calif. "They figure if:thev can win here, they can win pttywiiere. And to do it, they've passed around a pro-smoking petition th'at` they deliberately mislabeled a 'tobacco control' act. Control?" State election officials have agreed to investigate whether the petition campaign was properly conducted. "We've had hundreds of calls and letters complaining about the tactic," said-Melissa Warren, Chief Assistant Secretary of State. "They could jeop- ardize the qualification of the meas- ure for the ballot if we find there's sufficient cause." Campaign supporters say their pe- tition pitch was not misleading. .Keep in mind that this intitiative would extend smoking regulations to hundreds of places that currently don't have them." said Mr. Stttzen- berger. "We're also proposing strict- er rules on use of tobacco by youths. And we're not proposing :o change anything about smoking in public places." Whatever the case. the Philip Mor- ris counterattack is so high-profile, sc, fraught with the possibility of stun- ning public victory or defeat, that the rest of the tobacco industry. which has typically preterred to quietly push bills favoring smoking in state legislatures, has chosen to let Philip Morris proceed alone. At State Capital Level "Philip Morris briefed us and ol- fered us an option to be a part of it but we decided not to," said Maura Ellis, a spokeswoman for R. J. Reynolds, another leading American tobacco company. "We felt we had made our views known in various other ways. We may join in the future. Never say never." in most states, the tobacco industr}' concentrates most of its legal efforts at the capital, and in many capitals, including those of California and New York, few industries spend more heavily or freely. Company lobbyists tend to work in concert and lately they have been pushing hard for weak statewide smoking restrictions, the NEWSBRIF.liS intent being, as with the Philip Morris ballot initiative, to undercut patch- works of stronger, locally enacted restrictions. But the industry has made little headway with the legislative ap- proach, despite an especially deter- mined effort in Sacramento, the Cali- fornia capital, and in the meantime more and more cities and towns across the country are passing smok- ing ordinances. In fact, Philip Morris officials say it was just such lack of success in the state legislature that led them to go the initiative routc here. I he officials argue that they have a reasonable chance of success with the ballot initiative because polls indi- cate that few Antcricans favor a total ban on smoking and that many favor permitting smoking in designated, ,.vell-ventilated areas. If successful, ihe initiative would drastically undercut the tough smok- ing bans enacted in recent years by the 270 California communities, in- cluding Los Angeles and San Francis- co. It would send a message that if smoking bans can be overturned and weakened in the nation's most popu- lous and most virulently anti-smok- ing state, they can probably be over- turned and weakened in just about attv nthrr slate. Other States Looking Encouraged by California's suc- cess thus far in controlling tobacco, other states have begun taking a close Icmk at its model. especialh• the state tax and anti-smoking advertis- ing programs. Among them are Ari- zorrt. Arkansas, Colorado, Massachu- setts, Oregon and Virginia. A victory here by Philip Morris would also probably have major im- pact in Washington. Over the last few months, Congress has begun taking a more active interest in the smoking issue and the way the tobacco indus- try operates and is regulated. Many of California's smoking bans prohibit or strictly limit smoking in offices, restaurants and public build- ings. For example, no smoking is permitted in indoor restaurants in Los Angeles, and in San Francisco it is difficult to find an indoor smoking area other than in the home. Unlike in most other states, tobac- co companies have directly chal- lenged sonie local smoking regula- tions in California, including the Los Angeles and San Francisco ordi- nances. Thus far, the companies have enjoyed minimal success.

NEWSBRIEFS For the most part, California is the national leader when it comes to con- trolling smoking because of passage in 1988 of another ballot initiative - one that imposed higher taxes on tobacco products and mandated that some of the increased revenue be handed over to communites for use in anti-smoking campaigns. Since then, numerous anti-smoking community groups have sprung up and manv have strongly backed strict local smoking regulations. At the same time, many have also begun extensive anti-smoking advertising and education campaigns, often aim- ing their pitches at young people. Effect of Campai}•n The result? Tobacco consumption is down 30 percent in California, comoared with 10 percent in most other states, ac- cording to studies by the University of California. Further, the smoking rate among teen-agers hnrv is lev,rl- ing off whereas it continues to risv in most other states. Over the last several years, some of the increased revenue produced by the higher tobacco tax has been di- verted by the state from the tobacco education and advertising programs to various general health programs run by the state. State officials argue that this is a legitimate use of the money under the 1988 initiative. But anti-smoking groups contend that the officials are reacting to pressure from the tobacco industry, and they have filed suit to halt the diversions. "The industry never gives up," said Ms. Carol of Americans for Non- Smoker's Rights, "and that's our challenge. If we ever cave, especially in California, it won't be long before states with a lot less clout begin to crumble. Then we'll loose this war." news media, are primarily memos in which executives discuss whether to release some of their studies cr withhold them to protect business interests. Some portray soul-searching by company officials on how to pro- ceed. But a lengthy and bluntly worded memo written in 1963 by Addison Yeaman, then the corpora- tion's general counsel, said: "We are, then, in the business of selling nicotine, an addictive drug." The memo added that cigarettes help ease stress and prevent weight gain but also cause or predispose smokers to lung cancer, contribute to heart disease and "may well be truly causative in emphysema, etc., etc." Brown & Williamson says the documents were stolen by a dis- gruntled former employee who is trying to sabotage the LouisvillF, Ky., company, and that they have been taken out of context. The company contends Rep. Henry Waxman, D-Calif., pos- sesses the original stolen docu- ments and won't let the company see them so it can decide whether to respond to growing news media reports about them. On Monday, Jefferson County, Ky., Circuit Court Judge Thomas Wine ordered Waxman, fellow smoking opponent Rep. Ron Wy- den, D-Ore., and reporters posses- sing copies of the documents to let the company view them. Brown & Williamson spokesman Tom Fitzgerald said subpoenas based on the court order would reach Waxman and others by noon today. Waxman aides were consulting with lawyers about the court order, and had no immediate comment. Waxman, whose House Energy and Commerce health subcommit- tee has spearheaded recent attacks on the tobacco industry, possesses boxes of industry documents indi- cating what the companies knew about their products and when. Greensboro News & Record 17-May-1994 , p. B5 RJR EXEC RELINQUISHES CIGARETTE MANAGEMENT Greensboro News & Record 17-May-1994 , p. B4 TOBACCO FIRM WINS LOOK AT LEAKED MEMO WASHINGTON - A tobacco company won court permission Monday to subpoena two promi- nent congressmen and reporters in its defense against charges that cig- arette makers conspired against Americans' health. At issue are internal documents indicating that executives at Brown & Williamson Tobacco Corp. knew 30 years ago that smoking was dan- gerous and nicotine was addictive, and that they developed but shelved a safer cigarette. The documents, leaked to the NEWSBRIEES James W. Johnston, chairman and chief executive of R.J. Reyn- olds Tobacco in Winston-Salem, will turn over daily management of the company's domestic cigarette operations to Andrew J. Schindler. "Turning over the day-to-day management of the domestic busi- ness to Andy will enable me to focus on strategies for aggressively building our business around the world as well as external strategy development," Johnson said. Schindler, 49, joined R.J. Reyn- olds Industries in 1974 and most recently was executive vice presi- dent of operations. Wall Street Journal May 17,1994, p. A14 EX-ATTORNEY GENERAL HELPS TOBACCO COMPANY'S EFFORT LOUISVII.LE, Ky.-Former Attorney General Griffin Bell is helping Brown & Williamson Tobacco Corp. control the damage from a trove of confidential company documents that has been circu- lated to government officials, antito- bacco activists and the news media. Brown & Williamson, a unit of B.A.T Industries PLC, said a state judge in Kentucky issued a court order requiring Henry A. Waxman, (D., Calif.) to allow B&W to review company documents in his possession. Rep. Waxman has been chairing hearings investigating the to- bacco industry. B&W said the court order would also extend to Congressman Ron Wyden, (D., Ore.) and some news organizations. B&W said the documents were stolen from its law firm by a former paralegal. The documents include a 31-year-old memo in which a B&W executive dis- cusses the addictive properties of nico- tine. They also depict internal discus- sions about producing safer cigarettes. Mr. Bell said B&W's position "should not be based on isolated remarks made by individuals in 30-year-old docu- ments." Vol. 24, No. 6, June 3. 1994

RIEFS NEWSB Wall Street Journal May 17, 1994 , p. A16 B.A.T. INTERNATIONAL TO MAKE $200 MILLION OUTLAY IN UZBEKISTAN LONDON - British tobacco company B.A.T lndustries PLC. making its bigges; investment vet in the former Soviet blo1-. said it will spend S200 million to modernize and buy control of the state tobacco-pro:•- essing industry in Uzbekistan. The central Asian republic is a big tobacco growing and smoking zone, but it exports most of its tobacco to other former Soviet republics where it's rolled and re- turned for smoking. The B.A.T agreement is intended to reverse that trend, bolster- ing local cigarette production against the imports that dominate the market. The Uzbek investment confirms B.A.T's role as one of the industry's most aggressive international investors, follow- ing its $1 billion purchase last month of the tobacco business of American Brands Inc. In the East, it has invested about $35 million in a Ukrainian cigarette factory and S30 million for one in Hungary. The company also is discussing possible invest- ments in Russia, Kyrgyzstan, Belarus, Moldova and Poland, a B.A.T spokesman said. The Uzbek deal - following a similar, S200 million investment announced late last year in Kazakhstan by Philip Morris Cos. - underscores how eagerly the West- ern tobacco industry is rushing into the East these days. After China and the U.S., the former Soviet Union is the world's biggest ciga- rette market and the region has little of the health-awareness that is currently damping tobacco demand in the West. Many Western public-health authorities have decried the industr,v's eastward push. Defending the investment from what he called "the antismoking point of view," the B.A.T spokesman said: "It's hardly as if we are introducing the habit of smoking cigarettes in these places. But what the consumers there would like to have is high-quality cigarettes." Wall Street Journal May 17, 1994, p. B8 AT THE CHECKOUT Fastest declining product categories' based on super- market sales during the 12 weeks ended March 27 DrEWSBRIEFs Vol. 24. No. 6, June 3. 1994 - ~ 24

NEWSBRIEFS New York Times May 18, 1994 , p. A18 CIGARETTE MAKER TAKES THE OFFENSE ON CAPITOL HILL WASHINGTON. Mav 17, - Tne po- litical skirmish between touacco comaanies and tneir Capitol Hiit cr:; tcs escalated tooav as a witness at a House hearing accused a cigarette maker of trying to stifle his testtmO- ny, and the same company suopoe- naed six news reporters and two members of the House. Both actions arose from growing efforts by the company, the Brown & Williamson Tobacco Corporation, to deal with the public disclosure of in- ternal documents on the hazards of cigarette smoking that the company said were stolen from it. in the first instance, the Carter Administration's Health Secretary, Joseph A. Califano Jr., said in House testimony that Brown & Williamson tried to silence him by sending him a letter on Monday suggesting that any testimony mentioning the internal documents might violate a restrain- ing order issued in January by a county judge in Louisville, Ky. Mr. Califano, a lawyer, ignored the warning and spoke today at length about the documents, some of which showed that company officials chose to conceal internal • evidence in the 1960's and 1970's that cigarettes were addictive. The documents have re- cently been cited in articles in The New York Times and reports by oth- er news organizations. Mr. Califano told the health and environment suocommittee of the House Energy and Commerce Com- mittee that he would 'nave sought u.• regulate cigarettes as an addictive drug when he was Secretary had he known of the company's conclustons. And he called the company's letter to him on Monday "ludicrous." `Attempt to Intimidate' "I am appalled someone woulo send me something like this," Mr. Calitano said, referring to the letter "it is a blatant attempt to tnumtdate me and scare me oft from testitytng here today. I will not be intimidated." Brown & Williamson later issued a statement expressing surprise at Mr Califano's remarks and accusing him of exaggerating for political etfect the company's actions. But tne comnanv•s Qrave view (,i tne ntsciosur, ot the documents wa_ unaerscored later in tne aav, wnen i~ Utstrtct of Columbia murnctoal cou- tssued suoooenas to tne six renorter: ano the two Kenresentarnves. henr•, waxman ot Cantornta and Ron W\ :• aen ol uregon. both Democra:s. I ne remainina suopoenas were issued tc, a renorter in the Washtneton bureatu of Tne New York T tmes. Philip J. Hiits. and to Jonn Schwartz of The Vol. 24, No. 6, ,iune 3. 1994 Washington Post. Doug Levy of USA Todav. Claudia MacLechlan of th! National Law daurnul. Linda liougla~ of CBS News and Ricnard Harris oi National Public Radio. Tne subooenas ordered all eight people to orovide Brown & William- son witn any of its confidential docu- ments in their oossesston. In tne subpoenas, Brown & Wil- liamson did not seek to seize the documents permanently, but only to make copies of them. Tne company's apparent intention is to determine what documents have been given to lawmakers and reporters. to make it easier for the company to determine who provided them. Focus on Law Clerk The companv-s suspects include a former clerk at Brown & William- son's Louisville law firm, Merrell Williams, who company officials have accused of illegally making pho- tocopies of confidential papers in the law firm's files. Mr. Williams sued the company last year, claiming heart damage. caused by 29 years of smoking. Brown & Williamson has sued Mr. Williams, too, charging him with; stealing the documents, but company officials said he did not appear in' Louisville for a court-approved depo- sition. A company spokesman. Joel Helewicz, satd toda}•: "Those oocu-j ments, we believe, are stolen docu-; ments, stolen by a former law firm paralegal. Those documents are cov- ered by attorney-cltent privilege and a court iniunction." Mr. Waxman, the chairman of the health subcommittee, and Mr. Wyden said today that they would ignore the subpoenas. A lawyer for The Times, Adam Liptak, said the rewspaper would resist the subpoenas in court. "They seek unpublished iniorma- tion, gathered in the course of jour- naltstic activities, as well as materi- als that may tend to identity a confi- dential source," Mr. Ltptak said. "Brown & Williamson is not entitled to this tntormation under the shield laws and the First Amenoment." Constitutional Protection Tne general counsel for the House of Representatives, Thomas Spulak, said members were generally pro- tected by the Constitution's speech- and-denate provision, which exempts their official actions from outside le- gal action. The Supreme Court has extended that shield to Congressional committees. Mr. Spulak said, and the NEWSBRIEFS House will probably argue that as a result the subpoenas have no legal force. Mr. Wvaen called his subpoena "lit- tle more than an attempt to divert attention" from the damning nature of the documents. "The Health and Environmental Subcommittee, on which I serve, has been engaged in a lawful and tmpor- tant investigation into the actions of the tobacco industry," he said. "No one, not even the tobacco companies, can interfere with that." Today's House hearing was calle: to review a sheaf of documents tha: Brown & Williamson and other tobac- co companies had furnished at the committee's request. But Brown L Williamson requested a delay in its appearance, and Mr. Califano, nov, president of Columbia University : Center on Addiction and Substance Abuse, was the only witness. Mr. Califano said he had spoken to President Jtmmv Carter and tormer Surgeon General Julius Richmond in recent days anout the findings d!s- closed in the Brown & Wilitamson documents. 'Had We Known' "We all agreed to this," ne said. "Had we known then what the tobac- co companies knew, and had we been privy to their research on the addic- tive nature of nicotine and their abili- ty to manipulate the amount of mco- tine in cigarettes, the 1979 Surgeon General's report would have found cigarettes addictive, and we would nave moved to regulate them." The Surgeon General did not ee- ciare cigarettes addictive until 190~., and the Food and Drug Admtntstra- tton, which regulates addictive drugs, has not ruled that they fall within its jurisdiction. Brown & Williamson sought to counter the disclosures of its re- search today by releasing edited summaries of four other internal studies that the company said had reached "no conclusion" that nti;otine is addictive. The summaries, dating to the 1960's. nevertheless assumed that nicotine was addictive but added that the means by which it became addic- tive was not clear. They also stated that animals developed a toierance to ntcottne. a significant sign ol its ao- dicuve properties. "Present results offer no conclu- stve evidence tor am parucutar mechantsm involved in tolerance to nicotine, nor do they indicate a leaa to [he phenomenon of addiction." said ane summary, entitled "The Fate cf Nicotine in the Body." "We believe that both tolerance and addiction are intimately connected. and that tt would be most useful to mvesttgate [he two phenomena .... in target or- aans of the central nervous system."

NEWSBRIEFS New York Times May 18,1994, p. A22 MEDICARE'S BIG CIGARETTE BURN Smoking, as its adhei ents like to point out, is a private choice. But it is also a choice with public consequences. Just how extraordinary those conse- quences are is evident in a report issued this week by Joseph A. Califano Jr., head of Columbia Univer- sity's Center on Addiction and Substance Abuse. Out of $87 billion spent by Medicare for inpa- uc:nt hospital care this year, at least $20 billion is due to substance abuse. Drug abuse accounts for 3 percent; alcohol abuse, 17 percent; and smoking a whopping 80 percent. Those put in the hospital by cigarettes are, for the most part, suffering from lung cancer, coronary artery disease and chronic pulmonary obstruction disease. Because women who were heavy smokers - targets of the "You've come a long way, baby" school of smart sell - are just beginning to enter the covered group of people 65 or older, Mr. Califano figures the share of Medicare costs attributable to cigarettes can only increase. That share might eventually be outweighed by a rise in the number who quit smoking. Even so, Mr. Califano says, substance abuse will cost Medicare $1 trillion for hospital care over the next 20 years - and smoking will be responsible for most of it. Cigarettes are beginning to burn a big hole in the elderly's medical safety net. To mend it, Amer- ica had better start putting out the fire. Greensboro News & Record May 18,1994, p. A6 TOBACCO FIRMS ACCUSED OF TRYING TO INTIMIDATE WASHINGTON - A congress- man accused the tobacco industry Tuesday of intimidation in his in- vestigation into whether the indus- try conspired against Americans' health. "The tobacco industry may not like it, but theirs days of secrets ... are over," said Rep. Henry Wax- man, D-Calif. "The tobacco indus- try is engaging in a pattern of trying to intimidate people ... which will not be permitted to keep us from doing our work." He said he will resist Brown & Williamson Tobacco Corp. at- tempts to examine the confidential records of his congressional inves- tigation and expects its chief exec- utive to testify before Congress on Friday. Vol. 24. No. 6, June 3. 1994 rrEwsBtiEEFs At issue are internal documents showing Brown & Williamson exec- utives knew 30 years ago that smoking was dangerous and nico- tine was addictive and that they shelved a safer cigarette. Among the documents, given to the news media, is a July 1963 memo from company attorney Ad- dison YeamaL that says: "We are, then, in the business of selling nico- tine, an addictive drug." He added cigarettes ease stress and prevent weight gain but also "cause or predispose" smokers to lung cancer and other diseases. But the first surgeon general's report on smoking, issued six months later, couldn't prove ciga- rettes cause any of those problems. Brown & Williamson contends the documents were stolen by a disgruntled former employee who is trying to sabotage the Louisville, Ky., company and have been taken out of context. Chief executive Thomas Sandefur postponed con- gressional testimony about the doc- uments Tuesday, saying he couldn't respond to something that Waxman won't let him read. ' The company went on the offen- sive. Tuesday, it subpoenaed Wax- man, chairman of the House En- ergy and Commerce Committee's health subcommittee, fellow smok- ing opponent Rep. Ron Wyden, D- Ore., and several reporters who possess copies of the documents, seeking to examine them. And company attorneys wrote a former federal official that the doc- uments he was asked to discuss before Waxman's subcommittee on Tuesday are under a court gag order. The former adviser, Joseph Cali- fano, testified Tuesday the govern- ment would have cracked down on smoking 30 years ago had it known what Brown & Williamson knew. He said former President Carter and former Surgeon General Julius Richmond told him that they agree with his assessment. But the Johnson and Carter ad- ministrations each concluded they didn't have enough hard evidence about the dangers of smoking, Cali- fano said. "If we had known in 1964 what we know now, we could have turned our best minds and energy then to arresting this killer," Cali- fano said. "Now, 30 years and 9 million deaths later, we must move aggressively to stop the carnage." ~~1;

NEWSBRIEFS . Wall Street Journal May 19,1994 , p. 131 A CRAFTY LAWYER TURNS UP THE HEAT ON TOBACCO An army of lawyers, led by a flamboy- ant New Orleans attorney named Wendell H. Gauthier, is taking on the ~ tobacco industry in the most lavishly financed assault to date. Fifty law firms have promised an initial investment of $100;000 each to finance a class action on be- half of all people ad- dicted to cigarettes; the first payment of 525;000 is due by the end of May. More than 100 lawyer3 are working part time on the suit, and the group is preparing to buy a $1 million office - building in New Or- leans to serve as a document deposi- tary and headquar- Wendell H. Gauthfer ters for the case. Mr. Gauthier filed the putative.class action at the end of March in Louisiana federal court. A bantamweight man with a mischievous glint In his eye, Mr. Gauthier describes his lawsuft's.strategy as, "You addicted me. You knew it was addicting, and now you say it'sy my fault." Earlier suits unsuccessfully charged that the in- dustry had failed to warn smokers about health risks and sold a defective product. Mr. Gauthier also plans to argue that tobacco companies have targeted teen- agers, who are incapable of making a free gnd informed choice. The tobacco class action was filed just days after congressional hearings, on whether the tobacco industry is intention- ally maintaining nicotine at addictive levels in cigarettes. Testimony..and re- cently disclosedanternal.docdments from Brown & WIDiamson Tobacco Corp. sUg- gest that tobacco executives have long known and suppressed information that nicotine is addictive. That information is expected to test the industry's traditional legal defense that smokers know the health risks of smoking and are free to quit anytime. Tobacco companies have yet to pay a cent in damages for a smoking suit. Mr...Gauthier and his frequent co-coun- sel, Stanley M. Chesley of Cincinnati, who has been dubbed the "Master of Disaster" for his victories in big personal injury cases, are moving directly to the tobacco suit after helping negotiate the recent $4 billion settlement on behalf of women who claimed injuries from silicone-gel breast implants. The names of the other lawyers in the suit read like a "Who's Who" of the national plaintiff's bar. They include Mel- vin M. Belli of San Francisco; John P. Coale of Washington D.C., who is also representing victims of the recent train crash in North Carolina; Ronald L. Motley of Charleston, S.C., a leading asbestos law- yer; and Mark P. Robinson .ir. of Mission Viejo, Cal., who was co-coun-l in the 1979 Ford Pinto suit. Mr. Gauthier, 51 years old, views each new class action as a business start-up, and he functions much like a chief execu- tive, dividing tasks among difierent law firms. At a recent planning meeting for the tobacco case, he assigned one lawyer to work on the search for a headquarters for the legal team and cut short discussion approving stationery for the suit. He spent more time exploring security issues for the 2.5 million documents that are expected to be disclosed in discovery. An influential voice in New Orleans, Mr. Gauthier is a confidant of Edwin Edwards, the governor of Louisiana. He is also part owner of the New Orleans Saints football team and the head of a group of investors in a new casino project. He negotiates the narrow streets of the French Quarter in a Rolls-Royce while talking on his car phone. Local residents approach him on the street and call him by his first name; restaurateurs won't take his money. Beneath the good old boy demeanor is a killer- instinct, say experienced adversar- ies. Mr. Gauthier is "very aggressive and will do a lot more and go a lot further than most lawyers will." says William P. Kar- daras, a New York defense attorney who opposed Mr. Gauthier and a group of lawyers in the case stemming from the 1986 San Juan DuPont Plaza Hotel fire, which was settled for $235 million. "What- ever it takes to win, within the system, they will do," says Mr. Kardaras. "Whether you call that fair or unfair, I won't characterize." Mr. Gauthier is known for using uncon ventional tactics to keep people off guard. He greeted a reporter with an elaborate prank: Wearing a monkey mask and bran dishing a fake gun, he posed as an unstable whistle-blower peddling incriminating to- bacco industry documents while hidden cameras recorded the whole inadent. An- other time, he called a partner in the middle of the night and said, "The presi- dent of R.J. Reynolds has just confessed everything, get on it" and hung up. "You tend to discount him as just a clown. It throws you off your game," says Gary L. Bostwick, a defense attorney in the San Juan Hotel fire case. Mr. Gauthier once slipped Mr. Bostwick a pair of plastic handcuffs before a deposition, suggesting that Mr. Bostwick or his client would soon be needing them. Mr. Kardaras's advice to the cigarette companies: "Get the best defense lawyers they can and stay awake. They are very formidable adversaries." In the tobacco industry's lawyers, Mr. Gauthier will meet formidable opponents. So far, the tobacco industry has been able to outspend and outlast the small law firms that have pursued smoking liability cases. One experienced tobacco litigator, Marc Z. Edell, largely dropped his tobacco cases in 1992, pleading financial hardship after having spent 51.2 million in out-of-pocket expenses over 10 years. Tobacco company lawyers tied up one of Mr. Edell's expert witnesses in depositions for 22 days on one case. "To paraphrase Gen. Patton, the way we won these cases was not by spending all of (RJR's ) money, but by making the other son of a bitch spend all of his," an attorney , for RJR Nabisco Holdings Corp. wrote in a memo. "So far, the tobacco industry has had to fight only one victim at a time," says William S. Lerach, a San Dieg6 lawyer pursuing a separate class-action suit on behalf of people who have paid for nicotine patches to overcome their addiction to smoking. The tobacco giants "have been able to grind up every one of the individuai victims into a fine powder and get rid of them." The narrow focus on addiction is "go- ing to be more palatable to a jury," than previous tobacco cases, says Gregory Ma- zares, president of Litigation Sciences Inc., a firm that specializes in predicting how jurors will respond. Tobacco company lawyers say they will continue to prevail. "Jurors believe that people can quit smoking," says Chuck ivEWSSRIErs , I Vol. 24, No. 6, June 3, 1994 `4

NEWSBRIEFS Wall, associate general counsel for Philip Morris Cos. Mr. Wall doesn't believe the courts will certify the new cases as class actions because each smoker's case is different. "I don't think this is a new day," he says. Mr. Gauthier dismisses the tobacco companies' arsenal with characteristic bravura: "They're not going to outman us. They're not going to outfund us. And they're not going to outlast us." Wall Street Journal May 19, 1994 , p. B9 PHILIP MORRIS AGREES TO $250,000 IN FREE-CIGARETTE CASE NEW YORi: - Philip Morris Cob- agreed to pay New York State S250.000 tc• settie a dispute over tne company's distr:- bution of free sampies of Marlooro ciga- rettes. The announcement marks the first en- forcement action filed for violating Nev: York's ban on free distribution of ciga- rettes. Attorney General G. Oliver Koppel said. The ban was enacted in 1992. PPhilip Morris mailed out free samples of five packs of Marlboro cigarettes to more than 44.000 New Yorkers last sum- mer. state officials said. Philip Morris, in reaching the settlement, denied that its mailings violated the law. Public and political pressure against the tobacco industry "has made Philip Morris desperate for new customers" said Joseph Cherner, president of SmokeFree Educational Services Inc., a health advo- cacy group. The company "made a big mistake in underestimating New York state." The state's action was prompted by a complaint from a Massapequa Park, N.Y., resident whose husband received five free packages of Marlboro cigarettes in the mail just after he celebrated his one-year anniversary of having quit smoking after 38 years. Philip Morris said the cigarettes were sent only to respondents who completed a consumer survey. The respondents were at least 21 years old and had stated that they were smokers and that they were willing to receive cigarettes in the mail. The company said that it "admits no wrongdo- ing" and that it hasn't violated any law or regulation. Greensboro News & Record 19-May-1994, p. A3 AIRLINE-CABIN AIR CALLED UNFIT WASHINGTON - The smoke hhs cleared from airline cabins, but Congress is still hearing a litany of complaints of bad air quality from passengers and flight attendants. * "It's clear that people believe that the air quality is bad ... and getting worse," said Rep. James L. Oberstar, D-Minn.," chairman of the House Transportation aviation sub- committee.. While the recent ban on smoking on domestic airline flights has im= proved things, the airlines have switched from using pure outside air to a mixture of outside air and recirculated cabin air, Oberstar said. The process saves money. but has raised health concerns, Rep. Jerrold Nadler, D-N.I-., cautioned against putting too much faith in tests that show airline cabin air meets safety standards. "In the real world, on real planes with real passengers, the air qual- ity is substandard," Nadler said. "There is currently no legal stan- dard for how much fresh air a traveler is entitled Xo breathe.", . The subcommittee also ~consid= ered the government's effalrts to get certain cottntries to drop require- ments that insecticide be sprayed in airliner cabins while passenuers are aboard and to get foreign air- lines to ban smoking on lon f*- distance flights. But general cabin air quality was the prime focus of Wednesda5•',; hearing. "Currently, flight attendants and passengers on many flights are not provided adequate amounts of fresh air and, thus, may be exposed to unacceptable amounts of bac- teria, viruses and other potential health risks," Dee Maki, president of the Association of Flight Atten- dants, told the subcommittee. Because fresh air is mixed with recirculated air, cabin air is ex- changed only every seven or morr minutes, she saicl. 13efm• • 1990. tresh air was changed in rnhin • every three minutes. Greensboro News & Record May 21, 1994, p. G2 SCHOOL AIMS TO EXTINGUISH SMOKING Even though teenage smoking has reached a new high in the nation, Northeast Guilford High students and teachers are working to lower the statistics. The county's new student hand- book includes several new rules, including one that forbids students from using or possessing any to- bacco products on school property. If any student is caught violating the rule, he or she faces three days of out-of-school suspension. There are also school activities and clubs designed to discourage students from smoking in bath- rooms and littering on school premises. "It's really irritating to go into the bathroom and almost choke to death," says junior Latanya Graves. "You go into it smelling like perfume and go out smelling like smoke." The student council has posted various signs to warn students not to smoke in the bathrooms and has proposed putting up smoke detec- tors. "Human nature says, 'Smoke won't affect me,' " says history teacher Mary Yoder. "People don't realize the damage that smoking does, especially when you start at such a young age. "As far as smoke detectors go, they should install a sprinkler sys- tem (to douse students' cigarettes) too." Freshman President D'Jella Gray says, "If they say they're go- ing to put up smoke detectors, they need to do it instead of just saying they're going to." NEWSBRIEFs Vol. 24. No. 6, June 3. 1994 ~ ~; 2 8

Wall Street Journal May 20,1994, p. 131 CIGARETTES RIDING ON HARLEY'S APPEAL i APAN'S MOTORCYCLE fans can now smoke what they ride: Carolina Cigarette's Harley-Da- vidson cigarettes are catching on, according to importer PBI Interna- tional. The biker cigarettes, which come in white packages emblazoned with the Harley motif and are licensed by the motorcycle maker, are "popular because the name of Harley-David- son includes American taste and American spirit," says PBI account manager Reiko Kobayashi. "This is an American authentic." Americans, though. might be somewhat per- plexed by the slogan "Have you, Harley." Featured on television, in magazines and on subway walls, the spots show a rugged young stuntman perched atop a motorcycle. "We know the words might sound a little strange," chuckles a spokes- man at the cigarette maker's ad agency. But he adds that grammar wasn't a priority: "We wanted to use the name, which is very famous in Japan," to its best advantage. He offers this translation: "We are say- ing that if you smoke this, you can do anything." Anyway, he notes, garbled Eng- lish is nothing new in the Japanese ad world, where foreign words are picked up more for impact than for comprehension. Philip Morris K.K., for example, has used the same tactic in selling its Lark brand cigarettes with the puzzling but popular "Speak Lark'• campaign. Ms. Kobayashi adds that Japan's smokers are sucking up the brand: PBI started offering the Harley-Da- vidson brand on a limited basis last May and sells about 1 0 million ciga- rettes monthly. It hopes to triple that and is aiming for a 2% share of Japan's growing imported-cigarette market by the end of the 1994 fiscal year in March, Ms. Kobayashi says. Japan's tobacco market, of which foreign brands hold a more than 1717c share. was about 3.782 trillion yen in the 1993 fiscal year. Vol. 24. No. 6, June 3, 1994 NEWSBRIEFS Wall Street Journal May 20,1994, p. B2 SECOND-HAND SMOKE R.J. Reynolds Tobacco Co., a unit of RJR. Nabisco Holdings Corp., plans to run newspaper ads Monday arguing that sec- ond-hand smoke is not a significant health risk. The ad, according to the company, "is designed to provide the public with impor- tant facts to bring some balance to the debate surrounding second-hand smoke." Last week, a broad smoking ban in public buildings was approved by a Congres- sional subcommittee. R.J. Reynolds says the smoking ban is "simply not supported with science." Greensboro News & Record 20-May-1994 , p. A2 SMOKING GOES UP AMONG ADULTS AGES 18 TO 24 WASHINGTON - Fed- eral officials expressed fear on Thursday that the nation's long decline in smoking may be over. New figures show the steady decline since 1966 has halted, while smoking among young people has increased for the fnst time in a decade. The data, issued Thurs- day in the government's Morbidity and Mortality Weekly Report, show "a leveling-off in adult smoking in the United States for two years in a row, and that gives us reason for serious concern," said Dr. Michael Eriksen, director of the Federal Project on Smoking and Health at the Centers for Disease Control in Atlanta. "Another number that gives us cause for concern is what is hap- pening among young people, ages 18 to 24," he said. "Their smoking had been declin- ing every year since 1983, but for the first time their smoking went up, and went up by a lot." The percentage of young adults who smoke increased to 24.4 percent in 1992, the latest year for which 5g- ures - are available, from 22.9 percent in 1991. Smoking among teenag-- ers has remained virtually unchanged over the past decade, at about 19 per= cent. - John F. Banzhaf III, di- rector of the anti-smoking group Action on Smoking and Health, said he was "worried about the latest figures, but not sur- prised." "We may have gotten down to the hard core of smokers," Banzhaf said. - "Others who. smoked but were not addicted, or had mild addic- tions, • may all have quit by now.• And the only people left are those who are addicted so heavily that it will take much more than educa- tion to allow them to quit." One of the chief reasons cited by Erikson for the change in trend is advertising: Manufactures spent a record $4.6 billion on advertising and promotion in 1991, the latest figures. Thursday's data came from the annual National Health Inter- view Survey. rrEwss)2EErs C. 2~ .

NEWSBRIEFS New York Times May 20, 1994 , p. D17 CALIFORNIA ASSIGNS ANTI-TOBACCO ADS The California Department of Health Services has awarded its anu- smoktna account to Asher/Gould o: Los Angeles. The high-profile ac- count, with billings estimated at $23 million for two vears. was handled by Livingston & Company of Los Ange- les for the last two years. Bruce Silverman, president and chief creative officer of Asher/Gould, confirmed a ren_ ort of the appoint- ment this week in Adweek. He said his agency was awarded the account after a two-month review that also included the team of Stein Robaire Helm of Los Angeles and Paul Keye, an ad executive who had worked on the account for the last four years at agencies including Livingston. A campaign by Asher/Gould is ex- pected to begin in the fall. The previ- ous campaigns, with their frank at- tacks on cigarettes, have been cred- ited with helping Californians to quit smoking at rates far higher than those in the rest of the country. New York Times May 20,1994 , p. A16 COMPANY SPENT $1 MILLION TO PUT CIGARETTES IN MOVIES, MEMOS SHOW Au unusual glimpse into the busi- ness of both Hollywood and tobacco companies has been afforded by in- ternt.l memorandums from the Brown & Williamson Tobacco Corpo- ration. They show that the company spent a million dollars over a four- year period to put images of its ciga- rettes into the movies. The approach is called "product placement." It is legal and widely usc•d by businesses promoting all kind.; of products, but the scale and form of Brown & Williamson's efforts - the Hollywood figures accepted payment in the form of expensive gifts - is unusual for the practice. The internal documents that have come to light are audits the company conducted to see if it was getting its money's worth in placing images of cigarette packs and billboards in movies. It concluded it was not. The million dollars in placements, a company spokesman, Thomas Fitz- gerald, said today, "was a total fail- ure." The way the placement procedure worked, according to the documents, was that Brown & Williamson asked an intermediary in Hollywood to seek out directors and producers to ar- range for placement of cigarette packages and billboards in films, and in some cases to show actors smok- ing. The producers then would desig- nate who was to receive the money or gifts. In one deal, Associated Film Pro- motions, a firm now out of business, arranged with Sylvester Stallone for Brown & Williamson cigarettes to appear in a significant way in five of his feature films, and to "incorporate personal usage for all films other than the character of Rocky Balboa in Rocky IV, where other leads will have product usage," possibly at ringside. The price tag for the five films was. $500,000. The films and th..i. , _ oposed titles at the time, 1983, were: "Rhine- stone Cowboy," "Godfather III," "Rambo," "50/50" and "Rocky IV." The money was for the most part delivered in the form of expensive gifts. For example, $24,200 in "jew- elry" was listed in the audit as given to Sylvester Stallone. A watch for Mr. Stallone was listed at $7,290. An auto- mobile for Mr. Stallone came to $97,000. An American saddlebred horse for Mr. Stallone was $80,000. Cash payments of $2,000 and $8,000 were made to the property master and the producer on one of the Stal- lone films, according to the audit. Among the listing of payments was $25,000 for charity, to go to the Autis- tic Children's Foundation. The audit noted that deals had been made for 22 films between 1979 and 1983, with the Stallone deal by far the largest. In addition, advertising in movie theaters was listed at $300,000. If all the payments were made as noted in the audits, about $1.3 million would have been spent. Among the larger payments was $100,000 for the film "Harry and Son," including $50,000 in air travel and a$42;307 car for Paul Newman. About $20,00) was reportedly paid out for the James Bond film "Never Say Never Again," starring Sean Connery. "Jewelry for Sean Con- nery" was listed at $7,170. Other films and the amount spent for placement in them included, "The Tempest," $70,000; "Shaker Run," $5,000; "Blue Skies Again," $7.500; "Smokey and the Bandit II1," $10,000; "Tank," $25,000; "Where the Buys Are," $100,000; "Killing Ground," which on release was called "Sudden Impact," $50,000. The tobacco company's auditors reported that there were no written agreements about placement with movie companies or producers, and that the placements they got were sometimes disappointingly •fleet. in "Never Say Never Again," for exam- ple, the auditors said a pack of Super Kool Lights appeared on screen for one or two seconds but it was not possible to read the word Kool. Circumventing a Ban? Although product placement is a legal and common practice, smoking opponents like Alan Blum of Baylor University have argued that its use in films shown on television is a way of circumventing the 1969 law banning the advertising of cigarettes on tele- vision. But the Federal Trade Com- mission has never attempted to pros- ecute companies for the appearances. Brennan Dawson, an official of the Tobacco Institute, the industry's trade organization in Washington, said all the major companies had agreed since 1990 not to place their products in movies. 7 homas Fitzgerald, a spokesman for the Brown & Williamson company said the practice of placing ads in movies "was a total failure in our view" and was stopped about 10 years ago. "Obviously, it is something we tried but it just didn't work for us." he said. "It didn't seem an effective way of spending our money." Ellen Merlae, a spokeswoman for Philip Morris U.S.A., a domestic sub- sidiary of the f'hilip Morris C'otnpa- nies, said that Philip Morris U.S.A. has never paid for product placement in movies. But another subsidiary, Philip Morris International, has paid for placements in movies made out- side the United States, she said. Since many of the films shown in the United States are made in other countries, placements were se en in American theaters up to about three years ago. she said. when the practice w:u- stopped in international work as well. Films that included cigarette placements from the international subsidiary of Philip Morris were "Su- perman II" and a James Bond Film called "License to Kill." How many other companies kept up placements through their international corporate partners after the domestic tobacco companies agreed to stop making movie placements is unknown. But critics say that the continued widespread appearance of cigarette billboards and identifiable images of brands in movies and on television make them suspect that some deals continue to be made. NEWSBRIEFS Vol. 24, No. 6, June 3, 1994

NEWSBRIEFS ' Wall Street Journal 23-May-1994, p. B5 R.J. REYNOLDS FIGHTS BACK IN CAMPAIGN Amid growing antitobacco sentimen: and a series of damaging congressiona; hearings, tobacco executives decide it iS time to fight back. Under consideration: Project Truth, a massive advertising cam- paign. Project Truth is ultimately rejected as too controversial, as is a proposed slogan, "Being alive today is a risky business." "We hardly give (smokers) any com- fort telling them that," a Brown & Williamson execu- tive wrote in a memo dismissing the suggestion. That was in 1970. ` na Anwecuuw~~auv _ ir -ms uiNnxuwxue~w~~~wr ~r • Twenty-four years later, the tobacco industry is more threatened than ever and is taking forceful action to try to sway public opinion. Today.BTR Nabisco Hold- higs' R.J. Reynolds Tobacco unit is begin- ning a multimillion-dollar advertising campaign, with full-page newspaper ads, designed to provide its viewpoint in the debate on smoking. Philip Morris has also sporadically been using advertisements to present its side this year. . The embattled industry is fighting back in less visible ways as well. With a highly restrictive smoking ban under consider- ation in New York City, Philip Morris has raised with city officials the prospect of moving.its Park Avenue headquarters out of the city. "There really has been no threat, but we tried tomakeclear to the mayor's office that it is important that, since we have our world headquarters in New York, the climate remains favorable for all of our businesses," says Craig L Fuller, senior vice president. Philip Morris. °If it be- comes unfavorable, we might consider what our options might be in terms of more favorable -locations. That sentiment has been expressed by our representatives." Crisis management experts say. that such tactics are a sign of the industry's increasing isolation. "The people who buy newspaper ads are folks that have ex- hausted . all other means of getting their story across," says James Hasl, president of the Delahaye Group, a crisis-consulting firm. "If all else fails, take out an ad." • With public opinion already so nega- Vol, 24, No. 6, June 3, 1994 tive, image consultants say the tobacco companies have little to lose in fightir.~7 back. Still, the advertisements are ex- pected to do little to sway F,:Luc opinion. "The public does not necessarily want to hear from the companies," says Rober: Dilenschneider, chairman of the Dilensch- neider Group, a New York public relations firm. "They want to hear from people they know and trust. There must be someone in Hollywood who smokes." During congressional hearings •last month, R.J. Reynolds discovered that its chief executive officer, James W. John- ston, had considerable marquee value of his own. By denouncing congressmen as neo-Prohibitionists, Mr. Johnston was widely considered to be the most effective tobacco executive at the hearings. (He received thousands of letters after his appearance, several inquiring about his marital status.) In its advertising campaign, R.J. Rey- nolds plans to follow up on the themes of individual freedom that Mr. Johnston in- voked so effectively in his testimony. The first advertisement runs today in the New York Times, The Wall Street Journal, USA Today and publications that law- makers read such as the Washington Post, National Journal and Roll Call. The first ad tackles the subject of secondhand smoke. "Very little" is how much secondhand smoke ronsmokers are exposed to, the advertisement says. The ad is based on a research paper written by a toxicologist, Larry C. Hol- comb, who said that about half of the funding for the study, which was published in the journal Environment International, came from the Tobacco institute. The ad asserts: "In a month, a non- smoker living with a smoker would, on average, be exposed to secondhand smoke equivalent to smoking approximately 1'M cigarettes. ... What we are saying is that there are always two sides to every argu- ment." The ad, which features an attrac- tive middle-aged woman smoking. stresses "accommodation" and has a moderate tone. The tagline of the ad: "Together, we can work it out." Other ads are expected to address smoking bans, taxes and the rights of business owners. "We want to get a more reasoned debate than exists today," says Mr. Johnston. "What we are trying to do NEWSBRIEFs is give people a much fuller picture of what is going on." Individual freedom has long been a favorite industry theme. When asked if the company would be legally permitted to air simiiar advertising on television, Mr. Johnston swelled up and said, "If this is America. we can." Not according to at least one network. "We do not accept advertising on contro- versial issues," says a spokesman for ABC. "To talk about smoking in the con- text of a political debate would not be accepted for advertising on ABC." Although cigarette ads have been pro- hibited on television since 1971, Philip Morris undertook in 1989 a $60 million TV ad campaign for a nationwide tour of the Bill of Rights. Although there were pro- tests and a congressional hearing to deter- mine if the company was trying to circum- vent the ban, the ad, which didn't mention cigarettes or smoking, was permitted to run. In fact, the Reynolds executives seem to be itching for their ads to be attacked, so they can fight back on the free speech high ground. Newspapers can reject ads if they do not feel there is a factual basis for the claims made, but so far, none has refused to run the Reynolds ad so far. "If the ad is rejected, that puts a different spin on what we'll talk about" at a planned news conference today to announce the PR blitz, says a Reynolds executive. Regardless of its impact in Washing- ton and with the public, the ad campaign will provide encouragement and comfort to tobacco industry supporters and em- ployees, says a marketing executive. "It says, 'We are not .running away and hiding,' " says Bill Southard, president of Earle Palmer Brown, an advertising and public relations agency. "They are doing this to show that they are going to battle this thing to the end."

NEWSBRJIEFS Winston-Salem Journal 23-May-1994, p. A9 RJR AD CAMPAIGN R.J. Reynolds Tobacco Co. has a ntes- sage forthe world: There should be rea- sonable accommodations for both smok- ers and nonsmokers - not regulations that effectively ban the use of cigarettes. The company, which faces incrc.~asing attacks by anti-smoking groups, wIll be- gin a media campaign today to get its side .of the smoking debate before the public. The first newspaper advertisements, which were scheduled to appear this morning, challenge an assertion by the Environmental Yrotection Agency and health groups that secondhand cigarette smoke is dangerous to nonsmokers. The EPA released a report in January 1993 that said secondhand smoke kills about 3,000 nonsmoking Americans a year and causes hundreds of thousands of cases of respiratory illnesses in chfl- dren. Reynolds'lbbacco's ads say that: Nor.- smokers living with smokers are exposed on average to secondhand smoke equiva- lent to smoking about 1.5 cigarettes a month; nonsmoking waiters working full rtime in a restaurant that allows smoking are exposed on average to the equivalent of about two cigarettes a month; and nonsmokers sharing an office with a smoker would inhale .the equivalent mnoke of about.1.25 cigarettes. The calcaila- .tions are based on various published reports, including researclt by tobacco-company scien- tists and by outsiders. . Four:more advertisements"are being pre- pared, incIuding one that disputes charges that tobacco companies add. nicotine to cigarettes to cause addiction in- smokers. David FLshel, a senior vice president for public relations at Reynolds Tobacco, said that the content of the ads will vary as smoking issues arise.."It is an evolving thing," he said. No+ads will appear on television or radio because they might violate cigarette marketing restricbions; F5she1 said. Reynolds Tobaccoa will also send teams of company scientists and spokesmen on a 26- c[ty tour during. the next several weeks to discuss the company's perspective on a range of smoking issues and on what the govern- ment's regulatory role should be.` ~~~•Thomas C. Griscom, Reynolds Tobacco's ezeautive vice presidentfor external relations, said that few people realize the scope of pro- posed rules by the U.S. Occupational Safety Vol. 24, No. 6, June 3. 1994 and Health Administration for indoor-air quali- ty or details of a bill introduced by tobacco critic U.S. Rep. Henry A. Waxman of Califor- nia. . Griscom said that the proposals could force people to stop smoking in their own homes when anyone. such as a plumber or house- keeper, works there. Truck drivers might not be able to smoke in their cabs because the vehicles could be considered a workplace, he said. Businesses might be required to set aside rooms exclusively for smoking. "No work can be done in the room where people smoke," Griscom said. Reynolds Tobacco said that this goes be- yond the appropriate role of government regu- lation and would turn the federal government into a "national nanny." Griscom said, "I think it is a very chilling thing." The company says that the EPA report on secondhand smoking is flawed. Christopher R. E. Coggins, the principal research and development '- toxicologist for Reynolds Tobacco, said that the EPA study did no original research. Instead, it combined the results of other studies. The study also "cher- ry-picked" data and ignored other research that showed little evidence of harm from sec- ondhand smoke. Reynolds Tobacco, Philip Morris Cos. Inc. and several allies sued the EPA last June, asking a federal court in Greensboro to force the agency to withdraw the study on these grounds. The EPA has said it stands by its research. But Coggins said that a report by the Con- gressional Research Service. issued May 11 comes to many of;the same conclusions as Reynolds Tobacco. "It is not just us saying it," Coggins said. Griscom said that Reynolds Tobacco ex- pects health groups will respond strongly to the tobacco company's campaign. He said that the company welcomes it. "We want to encourage discussion," he said. NEwsBRIEFs

NEWSBRIEFS SECONDHAND SMOKE: HOW MUCH ARE NON-SMOKERS EXPOSED TO? With all the discussion today about second- hand smoke, you may be interested in how much you are exposed to. The answer, in our opinion, is very little. Expressing exposure to secondhand smoke in terms of cigarette equivalents is one way to gain a perspective. For example: I) In a~' month., a non-smoker living with a not necessarily. relevant to an assessment of the potential risk from secondhand smoke. In our opinion, secondhand smoke is not the same as the smoke a smoker inhales. What we are saying is that there are always two sides to every argument. Both sides need to be heard and evaluated in order to make an informed decision. We believe that the solution to most smoking imoker wouid,.on average, be exposed to second- , issues: can' be found in accommodation. There are .~+... . I W.. hand smoke equivalent• t6 smoking approximately ways for smokers and non-smokers to co-exist 1112 cigarettes! ~ 2) In a month, a non-smoking waiter ~,. : works eight hours a: day; five days a week . peacefully. And• we encourage discussion that will who "`help solve the issues without resorting to Govern- in a•''ment intervention. Clearly common sense should ~ restaurant would, on the -average, bexposed to secondhand smoke equivaient to smoking about 2 cigarettes' 3) In a month in a modern office where smok- ing was permitted, a non-smoker sharing an office with a smoker would, on•average, be exposed to the equivalent of smoking about 1114 cigarettesO tell everyone not to expose very young children to high levels of secondhand smoke. As it relates to smokers, in our opinion smoking is a risk factor for certain diseases. At R.J.Reynolds we believe the choice to smoke should be made only by adults. This opinion is brought to you in the inter- There are many ways to calculate cigarette , ests of an informed debate by the R.J.Reynolds equivalents, and no method •exactly predicts the "Tobacco Company. For further information please .. :, ~:., • rprecise amount of .secondhand s v~~moke a non- .,: ca17 l=8b0 366-8441. « af ;. , gsmoker is exposed ~~ 'Also, cigarette. t calcfi~ons are ?F ~ / TOGETHER, WE CAN WORK IT OUT NEWSBRIIEFS Vol. 24, No. 6, June 3. 1994

NEWSBRIEFS RESPONSE FROM 800 NUMBER ACCOMPANYING RJR AD Maura Ellis Remarks for Second-hand Smoke News Conference National Press Club -- Monday, May 23, 1994 Good morning. I'm glad all of you could be here. My name is Maura Ellis. I'm director of external communications for RJ. Reynolds Tobacco Company. With me is Dr. Chris Coggins, a toxicologist with our company. This morning we would like to begin a process that is long overdue. We want to bring some balance to the debate surrounding second-hand smoke and other issues concerning cigarettes. And we'd like to establish an open dialogue where members of the media and the public can better understand both sides of the issue. During the past couple of years there have been a lot of misconceptions about second-hand smoke - including claims that exposure to second-hand smoke is more dangerous than active smoking. But, as Dr. Coggins will detail in just a minute, studies show that second hand smoke is highly diluted - and, on average, people are exposed to very small quantities of second-hand smoke. THE ANTI-SMOKING INDUSTRY WANTS TO BRING BACK PROHIBTTION We believe these facts are important - and that it is important for the public to be fuIly acquainted with both sides of the issue - so people can make informed decisions about second-hand smoke. We also believe it's time to understand that various efforts to totally ban smoking in public places, including workplaces, are part of a broader effort to prohibit smoking in the United States. As Reynolds Tobacco's chairman told Congress last month ... the real issue is this: "Should cigarettes be outlawed?" Let's make no mistake about it. The goal of the anti-smoking industry is to bring back prohibition. When confronted, they will tell you they don't want prohibition. But their actions belie those claims. If you don't believe that's the case, just look at how extreme some of these efforts are - like trying to prohibit people from smoking outdoors, in public parks, in their cars or even their own homes. And consider this - alcohol prohibition started witr the anti-alcohol movement claiming that their goal was simply "temperance." THE EPA REPORT IS BASED ON FAULTY SCIENTIFIC ANALYSIS As you'll hear from Dr. Coggins ... the current efforts to prohibit smoking are based on a faulty analysis of the science by the EPA. And they fly in the face of what most Americans say they want. Surveys consistently show that Americans overwhelmingly oppose prohibition - especially when it's imposed by the government. They favor designated smoking areas - rather than total smoking bans. They believe that common courtesy and accommodation are the best solution. For example, a recent GaIlup/CNN/USA Today poll indicated that: • 86 percent of Americans believe that smoking should be legal; • 61 percent of Americans oppose smoking bans in restaurants; • 67 percent oppose workplace smoking bans; • and 78 percent oppose bans in hotels and motels. 0 rtEwsBIiIEFS Vol. 24, No. 6, June 3. 1994 ~~A ~1 4 F

NEWSBRIEFS Americans say they prefer peaceful coexistence - not government mandate - and not prohibition. In virtually every case, attempts to ban smoking are being driven by the EPA's risk assessment on second-hand smoke. As Dr. Coggins will point out, that report -- and its designation of second-hand smoke as a Group A carcinogen - has many weaknesses. In fact, just a week-and-a-half ago, the Congressional Research Service told Congress that the EPA's report suffered from serious flaws. In that testimony, and in a report submitted to Congress in March, the Congressional Research Service characterized the epidemiological evidence the EPA relied on as, quote, "weak" and "uncertain." ACCOMMODATION IS TBE ANSWER I would like to make Reynolds Tobacco's position very clear. We're not saying that smokers should be free to light up any time at any place, without considering other people. But we do believe that the 45 million American adults who choose to smoke should be, and can be, afforded reasonable accommodations. And we share the public's overwhelming opposition to government-imposed prohibition. There are common-sense ways to work out problems without turning 45 million Americans into outlaws and social outcasts. Now, I'd like to turn the microphone over to Dr. Coggins. After that, there'll be time for us to answer your questions. NONSMOKERS ARE TYPICALLY EXPOSED TO VERY SMALL AMOUNTS OF SECOND-HAND SMOKE We understand that some people find second-hand smoke annoying. No two ways about it. But we also know that most Americans prefer common courtesy and common sense - not government mandate - to solve any problems that might arise. We believe it is very important that the American public understand both sides of this issue - so that they can make informed choices. To that end, we're launching a public information campaign that opens the debate on a number of issues. Our first effort appeared this morning in a mmtber of majur dailies. I'm sure that many of you saw it. As this ad points out, nonsmokers are typically exposed to very small quantities of second- hand smoke. Let me give you a few examples. On average: • A nonsmoker living with someone who smokes at home would be exposed to the second- hand smoke equivalent of smoking about one-and-one-half cigarettes a month. • A nonsmoking waiter might be exposed to the equivalent of 2 cigarettes a month. • And a nonsmoker sharing a modern office with a smoker might be exposed to the equivalent of just one-and-one-quarter cigarettes a month. We believe this ad - and a series of others that will appear in national publications in coming weeks - will bring balance, and additional perspective, to this and other important issues facing the American public. these ads are designed to start a productive dialogue ... that will help the public understand that there are two sides to almost every issue - including this one. And people can't make informed decisions without information from both sides. Dr. Coggins and I would be happy to answer questions. NE WSBRIEFs Vol. 24. No. 6, June 3. 1994

NEWSBRIEFS Chris Coggins Remarks for Second-hand Smoke News Conference National Press Club - Monday, May 23, 1994 Good morning ladies and gentlemen. I am Dr. Chris Coggins. I am a board certified toxicologist and I am a principal scientist with RJ. Reynolds Tobacco Company. I have performed and published toxicological evaluations on tobacco smoke since 1976. Today, I shall first focus on a very basic issue: what are the amounts of second-hand smoke that nonsmokers are in fact exposed to? I shall then explain some of the significant flaws in the data that the EPA report on second-hand smoke is based on. Finally, I will illustrate just how fragile the EPA's conclusions are in light of data published prior to the release of its report. NONSMOKERS ARE EXPOSED TO MIIIUTE CONCENTRATIONS OF SECOND- HAND SMOKE. Just what is second-hand smoke? You must understand that second-hand smoke is not the same as mainstream smoke (or sidestream smoke): it is hundreds to thousands of times more diluted. Just how much second-hand smoke are nonsmokers exposed to? The answer is: very little. A review in 1993 of published data examined measurements of air duality in "smoking" and "nonsmoking" homes. The average concentrations of respirable suspended particulates were 22 micrograms per cubic meter for "nonsmoking" homes and 49 micrograms per cubic meter for "smoking" homes, giving an average difference (that is presumably due to smoking) of 27 micrograms per cubic meter. There were similarly small differences for "smoking" and "nonsmoking" offices, public buildings, restaurants and transportation. ` A microgram is a millionth of a gram: this set of units may not be famiIiar to everyone here, so let us look at a simple analogy using everyday terminology. If I had a large size (12 oz.) can of hair spray, and an unlimited number of "standard" size houses, amongst how many houses must I distribute the hair spray, evenly throughout, to increase the background concentration of particulates by 27 micrograms per cubic meter? The answer is that I could spray the contents of that can of hair spray, evenly throughout the air contained in every room, in almost 30,000 houses, or, a city slightly smaller than Silver Springs, Maryland. One of the oldest and most basic tenets of toxicology is that "the dose makes the poison." Thus, Paraceisus wrote over 400 years something that is still central to toxicologists today: "What is it that is not poison? It is the dose only that makes a thing not a poison." Put in plain Fn any material can be made dangerous, if the dose is big enough. But concentrations measured in "millionths of a gram per cubic meter" - the levels typically found for second-hand smoke - represent such minuscule doses that it is scientifically implausible that they could result in meaningful toxicological activity. In fact, animals exposed to second-hand smoke at concentrations hundreds of times higher than those that nonsmokers are typically exposed to show no meaningful changes at all. I personally conducted that work, which has been published in the peer-reviewed scientific literature. N NEWSBRIEFS Vol. 24. No. 6, June 3. 1994 ;; C~ ~?

NEWSBRJEFS THE EPIDEMIOLOGY STUDIES REPORT WEAK ASSOCIATIONS WITHOUT ADEQUATE CONTROL FOR POTENTIAL CONFOUNDERS Moving on to the EPA report: first, the EPA did not conduct any original health studies. Instead, the agency based its so-called risk assessment on selected statistical studies in epidemiology (the statistical study of the incidence of disease in human populations). According to a recent report by Dr. Jane Gravelle of the Congressional Research Service (the research arm of the Library of Congress) the EPA's analysis of these studies simply does not conform to established scientific principles. We have copies of the report for you. The EPA reviewed 30 worldwide epidemiology studies of spousal smoking and lung cancer: The 30 studies were extremely variable, with "relative risks" ranging from a high of 2 1/2 to below 1. Fully 80% of the studies did not achieve statistical significance, the traditional teslt that scientists use to see if the results are truly meaningful. The EPA's meta-analysis (a form of averaging) of 11 American studies, none of which was statistically significant, produced a relative risk of 1.19. Regardless of your views on second-hand smoke, these reported associations are weak. Epidemiologists interpret weak associations cautiously, largely because such associations are particularly susceptible to being produced by confounding factors (factors other than the one being investigated, which could also be associated with the disease being investigated). A simple example would be someone living in a high-smog area. DIET IS A MAJOR CONFOUNDING FACTOR IN LUNG CARCINOGENESIS Published studies confirm both the existence of confounding and its importance when interpreting data on second-hand smoke and lung cancer. In my exhibit I show some risk factors for lung cancer identified in a recent study funded by the National Cancer Institute, a study that was not considered by the EPA. This study, which is to date the largest single study on second-hand smoke, was specifically excluded by the EPA from their analysis, despite the fact that the study showed no increase in risk. On the bar chart you can see that the msjor fac.~r is a diet high in saturated fat, shown in red. Weaker risk factors (shown in yellow) include consumption of citrus fruit and juice, and a history of previous lung disease. The overall relatives risk for spousal smoking (shown in magenta), in this the largest study, is 1.0 which means that the study found no increase in risk. The protective effect of a diet high in beans and peas is shown on my chart in green (here the relative risk is significantly less than one). These new data demonstrate that a diet high in saturated fat may play a significant role in the development of lung cancer in nonsmokers. Yet, none of the studies relied upon by the EPA obtained information on dietary saturated fat, much less did they control for this important factor. Interestittgly, spouses of smokers are known to have very different diets than do spouses of nonsmokers. To summarize, (1) the amounts of second-hand smoke that nonsmokers are likely to be exposed to are vanishingly small, and (2), as such they are unlikely to be biologically important or toxicologically meaningful. Finally, (3), the reported association between second-hand smoke and lung cancer could easily be the result of confounding, given that it is such a weak association and given the strength of other known risk factors (such as diet). Thus any effort to ban smoking in all workplaces and public buildings is motivated not by sound, obiective science but by political considerations of what constitutes correct behavior. The Govetnment should not make thts decision for the private sector, or for individual Americans. MEwsB12IEFs Vol. 24, No. 6, June 3. 1994

NEWSBRIEFS Greensboro News & Record 24-May-1994, p. Al RJR AIMS MEDIA BLITZ AT ITS FOES Staggering under withering attacks from anti-smok- ing forces, R.J. Reynolds Tobacco is turning to an old nemesis for some help. The Winston-Salem cigarette producer launched a multimillion-dollar newspaper advertising campaign Monday and plans to send teams to 26 cities across the country to talk tobacco with any newspaper, magazine, television and/or radio station that will listen. -."In this country the media is the means of communi- cations; ' said David Fishel, senior vice president of public relations for the nation's second-largest ciga- rette maker. - "We want to be able to say to reporters there is another side to the story." The story for the past 30 years has been the dangers of smoking. And newspapers and other media.outlets - spurred by government and anti-smoking reports - have been relentless in their pursuit of the tobacco industry. 'There are now several proposed laws in Washington that would virtually ban smoking in public and private buildings and workplaces. Such laws would likely cripple the nation's $48 billion domestic cigarette industry. On Monday, Reynolds kicked off its campaign with expensive full-page advertiaementsan.-mvemi~ootion-- ally recognized newspapers, including The Washing- ton.Post, The New York Times and USA Today. -The advertisements-argue that secondhandsmoke is not as dangerous as the federal government and anti-smoking groups claim. . "With all the discussion today about secondhand smoke, you may b e interested in how much you are exposed to. The answer, in our opinion, is very little," the advertisements read. Scott Bailin, chairman of the Coalition on Smoking OR Health, called Reynolds'" campaign a public rela- tions stunt that attempts to question irrefutable facts about the dangers of- smoking. ----But, . so far, so good for Reynolds. Fishel said he has fielded nearly three dozen media calls about the campaign, and company spokesmen in Washington have seen similar interest. Wall Street Journal May 24, 1994 , p. A6 TOBACCO MAKERS IN QUERY ARE WARNED TO SAVE PAPERS WASHINGTOh - Rep. Henry Wax- man (D.. Calif.) warned tobacco compa- nies not to aestroy any internal docu- ments relating to his investigation of the industn•. Rep. Waxman. chairman of the Sub- committee on Health and the Environ- ment, said he was writing to the heads of five tobacco companies warning them that destroying documents relevant to a congressional investigation would be a criminal offense. His concern was sparked by develop- ments in a lawsuit filed in New Orleans on behalf of people addicted to cigarettes. In April, a federal district court judge ordered the five tobacco companies in- volved to preserve all documents related to the suit. But the tobacco companies say the order is overly broad and want it narrowed in scope. Chuck Wall, associate general coun- sel for Philip Morris Cos., said the cur- rent order essentially requires the com- pany to preserve all documents gener- ated by the company on any subject since 1974 until the litigation ends. The other companies involved are R.J. Reynolds Tobacco, a unit of RJR Nabisco Holdings Corp., American To- bacco Co., Liggett Group inc. and Loril- lard Inc., a unit of Loews Corp. Rep. Waxman said no matter what the court decides, documents relating to the congressional investigation legally can't be destroyed. He also blasted an R.J. Reynolds advertising campaign aimed at debunk- ing the idea that secondhand smoke poses a major health risk. Several full- page newpaper ads yesterday, said a nonsmoker living with a smoker on average would be exposed to the equiva- lent of 1.5 cigarettes a month. Rep. Waxman said the statement is mislead- ing because it focuses only on nicotine. Analyzing other components, studies have shown a nonsmoker is subjected to the equivalent of as many as 60 cigarettes a day, he said. NEwSSxtEFs Vol. 24, No. 6, June 3. 1994

NEWSBRWFS Wall Street Journal May 24,1994, p. B9 PHILIP MORRIS FACES MOUNTING PRESSURE FROM MAJOR INVESTORS TO BOLSTER STOCK 7 ne nressure is mounting on Philip Morris Cos. to take action to increase its languishing share price. Members of the Council of Institutional investors sent a letter to Philip Morris Chairman Michael A. Miles, urging him to "take seriously at your upcoming board meeting all options" to preserve the health of the company's nontobacco operations. One option the big investors plan to push the board to consider seriously is spinning off domestic tobacco operations. Philip Morris has a much-anticipated board meeting tomorrow, which follows the company's disclosure that it is contem- plating separating its food and tobacco operations to bolster its share price. The company's battered stock price has in- creased in the past few days amid rampant speculation that the company will an- nounce a spinoff or a stock buyback tomor- row. Philip Morris stock rose 51.50 yester- day to 555.25 in composite trading on the New York Stock Exchange. "We are concerned about the impact of recent events on the long-term health of the company's domestic operations," exec- utives at six large pension funds said in the letter to Mr. Miles. The stockholders re- quested a meeting with Mr. Miles to ex- press their concerns. Philip Morris declined to comment on its increasingly restive shareholders. The letter was faxed to the company in the late afternoon yesterday. "We want the board to do its duty and examine the various ownership structures, whether they are spinoffs, divestitures, partial spinoffs," said Jon Lukomnik, dep- uty comptroller for pensions for New York City and one of the authors of the letter. "My concern is that they deal with walling off the potential liabilities from the domes- tic cigarette industry," he added, refer- ring to the possibility of large legal judg- ments and increased government regula- tion. The New York City pension fund owns 5.7 million shares of Philip Morris. Other pension-fund administrators that signed the letter requesting the meeting are the nowerful California Public Em- ployees' Retirement System, the Florida State Board of Administration, the Inter- national Brotherhood of Teamsters, the Connecticut Retirement and Trust Funds and the United Food and Commercial Workers fund. William Patterson, of the Teamsters, said, "It's open to discussion whether tnere should be two companies or three companies." One plan favored by some investors is breaking tobacco into distinct international and domestic concerns. He said the group plans to push for isolating domestic tobacco in a separate compan~• with separately traded stock. To date, the international tobacco business has avoided many of the negative pressures that plague Philip Morris at home. Philip Morris stock has been battered during the past 15 months by a variety of ills. ranging from price cuts to ward off cheap cigarettes, and more recently a flood of new regulatory pressures and a pro- posed sharp increase in the cigarette tax. Greensboro News & Record 24-May-1994, p. B5 MISSlSSIPPI SUES TOBACCO COMPANIES NEW YORK - Anti-smoking campaigners hope Mississippi can set an example for other states as it tries to recover medical costs from the tobacco industry for taxpayer money spent on treating illnesses due to smoking. But the industry has a 40-year record of successfully defending itself against lawsuits from smok- ers, and will draw on that experi- ence in this case. Tobacco companies have never had to pay smokers who have sued them. The Mississippi suit comes as the industry faces an almost daily pub- lic relations battering over new evi- dence that suggests cigarette makers knew about the health dan- gers of smoking years ago but con- cealed the information. Industry critics have increased pressure for more regulation of cigarette smoking. The Food and Drug Administration is investigat- ing whether tobacco companies manipulate the nicotine level in cigarettes. A hefty tax increase on cigarettes is expected to be part of health-care reform legislation. Tobacco companies argue that smokers are fully aware of the is- sues surrounding smoking, partly because of the warning labels that are required on cigarette packs, but choose to smoke anyway. Tobacco industry analyst Law- rence Adleman of Dean Witter Dis- cover & Co. said there has been a worrisome "deterioration in the in- dustry's social position and accep- tance of its products in the United States." But he added: "The industry has had to handle these kinds of cases before and has dealt with them." Tobacco stocks, a barometer of investor faith in the industry's fu- ture, were mixed on Wall Street the day after the latest suit was filed in state court in Mississippi. Philip Morris Companies Inc., the biggest tobacco company, fell $1.50 a share to $53.75 on the New York Stock Exchange, erasing its $1.50 gain on Monday. But RJR Nabisco Holdings Corp., owner of the second biggest tobacco com- pany, rose 12'/z cents a shar•-, to $6.12'h. In its suit, Mississippi asked to- bacco companies to reimburse the state for millions of tax dollars spent on tobacco-related illnesses through government programs like Medicare and Medicaid. Officials estimate the total spent at $200 million a year. Smoking critics say if Mississippi wins, other states will be under pressure from their taxpayers to take similar action, particularly with heightened concern about taxes and health-care costs. NEWSBRIEFS Vol. 24, No. 6, d une 3, 1994

NEWSBRIEFS Wall Street Journal May 24, 1994, p. A2 MISSISSIPPI WANTS TOBACCO FIRMS TO PAY COST OF TREATING WELFARE RECIPIENTS IYilsstssiont oecame the nrst state to st!c the tooacco industry to recover the cost c' treating tobacco-related ilinesses among welfare recipients. The suit, filed by state Attorney Gen- eral Mike Moore and 11 private plaintiffs' Lettel' to Phfi[p IMiorris Members of the Council of Institutional Investors have sent a letter to Philip Morris's chairman, urging him to "take seriously" all options to preserve the health of, the company's nontobacco operations. Article on page B9. firms, is similar to efforts being planned in Florida and several other states. To- bacco companies have never had to pay any money to smokers who file lawsuits, but some lawyers think the industry's perfect record may be in jeopardy as new litigants such as state governments, with big bankrolls and fresh legal theories, enter the arena. The Mississippi lawsuit, which seeks tens of millions of dollars, cites recent revelations about tobacco-industry re- search on the dangers of smoking and alleges a four-decade strategy by the in- dustry to "mislead and confuse the public about the true dangers associated with smoking cigarettes." Legal Theories Besides seeking compensation for Med- icaid and other welfare costs. the state also is asking for damages from tobacco compa- nies under the legal theories of unjust enrichment and common-law public nui- sance. Tobacco company spokesmen said the companies will seek to use their tradi- tional, and widely successful, defenses to illness-related lawsuits. These include a contention that smokers make a deliberate choice to assume health risks. Also, the companies said they will argue that the state will have to sue on behalf of each Medicaid patient separately, instead of as a class. "I would point out that the costs of this litigation are going to be borne by the taxpayers of Mississippi," said Steve Par- rish, senior vice president and general counsel for Philip Morris Cos., New York. SeektoSueasaGroup But the attorney general and plaintiffs' lawvers said they intend to sue on behalf of Mississippi taxpayers as a whole, using statistical analyses to show the percentage of welfare recipients who got sick from smoking. The lawsuit also seeks punitive damages and money for any future to- bacco-related payments the state may have to make. "If we had to try 100,000 cases, we never would have brought this lawsuit," said Don Barrett. a Lexington. Miss.. tobacco-liabil- itv iawver who is workmg with the state on tne casr. "Tney're wntsu:nb past tne graveyard." Mr. Barrett said the state hasn't nromised the private lawyers an', • percentage of the potential damages. Tne attorney general instead plans to try to compel the tobacco companies to pay the private lawyers' fees. The state's suit also asks the court to block cigarette makers from "aiding, abet- ting or encouraging" sales of cigarettes to minors. "i recently asked my seven-year- old son if he knew the names of any cigarettes," Mr. Moore said. "In the blink of an eye, he shouted, 'Joe Camel!' " The suit was filed in a state court in Pascagoula. Miss.. that ordinarily handles divorce and family-law cases. Mr. Moore said he believed the issues in the suit would be more appropriately handled in that type of court, a so-called court of equity, and that the state would fare better there. The tobacco companies named as de- fendants are American Brands Inc., Old Greenwich, Conn.; RJR Nabisco Holdings Inc., New York; Brown & Williamson To- bacco Corp., Louisville, Ky., a unit of B.A.T Industries PLC; Philip Morris; Brooke Group Ltd., New York; and Loews Corp., New York. Six tobacco wholesalers also were named. "It would appear that this is an unpre- cedented ploy f&r suing tobacco compa- nies," RJR Nabisco said. "Beyond that, it changes nothing." The five other tobacco companies had no comment. Also sued were public-relations firm Hill & Knowlton Inc., which has repre- sented the tobacco industry in the past; the Tobacco Institute, a Washington trade association; and the Council for Tobacco Research. Hill & Knowlton, which stopped repre- senting, the tobacco industry in the late 1960s, had no comment on the lawsuit. It's relatively rare for a public-relations firm to be sued for the alleged misdeeds of a client. "This sounds very important," said Bob Dilenschneider, chairman and chief executive officer of the Dilensch- neider Group, a public-relations -firm. "If the PR firm is found to be a party, and made to pay damages, it will probably deter other PR firms" from working for tobacco clients, he said. The suit also indicated that law firms representing tobacco companies may be added to the litigation. Florida lawmakers paved the way for a similar, and potentially more significant, lawsuit last month. Gov. Lawton Chiles has until Saturday to act on a bill that specifically permits the state to file a class-action suit against the tobacco indus- try and forbids the use of traditional legal defenses such as smokers' assumption of risk. Wall Street Journal 26-May-1994, p. A3 PHIUP MORRIS TAKES No ACTION ON PLAN TO SPLIT After an unprecedented six-and-a-half- hour board meeting, directors of Philip Morris,Cos. said they took "no action" on a proposal to separate the company's food and tobacco businesses. But they announced two key executive moves that some investors viewed as a possible first step toward splitting the company into separate food and tobacco businesses. Moreover, people close to the company said the board hadn't perma- nently tabled the possibility of a separa- 'tion. - ' The widely awaited announcement fol- lowed a tense day on Wall Street, where AIf1a'1Cat1 Bkilldsl OIfdOOk Some anal•;ists think that American .Brands' atoek is getting a bad rap from investors. Heard on the Street, page CL Philip Morris's stock failed to open for trading all day. Traders said they couldn't recall when such a widely held stock failed to trade. Philip.Morris is.one of the 30 stocks that make up the Dow Jones Indus- trial Average and one of the most widely held stocks in the country. Philip Morris said the New York Stock Exchange_made the decision to -put off trading the stock .after an initial delay due to an imbalance of buy and sell orders. It then was halted pending news from the board meeting; the company made its announcement after the market closed. Investors said the creation of the two executive positions indicates that the com- .pany's food and tobacco operations eventu- ally will be split. Geoffrey C. 'Bible, 56 years old, executive vice president, world- wide tobacco, was named to the board and appointed vice chairman for world-wide tobacco, and R. William Murray, 5e. a current board member and president and. chiei operating officer. was named vice chairman for world-wide food. The addi- tion of Mr. Bible to the board increased its size to 19 members. Both men will report to Philip Morris's NEV@sBRIEFS Vol. 24. No. 6, June 3. 1994 ' 4 ~;

NEWSBRIEFS chairman and chief executive officer. Mi- chael A. Miles. It isn't clear what Mr. Miles's role would be if the company eventually separates. Last year. Mr. Miles, who comes from the food industry. was roundly criticized on Wall Street for his response to the surge in discount ciga- rettes. Mr. Miles slashed premium ciga- rette prices, hurting the company's stock price and profit. While the company's volume has improved, Philip Morris's stock price hasn't recovered, and institu- tional investors increasingly are becoming vocal critics of management. Philip Morris's stock is expected to fa)i today, according to analysts. after weei:s of gains based on investors' anticipation of a separation. "It certainly is disappoint- ing," said Bruce W. Gregory, a portfolio manager with Progressive Partners. "But I don't think it's dead longer term. Naming these two guys is an important first step." Philip Morris closed Tuesday at $53.75 a share, down $1.50 or 2.7%. In late trading yesterday, off the exchange floor, it was quoted at about 550.50. Beyond saying that the board consid- ered the proposal and "decided to take no action," Philip Morris wouldn't elaborate on whether the proposal was still under consideration. Some money managers felt that Philip Morris had mishandled its public pro- nouncements about a split, allowing specu- lation to build in the past month by making three separate announcements since April that such a move was under consideration. The announcement yesterday seemed de- signed to free the board to deliberate without the intense media and investor scrutiny. In addition to announcing that no action was taken, the New York based company told investors that a possible split wouldn't be .addressed at its June board meeting. "I think they are still working on it, but they just don't want all this pressure," said S. Leigh Ferst of Prudential Securi- ties Inc. "They are being very cagey." People dose to the company said the board was divided about the separation, maidttg for the unusually long meeting. They said Philip Morris board meetings typically adjourn before lunch. Yester- day's meeting ran -from 9:30 a.m. EDT until about 4 p.m. Not all analysts were so certain that the board would pursue a split. Gary Black of Sanford C. Bernstein & Co. said, "This is a very conservative board, saying the exter- nal environment is just too uncertain right now. The board is saying 'Let's not do anything rash.' " The impetus for a split has come in large part because of the mounting anti- tobacco climate. But company observers Vol. 24, No. 6, June 3. 1994 noted that a split would raise several diffi- cult issues, including whether the food unit might be liable for any future judgments against the tobacco side of the business in health-related lawsuits or other regulatory matters. And many inside the company don't favor splitting the businesses for strategic reasons, arguing that the com- pany is far better with diversified opera- tions. A Philip Morris spokesman yesterday declined to elaborate on the company's internal deliberations, but did say, "We are committed to both the food and tobacco businesses." ` Both- Mr. Murray and Mr. Bible are protegees of Philip Morris's former chair- man, Hamish Maxwell. Mr.-Maxwell is still an influential member of the Philip Morris board. "Mysense is they are looking to the old management," said a person close to the company. "These -guys are the ones that ran major portions of the company before there was a food business." ' Philip Morris acquired General Foods in 1985 and Kraft in 1988. Mr. Miles was a top executive at Kraft when it was ac- quired -by Philip Morris and is the first nonsmoker to head'the company. Wall Street Journal 26-May-1994, p. C1 AMERICAN BRANDS ATTRACTS SOME ANALYSTS NEW YORK - American Brands an- nounced a month ago that it was selling its U.S. tobacco operation. Result? After an initial flurry of buying, its stock has been bashed. Philip Morris, on the other hand, an- nounced yesterday that it currently will take no action on the possible separation of its tobacco operation from its food busi- ness. Result? Its stock is e::pected to get pummeled this morning, following a day- long halt in trading. What's wrong here? Sanford C. Bernstein analyst Gary Black says there's only one conclusion you can draw: American Brands is getting a bum rap. He upgraded his recommenda- tion from "neutral" to "outperform." "People are overlooking American Brands," Mr. Black argues. "You've got a cheap stock, you've got better-than- expected growth, you've got a 6% dividend yield and you've got an upside catalyst, which is the sale of the tobacco business. I think It's attractive." American Brands agreed in late April to sell its U.S. tobacco operation to B.A.T Industries for $1 billion. The news NEWSBRIEFS prompted a buying frenzy that pushed American Brands' stock to 34~'~ from 31%. Since then, however, the shares have been in retreat, closing yesterday at 32'i.., up 58 but not far above the 52-week low of 29%. In the past, American Brands "has not been viewed as willing to take dramatic action to enhance shareholder value," says Brian Rogers, manager of the $2.9 billion-asset T. Rowe Price Equity Income Fund. "This, to me, is a dramatic step. It implies that their mind set has changed. The short-term [market] reaction has been not to give them any credit for what they're doing." Following its recent slide, American Brands now boasts a tempting yield of 6.2%, and its shares trade at less than 12 times trailing 12-month earnings. The U.S. tobacco .operation was a relatively small contributor to those profits, last year gen- erating just 11% of American Brands' $1.5 billion in operating income (before the amortization of intangibles). What were the main sources of Ameri- can Brands' profit? The biggest single generator was the company's foreign to- bacco business, which isn't being sold. Analysts say the foreign operation is far less likely to get hit with lawsuits and antismoking legislation. American Brands' international tobacco division, which is the leading purveyor of cigarettes in the United Kingdom, generated 33% of operating income in 1993. An additional 56%a of operating income came from nontobacco businesses, includ- ing the company's liquor operation, Frank- lin Life Insurance subsidary and its office supplies, golf equipment and home-im- provement products divisions. Robert Leininger, an analyst with Ga- belli & Co., figures the company's fistful of businesses are together worth $45 a share. "We like the stock because we think it's very asset-rich," he says. "We don't be- lieve there are any more sacred cows at American Brands, in terms of selling off the divisions. They're actively looking to enhance shareholder value." If that's the case, why is American Brands' stock still so depressed? Goldman Sachs analyst Marc Cohen suggests split- ting off tobacco may not be the quick fix Wall Street expects. In addition to American Brands and Philip Morris, RJR Nabisco Holdings is considering such ac- tion. "The biggest surprise of all is that you could separate off the tobacco companies and get no increase in value," Mr. Cohen says. He thinks RJR and Philip Morris would help shareholders more if they bought back large amounts of their own stock and paid big dividends. Donald Yacktman, manager of the S154 million Yacktman Fund, concedes that he's surprised that American Brands "fell back as far as it did. Part of the concern

NEWSBRiEFS may be that they haven't finished the deal. Once the deal is done, you might see some change of attitude." Mr. Black, the Sanford C. Bernstein analyst, attributes American Brands' stock performance to the market's current hatred of tobacco stocks, rather than to any flaws in American Brands' strate*,. Investors. he says, still view American Brands as a tobacco stock, because the B.A.T deal hasn't been completed and because American Brands isn't selling its foreign tobacco operation. "Right now, people aren't looking at fundamentals," Mr. Black says. "All peo- ple are thinking about are potential law- suits and potential legislation." In buying American Brands' U.S. to- bacco business, B.A.T has agreed to in- demnify American Brands against any smoking-related lawsuits brought against the U.S. operation. "The probability of litigation coming back to haunt American Brands is low," Mr. Black says. Meanwhile, he sees the sale as a boon for American Brands. "Instead of looking for 5% long term lannual earnings] growth: I'm looking for 7%," he says. He notes that a 7% earnings-gtvwth rate puts American Brands on par with the average expected pace for companies in the Standard & Poor's 50o-stock index. But while the S&P 500 companies have an average dividend yield of less than 3°l0, American Brands' yield is more than 6%. "Somebody should be concluding that American Brands is pretty cheap," Mr. Black says. He estimates that American Brands will earn $3.05 a share this year. which puts the stock at less than 11 times esti- mated 1994 earnings. He believes there's no prospect of the dividend getting cut. Mr. Black notes that the company is •`suffi- ciently confident about their prospects that they raised their dividend" to a 32 annual rate at the same time they announced the sale of their U.S. tobacco operation. Greensboro News & Record 27-May-1994 , p. Al NEW LAW MAY COST TOBACCO COMPANIES TALLAHASSEE, Fla. - Gov. Lawton Chiles signed a law touted the nation's toughest anti-tobacco measure Thursday, giving Florida new legal tools to sue tobacco com- panies for the costs of caring for Medicaid patients stricken by smoking-related illnesses. The move came just days after Mississippi sued 13 cigarette manu- facturers seeking to make them reimburse taxpayers for the cost of smoking-related illnesses. "We're going to take the Marl- boro man to court," Chiles said. "With this law, Florida sends a loud-and-clear message to the to- bacco giants that they will be held accountable for sponsoring sick- ness and death." Walker Merryman, a vice presi- dent of the Tobacco Institute, which represents the nation's ciga- rette makers, said he knew of no similar state law. "This bill cheats thousands of Florida businesses and legitimate products out of the right to eviden- tiary protection and defenses," the institute said in a statement. If the law is not repealed in next month's special session, the to- bacco industry will challenge its constitutionality. The law would take effect July 1. "It's taxpayer money we're going to try to get back," Chiles said. "It's being used to subsidize the profit- ability of some of the largest con- glomerates in the country." Surgeon General M. Joycelyn El- ders and former Surgeon General C. Everett Koop had written letters in support of the bill. The measure, which moved through the legislature as an amendment to a Medicaid fraud bill that drew little scrutiny from lawmakers, focuses on the liability of third parties for Medicaid recipi- ents' health-care costs. It doesn't specifically mention tobacco. Florida's top business lobbyists had pleaded with Chiles to veto the measure, saying it would expose the manufacturers of many other products including beef, cars and pharmaceuticals to lawsuits. Greensboro News & Record 27-May-1994, p. A6 TOBACCO EXPLOITED PRESS, REPORT SAYS WASHINGTON - The Council for Tobacco Research may have funded important independent sci- ence, including research by three Nobel laureates, but it also manipu- lated the press to hide the dangers of smoking, a congressional report concluded Thursday. The report by the House Energy and Commerce health subcommit- tee says the Council for Tobacco Research conducted a massive public relations campaign that "ul- timately succeeded in shifting na- tional opinion" to disregard early science about the dangers. The council, funded by the to- bacco industry, transformed ob- scure scientific reports favorable to the industry into headline news, blanketed doctors with industry re- search and even forced some news reports critical of smoking to he rewritten, the report said. Dr. James Glenn, CTR's current chairman, denied the allegations in a subcommittee hearing Thursday. "We are scientists and we seek scientific truth," said Glenn, a sur- geon who has been president of Mount Sinai Medical Center in New York and dean of Emory Uni- versity's medical school. Many of the allegations aren't new. Government doctors and smoking opponents have long at- tacked CTR, and last year the Wall Street Journal labeled it "the lon- gest-running misinformation cam- paign in U.S. business history." NEwsBRIEFs Vol. 24, No. 6, June 3. 1994 - 6 4 ~

NEWSBRIEFS Greensboro News & Record 27-May-1994, p. B5 PHILIP MORRIS STOCK TAKES 6 PERCENT DIP NEW YORK - Philip Morris Companies Inc. stock sank by about 6 percent Thursday after the company indicated the issue of sep- arating its food and tobacco busi- nesses was off the front burner indefinitely. In a marathon meeting a day earlier, its board discussed but de- cided not to act on splitting the business that makes Marlboro ciga- rettes from the operation that pro- duces Kraft cheese, Oscar Mayer meats and Jell-O dessert. The company went further on Thursday by saying it was unlikely the issue would be "before the board in the forseeable future." Analysts said the decision does not set a precedent for RJR Na- bisco Holdings Corp., which has also stated it will consider dividing its food and tobacco businesses. Tobacco analyst Roy Burry of Kidder Peabody & Co. said chances remain even that RJR, the parent of R.J. Reynolds Tobacco in Winston-Salem, will divide Reyn- olds from the rest of its operations. Philip Morris stock was halted all day Wednesday while the board met. But trading reopened Thurs- day and Philip Morris sank $3121/s a share to $50.62'h on volume of more than 9.7 million shares on the New York Stock Exchange. The decline reflected disappoint- ment that the board 'had decided not to act on the breakup proposal or to approve other aggressive steps like a new share buyback to help boost the stock price. Some major investors have urged the consumer products conglomer- ate to consider splitting the com- pany in hopes of boosting the value of their stock. They argue the stock is underval- ued because of fierce price compe- tition, the possibility of higher federal taxes on tobacco sales and the threat of more regulations of the cigarette business due to rising health concerns. Anticipation of the board's deci- sion on the breakup issue grew as Wednesday's board meeting dragged on. It is unusual that the NYSE would require a daylong trading halt for such a prominent stock. After the markets closed and the meeting ended, the company issued a statement Wednesday about what had been done that created confu- sion for many analysts and inves- tors. It said the board considered a possible separation of the food and tobacco business but "decided to take no action." Company spokes- men were unable to say whether that meant the issue had been shelved or deferred for more study. In the same release, it an- nounced two key executive ap- pointments to the long-vacant posts of vice chairman for the worldwide tobacco business and the world- wide foods business. Company president R. 'W~'11iam Murray would head the foods busi- ness while Geoffrey C. Bible would become vice chairman of the to- bacco business. Some analysts felt the executive announcement meant the company has taken a first step toward the eventual separation of the busi- nesses. Others said the chances were slim that the company would proceed with a breakup anytime soon. Wall Street Journal May 27, 1994 , p. BI U.S. MAKES AMING TO GET CHINA IN THE HABIT U '~~ NDER FIRE IN the U.S. and U ~ Europe. where antismokin~ ~ J legislation and price wars hurt business. tobacco companies are looking to China for growth. Foreign-branc; cigarettes ac- counted for less than 1% of the 1.7 trillion cigarettes smoked in China last year. But as reform spreads and incomes rise. demand for interna- tional brands is increasing. Tang Wan. a 26-year-old tool wholesaler, says he switched from a domestic brand to Marlboro three years ago. "You feel a higher social position" when you smoke foreign cigarettes, says Mr. Tang. By law, tobacco importers must sell to the Chinese National Tobacco Corp., the state tobacco monopoly, A which is responsible for cigarette distribution. Cigarette advertise- ments are banned on television and in newspaners ana magazines. But that nasn't stopped tobacco compa- nies from promoting their brands. In Guangzhou, signs of tobacco comnanies' efiorts to woo China's 300 million smokers are evervwhere: At the train station, the parkin¢ lot is filied with electric blue umbrellas stamped with the gold-lettered logo of 555 State Exnress, a B.A.T Indus- tries brand. Along Beijing Road, the main shopping thoroughfare, a dou- ble-decker bus painted to resemble a giant box of B.A.T's Lucky Strike cigarettes cuts through traffic. Tobacco companies also are li- censing their names to clothiers and shoe manufacturers and sponsoring events. Philip Morris sells Western- style clothing in Shanghai and Bei- jing under the "Marlboro Classics" brand name and sponsors radio pro- grams, while R.J. Reynolds sponsors an annual "Salem Open" tennis tour- nament in Beijing. Wall Street Journal May 27, 1994 , p. A3 TOBACCO GROUP DRAWS CRITICISM IN WASHINGTON WASHINGTON - Rep. Henry Waxmar. (D.. Calif. ) attacked the work of a tobaccc.- tunden research body as "public relations masauerading as science" - a charge staunchiv denied by tne organtzation'. heae. At a contentious hearing, Rep. Wax- man, who is conducting a hign-profile investigation into the tobacco industry, charged that from its inception in 1954, the New York-based Council for Tobac6o Re- search, was a "ploy-a seemingly indepen- dent research body whose real purpose was to promote the idea that smoking is safe.' But James Glenn, the chairman of the group, which is sponsored by five tobacco companies, contended that the organiza- tion is an important source of funding for health research and insisted that the in- dustry "exerts no control over our activi- ties." He added, "We are scientists and we seek scientific truth." The hearing focused to a large extent on a front-page article that appeared in The Wall Street Journal on Feb. 11. 1993. That article described the council as "the NEwSBRtEFs ~ Vol. 24, No. 6, June 3. 1994 6 4

hub oi a massive effort to cast doubt on the links between smoking and disease." I: said that the "ostensibly independent council has spent millions of dollars ad- vancing sympathetic science" while some- times disregarding or cutting off "studies of its own that implicated smoking as a health hazard." Mr. Glenn. who declined to respond tc~ the Journal's questions before the story appeared, yesterday characterized the ar- ticle as "totally misrepresentative of our activities." He added, "There are so many inaccuracies included in the article, it would be impossible to make a full de- fense." "We believe the story to be accurate and fair, and in the 15 months since it appeared, no one from the industry has questioned a single fact in the piece," said Paul Steiger, the Journal's managing edi- tor. Yesterday, aides to Rep. Waxman re- leased a report that they said backs up a central contention of the Journal story: that the research council was founded to counter early studies about the potential health risks of smoking and was largely the brainchild of Hill & Knowlton, the giant public relations firm. The documents, which were part of the papers of the late John Hill of Hill & Knowlton, show that the tobacco compa- ntes mat founded the council agreed to fund medical research into questions of tobacco and health. But an early Hill & Knowlton memo also stressed that a main goal of the council was "to bring to public attention the fact that there is now no conclusive proof that cigarette smoking is a cause of lung cancer or other serious nrobiems of human health." One Hill & Knowlton memo lists a lon-, string of journalists, including Edward R. Murrow, Fred Friendly and William Ran- dolph Heatst Jr., who were contacted in an effort to ensure that coverage of cigarettes wasn't overly negative. John Berard, a senior vice president at Hill & Knowlton, yesterday dismissed the documents as "old stuff." He said the firm stopped representing the council in the late 1960s and doesn't represent any tobacco companies now. Some Republican members of Rep. Waxman's subcommittee criticized him for his relentless pummeling of the tobacco industry and defended the tobacco-re- search group. Rep. Alex McMillan (R., N.C.). called Rep. Waxman's investigation an "ongoing PR extravaganza." And Rep. Thomas Bliley (R., Va.), added, "As with other tobacco-related issues that this sut.- committee has considered recently, only one side of this issue has been aired in the " ~~~ , j......... Vol. 24. No. 6, June 3, 1994 NEWSBRIEFS Wall Street Journal May 27, 1994 , p. A4 PHILIP MORRIS SAYS IT WON'T CONSIDER SPLITTING FIRM IN "FORESEEABLE FUTURE" Philio Morris Cos. triea to quell specu- lation th-nt it mient soon snlit up its foo;: aC(1 toD:_..... . nuslnesce: sa.yi.n._° t.r matter isn t exnectea to come betore i:: ooara azain in tne "toreseeable tuture." Ashea to define "toreseeable future." a company spokesman said the board won't resurrect the issue for "severai months," if ever. On Wednesday. the company said di- rectors had decided to take no action on a Tobacco Research BWY Rep. fienry Warman attacked the work of a tobacco-funded research body as '°pubiic relations masquerading as sci- ence"--a charge denied by the organiza- tion's head. Article on page A4. separation of the food and tobacco busi- nesses. but it did announce two key execu- tive apnotntments that some investors viewed as the first step toward an eventual split. Yesterday's statement only added to the uncertainty about Philip Morris's in- tentions and didn't end speculation that the company would ultimately separate the two businesses. allowing its food assets to function unencumbered by growing antitobacco sentiment in Washington and a flurry of new tobacco-liability lawsuits. The latest statement further frustrated institutional shareholders, many of whom have been confused by F'hilip Morris's statements concerning a possible separa- tion. It led many analysts to conclude that whether it splits up or not, Philip Morris must take some kind of action soon to boost its stock and satisfy Wall Street, possibly a share-repurchase plan or a dividend increase. Stock Slumps The terse statement ended a recent speculative run on the company's stock. Philip Morris shares, which failed to open for trading on Wednesday, sank S3.125, or 5.876, to close at S50.625 in heavy composite trading on the New York Stock Exchange yesterday. "They pulled the legs out from under us," said Lawrence Adelman, analyst at Dean Witter Reynolds Inc. who down- graded his rating on the stock to "neutral" from a "buy" after yesterday's announce- ment. Mr. Adelman, who like many had expected the company to make a move toward splitting the company after Wednesday's board meeting, now believes it may be a year or longer before the NEWSBRIEFS company takes up the issue aga:r,. "This doesn't mean the issue is off the table, but you can't expect a company to deal with this in such a short period of time." he said. "There's greater pressure today than there was before" for Philip Morris to take some action to boost the stock price, said William Patterson, corporate affairs direc- tor of the International Brotherhood of Teamsters and an official of the union's nenston tunds. Mr. Patterson recenuy c:: ttcmatea it: a letter trom tnstttuttot... holaers to Philip Morris Cnatrman Mtcnaci A. Miles urging him to seriously consider att ontlans to ureserve me neaitn of t:. comnanv s nontobacco ooerattons. "Irs incumbent on tne comnanv ut define its direction, and it hasn't yet aone so." Mr. Patterson said. Added Jon Lukomnik. deputy controlle?- oi pensions for New York City and a co-author of the letter: "The industry's history of dealing with issues posed o~~ tonacco has, been one of denial. I hope denial doesn't extend into the ooardroom." The New York pension fund holds 5.: million shares of Philip Morris. Large Investors Are Upset What particularly riles some large in- vestors is that Philip Morris started tne speculation itself, issuing three separate announcements since April that a split-up was under consideration. By late May, speculation had reached a fever pitch, and Philip Morris's stock rose as high as 555.25 in the days before the Wednesday board meeting. Many investors and analysts felt the announcements of the past two days were an attempt to allow the company to con- siaer a split without intense investor scru- ttn v. "Tne comment tney gave was a masterpiece of flexibility," said one large institutional shareholder. "It doesn't shed much light on where they're coming from or where they're going. Where does that leave us? With our feet planted firmly in midair." Still others believe that the door has finally been closed on the possibility of a split. The first announcement "was a mistake by the board," said Roy D. Burry, analyst at Kidder, Peabody & Co. "They're basically telling us to forget it." If it doesn't split its operations, ana- lysts believe Philip Morris would institute a share-repurchase program or raise its dividend to boost its stock price, which has been battered by the drop in cigarette prices to combat private-label rivals, grow- ing regulatory pressures and a proposed increase in the cigarette tax. In January 1993. the company's shares traded as high as 577.625. The split "was a nice idea. but it's not the right time," said Gary Black of Sanford C. Bernstein & Co., who believes the issue may be raised again in six to nine months. "The environment's not going to get mi- raculously better by June." tV W ~ -P -0 0 i,, ~~~

NEWSBRIEFS Greensboro News & Record May 28, 1994 , p. A2 CORRECTION :GETrING IT RIGHT The Nm"&Reeurd•carec{s errorsitirit.sneWs cotumns3hatwne to ifs.atlenfions ttalso ' pubiiss#e.c irt this:spaca: appmpriate clarificalins. NEMRK--_: 411y:fistury hy:ihe Assoaatedi'ms,a6out intemai.tabacxo company,&0- mentsabfained.b}i..The New.Yak Iimes cabined ae erfoneuuS-ttesaiptiart of snie offisisi's - . .. . ~s~: ,..., .. .. _ ~ ;. . Th~ nu6al ~ tepat~t.#hat in one doaurterii fl~~eta! ~ for.tbe i3mnA: :~T~ai~cd~aP-~`~~:io~t ~.p[edispos®d pe~e tn fe~g a~;~oo~iDt~dd.~hea~t tRsaase:~d m~htxs~se etnIsm . _.~. 31ai;T~s~i~que~rrepodM;in.~;~tion ~at~:~el i~set,eras n~ ~ .:, ..... ~. :.:..:. . ,... ~saran`thar~~ ~~nci~ ha~is Greensboro News & Record 28-May-1994, p. A7 LAWMAKERS ASK ATTORNEY GENERAL TO INVESTIGATE TOBACCO EXECUTIVES WASHINGTON - Seven cong- ressmen asked the Justice Depart- ment Friday to begin a criminal investigation of tobacco companies on a variety of charges, from per- jury to racketeering. The letter, addressed to Attorney General Janet Reno, was written by Rep. Martin T. Meehan, D- Mass. It said: "We believe a crimi- nal investigation is warranted by information contained in the indus- try's own internal documents re- vealed in recent weeks by Rep. Henry Waxman, chairman of the House subcommittee on health and the environment, and the news me- dia. "Documents and testimony be- fore Mr. Waxman's panel offer compelling evidence that tobacco companies - through their execu- tives, their lawyers, their advertis- ing agencies, their lobbyists, their public relations agents, their scien- tists and their trade association of- ficials - have committed a series of serious crimes over a period of several decades." - The letter said documents from the Brown & Williamson Tobacco Corp. appeared to show "the to- bacco companies conspired to sup- press competition in the marketing of less hazardous cigarettes." It went on: "Evidence is also accumulating that company execu- tives perjured themselves when they testified that they had no knowledge of nicotine's addictive properties." A spokeswoman said the Justice Department needed to study the matter before responding. Brennan Dawson, a spokes- woman for the industry's Tobacco Institute, the Washington trade as- sociation, declined comment on the letter. Brown & Williamson did not return calls. Company officials, in interviews and congressional hear- ings since March, have insisted they have done no wrong. But Meehan differs - and used political cartoonist Garry Trudeau to help garner support for a probe. In circulating the letter among col- leagues, he included a copy of a recent "Doonesbury" strip in which Justice Department lawyers decide to prosecute tobacco offi- cials. The possible offenses listed in the letter include perjury, conspir- acy to obstruct Congress, conspira- cies in restraint of trade, conspiracy to defraud the public, mail fraud, wire fraud and racke- teering. rtEwssRIEFs The letter said the Justice De- partment was already investigating a possible conspiracy on the part of tobacco companies to suppress the marketing of a cigarette that is much less likely to set furniture on fire if it is dropped. The letter said that the compa- nies had apparently conspired to prevent the marketing of cigarettes that would be less likely to cause disease and that company execu- tives had been aware of cigarette addiction for the last 30 years. 9 4 5

Greensboro News & Record 28-May-1994, p. B7 RACING ADVERTISES SMOKES NEW YORK - As Emerson Fit- tipaldi drove to victory in the India- napolis 500 last year, the auto racing veteran helped his tobacco sponsor get an estimated $5 million worth of something it can't buy directly - TV exposure. Fittipaldi is in the Marlboro Team Penske racing stable and his car and uniform carry the cigarette brand's distinctive markings. He defends his title on Sunday against a field that includes two other Marlboro-backed drivers. Some anti-smoking advocates have accused tobacco companies of backing sports events like auto rac- ing at least in part to get TV expo- sure they have been unable to buy for more than two decades. The tobacco companies say that isn't the reason they back auto rac- ing. Philip Morris Companies Inc., Marlboro's owner and the world's biggest cigarette company, and the R.J. Reynolds Tobacco Co. say they support the sport because it at- tracts an above-average proportion of fans who smoke. "If racing were not televised at all, we would be involved with it anyway," said Ellen Merlo, a Philip Morris executive. Nonetheless, the sport has been drawing more TV coverage as ca- ble TV service has expanded. The exposure has become a valuable fringe benefit of sports alliances for an industry prohibited from ad- vertising on TV since 1971. Joyce Julius and Associates, an Ann Arbor, Mich: based firm that tracks brand exposure during tele- vised sports events, said Marlboro was mentioned four times and its name or logo was on the screen for nearly 14 minutes during the ABC telecast of the 1993 Indy 500 race. At the rates being charged for commercial time, the firm said the exposure was worth about $5.1 mil- lion. In addition to the victor PYtd- paldi, Marlboro was backing Paul Tracy in that race. Those two men and Al Unser Jr. will be driving Marlboro Team Penske cars or. Sunday. NEWSBRIEFS All three will be driving virtuallv indistmguishabie cars emblazoned with the Marlboro name and its bright red and white colors. They will each also have a-Marlboro logo patch on their uniforms. Wall Street Journal May 31, 1994 , p. B2 PHILIP MORRIS BUYS STAKE IN UKRAINE CIGARETTE PLANT PMlip. Morrls:Cos. is expected to announce today the purchase of a major- ity stake in a Ukraine cigarette plant, expanding_Its..tobacco_.fnterests in the former communist states. People close to the New York cigarette and food company.said it has agreed to buy 513'0f of theBharkov Tobacco Factory, a dgarette plant in the city of the same name.in.the eastern part of the country. Remaining shares are owned by factory maoagement and employees. Philip Morris will eventually expand its owner- ship interests = -. . - .. . - The-Rhsrrov plant in the Ukraine has capacity to produce five:billion ciganettes a year, but is maldng iess than half that amount due to lack of raw materials and the generally poor eeanomic condition of thecosuttry.~:. :.In :buying.ahe -stake, 'Philip Morris joins aompetitora $.A.T Industries PLC, RJR Nabtseo Holdiogs Cbrp., and 8eetatina pgaretteafrbrifcen GmbH in operating plants in the country. .. Philip .Mcrris.-also-owns controlling stakes in cigarette operations in Iiun- gary, -the (x.ech. Republic. Rase>cbxtan, Lithuaniasnd Rmtias Chemical & Engineering News May 23, 1994, p. 30 TOBACCO FIRM SUBPOENAS TWO CONGRESSMEN, SIX REPORTERS At press time, Brown & Williamson Tobacco Co. had asked the District of Columbia Superior Court to issue subpoenas to Rep. Henry A. Waxma1(D.-Calif.) and Rep. Ron Wyden (D: Ore.). Waxman diaits and Wyden sits on the House Energy & Commerce Subcommittee on Health & the Environment, which has been holding hearings on whether to regtilatee nico- tine in ciganettes. Six reporters have also been subpoenaed. The subpoenas order all eight to supply Brown & Williamson with any of the company's confidential documents in their possession. A source in the House General Counsel's Office tells C&IIV, "It is our opinion that the Congressmen sh.,-uld not honor the subpoenas or produce the documents. In the near future, we will take the proper legal steps to quash the subpoenas." Brown & Williamson's chief executive officer, Thomas Sandefur, was scheduled to testify before Waxman's cammittee last Friday. Testimony was expected to cover infor- mation contained in the documents. The company says the documents were stolen and improperlq released to the com- mittee and the pias.s. The company also says the documents are covered by attorney-client privilege and a court it#tutction. . f46 Vol. 24, No. 6, June 3. 1994

ABSTRACTS Nature May 12,1994, p. 154 GENETICALLY BASED N-ACETYLTRANSFERASE METABOLIC POLYMORPHISM AND LOW-LEVEL ENVIRONMENTAL EXPOSURE TO CARCINOGENS THE metabolic activation or inactivation of carcinogens varies con- siderablv in human populations, and . is partly genetically determined''Z. Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust''s. We have determined levels of DNA adducts in bladder cells and of 4-aminobiphenvl-haemo- globin adducts in 97 volunteers, together with the N-acetylation nott-inducible phenotype, the corresponding genotype, and the levels of nieotine-cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenvl adducts were higher than in rapid acetylators at low or null nicotine-cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing niootine-cotiuine levels. The N-acetyltransferase geno- type is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to 'risk assesQment' procedures. Chromatographia Vol. 38,1994, p. 521 NEW, UNIFIED NOMENCLATURE FOR CHROMATOGRAPHY The most important definitions, terms and symbols included in the new, unified Nomenclature for Chromatography issued by the International Union of Pure and Applied Chemistry (IUPAC) are outlined. Denn eben, wo Begriffe fehlen, Da stelit efn Wort zur rechten Zeit sich ein. Mit Worten 1B,6t sich trefflich streiten, Mit Worten efn System bereiten, An Worte lttJ3t sich trefflich glauben, Von einem Wort ltl,6t sich kein Iota rauben. * ABSTRACTS Vol. 24, No. 6, June 3, 1994 7 F, 4

ABSTRACTS Tobacco Science Vol. 38,1994, p. 35 REDUCED POPULATION GROWTH AND DELAYED DEVELOPMENT OF THE CIGARETTE BEETLE (COLEOPTERA: ANOBIIDAE) DUE TO THURINGIENSIN Three formulations of thuringiensin, the heat-stable P- exotoxin of Bacillus thuringiensis, were incorporated into diet medium (finely ground tobacco) of first instar cigarette beetles, Lasioderma serricome (F.). At 15 and 60 ppm (wt AUwt diet medium), larval mortality and development, and population growth over one generation were studied. Then the formulation found to be most effective was applied to diet at 15 to 75 ppm. Larvae of all instars were placed on the diet, allowed to develop, and percentage adult emergence was observed. The formulations, all from Abbott Laboratories, were ABG-6211 (1.5% Al [wdwt] emulsifiable concentrate), ABG-6162A (1.5% Al [wNwt) emusiflable concentrate) and ABG-6206 (10% Al [wNwt] wettable powder). Except for ABG-6211-15 and ABG-6162A- 15 (=15" = 15 ppm), all treatments induced larval mortalities of 68 to 100%; control mortality was 17%. Except for ABG-6211- 15, all treatments slowed larval development, especially at 60 ppm and especially ABG-6206. After eight weeks of exposure, the sole surviving ABG-6211-60 larva was still a 1st instar, while control larvae had begun pupation. All treatments at 15 ppm significantly (P<0.05) reduced population growth, especially ABG-6206-15 (96% reduction); all formulations at 60 ppm caused >99% reduction. In the dose-response test, adult emergence was significantly (P<0.01) correlated to the dose and to the interaction between dose and the stadium in which first placed on the diet. Additional key words: Nicotiana tabacum, tobacco, lastoderma semicome, p-exotoxin. Tobacco Science Vol. 38,1994, p. 38 ASSESSING THE QUALITY OF BURLEY TOBACCO PART 1: GRADE INDEX AND ASSOCIATED FACTORS This study determined an average yearly grade index (GID) from sales data for burley tobacco for the years 1959 - 1990. This index was used as a quality measure for each crop year. Several leaf-group, leaf-color, and seasonal-crop variables were significantly correlated with GID. Within the leaf groups, the leaf and lugs categories had a positive effect on GID, while tips, nondescript, and a combined group (TNM) had negative correlations. A tradeoff existed between these leaf groups in relation to the grade index. For the color groups, the tan groups within the lugs and leaf categories (CF, BF) and the tannish-red leaf group (BFR) had significant positive correlations with GID, while green color in the leaf, tips, and flyings groups had significant negative correlations with GID. Total crop production area had a significant negative correlation with GID, while it was positively correlated with the undesirable leaf groups of tips, nondescript, and TNM. This indicated that market quality was reduced when production area increased. The significantly correlated variables were used to develop a regression equation to predict GID. The equation had a regression coefficient of 0.935, and it predicted GID reasonably well for the 32-year period. Additional key words: Nicotiana tabacum, burley tobacco, quality, grade index. ABSTRACTS VoL 24, No. 6, June 3, 1994 ~? ~~

ABSTRACTS American Journal of Respiratory & Critical Care Medicine Vol.149,1994, p. 1209 THE UCLA POPULATION STUDIES OF CHRONIC OBSTRUCTIVE RESPIRATORY DISEASE: XI. IMPACT OF AIR POLLUTION AND SMOKING ON ANNUAL CHANGE IN FORCED EXPIRATORY VOLUME IN ONE SECOND We assessed the relative impact of residential exposure to community air pollution and habitual cigarette smoking on lung function by comparing the annuaiized rate of change in forced expiratory volume in 1 s (FEV,) in current, former, and never-smokers 25 to 59 yr of age residing in three demographically similar areas of the Southern California air basin who had been chronically exposed to (1) moderate levels of. photochemical oxidants and very low levels of other pollutants (Lancaster); (2) very high levels of photochem- ical oxidants, sulfates, and particulate matter (Glendora); and (3) high levels of sulfates, oxides of nitrogen, and probably hydrocarbons (Long Beach), together with moderate levels of sulfur dioxide. Of the 621 to 763 nonsmokers, 317 to 479 former smokers and 472 to 691 continuing smokers residing in the three areas who were studied initially, 53 to 64,49 to 59, and 43 to 54%, respectively, were retested. For male residents, area of residence and smoking category each had highly significant effects on FEV, decline (two-way ANCOVA; p< 0.001) without significant interaction (p > 0.4). After adjustment for baseline FEV,, age, height, and a history of allergy, the mean decline in FEV, attributable to living in Long Beach compared with living in Lancaster was 23.6 ml/yr, which was 71% of the rate of decline in FEV, (33.3 mllyr), attributable to smok ing > 1 pack of cigarettes per day. For female residents, a significant interaction was noted between area and smoking (p < 0.05). In female nonsmokers, but not consistently in female smokers, residence in either of the two most polluted areas was associated with a significantly greater annual decline in FEV,. These findings suggest that chronic exposure to air pollution has an independent adverse effect on lung function in male smokers, and possibly female smokers, residing in areas exposed to high levels of atmospheric pollution. Tashkin DP, Detels R, Simmons M, Liu H, Coulson AH, Sayre J, Rokaw S. The UCLA population studies of chronic obstructive respiratory disease: Xi. Impact of air pollution and smoking on annual change in forced expiratory volume in one second. Am J Respir Crit Care Med 1994;149:1209-17. ABSTRACTS VoL 24 No. 6, June 3, 1994 6 4 n

BOOKS RECENTLY RECF.NED IN THE LIBRARY QP POSTLABELLING METHODS FOR DETECTION OF DNA ADDUCTS 609 .D4 By: PHILLIPS, D.H., ED.; CASTEGNARO, M., ED.; P84 BARTSCH, H., ED. Subject: BIOLOGICAL MARKERS - CONGRESSES ENVIRONMENTAL MONITORING - METHODS DNA DAMAGE AUTORADIOGRAPHY - METHODS PHOSPHORUS RADIOISOTOPES DNA - ANALYSIS CARCINOGENS RA 1199_4 INTRODUCTION TO IN VITRO CYTO'I'OXICOLtX'Y : ~CHANISMS AND METHODS .15 B37 By: Subject: BARILE, FRANK A. TOXICITY TESTING - IN VITRO CELL CULTURE CELL-MEDIATED CYTOTOXICITY TOXICOLOGY RC BIOI.OCIC MARKERS IN IHMUNOTOXICOLOGY 582.17 .B5 Subject: IMMUNOTOXICOLOGY BIOCHEMICAL MARKERS BIOLOGICAL MARKERS ENVIRONMENTAL POLLUTANTS - ADVERSE EFFECTS HYPERSENSITIVITY IMMUNE SYSTEM - DRUG EFFECTS IMMUNOTOXINS - ADVERSE EFFECTS REF THE UNITED STATES GOVERNNCENT MNAL JK 421 .A3 Subject: POLITICS AND GOVERNMENT EXECUTIVE DEPARTMENTS - HANDBOOKS, MANUALS, ETC. GOVERNMENT - YEARBOOKS NEW BOOKS 6 D0 Vol. 24, No. 6, June 3, 1994

BOOKS RECENTLY RECEIVED IN THE LIBRARY TP PASTE FLOW AND EXTRUSION 1175 By: BENBOW, JOHN; BRIDGWATER, JOHN .E9 B46 Subject: EXTRUSION - PLASTICS; FOOD; CLAY PLASTICS - PROCESSING NEW BOOKS Vol. 24, No. 6, June 3, 1994

RECENTLY PUBLISHED THE EFFECTS OF UPHOLSTERY FABRIC PROPERTIES ON FABRIC IGNITABILITIES BY SMOLDERING CIGARETTES By: Dwyer, R.W. Fournier, L.G. Lewis, L.S. Furin, D. Ihrig, Arthur M. Smith, Shirley Hudson, W.Z. Honeycutt, R.H. Bunch, J.E. Published: Journal of Fire Sciences Vol. 12, 1994, p. 268 CONGRATULATIONS TO Art & Shirley RECENTLY PUBLISHED

ANALYSIS OF PAPER OR FIBER A Variable-Volume Optical Pressure-Volume-Temperature Cell for High-Pressure Cloud Points, Densities, and Infrared Spectra, Applicable to Supercritical Fluid Solutions of Polymers Up to 2 Kbar. ??y Gregg CJ; Stein FP; Morgan CK; Radosz M Journal of Chemical and Engineering Data; 39 (2) p219-224 APR 1994 ORDER # NH509 A new high-pressure variable-volume optical cell equipped with a sapphire window, a movable piston with a position sensor, and infrared fiber optic probes is described. The apparatus was tested by measuring the cloud points for the system propylene + poly(ethylenepropylene) at 100 and 150- degrees-C, the densities of ethylene and propylene up to 1000 and 600 bar, respectively, and the midinfrared spectra of hexane at 500 bar. (In English) Water Resistance of Poly(Imide-Siloxane) Adhesives - An IGC Surface Energetics Study. By Kalteneckercommercon JM; Ward TC Journal of Adhesion; 42 (1-2) p113-124 19931 ORDER # ND116 Inverse Gas Chromatography was utilized to examine the interaction of water vapor with the surfaces of a polyimide homopolymer and poly(imide-siloxane) random- block copolymers of increasing siloxane content. The studies employed 45-60 meter, thin-polymer-film mega-bore capillary columns to maximize surface area. The free energies of specific surface interaction with water and the dispersive components of the solid surface free energies were determined. An increase in the polymer siloxane content from 0-wt% to 10-wt% resulted in a decrease of approximately 4 kJ/mol in the free energy of water-specific surface interaction. A further increase in siloxane content to 30-wt%.was not found to increase surface water resistance significantly. Dispersive components of the solid surface free energies of the copolymers were comparable to values reported for poly(dimethylsiloxane) homopolymer. (Tn English) Vol. 25, No. 6, June 3, 1994

ANALYSIS OF PAPER OR FIBER Novel Mercury-Coated Carbon Fibre Voltamooetric Detector for Use in Adsorptive Stripping Flow Analysis. By Delpozo JA; Costagarcia A; Tunonbianco P Analytica Chimica Acta; 289 (2) p169-176 APR 29 1994 ORDER # NH533 The preparation and application of a novel mercury-coated carbon fibre flow microelectrode are reported. The possibility to use this device in a flow system combined with alternating current (ac) stripping voltammetry is also demonstrated using mitoxantrone (MXT) as probe compound. The electrode is easy to prepare. Special analytical advantages have been observed when a.c. stripping voltammetry is applied to the adsorbed molecule on the electrode due to the reversibility of the electrochemical process. Once the operating system has been optimized a limit of detection for mitoxantrone of 4.5 x 10(-11) M was found. Manipulation of flow conditions allows the study of different concentration ranges. The direct analysis of serum samples without sample pretreatment, is also discussed and provided a linear calibration range between 4.5 X 10(-7) M and 4.5 x 10(-6) M. (In English) Vol. 25, No. 6, June 3, 1994

ANALYSIS OF PESTICIDES How Variable Are Rates of Colonisation. By Wellings PW European Journal of Entomology; 91 (1) p121-125 19941 ORDER # NG455 The rates of spatial expansion of range following the introduction of animals to new areas are extremely variable between species. Data on a selection of species from a range of taxa show that these rates vary over about five orders of magnitude. The range expansion of a limited number of pest species of aphids have been mapped following colonisation. Studies on rates of colonisation are important as they are central to pest risk analysis. In addition, the observed variation in rates have significant implications for the development of realistic models of metapopulations. (In English) Determination of Handwash Removal Efficiency - Incomplete Removal of the Pesticide Chlorpyrifos from Skin by Standard Handwash Techniques. By Fenske RA; Lu CS American Industrial Hygiene Association Journal; 55 (5) p425-432 MAY 1994 ORDER # NJ102 This study was designed to develop standard procedures whereby the removal efficiency of handwash techniques can be determined. A known amount of the insecticide chlorpyrifos (Dursban(TM)), was transferred to the hands of volunteers, which were washed by a standard technique. The following experimental variables were studied: time between exposure and washing, washing solvent, and skin loading. Ethanol removed only 30% of the chlorpyrifos on skin at loadings of approximately 7 mug/cm2, with residence time on skin having no effect. Prewashing with ethanol increased removal efficiency. A 10% isopropanol/distilled-water wash removed 43% immediately following exposure, and 23% one hour post-exposure, with skin loadings of approximately 12 mug/cm2. Removal efficiency immediately following contact decreased for lower skin loading levels (21-23% for loadings of 0.1-1 mug/cm2). These findings indicate that substantial amounts of the insecticide were either absorbed through or adsorbed to the skin, and that pesticide residue levels recovered by standard handwashing techniques are unlikely to represent accurate estimates of dermal exposure. Approximately two-fold to five-fold underestimations of exposure can occur for pesticides with handwash procedures similar to those tested. All experimental variables studied can each alter significantly the fraction of total pesticide on skin that handwashing removes. If handwashing is to be used to estimate dermal exposure in the workplace, appropriate laboratory-based removal efficiency studies should be conducted prior to field investigations. Further efforts should be made to develop accurate and reproducible hand measurement techniques. (In English) Vol. 25, No. 6, June 3, 1994 So N W O• .P A 0 r ~55

ANALYSIS OF PESTICIDES Proposed Protocols for the Determination of Potential Ocular Effects of Organophosphorus Pesticides. By Hamernik KL Journal of Applied Toxicology; 14 (2) p131-134 MAR-APR 1994 ORDER # NG939 The US Environmental Protection Agency now requires ocular toxicity testing to support the registration of organophosphorus pesticides. As a first step toward guideline development for the conduct of these studies, preliminary protocols for ocular toxicity testing in the non-rodent and rodent are being proposed by the Office of Pesticide Programs. Proposed protocol parameters include determination of animal health status, measurement of plasma, erythrocyte and retinal cholinesterase activities, ocular assessment by routine ophthalmological examination, slit lamp biomicroscopy, fundic observations, tonometry, electroretinography and determination of objective refractivity, pupillary response and tracking. Gross and detailed histopathological examinations of ocular system components would also be conducted. Associated questions and concerns with regard to ocular toxicity testing are presented. The Agency plans to hold a workshop in the near future to discuss issues related to protocol refinement and guideline development. (In English) Vol. 25, No. 6, June 3, 1994

ANALYSIS OF TOBACCO Analysis of Ambient Polar and Non-Polar Volatile Organic Compounds (Vocs) by Thermal Desorption, High Resolution Gas Chromatography Mass Spectrometry (Td/HRGC/MS). By Kruschel BD; Bell RW; Chapman RE; Spencer MJ; Smith KV HRC - Journal of High Resolution Chromatography; 17 (3) p187-190 MAR 1994 ORDER # NH802-5 No abstract available (In English) Chromatographic Mass Spectrometric Determination of Volatile Organic Compounds in Contaminated Soil. By Rastyannikov EG; Drugov YS Journal of Analytical Chemistry; 48 (9 Part 1) p1012-1016 SEP 1993 ORDER # NG022 No abstract available (In English) -P ? Vol. 25, No. 6, June 3, 1994 W 3~~

.7.., ANALYTICAL CHEMISTRY (GENERAL) Choice of Stationary and Mobile Phases for Separation of Mixed Triglycerides by Liquid Phase Chromatography. By Heron S; Tchapla A Analusis; 22 (3) p114-126 APR 1994 ORDER # NH520-2 A systematic study of retention of homogenous saturated and unsaturated triglycerides has been made on different stationary phases (octadecyl, phenyl, mixed C18-CN bonded silicas) with various non-aqueous binary and ternary mobile phases. It allowed to determine optimal and simple conditions of analysis of mixed triglycerides in fats or oils. The use of combined optimization criteria to judge the quality of an entire chromatogram leads to propose the use of one column with polymeric behavior, with a binary and isocratic mobile phase (MeCN/CH2C12). The triglyceride composition being complex, the entire identification required fuller studies of the oils and fats by mass spectrometry/gas chromatography and mass spectrometry/liquid chromatography. (In French) Instrument-Induced Effects in the Analysis of Polycyclic Aromatic Compounds by Capillary Gas Chromatography with Atomic Emission Detection (GC-Aed). By Janak K; Ostman C; Carlsson H; Bemgard A; Colmsjo A HRC - Journal of High Resolution Chromatography; 17 (3) p135-140 MAR 1994 ORDER # NH802-1 Peak splitting of high molecular weight polycyclic aromatic compounds originating from the microwave plasma of an atomic emission detector (AED) coupled to a GC has been described and evaluated. The influence of the solute structure, solute concentration, and physical conditions in the AED (such as detector temperature, make-up gas flow, concentration of reagent gases and distance of column end from the plasma) have been studied. An explanation is presented for peak splitting, which is based on an insufficient solute decomposition and solute mass flow in the discharge tube. Modification of the instrument by introduction of additional make-up gas applied through the transfer line has been shown to improve peak shape and solute response. (In English) Vol. 25, No. 6, June 3, 1994 :it eJ J

ANALYTICAL CHEMISTRY (GENE:kAL) High Resolution Capillary Gas Chromatography and Gas Chromatography Mass Spectrometry of Protein and Non-Protein Amino Acids, Amino Alcohols, and Hydroxycarboxylic Acids as Their tert-Butyldimethylsilyl Derivatives. By Simek P; Heydova A; Jegorov A HRC - Journal of High Resolution Chromatography; 17 (3) p145-152 MAR 1994 ORDER # NH802-3 A simple, single-scep derivatization technique is presented for capillary GC-FID and GC-MS separation and identification of common protein and non-protein constituents of natural peptides as their tert- butyldimethylsilyl (TBDMS) derivatives. The tert- butyldimethylsilylation of more than sixty compounds was accomplished with high yields and a single peak observed for each component. The TBDMS derivatives of both the protein and non-protein substances, moreover, exhibit excellent separation on apolar capillary columns and can be resolved completely using a polydimethylsiloxane or 5 % phenyl polydimethylsiloxane column and, complementarily, a 50 % phenyl polydimethylsiloxane column. Retention data and molar responses of the TBDMS derivatives on the polydimethylsiloxane column are compiled. Direct coupling of the 5 % pnenyl polydimethylsiloxane column to an ion trap mass spectrometer enabled fast sepa==.tion and identification of the investigated components, at nanomole to picomole levels, on the basis of retention and mass spectral data, The general usefulness of the method is demonstrated by research into new biologically active peptides isolated from entomopathogenic fungi. (In English) Separation of Novolac Resin Oligomers and Related Industrial Materials by High Temperature Capillary Gas Chromatography. By Toth T; Garay F HRC - Journal of High Resolution Chromatography; 17 (3) p177-179 MAR 1994 ORDER # NH802-4 No abstract available (In English) . Vol. 25, No. 6, June 3, 1994 ~~ ~ ~

ANALYTICAL CHEMISTRY (GENERAL) LC-GC on-Line Coupling - Principles, Developments and Applications. By Modeste F; Caude M Analusis; 22 (3) p89-107 APR 1994 ORDER # NH520-1 The practical achievement of the on-line coupling of liquid chromatography (LC) with high resolution gas chromatography (GC) is described, featuring different eluent evaporation and solute-focusing techniques at the head of the capillary column in the GC apparatus. The respective advantages and drawbacks of each.methodology are discussed but the one, which uses partial evaporation of the effluent in the deactivated transfer precolumn, offers a great polyvalency whatever the volatility of transferred solutes may'be. The reconcentration techniques used call for the cold trapping or a derived process. The equipment is modified in the sense of a reduction of the internal diameters of the LC columns, to reach a compromise between the volume of the transferred liquid and the capacity of the capillary precolumn in the GC apparatus. With this aim, the utilized interfaces are mainly the 'direct transfer-line' and the 'loop-type transfer-line' for which, the respective advantages and drawbacks are discussed. Finally, examples of recent applications in many fields are given. (In French) Comparison of Two-Stage Retention Index Monitoring Capillary Gas Chromatography and Selected Ion Monitoring Capillary Gas Chromatography - Mass Spectrometry as Analytical Tools. By Enqvist J; Enqvist M HRC - Journal of High Resolution Chromatography; 17 (3) p141-144 MAR 1994 ORDER # NH802-2 Two-stage capillary GC with two-stage retention index monitoring is an efficient analytical technique which can be used for detection and determination of small amounts of volatile compounds in complex mixtures of hundreds or thousands of other compounds. The system employs two capillary columns, coated with different stationary phases, connected on-line with the aid of a micro valve; the first column acts as a pre-separating unit from which unresolved fractions of interest are cut (transferred) into another column for final, interference-free separation of the compounds to be determined. This technique has been compared with selected ion monitoring capillary GC-MS using a hydrocarbon mixture as a test sample for comparing resolution, repeatability, and the practical usefulness of the techniques. Results indicate that two-..tage capillary GC is very useful for mixtures containing compounds which produce mostly non-specific ions in the MS ion source whereas compounds producing specific ions can be easily analyzed by capillary GC - single ion monitoring MS even if they are not perfectly separated by a single capillary column. (In English) Vol. 25, No. 6, June 3, 1994

ANALYTICAL CHEMISTRY (GENERAL) Effects of pH and Organic Solvent on Chromatographic Behavior in Capillary Electrochromatography. By Kitagawa S; Tsuda T Journal of Microcolumn Separations; 6 (2) p91-96 MAR-APR 1994 ORDER # NH882-1 Electrochromatography is demonstrated using a 50 mum i.d. capillary column. The separation of solutes due to their different mobilities is obtained by the application of high voltage along the column. The elution times of solutes are dependent on the pH and composition of the eluent. Both electrophoretic and electroosmotic flow velocities are almost constant between 30 and 90% methanol in the eluent, and they increase with more than 90% methanol. The pH dependence of the electroosmotic flow velocity may be related to the dissociation of unreacted silanol groups on the surface of the ODS-silica particles. (In English) Shape Selectivity Assessment of Stationary Phases in Gas Chromatography. By Sander LC; Schneider M; Wise SA; Woolley C Journal of Microcolumn Separations; 6 (2) p115-125 MAR-APR 1994 ORDER # NH882-2 Column selectivity is examined for a series of smectic liquid crystalline columns and is compared with methyl and C18 polysiloxane columns for the separation of polycyclic aromatic hydrocarbon (PAH) isomers. A set of e,tended and condensed solute probes is described that provides a sensitive indication of variations in column shape selectivity. Examples of shape selectivity differences are presented for smectic liquid crystalline columns and 5% phenyl polysiloxane columns using various PAH isomer sets. Variations in selectivity have been observed among different smectic liquid crystalline columns, and this problem appears more significant than for methyl polysiloxane columns. The selectivity ratio for tetraphenylmethane and p-terphenyl provides a sensitive indication of column shape selectivity, with a change in elution order occurring between ordered (smectic liquid crystalline) columns and non-ordered (methyl polysiloxane) columns. Shape selectivity differences indicated by this test mixture are apparent for more complex PAH isomer mixtures. Despite stationary phase selectivity variability, smectic liquid crystalline columns offer considerable potential for solving difficult separation problems involving structured solutes. (In English) Vol. 25, No. 6, June 3, 1994 ~~i

ANALYTICAL CHEMISTRY ( GEIARAL ) Cyclodextrin PLOT Columns for the Gas-Solid Chromatographic Separation of Light Hydrocarbons and Inorganic Gases. By Reid GL; Armstrong DW Journal of Microcolumn Separations; 6 (2) p151-157 MAR-APR 1994 ORDER # NH882-3 Alpha and beta cyclodextrin (alpha- and beta-CD) were chemically bonded to porous layer fused silica open tubular columns and used as gas-solid chromatographic (GSC) stationary phases for the separation of C1 to C6 hydrocarbons and a variety of inorganic gases. In general, these cyclodextrin PLOT columns were superior to the analogous packed columns. The capillary columns show similar selectivities with an increase in efficiency and number of theoretical plates over the packed columns. The cyclodextrin stationary phases show good selectivities toward the light hydrocarbons and inorganic gases on capillary columns as short as ten meters. Subambient temperatures allow the baseline resolution of oxygen from nitrogen. These columns have been effectively utilized at temperatures up to 260-degrees-C without loss of efficiency or degradation of selectivity. (In English) Evaluation of Shape Selectivity of Liquid Crystals in Capillary Gas Chromatography. By Krupcik J; Valachovicova M; Kraus G Journal of Chromatography A; 665 (1) plll-116 APR 8 1994 ORDER # NG211-1 The shape selectivity of 4-octoxyphenyl 4-pentoxybenzoate as a liquid crystal stationary phase was monitored in the separations of o-, m- and p-xylene and cis- and trans-l,2- dimethylcyclohexane and -decalin in the temperature range 54-83 degrees C with both increasing and decreasing column temperatures in 5 degrees C steps. Retention indices were used to study the dependence of retention on temperature. The influence of temperature on the shape selectivity of the liquid crystal stationary phase was measured as the dependence of log alpha on 1/T. The use of saturated cyclic compounds for measuring the shape-selective properties of a liquid crystal stationary phase is superior to the use of xylenes as they are less polar than xylenes and their selectivity factors are more sensitive to selectivity changes. (In English) l Vol. 25, No. 6, June 3, 1994

ANALYTICAL CHEMISTRY (GENEgRAL) Determination of Toxaphene in Soil by Electron-Capture Negative-Ion Mass Spectrometry and Capillary Column Gas Chromatography. By Onuska FI; Terry KA; Seech A; Antonic M Journal of Chromatography A; 665 (1) p125-132 APR 8 1994 ORDER # NG211-2 Although toxaphene is now limited in use, interest in its analysis continues because of its persistence and widespread atmospheric transport in the environment and its presence in many dump-sites all ove_ :he world. Top soil samples collected from a dump site were analyzed for toxaphene residues. Analyses were performed by wall-coated open tubular column gas chromatography in tandem with electron-capture negative-ion mass spectrometry. Since the concentrations of toxaphene residues were at mg/kg levels, the application of a mass spectrometer as a substance- selective detector has been applied. Advantages of this mode of real-time acquisition in continuous repetitive scanning of mass spectra has significant advantages in comparison to the selected-ion monitoring technique. An average R.S.D. of 10% and recoveries of 90 to 109% were obtained. Levels down to 50 mu g/kg are obtainable. (In English) Purge-and-Trap injection Capillary Gas Chromatographic Determination of Volatile Aromatic Hydrocarbons in River Sediment. By Kuran P; Kubinec R; Ostrovsky I; Sojak L Journal of Chromatography A; 665 (1) p133-138 APR 8 1994 ORDER # NG211-3 Dynamic headspace and purge-and-trap with methanolic extraction techniques for the simple and rapid determination of trace amounts of volatile aromatic * hydrocarbons in river sediments were compared. The purge- and-trap technique with metanolic extraction using an external standard method gives a better representativeness of the analysed sample, a twofold higher precision and twofold lower detection limits. When the internal standard method is applied, the precision of both methods increases 3-4 tin.es and the detection limits decrease 4-5 times. (In English) Vol. 25, No. 6, June 3, 1994 ,:,,.,.:-. :_-_- ._-

ANALYTICAL CHEMISTRY (GENERAL) Determination of Fumaric Acid, Maleic Acid, and Phthalic Acid in Groundwater and Soil. By Dietz EA; Singley KF Journal of Liquid Chromatography; 17 (7) p1637-1651 19941 ORDER # NG421 When present at > 1 mu g/mL, each title compound was determined in groundwater by ion-exclusion chromatography after sample acidification and filtration. For groundwater with one or all analyte concentrations of < 1 mu g/mL, the acid anions were first concentrated from a 100-mL sample using a quaternary amine.anion-exchange cartridge. The acids were recovered by eluting the cartridge with 1 mL of 1 N H2SO4 and two 2-mL deionized water washes; this solution then was examined by anion-exclusion chromatography. For soil, the acids were extracted from a 10-g sample with 20 mL of 1 N H2SO4 and two 15-mL water washes. This extract was filtered then anal;zed by anion- exclusion chromatography. All analyses used 25-mu L injections into the HPLC column which was maintained at 60 degrees C and eluted with; a 0.6 mL/min. now of 0.02 N H2SO4. Analytes were monitored with a W detector operated at 200 nm. The analysis procedures for groundwater were validated with solutions which were fortified with from 50 ng/mL to 200 mu g/mL of each analyte; recoveries ranged from 90 to 110%. The soil method was validated using fortified samples which contained each acid at concentrations of from 5 to 160 mu g/g. Recovery values were between 81 and 120%. For samples exhibiting minimal detector response from compounds other than the acids of interest, 100-mu L injection volumes provided an estimated detection limit of 1 mu g/g for soil and 10 ng/mL for groundwater. (In English) Headspace Constituents of Opium. By Buchbauer G; Nikiforov A; Remberg B Planta Medica; 60 (2) p181-183 APR 1994 ORDER # NG093-1 The headspace of medicinal opium (Ph. Ned. 8) was analyzed by means of GC-FID, (+EI)-GC-MS (low and high resolution), and GC-FTIR. After olfactoric evaluation of the headspace sample by professional perfumers by the use of the CC- sniffing technique and after correlation tests with trained police dogs, more than 70 components were identified. With regard to the characteristic olfactoric properties of opium only one class of components, namely pyrazines, is of special interest. The synthetic mixture of 2-methyl-, 2,5-, and 2,6- dimethylpyrazine with 2-methoxy-3-isopropyl and 2-methoxy- 3-isobutylpyrazine was found to represent the original opium odour quite well. (In English) _ Vol. 25, No. 6, June 3, 1994

ANALYTICAL CHEMISTRY (GENERAL) Retention Indices of 28 Polychlorinated Biphenyls in Capillary Gas Chromatography Referred to 2,4,6- Trichlorophenyl Alkyl Ethers as Ri-Standards. By Morosini M; Ballschmiter K Fresenius Journal of Analytical Chemistry; 348 (8-9) p595-597 MAR 1994 ORDER # NC434 An homologous series of eight 2,4,6-trichlorophenyl alkyl ethers (TCPE) was synthesized. The TCPE has.been conceived to be used as retention index markers in the gas chromatography with the atomic emission detector (AED), the electron capture detector (ECD) and the mass spectrometric detector (MSD). On the basis of the TCPE, the retention indices of 28 polychlorinated biphenyls have been determined using the ECD, a 95% dimethyl 5% phenyl polysiloxane phase and six different temperature programs. (In English) Determination of Organophosphorus Insecticides in Edible Oils and Fats by Splitless Injection of the Oil into a Gas Chromatograph (Injector-Internal Headspace Analysis). By Grob K; Biedermann M; Giuffre AM Zeitschrift Fur Lebensmittel - Untersuchung und - Forschung; 198 (4) p325-328 APR 1994 ORDER # NG114-1 Direct injection of oil or fat into a moderately heated injector enables performance of a kind of head-space technique in the injector: oil or fat is diluted 1:1 with acetone and injected into a vaporizing chamber at 200- degrees-C. Components, for example organophosphorus insecticides, evaporate from the oil film on the insert wall and are transferred into the column in the splitless mode; thee oil slowly flows along the wall to the bottom of the insert and is retained there in a kind of a bag. Using a flame photometric detector, detectiop limits are below 10 mug/kg. (In English) Vol. 25, No. 6, June 3, 1994 4 .!

ENVIRONMENTAL TOBACCO SMO'1:E Acute Effects of Tobacco Smoking on Hunger and Eating in Male and Female Smokers. By Perkins KA; Sexton JE; Dimarco A; Fonte C Appetite; 22 (2) p149-158 APR 1994 ORDER # NF984 No abstract available (In English) Levels of Lead, Cadmium, and Mercury in Canadian Cigarette Tobacco as Indicators of Environmental Change - Results from a 21-Year Study (1968-1988). By Rickert WS; Kaiserman MJ Environmental Science & Technology; 28 (5) p924-927 MAY 1994 ORDER # NJ324 Close to 90% of Canadian domestic cigarette tobacco is grown within a small geographic area in southern Ontario. The lead, cadmium, and mercury contents of this geographically homogeneous plant material was determined as a potential indicator of environmental change. During the 21-year period (1968-1988) studied, the major decreases in concentrations of lead, cadmium, and mercury occurred during a 7-9-year period commencing about 1972. With respect to lead, this period of major change probably reflects progress in reducing levels in ambient air. Concentrations since 1979 have either stabilized (mercury) or decreased at a much slower rate (lead and cadmium) and may indicate that residual levels in the soil are now the primary determinants of uptake into tobacco plants in southern Ontario. From 1968 to 1988 levels of lead, cadmium, and mercury in mainstream smoke, which is inhaled by smokers, are estimated to have declined by about 62%, 39%, and 52%, respectively. (In English) Vol. 25, No. 6, June 3, 1994 .: ~~3

ENVIRONMENTAL TOBACCO SM&`KE Effect of a Mucoactive Compound (Co 1408) on Airway Hyperreactivity and Inflammation Induced by Passive Cigarette Smoke Exposure in Guinea-Pigs. By Hernandez A; Daffonchio L; Brandolini L; Zuccari G European Respiratory Journal; 7 (4) p693-697 APR 1994 ORDER # NG996 Environmental exposure to tobacco smoke contributes to the onset of several lung diseases, e.g. chronic bronchitis and asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound, CO 1408, on airway hyperreactivity and lung inflammation induced in guinea-pigs by passive cigarette smoke exposure. Animals were exposed to cigarette smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to histamine was assessed ex-vivo in lung parenchymal strips. As a measure of lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections, Passive smoke exposure potentiated histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment. with oral CO 1408 at 400 mg.kg(-1) but not 100 mg.kg(-l), completely prevented the cigarette smoke-induced airway hyperreactivity. 400 mg.kg(-l) CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of CO 1408 to modulate smoke-induced airway hyperreactivity and, to some extent, lung inflammation, an effect which might be of value in the therapy of obstructive pulmonary diseases. (In English) Environmental Tobacco Smoke - A Public Health Conspiracy - A Dissenting View. By Farland W; Bayard S; Jinot J Journal of Clinical Epidemiology; 47 (4) p335-337 APR 1994 ORDER # NG685-2 No abstract available (In English) Vol. 25, No. 6, June 3, 1994

ENVIRONMENTAL TOBACCO SMOKE Respiratory Health Effects of Passive Smoking - EPAs Weight- of-Evidence Analysis. By Jinot J; Bayard S Journal of Clinical Epidemiology; 47 (4) p339-349 APR 1994 ORDER # NG685-3 After an extensive review and assessment of the scientific evidence on the respiratory health effects of passive smoking, the U.S. Environmental Protection Agency has determined that the widespread exposure to environmental tobacco smoke in the United States presents a serious and substantial public health impact. The Environmental Protection Agency concluded that environmental tobacco smoke causes lung cancer in adult nonsmokers and increases the risk for a variety of noncancer respiratory disorders, especially in children. This article reviews evidence presented zn the Environmental Protection Agency's'1992 report on the respiratory health effects of passive smoking and responds to critical allegations levied by Gio Gori in his article " Science, policy, and ethics: the case of environmental tobacco smoke ", appearing in the same issue of this journal. Several recent studies appearing since the cutoff date for inclusion in the EPA report are also discussed. (In English) Environmental Tobacco Smoke - A Public Health Conspiracy - A Dissenting View - Respiratory Health Effects of Passive Smoking - EPAs Weight-of-Evidence Analysis Reply. By Gori GB Journal of Clinical Epidemiology; 47 (4) p351-353 APR 1994 ORDER # NG685-4 No abstract available (In English) Science, Policy, and Ethics - The Case of Tobacco Smoke. By Gori GB Journal of Clinical Epidemiology; 47 (4) p325-334 APR 1994 ORDER # NG685-1 The successful campaign against smoking will long be celebrated as a landmark achievement of public health. Recently, a prominent component of this campaign has been the portrayal of environmental tobacco smoke as a major health risk. To this day, however, the scientific basis for this later contention remains speculative. The elevation of heuristic hypotheses into official precepts raises an intriguing ethical question: Should a claim of best intentions justify representing conjecture as scientific knowledge in public policy formulation? (In English) Vol. 25, No. 6, June 3, 1994

f ENVIRONMENTAL TOBACCO SMOKE Decreased Fetal Weights in Rats Exposed to Sidestream Cigarette Smoke. By Rajini P; Last JA; Pinkerton KE; Hendrickx AG; Witschi H Fundamental and Applied Toxicology; 22 (3) p400-404 APR 1994 ORDER # NG988-1 Pregnant Sprague-Dawley rats were exposed to sidestream cigarette smoke (SS) for 6 hr a day, at a concentration of 1 mg/m(3) of respirable total suspended particulate material (TSP) on Days 3, 6-10, and 13-17 of pregnancy. Controls were kept in an identical chamber without smoke exposure. The animals were killed on Day 20 of gestation. No differences were found in maternal body weight gain or average daily food consumption between the smoke-exposed and control groups. The numbers of fetuses and of implantation sites per litter were comparable among the groups. None of the pups showed any gross malformations and no difference was found between controls and SS- exposed pups when examined for reduced skeletal ossifications. However, there was a small but significant reduction in mean pup weight. We conclude that intermittent exposure of rats to sidestream cigarette smoke at concentrations severalfold greater than those encountered in smokey public indoor environments causes intrauterine growth retardation. (C) 1994 Society of Toxicology. (In English) Short-Term Effects of Sidestream Smoke on Respiratory Epithelium in Mice - Cell Kinetics. By Rajini P; Witschi H Fundamental and Applied Toxicology; 22 (3) p405-410 APR 1994 ORDER # NG988-2 Male strain A/J and C57BL/6 mice were exposed on five consecutive days, for 6 hr a day, to sidestream smoke generated from Kentucky 1R4F reference cigarettes. Chamber concentrations were 1 mg/m(3) of total suspended particulate matter and 528 to 549 mu g/m(3) of nicotine. Cumulative labeling indices in the airways and in the pulmonary parenchyma were measured following 1, 3, or 5 days exposure to unfiltered or filtered sidestream smoke. A significantly increased labeling index was found in A/J mice in the epithelium lining large intrapulmonary airways and terminal bronchioles after 3 and 5 days exposure to unfiltered smoke, whereas following exposure to filtered smoke labeling indices remained normal. The alveolar labeling index was not increased following smoke exposure. In C57BL/6 mice, sidestream smoke did not produce signs of increased cell proliferation in the respiratory tract. It is concluded that the response to sidestream smoke inhalation in mice may depend upon the strain of mice examined. (C) 1994 society of Toxicology. (In English) -0 N co a~ ~ .t~ ~ r-n Vol. 25, No. 6, June 3, 1994

ENVIRONMENTAL TOBACCO SMd"KE Effects of Exposure to Nicotine and to Sidestream Smoke on Pregnancy Outcome in Rats. By Witschi H; Lundgaard SM; Rajini P; Hendrickx AG; Last JA Toxicology Letters; 71 (3) p279-286 MAY 1994 ORDER # NH358 Nicotine-delivering transdermal patches were applied to the back of timed-pregnant Sprague-Dawley rats. Pregnancy failure was 100% in animals exposed to 3.5 mg of nicotine per day during the entire pregnancy and 50% in animals exposed to the same amount during the first trimester. Application of 1.75 mg of nicotine per day resulted in a 50% pregnancy failure when exposure occurred during the entire pregnancy. In animals exposed for the first half of pregnancy to cigarette sidestream smoke, under conditions where plasma nicotine levels reached about 25% of those observed following exposure to 1.75 mg of nicotine per day, the average litter size was reduced by about 25%. It is concluded that continuous exposure to nicotine early during pregnancy may adversely affect pregnancy outcome in rats. (In English) -0 N co m P -p ~ Vol. 25, No. 6, June 3, 1994 J ~ •~

FLAVORS Flavorants from Garlic, Onion, and Other Alliums and Their Cancer-Preventive Properties. By Block E Food Phytochemicals for Cancer Prevention I; p84-96 1994) ORDER # BA14P-1 HPLC, cryogenic CC-MS and proton NMR spectroscopy are employed in the analysis of room temperature vacuum distillates and extracts of onion, garlic, and related members of the genus Allium [wild garlic, leek, scallion, shallot, elephant (or great-headed) garlic, chive, Chinese chive] using authentic samples of suspected thiosulfinate components to evaluate the methods. Eight or more thiosulfinates (RS(0)SR') and related organosulfur compounds (" Lwiebelanes, " cis- and trans-2,3-dimethyl-5, 6-dithiabicyclo[2.1]- hexane 5-oxides; (ZZ)-d,1-2,3- dimethyl-l,4-butanedithial S,S'dioxide) can be separated and identified in each plant extract, several for the first time. Research on the cancer preventative properties of the Allium flavorants is also summarized. (In English) Thermal Decomposition of Alliin, the Major Flavor Component of Garlic, in an Aqueous-Solution. By Yu TH; Shu CK; Ho CT Food Phytochemicals for Cancer Prevention I; p144-152 19941 ORDER # BA14P-2 Aqueous solutions of alliin, the major flavor precursor of garlic, were heated in a closed system at 180 degrees C under different pH conditions. The volatile flavor compounds generated were isolated by Likens-Nickerson simultaneous steam distillation/solvent extraction and quantified and identified by GC and GC-MS. A total of 49 volatile compounds were identified in this study. Except allyl alcohol and acetaldehyde, the majority of compounds identified were sulfur-containing compounds. A mechanism for the initial transformation of alliin to allyl alcohol and cysteine and further decomposition of cysteine was proposed which could explain the formation of many sulfur- containing compounds such as methyl sulfides, thiazoles, trithiolanes and dithiazines in this study. (In English) / Vol. 25, No. 6, June 3, 1994

FLAVORS High-Performance Liquid Chromatographic Determination of Glucosinolates in Brassica Vegetables. By Betz JM; Fox WD Food Phytochemicals for Cancer Prevention I; p181-196 19941 ORDER # BA14P-3 Glucosinolates are naturally occurring constituents of Brassica vegetables. The term refers to a class of more than 100 sulfur-containing glycosides that yield thiocyanate, nitrile, or isothiocyanate derivatives upon enzymatic hydrolysis. These compounds are important because of their potential toxicity and because epidemiologic and other evidence indicates that some of them may inhibit some carcinogenic processes when consumed as part of the normal diet. Accordingly, quantitation of these compounds in processed and unprocessed foods has become important.. Existing analytical methods are time consuming and labor intensive. Solid phase extraction (SPE) of broccoli extracts, followed by reverse phase ion pair high performance liquid chromatography (HPLC) of intact, nonderivatized glucosinolates, provides a rapid and simple method for evaluation of glucosinolate loss during food processing. (In English) Dete*mination of Free and Glycosidically Bound Organic Compounds in an Umbelliferous Vegetable Drink. By Rosen RT; Roshdy TH; Hartman TG; Ho CT Food Phytochemicals for Cancer Prevention I; p249-257 19941 ORDER # BA14P-4 Gas chromatography and gas chromatography-mass spectrometry was used to identify and quantitate free and glycosidically bound phytochemicals in an Umbelliferous vegetable drink supplied by the National Cancer Institute (NCI). This drink was a blend of tomato, celery and carrot juices with added spices. Over twenty organics that were present as glycosides were determined as were over sixty "free "(not glycosidically bound) compounds. Methodology included XAD column chromatography to separate the free from the bound fractions, followed by enzymatic cleavage of the glycosides, with subsequent determination by GC and GC-MS (In English) Fermentation-Derived Anticarcinogenic Flavor Compound. By Pariza MW Food Phytochemicals for Cancer Prevention I; p349-352 19941 ORDER # BA14P-5 Diets supplemented with Japaneee-style fermented soy sauce inhibit carcinogen-induced forestomach neoplasia in mice. An active anticarcinogenic principal was identified as 4- hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), a principal flavor/aroma compound. HEMF was effective in inhibiting benzo[a]pyrene-induced mouse forestomach neoplasia when fed at a level of 25 ppm (4 mg/kg body weight/day). (In English) Vol. 25, No. 6, June 3, 1994

FLAVORS Floral Odours in the 2`heophrastaceae. By Knudsen JT; Stahl B Biochemical Systematics and Ecology; 22 (3) p259-268 APR 1994 ORDER # NJ141-1 Floral scent was collected by head-space adsorption from seven species of the Theophrastaceae, viz Theophrasta americana, Deherainia smaragdina, Jacquinia keyensis, J. macrocarpa, J. sprucei, Clavija euerganea and C repanda. The chemical composition of the floral scent was determined with coupled gas chromatography-mass spectrometry (GC-MS). The floral scent composition accord with the generic delimitation within the Theophrastaceae; Theophrasta is characterized by a.fatty acid derived alcohol and an acid, Deherainia by fatty acid derived esters and an acid, and pyrazines, Jacquinia by benzenoids and phenyl propanoids with additionally trimethylcyclohexanes-derivatives of carotenoids in the orange-flowered species (J. macrocarpa, J. sprucei), and Clavija mainly by sesquiterpene hydrocarbons. We suggest that the trimethylcyclohexenes in the floral scent of the orange-flowered Jacquinia species are formed during anthesis through degradation of carotenoids in the corolla pigments. Floral morphology and scent chemistry suggest that Theophrasta and Deherainia are sapromyophilous, while Jacquinia and Clavija are melittophilous. Melittophily is suggested to be the ancient condition in the family, while the derived condition, sapromyophily, may have evolved independently in Deherainia and Theophrasta. (In English) Volatile Constituents of Palm Wine and Palm Sap. By Uzochukwu SVA; Balogh E; Tucknot OG; Lewis MJ; Ngoddy P0 Journal of the Science of Food and Agriculture; 64 (4) p405-411 APR 1994 ORDER # NF910 Palm wine and pasteurised palm sap volatiles were collected, concentrated on a Tenax GC and analysed by gas chromatography and gas chromatography-mass spectrometry. Eighty-two components were identified: 47 esters, 9 alcohols, 5 acids, 6 carbonyls, 2 acetals, 4 terpenes and 9 hydrocarbons. These had all been found prev'ously in conventional wines. 0ciour evaluation of the separated palm wine components as they eluted suggested that no one compound is responsible for the characteristic palm wine odour. The acetates of higher alcohols and the ethyl esters of straight-chain aliphatic C-6-C-10 acids seemed to be important and may play a big role in imparting the fruity nuances of characteristic palm wine odour. Their association with alcohols seemed also to be necessary for the expression of typical palm wine odour. The qualitative difference between palm sap aroma and palm wine aroma appeared to be due mainly to the presence of these esters and alcohols in palm wine and their apparent absence from palm sap, as well as to the presence of some low-boiling esters and alcohols in palm sap and their apparent absence from palm wine. (In English) Vol. 25, No. 6, June 3, 1994 .7 3

FLAVORS Kinetic and Immobilization Studies on Fungal Glycosidases for Aroma Enhancement in Wine. By Caldini C; Bonomi F; Pifferi PG; Lanzarini G; Galante YM Enzyme and Microbial Technology; 16 (4) p286-291 APR 1994 ORDER # NF876 The biochemical properties of a commercial glycosidase from Aspergillus niger (Cytolase PCL5, Genencor) were investigated. The product contains beta-glucosidase, alpha- arabinosidase, and aipha-rhamnosidase activities in a ratio considered ed suitable for aroma enhancement in wine- making. A kinetic study of these three activities was carried out, which included determination of kinetic constants; dependence of enzyme activity and stability on pH and temperature; and enzyme inhibition by glucose, fructose, glycerol, and sulfurous anhydride. These glycosidase activities were immobilized to a solid carrier with the aim of developing a continuous process for wine aroma enhancement. Immobilization was best achieved with silanized bentonite as the solid, activated carrier, with bound glutaraldehyde as the reactive arm at a protein: carrier ratio of 0.11. Immobilization reaction was carried out for 48 h at pH 4 and 30 degrees C. Under these conditions, 16 units of beta-glucosidase, 2 units of alpha- arabinosidase, and 4.5 units of alpha-rhamnosidase per gram of bentonite were immobilized. (In English) Flavour Release from a Protein-Stabilized Water-in-Oil-in- Water Emulsion. By Dickinson E; Evison J; Gramshaw JW; Schwope D Food Hydrocolloids; 8 (1) p63-67 MAR 1994 ORDER # NF915 The loss of a.volatile compound butan-l-ol into the gas phase from a protein-stabilized water-in-oil-in-water (W/O/W) multiple emulsion has been investigated using a head-space analysis technique. Incorporation of the butanol in the multiple emulsion droplets leads to a reduction in_the rate of release by about a factor of two. (In English) Flavor Enhancers - Their Probable Mode of Action. By Nagodawithana T Food Technology; 48 (4) p79 APR 1994 ORDER # NG990 No abstract available (In English) Vol. 25, No. 6, June 3, 1994

FLAVORS Relationships Between Micro-Organisms and Formation of Aroma Compounds in Fermented Dairy Products - Review. By Imhof R; Bosset JO Zeitschrift Fur Lebensmittel - Untersuchung und - Forschung; 198 (4) p267-276 APR 1994 ORDER # NG114-2 A compilation of publications on the analysis and formation of aroma compounds produced by microorganisms used in dairy production is presented. Literature published between 1970 and 1993 is reviewed whereas literature published before 1970 is covered by a bibliography of review articles. Special attention was given to the contribution of lactobacilli, streptococci. lactococci, and bifidobacteria on the formation of volatile aroma compounds in dairy products. Comparative quantitative data including complete citation of the references are listed in tables thus providing a quick access to an area of special interest with the help of key words. (In English) Study on the Cardboard Off-Flavour Formed in Butter Oil. By Widder S; Grosch W Zeitschrift Fur Lebensmittel - Untersuchung und - Forschung; 198 (4) p297-301 APR 1994 ORDER # NG114-3 The increase of (Z)-4-heptenal (1), (Z)-2-nonenal (II), (E)-2-nonenal (III) and 1-octen-3-one (IV), which may contribute to the off-flavours in butter oil, was quantified by stable isotope dilution assays in samples stored at 35-degrees-C. At a lower peroxidation level 2- and 3-tert-butyl-4-hydroxyanisol, 2,6-di-tert-butyl-4- methylphenol, aipha-tocopherol and gamma=tocopherol (additions of 0.47 mmol/kg each) inhibited the formation of I to III by 40-50% and that of IV by 20-30%. Acceleration of the autoxidation by the addition of copper ions (1 and 8.5 mg/kg) enhanced the inhibitory effect of the antioxidants. Sensory evaluations revealed that the cardboard off-flavour in butter oil was caused by a mixture of II (> 1.5 mug/kg) and III (> 23 mug/kg). (In English) r Vol. 25, No. 6, June 3, 1994

FOOD ADDITIVES Chemical Variability of the Essential Oil of Teucrium puechiae Greuter and Burdet on the Languedocian Coast (France). By Allain P; Eloualidi J; Puech S; Pellecuer J Biochemical Systematics and Ecology; 22 (3) p239-248 APR 1994 ORDER # NJ141-2 The composition of the essential oil of Teucrium puechiae Greuter and Burdet (Lamiaceae), shows no essential oil plasticity and, on the other hand, a very low chemical polymorphism. This small intrapopulational qualitative variability is probably the result of an adaptation to the environmental variation in Languedoc (French Mediterranean coast). However, the mode and growth rate, connected to the perturbations in dune ecology, have an effect on the quality of the essential oil. The natural selection seems to act upon the quantitative proportional aspect of the essential oil in seedling and young plants, by favouring the precocious elaboration of sesquiterpenes (terminal products). (In French) Chemometrics and Essential Oil Analysis - Chemical Polymorphism in 2 Thymus Species. By Canigueral S; Vila R; Vicario G; Tomas X; Adzet T Biochemical Systematics and Ecology; 22 (3) p307-315 APR 1994 ORDER # NJ141-3 The utility of multivariate analysis techniques in the study of infraspecific variability of essential oils is shown through its application to Thymus moroderi and T. antoninae. The composition and chemical polymorphism of their essential oils is investigated. Both taxa showed the same major constituents: 1,8-cineole, camphor, camphene and borneol, but several differences in their sesquiterpene fraction. Chemometric analysis of the oil of individual plants from different populations of the two species showed the existence of two types of essential oils in T. moroderi with different sesquiterpene composition and low degree of chemical polymorphism in the case of T antoninae. (In English) Vol. 25, No. 6, June 3, 1994 ;7 ~

FOOD ADDITIVES Screening of Substances for Their Effect on Varroa jacobsoni - Attractiveness, Repellency, Toxicity and Masking Effects of Ethereal Oils. By Kraus B; Koeniger N; Fuchs S Journal of Apicultural Research; 33 (1) p34-43 19941 ORDER # NH952 Tests were developed to enable the screening of substances for effect on the orientation of the honey bee parasite Varroa jacobsoni. Mites collected from young bees in an Apis mellifera carnica colony were used in the tests, which employed wax tubes incorporating the test substances. During a test, mites could remain in a tube containing a test substance or move from it into a tube of pure wax without the test substance. Twenty-two out of 32 tested ethereal oils had a clear repellent effect on the mites. Oil of clove and oil of cinnamon proved to be the only ones with a clear attractant effect on the mites. The most pronounced repellent effect was caused by oil of citronella. Oil of marjoram was clearly capable of masking odours. In toxicity tests, most of the tested oils caused a distinct increase in mortality of mites which were exposed to them incorporated in wax at a concentration of 0.1%. The other tested ethereal oils caused an increase in mite mortality at a concentration of 1.0% or more. The repellents oil of marjoram and oil of citronella, and the attractant oil of clove, were mixed into the comb foundation wax of test colonies. The infestation rates of V. jacobsoni in capped brood cells was clearly higher in colonies with oil of clove foundation than in control colonies with normal foundation. The infestation rate was only slightly lower in colonies with oil of citronella, but clearly lower in colonies with oil of marjoram foundation, than in control colonies. This result indicates that a treatment with oil of marjoram might be a way to decrease the population growth of this parasite. (In English) The Synthesis of (+)-Hedycaryol, Starting from Natural (-)- Guaiol. By Minnaard AJ; Wijnberg JBPA; Degroot A Tetrahedron; 50 (16) p4755-4764 APR 18 1994 ORDER # NF668 Starting from the readily available (-)-guaiol the germacrane sesquiterpene (+)-hedycaryol can be synthesized in a 7 steps reaction sequence in an overall yield of 16%. Additionally, (+)-gamma-eudesmol has been synthesized, also starting from (-)-guaiol. (In English) Vol. 25, No. 6, June 3, 1994 - ~1

FOOD ADDITIVES Prostacyclin Release in Experimental Diabetes - Effects of Evening Primrose Oil. By Stevens EJ; Carrington AL; Tomlinson DR Prostaglandins Leukotrienes and Essential Fatty Acids; 49 (3) p699-706 SEP 1993 ORDER # LW709 Alterations in release of endothelium-derived vasomotor agents could underlie microvascular and neuropathic complications in diabetes. This study examined release of the potent vasodilator prostacyclin, measured as immunoreactive 6-keto prostaglandin F-1 alpha from rat lung, kidney and peripheral nerve. Tissues were taken from control and streptozotocin-diabetic rats which had been treated for 8 weeks with either evening primrose oil (EPO) or, as a control for lipid intake, coconut oil (CO). Lung and kidney slices were incubated in the presence of acetyicholine (ACh), the calcium ionophore 4-Br-A23187, arachidonic acid (AA) or without agonist (basal). Segments of sciatic nerve, with their epineuria punctured, were incubated with or without 4-Br-A23187. Basal prostacyclin release from the lung was significantly higher in rats treated with EPO irrespective of diabetic state (increased by 60% in controls and by 77% in diabetics). Levels were reduced in CO-diabetics compared to EPO-controls (53% reduction) and CO-controls (30% reduction), although this did not rea:::, atatistical significance in the latter. nasal prostacyclin release was also significantly reduced in the kidney from CO-diabetics (40% reduction compared to CO-controls and 56% reduction compared to EPO-controls). In the presence of AA, lung prostacyclin release was significantly lower in CO-diabetic rats compared to all other groups (40% reduction compared to EPO-diabetics and 60% compared to both control groups) but there were no differences in renal release between any group, Prostacyclin release by nerves from CO-diabetic rats was significantly reduced (by 91-93%) compared to all other groups. Under ACh- and 4-Br-A23187-stimulated conditions release from any tissue did not differ significantly from basal. These data thus indicate reduced prostacyclin release from diabetic lung, kidney and nerve, which may be due in part to reduced cyclooxygenase activity. Deficits in release were attenuated, if not prevented, by treatment with EPO. This may further suggest a decreased availability of AA for prostacyclin production in diabetes. (In English ) Vol. 25, No. 6, June 3, 1994

FOOD ADDITIVES Identification of an Active Principle in Essential Oils and Hexane-Soluble Fractions of Curcuma Xar.thorrhiza Roxb Showing Triglyceride-Lowering Action in Rats. By Yasni S; Imaizumi K; Sin K; Sugano M; Nonaka G; Sidik Food and Chemical Toxicology; 32 (3) p273-278 MAR 1994 ORDER # NG419 Curcuma xanthorrhiza Roxb. (C. xanthorrhiza), known as temu lawak or Javanese turmeric, has been traditionally used in Indonesia for food and medicinal purposes. As little attention has been focused on the role of C. xanthorrhiza in lipid metabolism, the hypotriglyceridaemic ?~tivity and the active principles of the essential oil and hexane-soluble fractions prepared from C. xanthorrhiza were investigated in rats. The major component (approx. 65%) of the essential oil was identified as alpha- curcumene by capillary gas chromatography/mass spectrometry. Addition of essential oils (0.02%), prepared by steam distillation, to a purified diet resulted in a lower hepatic triglyceride concentration without influencing the serum triglyceride, whereas addition of the hexane-soluble fraction (0.5%) resulted in a lower concentration of serum as well as liver triglycerides. Rats fed the essential oil and hexane-soluble fraction had lower hepatic fatty acid synthase activity. The fraction containing alpha-curcumene, prepared from the hexane- soluble fraction by silica gel column chromatography, suppressed the synthesis of fatty acids from C-14!acetate in primary cultured rat hepatocytes. Thus, alpha-curcumene is one of the active principles exerting triglyceride- lowering activity in C. xanthorrhiza. (In English) In Vitro Antifungal Activity of Essential Oils Against Some Isolates of M.icrosporum Canis and Microsporum Gypseum. By Perrucci S; Mancianti F; Cioni PL; Flamini G; Morelli I; Macchioni G Planta Medica; 60 (2) p184-187 APR 1994 ORDER # NG093-2 No abstract available (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBACCO Aryl Hydrocarbon Hydroxylase Activity in Human Lung Tissue - In Relation to Cigarette Smoking and Lung Cancer. By Yoshikawa M; Arashidani K; Kawamoto T; Kodama Y Environmental Research; 65 (1) p1-11 APR 1994 ORDER # NH586 In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and smoking or lung cancer, AHH activities in fresh lungs (normal tissue, tumorous tissue, and surrounding tissue of tumor) obtained from lung cancer patients and non-lung cancer patients were measured. There were no differences in lung AHH activity in the lung lobes. In the non-lung cancer patients, AHH activities ranged from 0.13 to 2.37 (pmol 3 hydroxybenzo(a]pyrene/20 min/mg protein), and whereas in the normal tissues of the lung cancer patients they ranged from 0.19 to 5.05. Lung AHH activities showed normal distribution, and a large variation (26 times) was observed in normal tissues in the lung cancer patients. In most cases, AHH activities in the tumorous tissues and the surrounding tissue of the tumor were lower than those in the normal tissues of the lung cancer patients. In the non- lung cancer group, the means of AHH activity of the nonsmoker subgroup (NN) and the smoker subgroup (SN) were 0.62 and 0.96, respectively. On the other hand, in the lung cancer group the means of AHH activity of the nonsmoker subgroup (NC) and smoker subgroup (SC) were 0.85 and 1.05, respectively. Statistically significant differences were observed between NN and SN, NN and NC, and NN and SC. These results suggest that human lung AHH activity was increased by cigarette smoke as in rodent lungs, and the distribution of basal AHH activity in lung tissue of the nonsmokers group in the lung cancer patients shifted toward high levels compared to the nonsmokers group in the non-lung cancer group. The effect of the histological cell types of the lung cancer on the AHH activity was not observed in this study. (C) 1994 Academic Press, Inc. (In English) Carotenoids - Functions and Fallacies. By Thurnham DI Proceedings of the Nutrition Society; 53 (1) p77-87 MAR 1994 ORDER # NG473 No abstract available (In English) Vol. 25, No. 6, June 3, 1994 ~~ 8 ~

MEDICAL ARTICLES ON TOBACCO Cardiovascular Autonomic Reflexes in Heavy Smokers. By Piha SJ Journal of the Autonomic Nervous System; 48 (1) p73-77 JUN 1994 ORDER # NH530 In order to study the effect of smoking on cardiovascular function, 25 healthy subjects with an average smoking history of 25 +/- 9 pack-years were examined using the Valsalva manoeuvre and the deep-breathing test. For each smoker there was a healthy, non-smoking control subject of matching age, sex and body mass index During the tests, heart rate and blood pressure were recorded continuously. Compared with the controls, the smokers had (1) a smaller increase in heart rate during the strain phase of the Valsalva manoeuvre (P = 0.04); (2) weaker rebound increases in arterial pressure after the Valsalva strain (P = 0.007 for systolic and P = 0.02 for diastolic blood pressure); (3) smaller reflex bradycardia after the Valsalva strain (P = 0.02); and (4) a longer latency between post-strain rises in pressure and bradycardia (P = 0.001). This suggests that diminished blood pressure responses occur as a consequence a chronic dysregulation of peripheral vasoconstriction, while diminished heart rate responses are due to attenuated blood pressure responses. A prolonged latency may be a sign of a dysfunction of parasympathetic baroreflex control. It is concluded that heavy smoking is accompanied by a disturbance of cardiovascular autonomic control. (In English) Smoking and Leukemia - Evaluation of a Causal Hypothesis. By Kabat GC; Augustine A; Hebert JR American Journal of Epidemiology; 139 (8) p849-852 APR 15 1994 ORDER # NJ044-2 No abstract available (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBAC"CO Increased Sister Chromatid Exchange Frequency in Peripheral Lymphocytes of Nasopharyngeal Carcinomaa and Cervical Cancer Patients. By Wang LY; Lai MS; Huang SJ; Hsieh CY; Hsu MM; Chen CJ Anticancer Research; 14 (1P) p105-107 JAN-FEB 1994 ORDER # NH785 The specific aim of this study was to compare the frequency of sister chromatid exchange (SCE) in peripheral lymphocytes using it as a biomarker of integral exposures to carcinogens in 14 untreated newly-diagnosed nasopharyngeal carcinoma (NPC) patients, 16 untreated new'_1.3iagnosed cervical cancer patients, and 30 healthy controls matched with patients on age, sex, cigarette smoking and alcohol drinking. Peripheral lymphocyres were cultured in RPMI 1640 medium containing 20% fetal calf serum and 6 mu M phytohemagglutinin. After culture for 24 hours, 20 mu M 5-bromo-2-deoxyuridine was added into the medium. Colcemid solution was further added after 70 hours. Harvested cells were stained with Hoesch 33258, illuminated, and restained with Giemsa. The SCE frequency was scored by two readers independently and blindly. The results showed a significantly increased SCE frequency in lymphocytes for NPC patients (mean +/- standard error = 14.7 +/- 1.7 SCEs/cell) compared with their matched controls (10.1 +/- 0.7 SCEs/cell) and for cervical cancer patients (12.0 +/- 0.9 SCEs/cell) compared with their matched controls (9.2 +/- 0.7 SCEs/cell). These results suggest that NPC and cervical cancer patients have a higher integral exposures to both viral and chemical carcinogens than marched controls. (In English) Failure of Cigarette Smoking to Explain International Differences in Mortality from Chronic Obstructive Pulmonary Disease. By Brown CA; Crombie IK; Tunstallpedoe H Journal of Epidemiology and Community Health; 48 (2) p134-139 APR 1994 ORDER # NH964 Study objective - The study aimed to explain international differences in rates and trends of chronic obstructive pu_.monary disease (COED) using two measurements of cigarette smoking, the major risk factor for this disease. Design - Mortality data for COPD were obtained from the World Health Organisation for 31 countries from 1979 to 1988. Smoking data were obtained for most countries. COPD rates were compared to the percentage of current smokers and past levels of cigarette consumption. COPD trends were compared to past consumption trends. Main results - In men, Romania had the highest COPD mortality and Greece the lowest throughout the period. English speaking countries occupy most of the other top positions, and southern European countries and Japan the low positions. Women show a similar ranking to men (r=0.75; p<0.01 (1988)). Mortality rates in men are, in general, two to four times those in women. Most countries show either a decrease or no change in COPD mortality over the period. In women the opposite is true - no clear relationships are seen when comparing rates and trends of COED with measures of smoking. Conclusion - This failure to explain international COED differences suggests that national data on COPD may be unreliable or national cigarette smoking data are inadequate, or both. (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBACt0 Impaired Alveolar Macrophage Accessory Cell Function and Reduced Incidence of Lymphocytic Alveolitis in HIV-Infected Patients Who Smoke. By Twigg HL; Soliman DM; Spain BA AIDS; 8 (5) p611-618 MAY 1994 ORDER # NH951 Objective: To determine the effects of smoking on alveolar macrophage (AM) accessory cell (AC) function and the incidence of lymphocytic alveolitis in asymptomatic HIV- infected individuals. Methods: AM AC function in smoking and nonsmoking HIV- positive volunteers was measured in concanavalin A and pokeweed mitogen assays. Mitogen-induced AM-T-cell adherence was determined. AM cytokine secretion was analyzed by interleukin (IL)-6 bioassay and IL-1 enzyme- linked immunosorbent assay (ELISA). The incidence of lymphocytic alveolitis in both groups was determined. Results: AM from smokers were significantly poorer AC than AM from nonsmokers. Though AM-T-cell adherence was unaffected by smoking, IL-i and IL-6 secretion was significantly impaired. Lymphocytic alveolitis was significantly less common in HIV-infected smokers. Conclusion: Smoking reduces AM AC function in HIV-infected individuals, probably by impairing secretion of cytokines important in T-cell proliferation. This may explain the decreased incidence of lymphocytic alveolitis in HIV- infected people who smoke. (In English) Genetically Based N-Acetyltransferase Metabolic Polymorphism and Low Level Environmental Exposure to Carcinogens. By Vineis P; Bartsch H; Caporaso N; Harrington AM; Kadlubar FF; Landi MT; Malaveille C; Shields PG; Skipper P; Talaska G; Tannenbaum SR Nature; 369 (6476) p154-156 MAY 12 1994 ORDER # NK971 THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined(1,2). Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degraes of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust(3,4). We have determined levels of DNA adducts in bladder cells and of 4-aminobiphenyl- haemoglobin adducts in 97 volunteers, together with the N- acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine-cotinine in the urine. We find that among the slow acetylators, 4- aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine-cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine-cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to 'risk assessment' procedures. (In English) Vol. 25, No. 6, June 3, 1994 ;~

MEDICAL ARTICLES ON TOBACCO Risk-Factors for Parkinsons Disease - Case-Control Study in the Province of Caceres, Spain. By Morano A; Jimenezjimenez FJ; Molina JA; Antolin MA Acta Neurologica Scandinavica; 89 (3) p164-170 MAR 1994 ORDER # NH931 This case-control study, performed in a mixed rural and urban province, of 74 patients with Parkinson's disease (PD) and 148 unselected age and sex-matched controls, attempted to look possible risk factors for PD. Rural living, well-water drinking, positive family history for PD and postural tremor, were associated to an increased risk for PD, with results regarding exposure to pesticides near to statistical significance. Alcohol-drinking habit in males were associated to a decreased risk for PD, with results regarding cigarette-smoking habit in males near to statistical significance. We did not find association between the risk for PD and the following variables: 1)exposure to industrial toxins; 2) agricultural work; 3)cranial trauma; 4) previous common illnesses including some infections, arterial hypertension, diabetes mellitus, coronary heart disease and thyroid disease; 5) coffee and tea drinking habits. (In English) Cigarette Smoking and Functional Ovarian Cysts. By Holt VL; Daling JR; Mcknight B; Moore DE; Stergachis A; Weiss NS American Journal of Epidemiology; 139 (8) p781-786 APR 15 1994 ORDER # NJ044-1 This population-based case-control study assessed the effect of current cigarette smoking on the risk of functional ovarian cyst development. Cases were all 15-39 year-old enrollees of Group Health Cooperative of Puget Sound (GHC) who had either an inpatient primary diagnosis of functional ovarian cyst in 1988 or 1989 (n = 61) or an outpatient primary diagnosis of functional ovarian cyst at five GHC primary care clinics (n = 37). Controls were randomly selected'enrollees matched to cases on age, primary care clinic, and enrollment dat(~ (n = 239). A total of 36.7% of cases and 20.5% of controls were determined by medical record review to be current smokers. Compared with women who were not current smokers, the relative risk of a diagnosed functional ovarian cyst among smokers was 2.0 (95% confidence interval 1.1-3.5). This finding, in an area of little previous research, provides a promising lead in the investigation of the etiology of functional ovarian cysts and the effects of smoking on ovarian function in general. (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBACCO Cigarette Smoke Chemistry - Conversion of Nitric Oxi.de to Nitrogen Dioxide and Reactions of Nitrogen Oxides with Other Smoke Components as Studied by Fourier Transform Infrared Spectroscopy. By Cueto R; Pryor WA Vibrational Spectroscopy; 7 (1) p97-111 MAY 1994 ORDER # NH507 Nitric oxide is both a critical biological toxin and an important messenger molecule, signalling events as diverse as nerve transmission and smooth muscle relaxation. Fresh cigarette smoke contains from 300 to 500 ppm nitric oxide. While there have been reports of the rate of oxidation of nitric oxide to nitrogen dioxide in cigarette smoke, none have utilized a real-time method and provided detailed kinetic data and modelling. In this paper we present a Fourier transform infrared spectroscopy (FT-IR) method for the simultaneous determination of nitric oxide and nitrogen dioxide in gas phase cigarette smoke and in a number of gaseous mixtures that model smoke. The method uses multivariate least-squares regression analysis, which allows simultaneous quantitation of several components even in the presence of overlapping peaks, and fast data acquisition for kinetic analysis. Model systems containing mixtures of nitric oxide and isoprene, methanol, and/or acrolein and acetaldehyde in air were studied. The concentrations of nitric oxide, isoprene, etc., in the model systems were chosen to duplicate those in authentic cigarette smoke. In our best model (a mixture of nitric oxide, methanol, and isoprene in air) the disappearance of nitric oxide and the appearance of nitrogen dioxide follow time courses that closely duplicate those for cigarette smoke. Furthermore, the production of nitrogen dioxide follows a time course that agrees with our previously published rate of the development of organic free radicals in cigarette smoke. The present work, therefore, substantiates the steady-state mechanism we previously proposed for the production of free radicals in gas phase cigarette smoke. (In English) Dietary Cytocbrome P-450 Modifiers in the Control of Estrogen Metabolism. By Michnovicz JJ;.Bradlow HL Food Phytochemicals for Cancer PrevenLion l; p282-293 19941 ORDER # BA14P-10 Extensive studies of the cytochrome P450 enzymes, and of the related system of Phase II drug-detoxifying enzymes, have pointed the way to understanding how dietary components affect the metabolism of drugs and hormones in humans. Estrogens are metabolized by P450 enzymes to produce both 2-hydroxyestrogens and 16 alpha- hydroxyestrogens. Many phytochemicals in our diets are capable of altering the relative amounts of these metabolites formed in a given individual. Since formation of different estrogen metabolites is linked to breast and uterine cancer risk in women, several natural products may exert their beneficial effects through a modification of hormone metabolism. Our studies have focused on the structure-activity relationship between dietary indoles derived from cabbage-type vegetables and estrogen P450- dependent metabolism. We propose that phytochemicals active in these P450 pathways may be useful as chemopreventive agents in humans. (In English) Vol. 25, No. 6, June 3, 1994 ,. - ~85

MEDICAL ARTICLES ON TOBA.'CO Replacing Creatinine Measurements with Specific Gravity Values to Adjust Urine Cotinine Concentrations. By Haddow JE; Knight GJ; Palomaki GE; Neveux LM; Chilmonczyk BA Clinical Chemistry; 40 (4) p562-564 APR 1994 ORDER # NE582 Creatinine and specific gravity (relative density) measurements both allow differences in urine concentration to be taken into account in determining urine cotinine concentrations. In this study we demonstrate that the variance of urine cotinine measurements is reduced comparably when either creatinine or specific gravity measurements are used for correction. This reduction in variability improves the correlation between urine cotinine measurements and clinical endpoints. In this study, the clinical endpoints were pulmonary function in a population of nonsmoking children with asthma, 42% of whom were reported to have been exposed to environmental tobacco smoke. When corrected by either creatinine measurements or specific gravity values, the urine cotinine measurements performed as well dr better than reported exposure (and comparably with each other) in assessments of lung function. A dose-response relationship was also more consistently apparent. Specific gravity values can be used reliably in place of creatinine values to adjust urine cotinine measurements for both research and clinical purposes. (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBAeCO Inhibition of Aldosterone Synthesis in Rat Adrenal Cells by Nicotine and Related Constituents of Tobacco Smoke. By Skowronski RJ; Feldman D Endocrinology; 134 (5) p2171-2177 MAY 1994 ORDER # NG467 Previous work has shown that nicotine and related constituents of tobacco smoke inhibit selected P450 enzymes in the glucocorticoid and sex steroid synthetic pathways. Because aldosterone synthesis is also cytochrome P450 dependent, we hypothesized a similar inhibitory action on aldosterone production. In this study we examined the effects of nicotine, anabasine (a related alkaloid), and cotinine (the major metabolite of nicotine) on in vitro aldosterone synthesis. Freshly isolated rat adrenal cells were assayed for corticosterone and aldosterone production in the basal state and after stimulation with ACTH or angiotensin-II (ANG-II). The addition of nicotine, anabasine, and cotinine in concentrations up to 100 mu M did not inhibit stimulated corticosterone production. However, there was a potent dose-dependent inhibitory action of all three tobacco compounds on aldosterone production. The relative inhibitory potency was: cotinine > anabasine > nicotine. When employed at a concentration of 100 mu M, the three compounds inhibited ACTH-stimulated aldosterone synthesis by 75%,44%, and 21%, respectively ANG-II-stimulated aldosterone synthesis was inhibited by 92%, 78%, and 62%, respectively. The plasma cotinine concentration range attained in tobacco smokers is between 1-10 mu M. When tested with H-3!corticosterone and H-3!progesterone as exogenous substrates, 1-10 mu M cotinine caused a significant dose-dependent inhibition of ACTH- and ANG-II- stimulated aldosterone synthesis. Cotinine substantially blocked the conversion of corticosterone to 18- hydroxycorticosterone, implicating the 18-hydroxylase or corticosterone 18-methyloxidase-I (CMO-I) step as the major site of inhibition. In summary, our results indicate that tobacco compounds cause direct and specific inhibition of aldosterone synthesis, primarily at the CMO- I step. This enzymatic blockade would be expected to result in activation of the renin-angiotensin system in vivo. We postulate that chronic stimulation of the renin- angiotensin system by this mechanism might contribute to the cardiovascular damage that occurs with long term tobacco use. (In English) Vol. 25, No. 6, June 3, 1994

MEDICAL ARTICLES ON TOBACCO Epidemiological Studies and the Prevention of Stroke. By Bonita R Cerebrovascular Diseases; 4 p2-10 19941 ORDER # NH025 The contribution of epidemiological studies of stroke has been fundamental to understanding the occurrence, natural history and the potential for both primary and secondary prevention. Descriptive studies of routinely available data such as death statistics provide some idea of the magnitude of the problem, differences between and within countries, and trends over time. Measuring the incidence of stroke, however, requires special population-based studies which are, unfortunately, expensive and difficult to accomplish and, until recently, provide limited information on the frequency, etiology and natural history of pathologically distinct types of stroke. Analytical studies, in particular the long-established cohort studies, have contributed to an understanding of the risk factors for stroke. Randomized controlled trials on the treatment of raised blood pressure confirmed findings from the observational studies that reducing blood pressure also reduced the relative risk of stroke. Increasing knowledge about stroke subtypes, which may behave in different ways in terms of prognosis and response to therapy, has resulted in further clinical trials tailoring potential therapies according to the precise categorization of subtypes. Few epidemiological studies have been established which can shed light on the reasons for the substantial decline in stroke mortality in recent decades. The available evidence suggests that an improvement in case fatality is the most likely explanation, rather than improvements in incidence. In turn, improvements in case fatality may reflect better management in the acute phase or changes in the natural history of the disease. Epidemiological studies of stroke can contribute to developing more cost-effective strategies for the prevention and control of cerebrovascular disease. (In English) Vol. 25, No. 6, June 3, 1994 S

MEDICAL ARTICLES ON TOBACCO Predictors of Mortality and Recurrence After Hospitalized Cerebral Infarction in an Urban Coffimuiity - The Northern Manhattan Stroke Study. By Sacco RL; Zamanillo MC; Kargman DE; Shi T Neurology; 44 (4) p626-634 APR 1994 ORDER # NG065 Objective: To identify determinants of recurrence and mortality after ischemic stroke in a mixed-ethnic region. Background: The determinants of ischemic stroke outcome are not uniformly characterized and will be of increasing importance as the frequency of ischemic stroke survivors increases in our aging population. Methods: A cohort of 323 patients (40% black, 34% Hispanic, 26% white) with cerebral infarction from northern Manhattan over age 39 were followed for a mean of 3.3 years, with only 6% lost to follow-up. Cumulative life table risk of mortality and recurrence was calculated. Risk factors classified at the time of index ischemic stroke were selected based on univariate analyses and then entered into a Cox proportional hazards model for mortality and for recurrence. Results: The life table cumulative risk of mortality was 8% at 30 days, 22% at 1 year, and 45% at 5 years after ischemic stroke. The immediate cause of death was related to vascular disease in 60%. After age adjustment, the significant predictors of mortality were congestive heart failure (risk ratio RR! = 2.6), admission glucose >140 mg/dl (RR = 1.7), and presentation with either a large dominant, nondominant, or major basilar syndrome (RR = 2.0). Patients with a lacunar syndrome had a better survival (RR = 0.6). Recurrent strokes occurred in 72 patients. The life table cumulative risk of recurrence was 6% at 30 days, 12% at 1 year, and 25% at 5 years after ischemic stroke. Ethanol abuse (RR = 2.5), hypertension requiring discharge medications (RR = 1.6), and elevated blood glucose within 48 hours of index ischemic stroke (RR = 1.2 per 50 mg/dl) were the independent predictors of recurrence. Among 30-day survivors, the effect of ethanol abuse was greater (RR = 3.5), indicating its impact on late recurrence. Conclusions: After accounting for age and presenting syndrome, initial glucose predicts stroke mortality and recurrence after ischemic stroke. This association may reflect uncontrolled and undiagnosed diabetes in our urban population. Furthermore, ethanol abuse may be a determinant of ischemic stroke recurrence. Reduction of the stroke public health burden will require targeted modification of such conditions and behaviors. (In English) Vol. 25, No. 6, June 3, 1994

NITROSAMINES Absence of Volatile N-Nitrosamines in Cooked Nitrite-Free Cured Muscle Foods. By Shahidi F; Pegg RB; Sen NP Meat Science; 37 (3) p327-336 19941 ORDER # NH142 Nitrite-free cured pork systems were prepared using the preformed cooked cured-meat pigment (CCMP) and sodium ascorbate. Absence of volatile N-nitrosamines in cooked nitrite-free systems was confirmed using a gas chromatography-thermal energy analyzer (GC-TEA) methodology. Similar results were obtained when cod, cod surimi or mixtures containing pork with 15 or 50% cod or cod surimi were used. However, counterpart samples cured with sodium nitrite (156 ppm) and sodium ascorbate (550 ppm) produced N-nitrosodimethylamine at 1.0 ppb levels or less. Results demonstrate that nitrite-free curing of meat and meat/fish systems containing the preformed CCMP is successful in yielding products devoid of volatile N- nitrosamines. (In English) Antimutagen and.Anticarcinogen Research in Japan. By Namiki M Food Phytochemicals for Cancer Prevention I; p65-81 19941 ORDER # BA14P-6 Marked changes in Japanese food and diet over the past 40 years have resulted in significant elongation of the average life expectancy along with an increase in cancer deaths involving changes in incidence distribution. Following progress in studies on mutagenesis, carcinogenesis and oxygen diseases, studies on antioxidants, antimutagens and anticarcinogens in food are being promoted in Japan as an important part of research in the physiological functionality of food. Various novel physiological activities are being elucidated in Japanese traditional foods, e.g. antimutagenicity of tea catechins, sea weeds and flavoring compounds, antioxidative and antiaging activities of sesame, spices, tea, fermented foods and others. Various oligosaccharides and dietary fibers are being developed to improve colonic microflora correlated to carcinogenesis. (In English Vol. 25, No. 6, June 3, 1994

NITROSAMINES Behavioral Effects of Smokeless Tobacco on the Neonate and Young Sprague-Dawley Rat. By Paulson RB; Shanfeld J; Vorhees CV; Cole J; Sweazy A; Paulson JO Teratology; 49 (4) p293-305 APR 1994 ORDER # NG664 Three dosages of Smokeless Tobacco (ST) extract were given to pregnant Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The three dosages contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), 4.0 mg/kg nicotine (STD-2), and 6.0 mg/kg nicotine (STD-3). Dams were intubated three times per day at 8 a.m., 11 a.m., and 2 p.m., providing total daily ST dosages of 4 mg/kg, 12 mg/kg, and 18 mg/kg, respectively. Controls received equivalent volumes of water by gavage. Dams were allowed to deliver, and all biological mothers raised their own pups. On postnatal day 1 (PND 1), litters were culled to 4+/- 1 females and 4+/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included surface righting, negative geotaxis, swimming development, open field activity, and active avoidance in shuttle box. Our results show that the two higher doses resulted in reduced maternal weight gain. During the pre-weaning period, significant pup weiy:.,, reductions were noted in the STD-2 pups until PND6, and in the STD-3 group until PND15. In the STD-1 group no statistically significant weight reduction was noted on PNDs 1 and 3, but starting with PND6, pup weights surpassed control group weights. This weight difference persisted throughout the post-weaning period also (P < .05 on PND30 and PND42). The STD-3 pup weights continued to be consistently and significantly (P < .05) reduced throughout the post-weaning period (except on PND24j; likewise, the STD-2 pups continued to have lower weights, but at a significant level P < .05) on PND30 only. The incidence of deaths was increased in a dose-related manner. No significant differences were noted for pinna detachment and incisor erpton; however ST-treatment was significant in affecting earlier eye opening and vaginal patency. N significant ST treatment effects were seen on netive geotaxis, but for surface righting a decreasedsuccess rate was noted for the ST-treated groups. Significant differences were noted in swimming development, with the STD-2 pups performing best. Open field activity, as expected, increased from the preweaning to post-weaning periods. During the pre weaning period the STD-3 pups were more active, and during post-weaning, the STD-1 pups were more active, but no differences were noted in vertical activity or in the number of stereotypical movements. No treatment-related differences were noted in the active avoidance shuttle box. We conclude that at high doses ST reduces pre-and post- weaning offspring weight gain and increases fetal mortality. ST at the low dose appears to, have the opposite effect, in that these offspring weights actually exceed control weights. ST also alters activity levels and swimming development, while no differences are noted in the rats' performance in active avoidance tests on learning. Therefore, ST exposure during the embryonic and fetal stages of rat development produces developmental toxicity and suggests that its effects may be comparable to results observed by other investigators using smoked tobacco. .(C) 1994 Wiley-Liss, Inc. (In English) Vol. 25, No. 6, June 3, 1994

NITROSAMINES Changes in Secondary Structure of DNA of Rat Embryos Following Treatment with 1,2-Diethylhydrazine and Dimethylnitrosamine in Vivo. By Huang PHT; Catalano A Teratogenesis Carcinogenesis and Mutagenesis; 14 (2) p53-64 19941 ORDER # NH681 1,2-Diethylhydrazine (DEH) and dimethylnitrosamine (DMN) are indirect acting carcinogens that require metabolic activation to exert their potency. DEH is a transplacental carcinogen and teratogen in Wistar rats when administered by i.p. injection on day 12 of gestation. DMN is embryotoxic during this period. In this study, gravid Wistar rats were injected i.v. with DEH (10, 15, or 20 mg/kg) or i.p. with DMN (10 or 30 mg/kg) and the effects on the embryos 24 hours later were observed. Controls were similarly injected with saline vehicle. The incidence of resorptions increased after treatment with 20 mg DEH/kg. DEH treatment also resulted in decreases in embryo wet weights and total DNA that were not dose dependent. Treatment with DMN did not affect embryonic wet weights and total embryonic DNA amount when compared to the saline- treated controls. The effects of DEH and DMN on DNA synthesis in vivo were monitored by injecting [methyl-C- 14]-thymidine 1 hour prior to embryo death. DEH induced significant increases in thymidine incorporation into embryo DNA but the increases were not proportional to the doses administered. DNA synthesis was significantly decreased in embryos treated with 30 mg DMN/kg. The DNA of treated and control embryos was fractionated by benzoylated DEAE-cellulose (BD-cellulose) chromatography to determine differences in DNA secondary structure following treatment. BD-cellulose chromatography separates double-stranded DNA from DNA containing single-stranded regions by step elution with 1 M NaCl solution and caffeine solution, respectively. Embryonic DNA was monitored by in vivo labelling with [methyl-H-3]-thymidine on days 6 and 7 of gestation. Significant dose dependent increases in percentages of caffeine-eluted DNA (%CE-DNA) compared to controls were detected after treatment with 10, 15, and 20 mg DEH/kg and 10 and 30 mg DMN/kg. The relative %CE-DNA is expressed as the ratio of %CE-C-14-labelled DNA to %CE-H-3-labelled DNA. Litters treated with 10, 15, and 20 mg DEH/kg had relative %CE-DNA values significantly lower than controls. The results support the hypothesis that initiation mechanisms of transplacental carcinogenesis and teratogenesis are different. The pertinence of %CE-DNA and relative %CE-DNA values to the study of transplacental carcinogenesis and teratogenesis is discussed. (C) 1994 Wiley-Liss, Inc. (In English) Vol. 25, No. 6, June 3, 1994 2 ~9

NITROSAMINES Inhibition of Esophageal Tumorigenesis by Phenethyl Isothiocyanate. By Stoner GD; Galati AJ; Schmidt CJ; Morse MA Food Phytochemicals for Cancer Prevention I; p173-180 19941 ORDER # BA14P-8 Phenethyl isothiocyanate, a naturally occurring constituent of cruciferous vegetables, is a potent inhibitor of nitrosamine-induced esophageal cancer. F344 rats fed diets containing phenethyl isothiocyanate at 1.5, 3 and 6 mmol/kg diet, before and during treatment with the carcinogen N-nitrosobenzylmethylamine, developed 89-100% fewer esophageal tumors than carcinogen-treated control rats. Phenethyl isothiocyanate exhibited inhibitory effects against both preneoplastic lesions and neoplastic lesions. The effects of phenethyl isothiocyanate (10, 25, 50 and 100 mu M) on DNA. methylation by N- nitrosobenzylmethylamine in cultured explants of rat esophagus were also investigated. Phenethyl isothiocyanate produced a dose-dependent inhibition in the levels of DNA methylation at the N-7 (20-89%) and 0-6 (55-93%) positions of guanine. Therefore, a strong correlation was observed between the inhibitory effects of phenethyl isothiocyanate in vivo and in vitro. (In English) Comparative Study of Ellagic Acid and Its Analogues as Chemopreventive Agents Against Lung Tumorigenesis. By Castonguay A; Boukharta M; Jalbert G Food Phytochemicals for Cancer Prevention I; p294-302 19941 ORDER # BA14P-9 The polyphenol ellagic acid inhibits lung tumorigenesis induced by a nicotine-derived nitrosamine in A/J mice. This inhibition was related to the logarithm of the dose of ellagic acid added to the diet. The biodistribution of ellagic acid was studied in mice gavaged with ellagic acid. Pulmonary levels of ellagic acid reach a maximum 30 min after gavage and were directly proportional to the dose between 0.2 and 2.0 mmol EA/kg b.w. Ellagitannins extracted from pomegranate are hydrolyzed extensively in mice leading to the excretion of ellagic acid in the feces and urine. Feeding mice pomegranate ellagitannins (10 g/kg diet) did not inhibit lung tumorigenesis. (In English) Vol. 25, No. 6, June 3, 1994 i

NITROSAMINES Nitrate, Nitrite and Volatile N-Nitroso Compounds in the Urine of Schistosoma Haematobium and Schistosoma Mansoni Infected Patients. By Mostafa MH; Helmi S; Badawi AF; Tricker AR; Spiegelhalder B; Preussmann R Carcinogenesis; 15 (4) p619-625 APR 1994 ORDER # NE665 The present study presents, for the first time, the amounts of nitrate, nitrite and volatile N-nitroso compounds in saliva and urine samples of Schistosoma haematobium and Schistosoma mansoni infected patients. Mid- morning saliva and 24 h urine samples were collected from male patients infected with S.haematobium (n = 129 saliva and 79 urine samples) and S.mansoni (n = 64 saliva and 65 urine samples) and in a comparative control group of healthy individuals (n = 27) from the Nile Delta region of Egypt. Saliva samples were analyzed for the presence of nitrate and nitrite; while urine samples were analyzed for the presence of nitrate, nitrite and volatile N-nitroso compounds. In the control group, N-nitroso-dimethylamine (NDMA) was detected at concentrations (mean +/- SD) of 0.27 +/- 0.47 mu g/day. N-nitrosopyrrolidine (NPIP; 0.6 mu g/day) and N-nitrosopyrrolidine (NPYR; 0.4 mu g/day) were also present in one sample. S.mansoni infected subjects showed significantly (P < 0.001) higher levels of 2.9 +/- 2.9 mu g/day NDMA and a higher frequenc;y if NPIP (in 40/65 samples; 0.4 +/- 0.3 mu g/day) and NPYR occurrence (in 59/65 s?mples; 0.9 +/- 0.9 mu g/day). Significant further increases in the excretion of volatile N-nitroso compounds were found in S. haematobium-infected patients with mean daily excretion of 19.2 +/- 21 mu g/day NDMA (in all samples; P < 0.001), 1.6 +/- 2.3 mu g/day NPIP (in 56/79 samples; P < 0.001) and 1.3 +/- 1.9 mu g;day NPYR (in,58/79 samples; P < 0.1). The differences either in salivary nitrite/nitrate or in urinary nitrite between the three distinct groups were not significant. However, the urinary excretion of nitrate was elevated from 139 +/- 82 mg/day in the control group to 249 +/- 126 mg/day in S.mansoni infected patients (P < 0.001) and to 174 +/- 176 mg/day in S.haematobium infected subjects (P < 0.005 in comparison to S.mansoni infected group). These results suggest a possible role of N-nitroso compounds in the etiology of schistosome-associated bladder cancer and imply a partial participation of S. mansoni in the multistage process of urinary schistosomiasis-associated bladder carcinogenesis. (In English) Vol. 25, No. 6, June 3, 1994 ~9 A

NITROSAMINES Inhibition of Chemical Toxicity and Carcinogenesis by Diallyl Sulfide and Diallyl Sulfone. By Hong JY; Lin MC; Wang ZY; Wang EJ; Yang CS Food Phytochemicals for Cancer Prevention I; p97-101 19941 ORDER # BA14P-7 The effects of diallyl sulfide (DAS) and its metabolite diallyl sulfone (DASO(2)) on the hepatotoxicity induced by acetaminophen (APAP) as well as on lung tumorigenesis induced by the tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were studied. APAP at a dose of 0.4 g/kg (for rats) or 0.2 g/kg (for mice) c^.used a severe hepatotoxicity as manifested by the elevation of serum activities of glutamic-pyruvic transaminase and lactate dehydrogenase, and liver centralobular necrosis. A dose- and time-dependent antidotal effect of oral DASO(2) against APAP-induced hepatotoxicity was demonstrated; DAS was slightly less effective. In the carcinogenesis experiments, 100% of female A/J mice treated with a single dose of NNK (100 mg/kg, i.p.) developed lung'tumors with an average tumor multiplicity (tumors/mouse) of 7.2. Administration of DAS (200 mg/kg/ day, p.o.) for 3 days prior to NNK treatment decreased the lung tumor incidence to 38% and tumor multiplicity to 0.6. A single dose of DASO(2) (100 mg/kg, p.o.) given 2 hr prior to NNK treatment reduced the lung tumor incidence by 50% and tumor multiplicity by 91%. Metabolic activation of NNK was significantly inhibited in the lung and liver microsomes prepared from DAS-treated mice. These results clearly demonstrate that DAS and DASO(2) are effective agents against APAP-induced hepatotoxicity and NNK-induced lung tumorigenesis, most probably working by inhibition of the metabolic activation of the related toxicant and carcinogen. (In English) Vol. 25, No. 6, June 3, 1994

NITROSAMINES Liver Fluke Infection and Cholangiocarcinoma - Model of Endogenous Nitric Oxide and Extragastric Nitrosation in Human Carcinogenesis. By Haswellelkins MR; Satarug S; Tsuda M; Mairiang E; Esumi H; Sithithaworn P; Mairiang P; Saitoh M; Yongvanit P; Elkins DB Mutation Research; 305 (2) p241-252 MAR 1 1994 ORDER # NB677 Cancers arising during bacterial, viral and parasitic infection provide useful models to investigate the link between inflammation and carcinogenesis. Because the inflammatory agent is known, relationships between immune responses, the production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N-nitroso compounds, anc cancer risk can be explored. This paper first describes the close relationship between infection with the liver fluke, Opisthorchis viverrini, and cholangiocarcinoma in humans. Data are then presented which demonstrate an elevation in levels of salivary nitrite and urinary and plasma nitrate among men with moderate and heavy liver fluke infections compared to uninfected controls which was absent 4 months after the parasites were cleared with praziquantel. Because of the strict control over subject selection and dietary intake plus the absence of the increase following treatment, we conclude that the higher levels of nitrate and nitrite reflect endogenous generation of nitric oxide resulting from liver fluke infection. Excess nitric oxide generation in the inflamed tissue is likely to lead directly to the formation of N- nitroso compounds mediated by activated macrophages. Further work will attempt to demonstrate a link between this increase and both parasite-specific immune responses and the risk of cancer. (In English) Vol. 25, No. 6, June 3, 1994

STORED PRODUCTS The Potential of Gene Technology and Genome Analysis for Cool Season Food Legume Crops - Theory and Practice. By Kahi G; Kaemmer D; Weising K; Kost S; Weigand F; Saxena MC Euphytica; 73 (1-2) p177-189 19941 ORDER # NG439 The potential of plant gene technology encompasses a multitude of different techniques ranging from the isolation of useful genes, their characterization and in vitro manipulation to the reintroduction of the modified constructs into target plants, where they are expressed at a rate that alters the phenotype of the plants. Genome analysis, on the other hand, aims at characterizing the genome architecture and function(s). Plant gene technology has catalyzed progress in plant breeding, as will be exemplified by a few examples, but has not yet been applied to food legume improvement on a large scale. Genome analysis, however, has a series of practical implications, as is illustrated by the successful introduction of DNA fingerprint and PCR fingerprint techniques to chickpea (Cicer arietinum L.) breeding and Ascochyta rabiei pathotyping. The present overview addresses both areas of plant molecular biology to illustrate their potential for food legume breeding. (In English) Stored Product Integrated Pest Management. By Kenkel P; Criswell JT; Cuperus GW; Noyes RT; Anderson K; Fargo WS Food Reviews International; 10 (2) p177-193 19941 ORDER # NG107 No abstract available (In English) Vol. 25, No. 6, June 3, 1994 ~97

TOBACCO AND TOBACCO SMOKEZ" Folate and vitamin B12 status and chromosomal damage in the buccal mucosa of smokers and nonsmokers By Piyathilake, Chandrika Jayanthi 192 pp. Avail. Univ. Microfilms Int., Order No. DA9405296 From: Diss. Abstr. Int. B 1994, 54(9), 4608 1993 ORDER # CA 120:268977n Unavailable (In Eng) Composite fuel element for smoking articles. EP 588247 Eur. Pat. Appl., 20 pp. 1994 ORDER # CA 120:266156v Fuel elements are provided with a composite support member which assists in retaining the fuel element within the cigaret during smoking. The fuel elements burn at a lower av. temp. than previously known carbanaceous fuel elements. Preferably, the fuel element comprises .gtoreq.2 different materials contiguous throughout their length, including one material which burns, and another material which preferably does not burn, or burns more slowly than the burnable material. The nonburning material is advantageously a heat exchanger, such as graphite. Preferably, the nonburning support or retaining member extends beyond the periphery of the burnable material, such that it interacts with the insulating jacket which surrounds the fuel elements, locking the same in place, particularly during smoking. (In Eng) Cigaret filter for the administration of taurine by inhalation. EP 591048 Eur. Pat. Appl., 6 pp. 1994 ORDER # CA 120:266155u TaurinA is incorporated into cigaret filters, optionally as a powder together with water- or physiol. saline-contg. micrccapsules. A taurine soln. is created in the filter when the microcapsules are broken by finger-applied pressure. Taurine alleviates some of the noxious effects of cigaret smoke. (In Fr) Determination of air permeance for cigaret paper By Zhang, Shaoling Liu, Lianxiang Ding, Shumei Zhongguo Zaozhi, 12(2), 38-43 1993 ORDER # CA 120:266095z Air permeance of cigaret paper can be detd. by 3 types of app., i.e. PPM-100, Schopper and modified Schopper with a test area of 2 cm2 according to ISO 5636/2 and ISO 2965. Some relations between the test results detd. by those app. were established. It is recommended that the manufs. of cigaret paper should formulate the relation between the results detd. by those app. for their own products. (In Ch) Vol. 25, No. 6, June 3, 1994

TOBACCO AND TOBACCO SMOKE Colorimetric reagent and method using saliva sample for screening of the functional condition of the body (disease diagnosis) CA 2072423 Can. Pat. Appl., 20 pp. 1993 ORDER # CA 120:265327q A reagent is disclosed for screening of the functional condition of the body using a saliva sample from the person, differing in the aim of increasing selectivity and sensitivity; the aq. reagent contains ferric ions, chloride ions, and an aliph. multi-atom alc. at 0.05-3. 0 M; 0.05-4.0 M, and 0.1-5.0 M, resp. Saliva is mixed with the reagent and the screening is conducted by monitoring the changing color of the mixt. The color of the mixt., when compared with a std., diagnoses the conditions of hypertension, diabetes, and other disturbances of the endocrine system, including dysfunctions of adrenocorticotropic hormone, adrenaline, and insulin. The alc. is e. g. ethylene glycol or glycerin. (In Eng) Immunological effects of acute and chronic nicotine administration in rats By McAllister, Cathy G. Caggiula, Anthony R. Knopf, Steven Epstein, Leonard H. Miller, Anna L. Antelman, Seymour M. Perkins, Kenneth A. J. Neuroimmunol., 50(1), 43-9 1994 ORDER # CA 120:263649x The authors previously demonstrated that acute nicotine administration decreased the response of rat blood leukocytes (PBL) to Con A (ConA). The authors now extend those findings to a comparison between the effects of acute and prolonged nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single injection suppressed the PBL response to ConA and phytohemagglutinin (pHA); tolerance developed by ten injections. In contrast, acute nicotine did not affect SL response to ConA and reduced the PHA response only at the highest concn. Ten nicotine injections enhanced SL responsiveness to PHA. The only change in PBL subsets was an increase in CD8+ cells following ten injections. (In Eng) Vol. 25, No. 6, June 3, 1994 _90 I

TOBACCO AND TOBACCO SMOKE Increased dependence on blood glucose in smokers during rest and sustained exercise By Colberg, Sheri R. Casazza, Gretchen A. Horning, Michael A. Brooks, George A. J. Appl. Physiol., 76(1), 26-32 1994 ORDER # CA 120:263648w To evaluate the hypothesis that smoking increases the dependence on blood glucose as a fuel, seven male smokers [28.7 .+-. 1.7 (SE) yr, 77.7 .+-. 4.3 kg] and seven nonsmokers (NS; 29.1 .+-. 0.9 yr, 78. 7 .+-. 5.3 kg) were studied in the post-absorptive condition. NS received a primed continuous infusion of [6.6-2H] glucose and [1- 13C] glucose during 90 min of rest and 60 min of exercise at 49. 7 .+-. 0.8% of peak 02 consumption on one occasion; chronic smokers continued their overnight abstinence from smoking (CS) for one trial but, on another occasion, acutely smoked (AS) two cigarets immediately before resting measurements and another cigaret before exercise. Plasma glucose levels were similar among all groups at all times during the trials; however, the glucose rates of appearance ( Ra) at rest in CS (1.96 .+-. 0.14 mg cntdot. kg-1 cntdot. min -1) and AS (2.02 .+-. 0.14) were higher than in NS (1.41 .+-. 0.15, P < 0.05). With exercise, the glucose Ra values rose in all groups above resting values but were significantly greater in CS (4.76 .+-. 0.50) and AS (4.71.+-.0.53) than in NS (3.31 .+-. 0.16). Glucose oxidn. during exercise was elevated in smokers (2.31 .+-. 0.37 mg cntdot. kg-1 cntdot. min -1 in CS and 2.18 .+-. 0.34 in AS) compared with NS (1.09 .+-. 0.18, P < 0.05). Nicotine levels correlated with the glucose Ra in AS (r = 0.93, P < 0.01). In conclusion, the results indicate that long-term smoking, independent of acute smoking, increases the dependence on blood glucose as a fuel during rest and sustained submaximal exercise. (In Eng) , Vol. 25, No. 6, June 3, 1994 '47 () 0

TOBACCO AND TOBACCO SMOKE Effects of benzo[alpyrene and nicotine on prostaglandin synthesis in buccal pouch and submandibular glands of the Syrian hamster By Wu-Wang, C. Y. Wang, S. L. Brigham, M. Correa, A. Slomiany, A. Slomiany, B. L. Arch. Oral Biol., 38(12), 1045-50 1993 ORDER # CA 120:263647v Adult male Syrian hamsters were treated by swabbing the apex of the buccal pouch with corn oil (control, C), 1 mM benzo[a]pyrene (BP), nicotine (NC), or BP + NC in corn oil, twice daily, 5 days a week. After a 4-wk treatment, the pouches and submandibular glands were dissected and used for the detn. of endogenous prostaglandin (PG) prodn. and studies on in vitro PG synthesis. Of the three PGs analyzed (PGE2, PGF2.alpha. and 6-keto-PGFl.alpha.), PGE2 was predominant in the pouch and the glands. BP or NC alone had only a weak effect on PG synthesis in both tissues. However, the combination of BP and NC had a synergistic effect, causing diminished PG synthesis in both tissues. In buccal pouch, BP + NC significantly decreased the concns. of endogenous PGE2 and PGF2. alpha., (PGE2: 0.669 .+-. 0.254 vs. 1.698 .+-. 0.460, PGF2.alpha.: 0. 273 .+-. 0.090 vs. 0.625 .+-. 0.272 ng/g tissue; BP + NC vs. C; mean .+-. SD, n = 5, p < 0.05). Similarly significant results were also found for in vitro PG synthesi's (PGE2: 0.541 .+-. 0.249 vs. 1. 399 .+-. 0.340, PGF2.alpha.: 1.045 .+-. 0.428 vs. 2.133 .+-. 0.510 ng/g tissue; BP + NC vs. C; mean .+-. SD, n= 5, p < 0.05). In submandibular glands, BP + NC significantly diminished the concn. of endogenous PGE2 (1.183 .+-. 0.175 vs. 2.379 .+-. 0.488 ng/g tissue; BP + NC vs. C; mean .+-. SD, n = 5, p < 0.05). The synthesis of 6- keto-PGF1.alpha. in both tissues, and the synthesis of PGF2.alpha. in submandibular gland, were slightly decreased with all treatments. (In Eng) Vol. 25, No. 6, June 3, 1994 10 N Er3 rn A .~+ P ~ 7101

TOBACCO AND TOBACCO SMOKZ'' Evidence for nicotine-induced skin flap ischemic necrosis in the pig By Forrest, Christopher R. Xu, Ning Pang, Cho Y. Can. J. Physiol. Pharmacol., 72(1), 30-8 1994 ORDER # CA 120:263646u The objectives of this project were to investigate the potential deleterious effects and mechanism of action of nicotine, a major byproduct of cigaret smoking, in skin flap surgery in the pig. It was obsd. that 4-5 wk of i.m. nicotine injections (4 mg/kg; twice daily) significantly (p < 0.05) decreased the skin flap capillary blood flow and the length and area of skin flap viability in the pig. This nicotine treatment also induced a 1.6-fold increase in skin flap tissue content of norepinephrine compared with the saline- treated control. The estd. mean wet skin tissue content of norepinephrine (5 times. 10-7 M) was much higher than the circulating level of norepinephrine (1.8 times. 10-9 M) in nicotine- treated pigs. This level of norepinephrine (5 times. 10-7 M) was seen to induce a significant vasoconstrictor effect (75% increase over basal perfusion pressure) in isolated perfused pig skin flaps. It was also obsd. that the vasoconstrictor effect of norepinephrine was significantly (p < 0.05) enhanced the presence of 10-4 M N. omega.-monomethyl-L-arginine or NG-nitro-L-arginine, an endothelium- derived relaxing factor - nitric oxide (EDRF/NO) synthesis inhibitor. This vasoconstrictor effect was further enhanced in the presence of NG-nitro-L-arginine and 10-5 M indomethacin, a cyclooxygenase inhibitor. Taken together, these observations indicate that 4-5 wk of nicotine treatment likely to be mediated, at least in part, by locally released norepinephrine induced by nicotine treatment. Furthermore, norepinephrine also induced skin flap local release of EDRF/NO and a vasodilating prostanoid that in turn attenuated norepinephrine's vasoconstrictor effect in the skin vasculature. (In Eng) Vol. 25, No. 6, June 3, 1994 702

TOBACCO AND TOBACCO SMOKe" Effects of nicotine on production of endothelin and eicosanoid by bovine pulmonary artery endothelial cells By Suzuki, N. Ishii, Y. Kitamura, S. Prostaglandins, Leukotrienes Essent. Fatty Acids, 50(4), 193-7 1994 ORDER # CA 120:263645t To clarify the relationship between cigaret smoking and regulators of vascular tone derived from endothelium, the authors studied the acute and subacute effects of nicotine on endothelin and eicosanoid prodn. by bovine pulmonary artery endothelial cells (BPAEC). The acute effects of nicotine were assessed by measuring the release of endothelin, prostaglandin 12 (PGI2), the thromboxane A2 (TXA2) from BPAEC after their incubation with a medium contg. various concns. of nicotine (10-9 M - 10-3 M) for 24 h. The subacute effects were assessed after 1 wk's culture of BPAEC in the presence of nicotine ( 10-7 M, 10-3 M). Acute exposure to a high concn. of nicotine (10-5 M - 10-3 M) led to a significant inhibition of endothelin prodn. by BPAEC. Nicotine, 10-3 M, inhibited PGI2 prodn., but led to release of lactate dehydrogenase. Subacute exposure to nicotine (10-3 M) also inhibited the prodn. of endothelin and PGI2 by BPAEC. A high concn. of nicotine reduced the prodn. of endothelin and PGI2 by BPAEC, probably due to the cytotoxicity of nicotine. Concns. of nicotine comparable to the plasma levels of nicotine found in smokers (10-9 - 10-6 M) did not affect the release of endothelin and PGI2 from BPAEC. The mechanism of nicoLine-irrduced vasoconstriction may be independent of the release of endothelin or PG derivs. from endothelial cells. (In Eng) Synergistic effects of mineral fibers and cigaret smoke on the production of necrosis factor by alveolar macrophages of rats By Morimoto, Yasuo Kido, Masamitsu Tanaka, Isamu Fujino, Akihiro Higashi, Toshiaki Yokosaki, Yasuyuki Br. J. Ind. Med., 50(10), 955-60 1993 ORDER # CA 120:263643r The objective of this study was to evaluate the combined effects of mineral fibers and cigaret smoke on the prodn. of tumor necrosis factor (TNF) by alveolar macrophages. Rats were exposed to cigaret smoke in vivo, and prodn. of TNF by alveolar macrophages was measured in the presence of mineral fibers in vitro. For smoke exposure, rats were divided into two groups. Five were exposed to a daily concn. of 10 mg/m3 of cigaret smoke for an eight hour period, and five rats (controls) were not exposed to smoke. Bronchoalveolar lavage was performed after exposure to smoke and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibers on a microplate for 24 h. Activity of TNF in the supernatant was detd. by the L-929 fibroblast cell bioassay. When alveolar macrophages were not stimulated by mineral fibers, prodn. of TNF by rats exposed to smoke and unexposed rats was essentially the same. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibers, prodn. of TNF by alveolar macrophages from rats exposed to smoke was higher than that by alveolar macrophages from unexposed rats. The findings suggest that cigaret smoke and mineral fibers have a synergistic effect on TNF prodn. by alveolar macrophages. (In Eng) Vol. 25, No. 6, June 3, 1994

TOBACCO AND TOBACCO SMOKE Expression of myc, fos, and ha-ras in the livers of furan-treated F344 rats and B6C3F1 mice By Butterworth, Byron E. Sprankle, Catherine S. Goldsworthy, Susan M. Wilson, Daniel M. Goldsworthy, Thomas L. Mol. Carcinog., 9(1), 24-32 1994 ORDER # CA 120:263580t Furan administered by gavage for 2 yr has been reported to induce hepatocellular carcinomas in male and female B6C3F1 mice and in male but not female F344 rats. Chronic exposure studies in the authors' lab. using bioassay conditions showed extensive hepatocellular toxicity and sustained increases in regenerative cell proliferation after 1, 3, and 6 wk of treatment in male and female rats and male mice. Altered expression of growth-control genes assocd. with this hyperproliferative state may enhance the susceptibility of these genes to mutation or may provide a selective growth advantage to preneoplastic cells. Quant. northern blot anal. of mRNA was used to examine the expression of the oncogenes myc, fos, and Ha-ras in the livers of animals treated with furan. In male rats, a single administration of 30 mg/kg furan produced necrosis and a subsequent wave of cell proliferation 48 h after treatment and induced transient peaks in the expression of myc, fos, and Ha-ras 6-24 h aftei treatment. In male rat liver from the authors' cell proliferation studies, only a slight increase in myc expression was seen at the end of week 1 of treatment. However, beginning at week 3 and increasing at week 6, up to a 15-fold increase over control values was obsd. in the expression of myc in the treated animals. The only other notable increase in expression obsd. in any animals from the cell proliferation study was a threefold increase in myc at week 6 in treated female rats. The absence of an increase in Ha-ras expression in the male mouse liver suggests that the unique pattern of Ha-ras mutations previously reported in furan-induced mouse liver tumors is not due to increased mutational susceptibility related to overexpression of this gene. The lack of sustained expression of myc, fos, and Ha-ras in rapidly proliferating liver suggests that continuous expression of these genes is not necessary to maintain increased rates of cell replication. The large increase in myc expression in male but not female rats suggests an adaptive change that may be related to the sex-specific incidence of furan-induced hepatocellular carcinomas in rats. (In Eng) cn 0 Vol. 25, No. 6, June 3, 1994 '704

TOBACCO AND TOBACCO SMOKE Cytochrome P-450-dependent biotransformation of 2- acetylaminofluorene in cell-free preparations of human embryonic hepatic, adrenal, renal, pulmonary, and cardiac tissues By Namkung, Moses J. Yang, Hsueh-Ying L. Juchau, Mont R. Drug Metab. Dispos., 22(2), 331-7 1994 ORDER # CA 120:263561n Human embryonic hepatic, renal, adrenal, pulmonary, and cardiac tissues (gestational age = 50-60 days) were probed for functional P 450 isoforms with 2-acetylaminofluorene (AAF) in cell-free prepns. Each of these tissues exhibited P 450-dependent hydroxylation at several positions on the AAF mol., although activities in renal, pulmonary, and particularly cardiac prepns. were generally low. N- hydroxylation activities were marginal to undetectable in all five tissues, but 7-hydroxylation was detectable in each tissue. Highest arom. ring-hydroxylation activities were obsd. in hepatic tissues, and adrenal tissues also exhibited relatively high activities for ring-hydroxylation, particularly at carbon-7. The 9-hydroxylated AAF metabolite (9-OH-AAF) was the predominant metabolite for all human embryonic tissues, but generation via catalysis by P 450 isoforms appeared to be minimal/negligible. Activity profiles for human embryonic tissues (days 50-60 of gestation) were compared with those of 12 sep., vector-expressed human P 450 isoforms, with those of human fetal tissues (days 72-140 days of gestation), with those of various rodent embryonic tissues, and with those of adult rhesus monkey and adult rat tissues pre-exposed to inducing agents. (In Eng) The influence of maternal nicotine exposure on neonatal lung alveolar epithelial status: an electron microscope study. By Maritz, G.S. Scott, L. Thomas, R A. Cell Biol. Int., 17(12), 1085-9 1993 ORDER # CA 120:263559t The aim of the present study was to investigate the effect of maternal nicotine exposure (1 mg nicotine/kg body mass/day) on neonatal lung alveolar epithelial cells. Rats (Wistar descendants) were used. The data illustrate that maternal nicotine exposure during pregnancy and lactation resulted in alveolar fenestrations, blebbing and rupturing of the blood-air barrier. The type I pneumocyte appears to be more sensitive to the effect of nicotine than the type II pneumocytes. (In Eng) Vol. 25, No. 6, June 3, 1994 "~~~

TOBACCO AND TOBACCO SMOKE''~.' Evidence supporting the role of DHA pyridyloxobutylation in rat nasal carcinogenesis by tobacco-specific nitrosamines By Trushin, Neil Rivenson, Abraham Hecht, Stephen S. Cancer Res., 54(5), 1205-11 1994 ORDER # CA 120:263513y The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) both induce nasal tumors in rats and have a common metabolic activation pathway leading to pyridyloxobutylation of DNA. In this study, the authors used gas chromatog.-mass spectrometry to compare levels of 4- hydroxyl-l-(3-pyridyl)-1-butanone-releasing adducts formed by pyridyloxobutylation of rat nasal mucosa DNA after treatment with either NNK, NNN, or deuterated analogs of NNK. The latter were [4,4- D2]NNK, a stronger nasal cavity carcinogen than NNK, and [CD3]NNK, which has carcinogenic activity equiv. to NNK. The authors also investigated toxicity to the nasal mucosa and levels of 06- methylguanine in the DNA of this tissue in rats treated with NNK and its deuterated analogs. Rats were given 3 times weekly s.c. injections of the resp. nitrosamines for 4 wk and then sacrificed 24 h after the final injection. The nasal mucosa was sepd. into the olfactory and respiratory positions. In the rats treated with [4,4- D2]NNK, levels of 06-methylguanine in DNA from both the olfactory and respiratory portions of the nasal mucosa were significantly lower and levels of 4-hydroxy-l-(3-pyridyl)-1- butanone-releasing DNA adducts higher than in.the rats treated with equiv. doses of the less carcinogenic compds. NNK or [CD3]NNK. 4-Hydroxy-l-(3-pyridyl)-1- butanone-releasing adducts were also detected in the nasal mucosa DNA of the rats treated with NNN. In the comparative study of NNK and its deuterated analogs, the histol. of the nasal mucosa did not appear to be markedly different among these groups. Collectively, the results of this study provide strong evidence that DNA pyridyloxobutylation is important in rat nasal cavity carcinogenesis by NNK and NNN. (In Eng) Development of mutagenicity tests utilizing mouse peritoneal exudate cells By Nishi, Y. Hen'igensei Shiken, 2(4), 246-55 1993 ORDER # CA 120:263497w An assay system was developed to detect genotoxic agents utilizing the peritoneal exudate cells (PECs) from mice. In the PECs, there are many lymphocytes which could be stimulated into mitoses upon treatment with Escherichia coli lipopolysaccharide and 2- mercaptoethanol. In the peritoneal lymphocytes, sister chromatid exchanges (SCEs) were dose-dependently induced upon treatment with cyclophosphamide. The long exposure to cigaret smoke, and the strain difference to UV light-induced SCEs were also evaluated using this system. The PECs were also applicable to an alk. elution assay. Upon treatment with alkylating agents, DNA strand breaks were significantly induced in PECs. The PEC assay can be an excellent system since the cells are readily recovered and detect the effect sooner and for longer periods than the cells from other organs. (In Japan) Vol. 25, No. 6, June 3, 1994 w~~

TOBACCO AND TOBACCO SMOKE Ovarian hormone status, life-style factors, and markers of bone metabolism in women aged 50 years By Leino, A. Jarvisalo, J. Impivaara, 0. Kaitsaari, M. Calcif. Tissue Int., 54(4), 262-7 1994 ORDER # CA 120:261545m Fifty-year-old women attending a health examn. were divided by their ovarian hormone status into four groups: premenopausal, perimenopausal, postmenopausal without ovarian hormone replacement therapy (HRT), and postmenopsausal with HRT. Information on life- style factors was obtained with interviews and questionnaires. Bone mineral d. at the calcaneus was assessed with single-photon absorptiometry, and several serum and urine markers of bone metab. were measured. Postmenopausal women without HRT had significantly higher levels of fasting serum alk. phosphatase, osteocalcin, total and ionized calcium, phosphate, and fasting urinary hydroxyproline than those in the three other study groups. No difference was found in bone mineral d. between the premenopausal and postmenopausal groups. Postmenopausal women without HRT showed a marked correlation between serum osteocalcin and urine hydroxyproline. Both markers showed significant correlations with serum calcium, phosphate, and alk. phosphatase. Multivariate analyses showed a statistically significant assocn. of ovarian hormone status and body mass index with most measured markers of bone metab. 'Ic.c assocn. between aic. consumption and serum osteocalcin was highly significant. Ciaaret smoking was assocd. with levels of serum alk. phosphatase and total and ionized calcium. A weak assocn. was found between coffee drinking and serum alk. phosphatase. (In Eng) Tri.methylamine oxide and related compounds for cancer prophylaxis WO 9406413 PCT Int. Appl., 28 pp. 1994 ORDER # CA 120:261338w A method of anticancer prophylaxis comprises chronic maintenance administration of trimethylamine oxide, analogs and derivs. thereof and precursors (collectively referred to as trimethylamine oxide- class compds.); unit dosage forms for the method are also disclosed. In particular embodiments, the method comprises administration of a trimethylamine oxide-class compd. in the range of .gtoreq.35 mg/kg at least approx. every 1-5 days, alternatively, maintained blood levels of approx. 100 mM. The efficacy of trimethylamine oxide in cancer prophylaxis in rats treated with dimethylbenz-(a)-anthracene is described. (In Eng) -0 N) W ON -PA Pb C11 W Vol. 25, No. 6, June 3, 1994 7 417

TOBACCO PHARMACOLOGY Acat Inhibitors as Antiatherosclerotic Agents - Compounds and Mechanisms. By Matsuda K Medicinal Research Reviews; 14 (3) p271-305 MAY 1994 ORDER # NG579 No abstract available (In English) Relationship of Electroeacephalographic and Cardiovascular Changes to Plasma Nicotine Levels in Tobacco Smokers. By Kadoya C; Domino EF; Matsuoka S Clinical Pharmacology & Therapeutics; 55 (4) p370-377 APR 1994 ORDER # NG973 Objective: The effects of smoking one tobacco or placebo cigarette on the mean change in voltage of the electroencephalogram (EEG), arterial blood pressure, heart, and eye blink rates were correlated with the increase in plasma nicotine, exhaled carbon monoxide, and carboxyhemoglobin levels. Methods: Twenty nonsmokers (age range, 19 to 42 years; mean age +/- SE, 27.0 +/- 1.9 years) and 65 regular tobacco smokers (age range, 20 to 48 years; mean age +/- SE, 27.7 +/- 0.8 years) were studied about 10 to 12 hours after overnight tobacco deprivation and immediately after inhaling air through a straw or after smoking one of their own brands of cigarettes, respectively. Results: An increase of at least 10 ng/ml plasma nicotine was needed to obtain a statistically significant decrease in alpha, and an increase in beta EEG activity. An increase of at least 15 ng/ml plasma nicotine was needed to obtain a statistically significant decrease in delta EEG activity. The mean dominant alpha frequency, heart rate, systolic and diastolic blood pressure, exhaled carbon monoxide, and carboxyhemoglobin levels increased significantly with increasing plasma nicotine concentrations. Conclusions: Measurement of plasma nicotine levels is especially important to quantify the relationship between tobacco smoking, mean EEG activity, and cardiovascular changes. Nicotine plasma concentrations greater than 10 mu g/ml produce consistent and statistically significant changes in brain wave activity. Smaller increments in plasma nicotine produce less consistent EEG changes. (In English) Vol. 25, No. 6, June 3, 1994 ~"®~

TOBACCO PHARMACOLOGY Effects of Concentrated Cigarette Smoke on Respiratory Tract Clearance in the Ferret. By Phalen RF; Rasmussen RE; Mannix RC; Oldham M Inhalation Toxicology; 6 (2) p125-138 MAR-APR 1994 ORDER # NJ195 This study was performed to assess the effects of two high concentrations (about 380 mg/m(3) and about 38 mg/m(3)) of inhaled cigarette smoke on tracer particle clearance from the head airways region and the thoracic (primarily deep lung) region of ferrets exposed during postnatal respiratory tract development. Ferrets were exposed 2 h/days, 5 days/wk to purified air or to the smoke aerosols starting at 5 wk of age, for a total of 15 wk of exposure. Three weeks prior to the end of the 15-wk exposure regimen, radiolabeled tracer particles were deposited by inhalation, and the clearance rates from the head airways and thoracic regions were monitored for 78 days. The head airways counting data were accurately fit by a double exponential function, reflecting fast-clearing and slow-clearing components. The thoracic counting data were adequately fit by a single exponential function. Statistically significant accelerations of particle clearance rates were observed for the slow-clearing and fast-clearing phases of clearance from the head airways region for both the higher and lower concentration groups; the results implied a dose- response relationship. Only in the case of the higher concentration group was significant slowing observed in the thoracic region analysis, indicating that the head airways region was perhaps the area of greater impact of the smoke aerosol. (In English) Vol. 25, No. 6, June 3, 1994 71 0 9