Tobacco Documents Online

20 STATISTICS AND RISK ASSESSMENT [76] "Who's Exaggerating?" A.M. Finkel, Discover May: 48-51, 54, 1996 [See Appendix A] OSHA Director of Health Standards Adam Finkel aefends the process of risk assessment in this commen- tary, which appears in a popular scientific magazine. IN EUROPE & AROUND THE WORLD REGION 1-WESTERN EUROPE REGULATORY AND LEGISLATIVE MATTERS [77] Hospital Food Outlets in Ireland Required To Reserve Nonsmoking Areas As of May 1, 1996, the Irish Health Board is requir- ing owners of food outlets in hospitals and clinics to make at least one-half of their seats nonsmoking. According to a press report, the food outlet owners will be responsible for publicizing and enforcing the new rules. See Irish Ira-endent, April 23, 1996. [78] Smoking Ban Suspended in Housing for the Elderly A smoking ban imposed last summer by the Council of the Vale of Glamorgan in communal areas of housing complexes for the elderly has reportedly been suspended following complaints. An investigation is apparently underway into the cost of providing smoking areas. See South Wales Echo, April 23, 1996. [79] European Commission Not Expected To Develop IAQ Legislative Proposals The European Commission reportedly does not foresee developing legislative proposals on IAQ in the immediate future, according to Commissioner Edith Cresson. Cresson apparently made the statement in response to an inquiry by MEP Martina Gredler, who had asked whether the commission intends "to take a pioneering role in the field of indoor pollution through the adoption of a new regulation." "The Community already has a corpus of legislation dealing with worker ETS/IAQ REPORT, ISSUE 123 protection and which covers inter alia air quality within the workplace," Cresson was quoted as saying. Cresson also responded to Gredler's inquiry about "indoor pollution" research conducted by the Joint Research Centre QRC) and the dissemination of its findings. Cresson explained that the JRC research, which has been underway since 1986, is being con- ducted within the framework of the European research network called "the European collaborative action on indoor air quality and its impact on man." She said that its reports had been made widely available through mailings to about 900 researchers, universities and institutes, and that its findings are published in the open scientific literature and are partially contained or cited in the reports of the European collaborative action. See Written Question E-3428195 by Martina Gredler (ELDR) to the Commission; 3428/95ENAnswer Given by Mrs. Cresson on Behalfofthe Commission, February 8, 1996; Journal of the European Communi- ties, April 25, 1996. OTHER DEVELOPMENTS [80] Lancet Editorial Calls for Scrutiny of Discrimi- natory Treatment of Smokers An editorial in a recent issue of The Lancet, while complaining about the government's lack of interest in public health, claims that a local initiative giving preference in adoption to nonsmoking couples deserves the public's most critical scrutiny "lest we risk losing control over our moral choices about health to the prejudices of governments." The editorial also states, "most people might consider it absurd not to allow a couple to adopt a child because they indulge in a habit that although dangerous to their own health poses an unquantifiable and probably tiny threat to-that of their children." According to the editorial, government-funded public health campaigns have had little effect and are giving way to coercive discrimina- tion. See The Lancet, May 4, 1996. [81] British and Australian Scientists Claim Link Between Radio Waves and Allergies A team of British and Australian scientists have reportedly found a possible link between radio waves and allergic reactions, which they claim could explain the large increase in the number of individuals with SHB 93140321

MAY 10, 1996 asthma. The team's findings, which apparently are to be published soon, suggest that the frequencies at which televisions, computers and mobile telephones operate might trigger and/or exacerbate allergic reactions in sensitive lungs. John Holt, a member of the research team, is quoted as stating, "There is no question that factors such as air pollution and other antigens are involved. But I think our findings show that electromagnetic radiation has made it ten times worse." The team of scientists is led by Peter French, medical director at the Centre for Immunology and Cancer Research at St. Vincent's Hospital, Sydney. See The Times, April 30, 1996. [82] British Survey Results Support Nonsmoking Policy A survey of 490 customers of seven pubs in Avon, conducted by the antismoking group called Breathe Easy, has purportedly found that more than 90 percent of the pubs' customers would not object to a nonsmok- ing policy and that 47 percent were more inclined to go to a nonsmoking pub. The findings were criticized by the British smokers' rights group FOREST, as being biased and flawed. According to FOREST, the Breathe Easy survey was conaacted in pubs that already had nonsmoking policies. See The Publican, April 15, 1996. [83] North Yorkshire Policy To Give Nonsmokers Priority in Adopting and Fostering Children City councilors in North Yorkshire, Britain's largest local authority, have reportedly decided to back a policy that would give nonsmokers priority in adopting or fostering children younger than age 2. The council's social services subcommittee was apparently told that ETS can lead to impaired lung growth and slow development. However, the city of York apparently will not be following the policy. The city's assistant director of children's services was quoted as saying that they wanted to avoid any "arbitrary or artificial" barriers to people becoming foster parents. Prior to North Yorkshire's adoption of the policy, the Liberal Democrat chair of its social services subcom- mittee was quoted as stating, "We are a responsible council, and we must consider this as part of our approach on smoking. There will be plenty of discus- sion, but people are more and more aware of the harm 21 caused by smoking, which is increasingly banned in public places." When the proposed policy was announced, the British smokers' rights group FOREST lodged a protest, stating that the proposal was not based on fact and that there is no well-founded scientific foundation for ETS health claims. An editorial in a regional newspaper also argued that such a "hard and fast" ruling could be dangerous. "If someone smokes it does not necessarily make them a better or worse parent...Certainly there is more to parenthood than providing a nicotine free environment," it stated. Further details about the council's proposal appear in issue 122 of this Report, April 26, 1996. See Reuters, Northern Echo, April 23, 1996; Northern Echo, Echo Yorkshire Evening Post, April 26, 1996. [84] French Passenger Indicted for Smoking During Flight A Boston grand jury has reportedly dropped charges against French nightclub owner Regine Choukroun for her involvement in a conflict with airline personnel over her son's smoking during a trans-Atlantic flight. Choukroun's son, Lionel Rotcajg, has apparently been indicted on charges of interfering with an American Airlines crew. Initial reports indicated that Rotcajg had assaulted and threatened the crew in mid-air. Further details about the incident appear in issue 122 of this Report, April 26, 1996. See International Herald Tribune, May 3, 1996. [85] European Parliament Approves "Leaders Against Tobacco" Program European political and social leaders, as well as high-profile individuals from the scientific and artistic communities, will apparently be asked not to smoke in public as part of a "European Leaders Against To- bacco" initiative to be conducted in conjunction with the Europe Against Cancer program. The program, which has been approved by the European Parliament, will involve a media campaign directed by the Euro- pean Commission. The European Leaders initiative was proposed by Euro MP Jose Luis Valverde, who reportedly stated that citizens must be protected from the "negative effects" of tobacco smoke. See Actualidad Tabaquera, April 1996. SHB

22 REGION 2-AUSTRALIA REGULATORY AND LEGISLATIVE MATTERS [86] Woodford Prison Implements Smoking Ban Prisoners and staff will reportedly be banned from smoking anywhere within Woodford prison. A spokes- man for the Queensland Corrective Services stated that the situation would be monitored as concerns aLc ,tt increased tensions in the prison have been expressed by the Prisoners Legal Service, the Civil LibPrries Council and the State Public Services Federation. Previously banned nicotine patches and chewing gum may apparently be permitted. See Proserpine Guardian, March 28, 1996; TVQ10, BTQ7 `News ; April 19, 1996; Courier Mai4 April 20, 1996; Morning Bulletin, Apri122, 1996. REGION 3 JAPAN OTHER DEVELOPMENTS [871 Asahi Will Not Export "Smoklin" Fiber but Other Companies Move Ahead Rejecting an estimated JA$4 to JA$5 billion in potential sales, Asahi Chemical Industry Co., Ltd., has reportedly decided not to export its "Smoklin" deodor- izing f ber to avoid the possibility of becoming embroiled in smoking and health litigation in the United States. A company official was quoted as stating, "It is possible for us to be sued by, for example, lung cancer patients who may mistakenly conclude that the fiber eliminates harmful ingredients." Asahi claims Smoklin fiber can absorb and neutralize 80 to 90 percent of the acetaldehyde, ammonia, acetic acid and other substances found in tobacco smoke. The company developed the fiber in July 1994 and has applied for patents in Japan and other countries. A press report indicates that Asahi's decision not to export the fiber conflicts with advice received from U.S. importers who apparently told Asahi officials that it would face minimal product liability risk in the United States. The company evidently decided not to export the fiber to other countries to avoid trade-discrimination lawsuits by U.S. companies. ETS/IAQ REPORT, ISSUE 123 Other Japanese companies are reportedly moving ahead with products that control ETS and odor. Shiseido, for example, is marketing a product that apparently removes accumulated odors from human hair. Tornex, a Japanese air conditioning manufac- turer, has reportedly developed a device that generates tornado-like air currents to keep ETS from drifting toward nonsmokers. Matsushita Electric Industrial Co. and Sharp Corp. have also introduced fans and air cleaners to control ETS. See The Daily Yomiuri, February 6 and 11, 1996; The Nikkei Weekly, March 18, 1996; The Japan Times, April 25, 1996. REGION 4-EASTERN EUROPE AND THE MIDDLE EAST REGULATORY AND LEGISLATIVE MATTERS [88] Antismoking Law Takes Effect in Poland As of May 1, 1996, a new law took effect that reportedly restricts indoor smoking in workplaces, public buildings, hospitals, schools, sports centers and similar sites to specially designated areas. If such areas are not provided, smoking is prohibited. Violators face fines of up to US$2,000, approximately one-half of the annual wage earned by an average Polish worker. The law also bans tobacco sales at medical and sports centers. See Polish Press Agency, Reuters, United Press Internationa4 May 1, 1996. [89] Iranian Parliament Withdraws Law Banning Smoking in Public Places The Iranian parliament has reportedly withdrawn a law it had passed, which prohibits smoking in public places and the sale of cigarettes on the streets, because of opposition from the Guardian Council. The coun- cil, a senate-like group composed of six theologians and six jurists that reviews parliament decisions before they take effect, had ruled that the law was unconstitutional because it would reduce tax revenues from tobacco sales without finding another source of income. The parliament had narrowly approved the law on April 28, 1996, despite reported spirited opposition from members who smoke. See Agence France Press, 93140323 SHB

MAY 10, 1996 Deutsche Presse Agentur, Reuters, United Press Interna- tiona4 April 28 and May 1, 2, 5, 1996. REGION 5-CANADA REGULATORY AND LEGISLATIVE MATTERS [90] Vaughan To Provide Exemptions to Anti-Smoking Bylaw, While Oshawa, Kanata Consider More Restrictions The city of Vaughan has reportedly created temporary exemptions from what has been called the toughest antismoking bylaw in Canada. As originally drafted, the bylaw would have prohibited smoking in all public places as of May 1, 1996. The city council recently amended the measure, however, to exempt banquet halls, bars and taverns, billiard and bingo halls, and institutional-residential buildings until September 30. The city reportedly plans to develop permanent exemp- tions for these establishments by June 30. Preliminary reports indicate that separately ventilated smoking areas might be permitted in the facilities. Meanwhile, approximately 35 speakers apparently debated plans to increase public smoking restrictions in Oshawa during a recent meeting of the city's fire protection and general purposes committee. City officials are reportedly considering increasing the number of bingo hall tables reserved for nonsmokers from 10 to 15 percent. Opponents of the move contend that the increase would result in reduced business. A spokesman for the Oshawa West Lyons Club reportedly stated that the club raises most of the money it donates to the pediatric diabetic unit at the city's General Hospital from bingo. Without the bingo proceeds, he argued, "It's going to close. These kids are going to suffer." Kanata has reportedly become the sixth municipality in Ottawa-Carleton to support a proposed regional ban on smoking in the workplace. The council condition- ally endorsed the ban, but apparently wants the region to come up with a plan to share the costs for enforcing it. The city council also shelved a proposal to prohibit smoking in restaurants, apparently due to concerns over the legal costs of defending the measure and the possibility it would drive businesses to other cities. The 23 council apparently decided to observe how the Vaughan bylaw faresagainst legal challenges before making a decision. Kanata's current bylaw prohibits smoking in 70 percent of the city's restaurants. See The Ottawa Citizen, April 27, 1996; The Toronto Star, May 2, 1996. [91] Soo Jail Order To Meet Clean Air Regulations Likely To Affect Other Jails in Ontario System Soo provincial jail officials have reportedly been ordered to implement a plan by March 1998 that will ensure that the jail's IAQ is as good as that of commer- cial buildings where smoking is not permitted. The order requires that the first stage of the plan be in effect by June 8, 1996. Corrections Ministry officials have apparently admitted that the order effectively sets the rules for all 45 jails in the province. The order is purportedly based on a finding that scientific consensus links ETS to lung cancer, other respiratory ailments, heart disease, and reproductive system ailments; that there is no safe level of ETS exposure; and that Ontario's workplace safety law requires an employer "to take reasonable precautions in the circumstances for the protection of workers." A Corrections Ministry official is quoted as stating that there are ff..v ways to achieve clean air other than by prohibiting smokin~, adding that separately venti- lated prisoner smoking lounges in most of Ontario's old concrete and limestone jails could not be created at an acceptable cost. Jail management and union officials estimate that 75 to 90 percent of inmates and about one-third of jail guards smoke. See The Toronto Star, April 25, 1996. REGION 6-LATIN AND SOUTH AMERICA REGULATORY AND LEGISLATIVE IVIATTERS [92] Brazil's Justice Tribunal Nullifies Sao Paulo Smoking Fines The chief judge of the Brazilian Justice Tribunal has reportedly stated that all fines imposed by Sao Paulo officials to enforce the city's recently overturned restaurant smoking ban have been nullified. The statement comes in the wake of the tribunal's decision to overrule a September 1995 decree by Mayor Paulo SHB

24 Maluf that prohibited smoking in all Sao Paulo restaurants. The decision to block the fines apparently covers all 50,000 members of the Sao Paulo Hotels, Restaurants, Bars and Food Establishments Federation, and was greeted by celebration in many federation restaurants. Additional information about the tribunal's prior ruling appear in issue 122 of this Report, April 26, 1996. See Sexta-Feira, April 19, 1996. REGION 7-ASIA REGULATORY AND LEGISLATIVE MATTERS [93] Punjab House of Representatives Urges Smok- ing Ban Legislation The Punjab House of Representatives has reportedly passed a resolution recommending that Parliament enact legislation banning the use of tobacco in public places in the state and all forms of tobacco advertising. See Indian Express, March 22 1996. OTHER DEVELOPMENTS [94] Chinese Children s Army To Stop Smokers in Pub:ic Places A year-long publicity campaign, during which 500,000 children will reportedly try to persuade family members to quit smoking and to "stop people who puff cigarettes in public places with 'no-smoking' signs," has been launched, according to a news report. Government officials were quoted as saying, "The youngsters have formed a mini-army of peaceful persuaders in a nationwide drive to curb the increase in the country's smoker population," which is said to number 350 million, or 29 percent of China's 1.2 billion people. Since last year, 26 Chinese cities have banned smoking in public places. Beijing will impose its own ban as of May 15, 1996. See Xinhua News Agency, Agence France Presse, April 30, 1996. ETS/IAQ REPORT, ISSUE 123 WORLD AIRLINE NEWS [95] Air France Flights Feature "Smoker's Bar" All Air France flights between Houston and Paris reportedly feature a "bar fumeur," separate lounge areas for smoking in economy class and in first/business class. With the introduction of the bar fumeur, all assigned seating areas are smoke-free. The bar fumeur, an Air France exclusive, is described as a semi-enclosed _ lounge and bar area equipped with a smoke-extracting fan that draws out fumes and keeps the entire aircraft cabin smoke-free. Air France apparently plans to add the smokers' bars to flights from Paris to Los Angeles, San Francisco and Washington Dulles in June; New York (JFK) in September, and Miami and Newark, New Jersey, in November. See Reuters, Business W7re, March 19, 1996; USA Today, April 2, 1996; The Houston Chronicle, April 14, 1996. SHB

MAY 10, 1996 APPENDIX A The numbers assigned to the following article summaries correspond with the numbers assigned to the synopses of the articles in the texr of this Report. LUNG CANCER [47] "Pulmonary Carcinogenicity of CigarettL Sidestream Smoke in A/J Mice," H.P. Witschi and KE. Pinkerton, The Toxico!ooist30(1, Part 2): 1036, 1996 "A total of 48 male strain A/J mice were exposed to sidestream smoke (SS) generated from Kentucky 1 R4F reference cigarettes (Controls: filtered air). Chamber concentrations were 90 mg/m3 of total suspended particulate, 246 ppm CO and 17 ug/mj of nicotine. Animals were exposed for 20 weeks, 6 hours a day, 5 days a week. After 5 months, half of the animals were killed. We found that at this moment 33% of the SS exposed and 11 % of the controls had lung tumors (tumor incidence and multiplicity not significantly increased). The remaining animals were allowed to recover in air and were killed 9 months after the [beginning] of the experiment. In the SS exposed groups, 20 out of 24 animals (84%) had one or several lung tumors and the average number of tumors per lung was 1.38 [plus/minus] 0.22. Both tumor inci- dence and multiplicity was statistically higher than in controls, where we found an incidence of 38% (9/24) and multiplicity of 0.42 [plus/minus] 0.14. Analysis of cell proliferation in the respiratory tract showed an initially increased, but then decreasing labeling pattern in the epithelia of the airways and a consistently increased labeling patterning in the nasal cavity. Under appropriate conditions, SS thus produces lung tumors in mice." CARDIOVASCULAR ISSUES A-1 [48] "Cardiovascular Disease and Occupational Exposure to Environmental Tobacco Smoke," D.M. Aviado, American Industrial Hygiene Association journal57: 285-294, 1996 "The current article was prepared for submission prior to the OSHA hearings that started in September 1994.... Among the 75 references used in this article, only 25% were included in the OSHA notice, without reference to the other 75%." "In a sealed unventilated enclosure 100 m3 it is possible to estimate the number of cigarettes burning continuously, simultaneously, and completely, to attain the PEL recommended by OSHA. For nicotine the maximum reported SSS collected is 8.2 mg/cigarette. On the basis of PEL (0.5 mg/m3) it would take six burning cigarettes to attain the PEL in the chamber (0.5 x 100 divided by 8.25). However, as noted in the following section, measurements of nicotine levels as ETS in public places are 9333 to 466,666 times less than the PEL. Thus, under actual potential exposure conditions, the dilution of cigarette smoke by the size of enclosure and ventilation means that constituent levels would be hundreds and even hundreds of thousands of times lower than implied by calculation of cigarette equivalents." "Nicotine has the lowest cigarette equivalent among smoke constituents reviewed by the author. Examining the other constituents reported in ETS, only carbon monoxide and nitrogen dioxide have fewer than 100 cigarette equivalents. Phenol has more than 5000; benzene has more than 10,000; toluene, more than 20,000; acetone, more than 200,000; and benzo [a] pyrene, more than 200,000 cigarette equivalents." "[T]he range of published concentrations are consid- erably less than the current accepted PEL, as follows: carbon monoxide, 2.7 to 50 times PEL; nitrogen oxide, 208 to 2778 times PEL; nitrogen dioxide, 66 to 238 times PEL; nicotine, 10 to 500 times PEL; acetone 2000 to 6667 times PEL; benzene, 102 to 1667 times PEL; and benzo[a]pyrene, 262 to 71,852 times PEL." "The 20 chemicals listed ... when individually used in factories below the corresponding PEL, have not been associated with heart disease nor with any adverse SHB

A-2 effect on corresponding target organs, i.e., mucosal surfaces, skin, blood, nervous system, lungs, kidneys, and liver.... A causal association between worker exposure to industrial chemicals and occupational heart disease can only be established by extensive chemical analysis, animal experiments, and human s.udies. The available studies on ETS exposure are inadequate to address causality of occupational heart disease." "The proposed rulemaking regarding ETS in the workplace, since it is based on mortality data on spousal diseases and household smoking without controlled ETS occupational exposure, has no prece- dent in the formulation of work standards." "Repeated attempts to induce coronary atherosclerosis in experimental animals by inhalation of cigarette smoke have failed." "It is the author's opinion that cholesterol feeding experiments may be useful as a model in elucidating secondary influences of hormones, drugs, and chemi- cals on the primary process of atherosclerosis. Such studies, however, are very difficult to interpret, because they involve the simultaneous examination of several potential factors in heart disease. The same general remarks apply to experimental testing of carbon monoxide in levels far exceeding those reported for ETS exposure." "Any reported increase in fibrinogen level in the blood of ETS-exposed subjects may not be relevant to a potential ielationship with coronary atherogenesis." "In vitro studies of platelet aggregation in blood derived from smokers have yielded inconsistent results, which bring into question the applicability of this method to ETS exposure in nonsmokers." "The occurrence of cardiac arrhythmias by industrial chemicals does not support the proposition that because the same chemicals may be reported at minute levels in ETS, then ETS also may lead to the development of heart disease in workers." "Since the proposed rulemaking notice for indoor air quality is for the specific purpose of preventing cardio- vascular and respiratory tract disease, this review concludes by comparing the means used to argue for disease causation by occupational exposure.... For the issue of ETS exposure and coronary heart disease, there are questions and debatable answers as to whether ETS/IAQ REPORT, LSSUE 123 chemical studies, human observations, animal experi- ments, and mechanistic studies support a causal associatior. between ETS exposure and occuF•.tional heart disease." "Regulation of ETS as a complex mixture in the workplace can follow that of other complex mixtures by adopting established work standards for four ETS constituents: nicotine, carbon monoxide, benzo[a]pyrene, and carbon disulfide. Although available data on chemical analysis of ETS in the workplace do not show levels exceeding work standards, it may be necessary for interested groups to decide whether additional mea- surements are necessary, using modern techniques that were not available more than a decade ago." [49] "Prevalence of Coronary Artery Disease and Its Risk Factors in the Urban Population of So;:th and North India," R. Begom and R.B. Singh, Acta Cardiologica L(3): 227-240, 1995 "The present epidemiologic study has shown that the prevalence of CAD [coronary artery disease] was 139 per 1000 in South Indians between 26-65 years of age. CAD was 61.6% greater than in North Indians (86 per 1000) and 26.4% higher than in British (110 per 1000). The prevalence was highest in the 5th decade in both South and North Indians. CAD was more .::)mmon in middle and higher income groups com- pared to lower income groups in both South and North Indians. In both areas, CAD was more common in males than in females." "Hypercholesterolemia, hypertension, diabetes mellitus, smoking and central obesity (in South Asians) are major risk factors of CAD and their role in the pathogenesis of CAD is well established. In the present study, mean body weight, body mass index, waist-hip girth ratio, systolic and diastolic blood pressures in females, diastolic blood pressures in males, blood iipoproteins and fasting glucose were comparable in South Indians and North Indians. However systolic blood pressure in males and 2 hour blood glucose in both sexes were significantly higher in South Indians than in North Indians. Body mass index (in both south and North Indians) was low but the rate of central obesity was very high.... The prevalence of smoking was significantly higher in male South Indians com- pared to North Indians (44.6 vs. 30%). However low fat intake with higher smoking had less adverse effect. SHB 93140327

MAY 10, 1996 The prevalence of CAD was significantly higher among smokers and exsmokers. Passive smoking was more common in South Indian females than North Indiau females. The prevalence of CAD among South Indian females was significantly higher in passive smoking which is an independent risk factor of CAD." [501 "Characteristics of Leisure Time Physical Activity Associated With Decreased Risk of Premature All-Cause and Cardiovascular Disease Mortality in Middle-Aged Men," N. Haapanen, S. Miilunpalo, I. Vuori, P. Oja, and M. Pasanen, American Journal of Epidemiology 143: 870-880, 1996 "The association between leisure time physical activity and the risk of all-cause and cardiovascular disease mortality was analyzed in a Finnish cohort of 1,072 men aged 35-63 years who were followed up for 10 years and 10 months. During the period, 168 deaths were recorded, 93 of which were the result of cardiovascular diseases. Leisure time physical activity was assessed by several measures: 1) a single question combining an estimate of the frequency and intensity of the total amount of leisure time physical activity, 2) a compiled measure of leisure time physical activity derived from three separate questions concerning the intens;ty and frequency of activity, 3) a physical activity energy expenditure index computed as an estimate of weekly energy expenditure for leisure time activity and commuting to work, and 4) 16 separate specified activities of daily living and domestic chores included in the leisure time physical activity index." "The mortality rates for both all causes and cardiovas- cular diseases were highest among people suffering from disease or symptoms that prevented them from participating in physical activity and among current smokers, nonparticipants in working life, and single, divorced, or separated men. Body mass index, physical load at work, alcohol consumption, perceived health status, socioeconomic status, self-reported chronic diseases, and residential status were also considered potential confounders, but these variables did not have a confounding effect in this study." "The age-adjusted all-cause and cardiovascular disease mortality rates were, with the exception of strenuous household activities, highest in the most inactive groups. In comparisons of the mortality attributed to a A-3 sedentary lifestyle and smoking, the age-adjusted all-cause mortality rate of sedentary persons was close to that of current smokers. In the case of cardiovascular disease mortality, the rate for physically sedentary men slightly exceeded that for current smokers." "We can conclude that this 10-year and 10-month follow-up of a representative adult cohort in northeast- ern Finland supports the hypothesis that a low level of physical activity is a risk factor for both all-cause and cardiovascular disease mortality. The observed risk related to inactivity was higher than that in many former studies and close to the relative risk observed in the association between physiologically measured physical fitness and total or cardiovascular disease mortality. The increased risk of death among sedentary men was verified by the leisure time physical activity energy expenditure index and some specific activities of daily living and domestic chores. Because the measures comprehensively describe the subjects' energy expenditure in all leisure time physical activi- ties, they may minimize the possibility of misclassifying subjects' physical activity status. Our results are consistent with recent statements suggest- ing that, for minimum health benefits, energy expenditure in leisure time activities should be at least 700-800 kcal per week. Furthermore, our results are in agreement with the recommendation encouraging individuals to engage in activities requiring up to 2,000 kcal per week for maximum health benefits." [511 "Dietary Antioxidant Vitamins and Death from Coronary Heart Disease in Postmenopausal Women," L.H. Kushi, A.R. Folsom, R.J. Prineas, P.J. Mink, Y. Wu, and R.M. Bostick, New England Journal of Medicine 334: 1156-1162, 1996 "We studied 34,486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease." "This prospective study of postmenopausal women provides evidence of an inverse association of coronary heart disease with the intake of vitamin E from food. Women in the highest quintile of vitamin E intake had SHB

A-4 less than half the risk of death from coronary heart disease of women in the lowest quintile. This inverse association was not seen for the intake of vitamin E from supplements. There was also a suggestion of an inverse association between mortality from coronary heart disease and overall vitamin A intake, but this association was no longer apparent after adjustment for other risk factors. Vitamin C appeared, if anything, to be positively associated with the risk of death from coronary heart disease." "The inverse association of vitamin E intake with the risk of death from coronary heart disease is generally consistent with the findings of a growing number of epidemiologic studies." "Vitamin E intake is also associated with a more healthful cardiovascular risk profile." "[T]he findings presented here do not constitute definitive evidence of an inverse association between Vitamin E intake and mortality from coronary heart disease.... The observations with regard to vitamins A and C are similarly not definitive, but they suggest that increased intake of these vitamins is not likely to lower the risk of death from coronary heart disease." [52] "Cigarette Tar Does Not Promote Arterioscle- rotic Plaque Development," A. Penn, K. Keller, L.C. Chen, A. Nadas, and C.A. Snyder, The Toxicologist30(1, Part 2): 1377, 1996 "We reported previously that a) inhalation of either mainstream or sidestream cigarette smoke (CS) ETS/IAQ REPORT, ISSUE 123 cockerels compared to both the TAR and DMSO groups. There were no significant differences in plaque size between DMSO and TAR cockerels. Although CS is clearly the single greatest known environmental cause of cancer, as well as a major contributor to heart disease, there is little evidence that the tar fraction is the primary source of environmentally relevant, CS toxicants. The results reported here, combined with our previous findings, suggest that the major health threatening components of CS are in the vapor phase." [53] "Randomized Controlled Trial of Vitamin E in Patients with Coronary Disease: Cambridge - Heart Antioxidant Study (CHAOS)," N.G. Stephens, A. Parsons, P.M. Schofield, F. Kelly, K. Cheeseman, M.J. Mitchinson, and M.J. Brown, The Lancet 347: 781-786, 1996 "We tested the hypothesis that treatment with a high dose of alpha-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischaemic heart disease." "In this double-blind, placebo-controlled study with stratified randomization, 2002 patients with angiographically proven coronary atherosclerosis were enrolled and followed up for a median of 510 days. 1035 patients were assigned alpha-tocopherol (capsules containing 800 IU daily for first 546 patients; 400 IU daily for remainder); 967 received identical placebo capsules. The primary endpoints were a combination of cardiovascular death and non-fatal MI as well as - non-fatal MI alone." promotes aortic arteriosclerotic plaque development; b) "We found that alpha-tocopherol, in a higher dose butadiene, a vapor-phase component of sidestream than in previous studies, reduced the risk of the smoke, promotes plaque development at 20 ppm, only primary trial endpoint (a combination of death and 2X higher than the threshold limit value; and c) non-fatal MI) by 47%. This benefit was due to a individual tar fraction carcinogens in CS either do not reduction in the risk of a non-fatal myocardial infarc- promote plaque development or do so only at high tion of 77% and this_treatment effect was apparent concentrations. Here we asked whether exposures to after 200 days. The effects on the combined endpoint concentrated CS tar promote plaque development. were not due to a reduction in cardiovascular death; Mainstream CS tar ... was solubilized ... and injected indeed, there were more cardiovascular deaths among into cockerels, 1X/wk. Negative controls were injected alpha-tocopherol recipients than among placebo weekly with DMSO and positive controls with 7, 12 recipients. By contrast with the delayed effects of dimethylbenz(a)anthracene (DMBA).... Plaque F,,,u./rr rI„, ;-p^-l ~«t. -- A„p rn sn PY.-psq rNF ~

MAY 10, 1996 must await the results of longer-term multicentre trials designed with mortality as a primary endpoint." "This study could not directly address the mecha- nism by which alpha-tocopherol reduces the risk of myocardial infarction.... However, we believe that inhibition of oxidation is likely to exert its main effects by modification of plaque enlargement or plaque rupture." "Our findings are the first from a prospective clinical trial to be consistent with the lipid oxidation theory of human coronary artery disease. Our findings support the use of a high dose of alpha-tocopherol to prevent non-fatal MI in patients with angina and coronary atherosclerosis, although there was no benefit in terms of cardiovascular death or total mortality." RESPIRATORY DISEASES AND CONDITIONS -- ADULTS - _ [54] "Effect of Active and Passive Smoking on Ventilatory Function in Elderly Men and Women," C. Frette, E. Barrett-Connor, and J.L. Clausen, American Journal of Epidemiology 143: 757-765, 1996 "Although it is well known that pulmonary function declines with age and that this decline is accelerated by cigarette smoking, the effects of such factors are not well established in elderly individuals. The authors examined the effect of active and passive smoking on ventilatory function assessed by spirometry in 1,397 community-dwelling men and women aged 51-95 5 years and observed that active smoking affected ventilatory function into advanced old age." "Of the 176 never smoking men, 59 percent were exposed to smoke at home, as were 75 percent of the 415 never smoking women. Nonsmokers exposed to smoke were significantly younger (in years) than the others. Passive smokers had a FEV, (in liters) similar to never exposed subjects ... Male passive smokers had a lower FVC (in liters) than the nonexposed men, with a difference of borderline significance. No difference was observed in women. No difference in FEFa5-;5 was observed between subjects exposed to smoke at home A-5 in men or in women. Including sex in the model (instead of stratifying) did not change the results, and there %•ss no interaction with sex. The rel-tion of FEV, to age did not differ significantly in those exposed to passive smoking compared with the unexposed. The decrement of FEV, was equal to 38 ml per year in men and 30 ml per year in women." "In this community-dwelling cohort, pulmonary function continued to decrease with age in elderly nonsmoking men and women. Ventilatory function aging was accelerated by active smoking. A beneficial effect of quitting smoking, especially before age 40, was evident. Exposure to passive smoking at home was unrelated to ventilatory function loss." "Studies of passive smoking have ... yielded conflict- ing results. Some authors reported an association between secondary exposure to cigarette smoke and reduced ventilatory function in adults, although the pulmonary function parameters that were found to differ varied in different studies....[D]ifherent results may be explained by the heterogeneity of the methods, such as assessment of tobacco exposure (in the house- hold or at work), the design of the study (case-control or prospective), and the population sample (volunteers or population-based, rural or urban, and young or older individuals). The lack of association between passive smoking and pulmonary function in Rancho Bernardo is consistent with the only other population-based study of passive smoking in older men and women. The failure to demonstrate a clear effect of passive smoking on ventilatory function could be attributable to several factors. Survival bias may underestimate the effect of passive smoking . . . In addition, the typical three-bedroom house for this middle- to upper-middle class cohort, coupled with the temperate climate in Southern California, makes it more likely that nonsmoking spouses receive less exposure to secondhand smoke than might be the case if they lived in smaller residences and were housebound in the winter. In addition, the questionnaire used here did not make a distinction between past and present exposure and did not query exposure to secondhand smoke outside the home. This assessment of exposure to passive smoking was relatively crude, possibly leading to an underestimate of harmful effects. To address the issue of the effects of passive smoking on ventilatory function in the elderly, future studies SHB

A-6 should better assess past and current exposure to tobacco smoke in the home and elsewhere." RESPIRATORY DISEASES AND CONDITIONS -- CHILDREN [551 "The Attack of Asthma," E. Friebele, Environ- mental Health Perspectives 104: 22-25, 1996 "The number of people with asthma increased by 42% in the last decade, according to a recent report by the Centers for Disease Control. Not only is asthma becoming more prevalent, but it is also more severe. According to the National Heart, Lung, and Blood Institute, the number of people who die of asthma jumped 58% between 1979 and 1992. Emergency room visits and hospital admissions for asthma are increasing. Children, ethnic minorities, and the urban poor are at the greatest risk. Researchers suspect that a variety of factors such as air contaminants and height- ened exposure to aeroallergens in airtight homes trigger bouts of asthma or cause chronic airway inflammation that may lead to permanent lung dysfunction." "What could be making a respiratory disease, trig- gered by an allergic response and aggravated by a multitude of factors, more common, more acute, and potentially more fatal?" "The rising number of asthmatics might be attributed to increased awareness among physicians, said Gale Weinman of the National Heart, Lung, and Blood Institute (NHLBI). 'Physicians may now be recogniz- ing ailments previously diagnosed as a cold or bronchitis as the long-term, chronic illness of asthma. However, increased diagnosis of asthma cannot [totally] explain the rise in its prevalence,' she said." "For the 70-75% of asthmatics who have allergic asthma, their respiratory systems have developed a very specific response to a specific allergens [sic]. Nonallergic asthmatics, on the other hand, may wheeze after exercising or taking aspirin, and show little sensitivity to allergens. Asthma and allergies appear to be inher- ited separately, but they are mysteriously associated." "The increase in asthma is not unique to the United States.... In Great Britain, deaths and hospital ETS/IAQ REPORT, ISSUE 123 admissions due to asthma doubled between 1979 and 1985. In Finland, the proportion of military recruits with asthma increased 20-fold between 1961 and 1989." "Asthma is the number one cause of absenteeism for schoolchildren and a common reason for adult absen- teeism from work." "Though death from asthma is relatively rare, it is becoming more frequent. Asthma mortality in the United_States declined by nearly 8% per year during the 1970s, but by 1977, the trend reversed, and the number of deaths due to asthma began to climb steadily, increasing about 6% per year." "Most asthma deaths occur in urban areas." "Although some evidence suggests that asthma's death tcll could be leveling off, the rising rate of hospital admissions and emergency room and doctor's office visits for asthma suggests that the disease is becoming » more severe. "Blacks, Hispanics, and people living in urban environ- ments seem to be at the greatest risk for asthma." "These findings raise important questions about why the economically disadvantaged are at greatest risk of dving from asthma. 'Poverty is assol-;-red with all sorts of diseases,' said Gergen [Peter] [of the National :nstitute of Allergy and Infectious Diseases]. `Pour people in the United States die more than the rich of all causes, and the gap is widening. General health is poorer, as well as access to medical care. Exposure, environmental quality of life, stress, and social factors all play a role,' said Gergen." "Spurred by the alarming statistics, researchers are focusing on direct exposures to allergens indoors where people are spending more of their time. Allergen levels are thought to be higher in less well-ventilated homes, where moisture accumulates, allowing mildew and molds to grow." "'We're also concerned about second-hand tobacco smoke,' said Alfred ATunzer, pulmonary specialist at Washington Adventist Hospital and former president of the ALA. 'There is increasing evidence that child- hood exposure to environmental smoke can be a predisposing factor to developing asthma."' -"Infants of women who smoke have higher levels of the antibody immunoglobin E (IgE) in umbilical cord SHB 93140331

MAY 10, 1996 blood compared to infants of nonsmokers, indicating an immune reaction. Whether children born to smoking mothers develop asthma pre- or postnatally is an unanswered question." "Increasing asthma incidence cannot totally be explained by smoking in the United States, however. Between 1965 and 1990, cigarette smoking in the United States declined by 40%. Though the greatest number of smokers are 25-44 years of age, poorly educated, and live below the poverty level, according to statistics from the CDC's Office on Smoking and Health, the proportion of smokers in this group is also following a downward trend." "Other studies are exploring the influence of a child's surroundings during the vulnerable first weeks and months of life. It is precisely during this period, scientists believe, that the environment of a child with a genetic disposition can tip the scales toward develop- ing a full-fledged allergy." "`The consensus seems to be that the environment is playing a tremendous role in the increasing prevalence of asthma,' said Munzer. In addition to the provoca- tion of asthma by allergens, he says, `air pollution is a big factor."' "The nation's air has improved dramatically in the past 25 years. Emissions of soot and smog-forming volatile organic compounds have decreased signifi- cantly in the United States since 1970 despite crowded highways where more vehicles are driven twice as many miles. Release of sulfur oxide has decreased by 30% since 1970. Between 1988 and 1993, overall industrial emissions of toxic compounds decreased by 39%." "The distribution of asthma in other countries also fails to implicate pollution as an aggravating factor. Some of the highest asthma mortality rates occur in Australia and New Zealand, which have excellent air quality. Asthma is more prevalent in rural areas of the Scottish highlands, which have some of the lowest ozone concentrations in the world, than in more urban and polluted parts of the United Kingdom, according to a recent report." "In spite of overall improvements in air quality, many Americans are not breathing risk-free air, according to EPA Administrator Carol Browner. Almost 100 million people live in areas where the air does not meet A-7 national air quality standards. Eighty percent of Hispanics and 65% of blacks live in 'nonattainment areas' for air standards." "The question remains whether small particles in the atmosphere provoke asthma episodes." "While many factors that provoke asthma, such as air pollution and cigarette smoking are decreasing, the disease is becoming more prevalent. Its increasing severity is concentrated in urban pockets where children live under poor conditions, are frequently exposed to allergens and air pollution episodes, and have sporadic medical care. Research suggests that education, controlling exposure to antigens in the indoor environment, and improving urban air quality could improve the quality of life for these children." [56] "Fungus Spores, Air Pollutants, and Other Determinants of Peak Expiratory Flow Rate in Children," L.M. Neas, D.W. Dockery, H. Burge, P. Koutrakis, and F.E. Speizer, American Journal of Epidemiology 143: 797-807, 1996 "The present investigation has replicated the previous Uniontown summer study [of haze episodes and daily variations in symptoms and peak expiratory flow rates] in a cohort of children in State College, Pennsylvania, and has included daily measurements of specific pollen and fungus spore concentrations." "Airborne spore concentrations of Cladosporium, Epicoccum, and Coprinus were associated with deficits in the mean deviation of morning PEFR for the entire cohort." _ "Precipitation afE°cted both the mean deviation in PEFR and the concentrations of airborne contaminants." "In this study, a 12-hour daytime time-weighted exposure to an additional 125-nmol/m3 particle-strong acidity was associated with a mean 1.2-liters/minute decrease in evening PEFR.... Cough episodes were associated with 12-hour daytime exposures to particle-strong acidity and total sulfate particles." "The principal determinants of the day-to-day variation in PEFR among children include time of observation, growth, temperature, precipitation, air pollutants, and airborne aeroallergens. The effects of time of observation, growth, and temperature are very consistent across two studies, with similar measure- SHB

A-8 ments for comparable children's cohorts. In this study, airborne spore concentrations of Cladosporium, Epicoccum, and Coprinus were associated with deficits in the mean deviation of morning PEFR for the entire cohort; and five children showed significant child-specific declines in morning PEFR v.th increased Ganoderma spore concentrations. The effect of particle-strong acidity on the mean deviation in evening PEFR was somewhat less in this study. These data are not incompatible with the previous finding of an association of PEFR with aerosol acidity among the Uniontown children. These results are also compatible with a respirable particle hypothesis. Daytime expo- sures to ozone and particulate air pollutants were associated with the increased incidence of summertime cough and cold symptoms that evening or on the subsequent morning. Precipitation days and fungal spore concentrations did not confound the association of PEFR with the levels of particulate air pollutants. Fungus spore concentrations affected the mean devia- tion in morning PEFR, and air contaminants affected the mean deviation in evening PEFR. We conclude that summer episodes of excessive aerosol acidity and particulate pollution are acutely associated with declines in peak expiratory flow rates and increased incidence of cough and cold episodes in children. Similar, if not stronger, effects were associated with variation in fungus spore counts, which suggests that additional exploration of the influence of aerobiologic contaminants in conjunction with summertime haze episodes is warranted." [57] "The Impact of Lung Development on Respiratory Disease Later in Life," L.I. Landau, Monaldi Archives of Chest Diseases 3: 167-169, 1995 "The airways are fully mature in their structure and branching pattern at birth, and no major changes occur after birth. However, considerable alveolar develop- ment occurs in early postnatal life and probably continues through to adult life, although the peak development is completed within the first 3-4 yrs. After 8 yrs of age, there is most probably a greater increase in size than in number of alveoli. The growth of blood vessels supplying the conducting airways parallels the development of the airways." "The effect of various insults on lung growth and function will depend on the timing of that insult. It is ETS/IAQ REPORT, ISSUE 123 becoming increasingly clear that insults from concep- tion until early school years may have profound effects on lung development, which persist into later life." -"Genetic disorders are present from conception but their effect on the lungs will depend on the disease process that results from the genetic abnormality." "Those at risk of subsequent atopy and asthma may have abnormalities detected at birth, such as increased airway responsiveness, and raised cord blood immuno- globulin E (IgE) levels. Although these may evolve in relation to in utero exposure to allergens or mediators from the mother, the genetic predisposition is a vital component of this response." "Gender is a very important factor influencing lung development and the increased predisposition of boys for lower respiiatory tract symptoms and asthma during early childhood. Boys have lower flow rates for lung size than girls from birth until puberty." "There is increasing evidence that in utero events have an effect on lung development manifest at birth, which may predispose to respiratory symptoms in infancy, asthma during early childhood and young adult life, and chronic lung disease in later adult life. Those with the familial predisposition demonstrate a maternal pattern of inheritance to atopy and asthma. This may be genetic with paternal imprinting, so that the gene acquired from the father is not expressed. It could equally be related to allergen exposure transplacentally or to the movement of m..eiiators from the mother to the foetus. The presence of abnormalities at birth does suggest that aims at prevention of asthma will need to take into account events during pregnancy." "Maternal smoking has now been well documented as an important cause of lower respiratory tract symptoms during the first 2 yrs of life. Babies of mothers who _ smoke have reduced flow rates and increased airway responsiveness present soon after birth and before symptoms have developed. The timing of the effect of smoking on the foetus has not yet been definitely identified, and it may be gender specific. However, in line with other effects of tobacco smoke, the major influence probably occurs after the first 3 months of gestation. The effect appears more marked in girls and may, in fact, represent a masculinization of the female during intra-uterine lung development." SHB g3140333

MAY 10, 1996 "Young, et al. reported a cohort in whom up to 10% of apparently normal infants were found to have considerably reduced flow rates soon after birth. These infants had a very high rate of subsequent lower respiratory tract symptoms and asthma. Although many can be shown to have had a high risk oi'ast .:na on the basis of family history and exposure to environ- mental tobacco smoke, there are almost certainly many more risk factors and insults predisposing to abnormal airway development during foetal life that have not yet been identified." "Bacterial infections in early life cause considerable lung damage but, in the developed world, are rarely associated with long-term functional disability." "The effect of viral infections during the first year of life on subsequent lung development and function is particularly interesting. Although uncommon, some can certainly cause significant, permanent damage." "On the other hand, there is some evidence that a reduction of viral infections during early life may be associated with sensitization to common allergens rather than tolerance." "Bronchial responsiveness appears to decrease with age. However, tests of airway responsiveness in differ- ent sized children are difficult to interpret, as one can never been sure whether the challenge dose is equiva- lent. Whether airway responsiveness does decrease with age or not, it appears likely that those with increased airway responsiveness will maintain this status, with allergen exposure through early life leading to subse- quent atopy and asthma." "Chronic obstructive airways disease in adults has frequently been shown to be associated with childho-id respiratory trouble. It is becoming increasingly clear that these childhood respiratory symptoms are not the cause of subsequent lung disease but a reflection of abnormalities of luing development through intra-uterine life and early postnatal life. Prospective longitudinal studies are giving us important insights into these events, and should lead to interventions which will prevent respiratory illness both in childhood and later adult life." A-9 [58] "Breastfeeding as Prophylaxis Against Atopic Disease: Prospective Follow-Up Study Until 17 Years Old," U.M. Saarinen and M. Kajosaari, Lancet 346: 1065-1069, 1995 "Environmental exposure during early infancy may be particularly important for sensitization and later devel- opment of atopy, probably because of the physiological immaturity of the immune system. The possibility of a primary defect in intestinal absorption of macromol- ecules in atopic individuals has also been suggested." "The role of breastfeeding and/or avoidance of cows' milk-based formulas in early infancy has been the focus of much controversy.... The purpose of the present study was to evaluate the very-long-term effects of breastfeeding by assessing the occurrence of atopic manifestations in the same prospective series through- out childhood and adolescence in a follow-up study until the age of 17 years." "The results of this prospective, very-long-term follow-up study from infancy until early adulthood indicate that breastfeeding can protect against develop- ment of atopic disease. In the group with short or no breastfeeding there was a consistently higher prevalence of atopy, which increased to a demonstrable difference at 17 years of age. When the• gr.,,.p with short or no breastfeeding was compared with the prolonged breastfeeding group, atopy was observed in 65% and 42% of subjects, respectively, and substantial atopy in 54% and 8%. The difference in substantial atopy was significant irrespective of positive or negative atopic heredity. Unexpectedly, the differences between the infant feeding groups were pronounced at the age of 17 years." "According to our follow-up data, breastfeeding for 6 months or longer is required for prophylaxis of atopic eczema for the first 3 years of life. On the other hand, exclusive breastfeeding for longer than 1 month already seems beneficial in preventing food allergy with its prevalence peak at 3 years, and respiratory allergy with the prevalence peak at 17 years. With regard to sub- stantial atopy at the age of 17 years, greatest benefit was achieved by prolonged breastfeeding." "Heredity has hitherto been considered to be the strongest predictive risk factor for atopic disease. In our series, the differences in atopy among children grouped according to early milk feeding were of the same order SHB

A-10 of magnitude as were the differences caused by positive or negative atopic heredity; at the age of 17 years, the differences due to infant feeding were even more pronounced, suggesting an influence of early milk feeding that may exceed the heredity burden." OTHER CANCER [59] "Relation of Breast Cancer with Passive and Active Exposure to Tobacco Smoke," A. Morabia, M. Bernstein, S. Heritier, and N. Khatchatrian, American journal ofEpidemiology 143: 918-928, 1996 "It is ... paradoxic that the work on passive smoking has consistently shown a tendency toward an increased risk of breast cancer while studies on active smoking have failed to demonstrate an association. This appar- ent contradiction may stem from not separating passive smokers from the unexposed when assessing the effect of active smoking.... If passive smokers are at greater risk of breast cancer than are the unexposed, grouping passive smokers with the unexposed in the referent category may reduce thc excess risk for active smokers to nonsignificant levels. This was the a priori hypoth- esis that motivated the design of the present study." "There were 126 cases (52 percent) and 620 controls (60 percent) who were never active smokers. Among them, 28 cases (22 percent) and 241 controls (39 percent) were neither active nor passive smokers and were used as the referent 'unexposed' group." "[T]he adjusted odds ratios of breast cancer for ever active smokers, compared with women unexposed to either passive or active smoke, were 2.2 (95 percent CI 1.0-4.4) for an average lifetime consumption of 1-9 cigarettes per day, 2.7 (95 percent CI 1.4-54) for 10-19 cigarettes per day, and 4.6 (95 percent CI 2.2-9.7) for 20 or more cigarettes per day." "To examine the effect of cleaning up the referent category from the passive smokers, we computed the odds ratios using never active smokers as the referent category, that is, pooling passive smokers with the unexposed. Among ever active smokers, the two-step odds ratios were 1.2 (95 percent CI 0.8-2.0) for 1-9 ETS/IAQ REPORT, ISSUE 123 cigarettes per day, 1.7 (95 percent CI 1.1-2.5) for 10-19 cigarettes per day, and 1.9 (95 percent CI 1.2-2.9) for [greater than or equal to] 20 cigarettes per day (not shown in a table)." "[A] mong nonactive smokers, the multivariate odds ratio for ever being exposed to passive smoking at home, at work, or during leisure time for at least 1 hour per day for at least 12 consecutive months of smoking was 2.3 (95 percent CI 1.5-3.7). The odds ratio became 3.2 (95 percent CI 1.7-5.9) after addi- tional adjustment for saturated fat and alcohol intakes. There was no statistically significant trend according to the number of hours per day-years; the two-step odds ratios were 3.1 (95 percent CI 1.5-6.2) for 1-50 hours per day-years and 3.2 (95 percent CI 1.6-6.3) for more than 50 hours per day-years." "The present results suggest that both passive and active smoking increase breast cancer risk. They seem biologically plausible, since it is reasonable to postulate that constituents of tobacco smoke have a direct and/or an indirect influence on the carcinogenic process leading to breast cancer." "[T] he observed associations for active smoking are surprisingly strong in contrast to those of most previ- ous studies." "[A] detailed assessment of lifetime exposure may be necessary to show the relation of active smoking with breast cancer." "The present results are not directly comparable with previous literature reports on active smoking and breast cancer since, to our knowledge, none of them separated passive smokers from subjects unexposed to active and passive smoke. Removing passive smokers from the referent category increased the odds ratio by a factor of 1.5-2.5 according to the active smoking category. It is therefore possible that the strength of the breast cancer-smoking association has been underestimated in the available body of literature." "Lifetime exposure to passive smoking is clearly difficult to assess. In the present study, to be classified as a passive smoker, a woman had to have been exposed at least 1 hour per day for 1 consecutive year or more. This definition was relatively strict in order to identify women with at least one period of substantial exposure in their lifetime. It was more difficult to assess accu- SHB 93140335

MAY 10, 1996 rarely the number of hours per day of passive smoking, especially during leisure time. Misclassification orthe_ intensity of exposure may therefore have diluted a__ possible dose-related effect." - "For comparison purposes with the_litera_ture, we computed the odds ratio of passive smoking among women ever married to an active smoker compared with women never married to an active smoker. The t<vo-step odds ratio was 2.0 (95 percent CI 1.1-3.7) (not shown in a table). The lower bound of the confidence interval was consistent with the odds ratio of 1.4 computed by Wells. However, this proxy measure for passive smoking probably underestimates the association, since women married to nonactive smokers may have been exposed at home by someone other than their spouse. They also may have been exposed somewhere other than at home." "Being exposed to passive smoking 2 hours per day for 25 years was equivalent to having actively smoked an average of 20 cigarettes per day for 20 years. This was disturbing, since the effect of passive smoking was not a priori expected to be as strong as that of active smoking. A similar problem is encountered when studying cardiovascular diseases.... A better under- standing of the biologic effect of tobacco smoke on the mammary gland is needed to decide whether this phenomenon reflects a different etiologic mechankm from that for lung cancer. Direct exposure to tar deposition should not be an issue for breast cancer or atherosclerosis." "The risk factors of breast cancer were incorporated as potential confounders in logistic regression models. Alcohol and saturated fat intakes were not strong confounders." "The present study had limited statistical power to perform subgroup analyses.... None of them indi- cated that the effects of passive and active smoking could be limited to a subgroup of women." "A strength of the present study design was to incorporate variables allowing us to quantify potential selection, detection, and recall biases." "[S]eparating passive smokers from unexposed women resulted in a group of 28 cases in the referent category. The odds of being unexposed drive the findings related to passive smoking. We were not able to identify a methodological flaw that could have A-ri generated the relatively small proportion of cases unexposed to active and passive smoke. The most serious consequence of an_ unsuspected bias for the present results would have been that some truly unexposed women had been classified as passive smokers." "The present study findings do not allow us to conclude that there is a causal association between smoking and breast cancer. There is no dose-response relation between the intensity of passive smoking and the odds ratio of breast cancer. The strengths of the associations for passive and active smoking are of similar magnitude, while one would expect the risk of one's own smoke to be much larger." "However, recent reports offer evidence that can reconcile these apparent incongruities with a plausible biologic mechanism. ...`3Ue can speculate that women who develop breast cancer as a consequence of passive smoking are likely to be slow acetylators, rapid acetylators being able to metabolize low doses of the toxin." "The absence of a dose-response relation for passive smoking, if true, may be due to a low threshold of exposure among slow acetylators. Above that threshold, the risk associated with passive smoking would increase rapidly and then plateau. The latter hypothesis would also explain the relatively small magnitude of difference between the odds ratios for passive and active smoking." "In conclusion, the present findings may be surpris- ing, but they suggest uiat it is important to consider the effect of passive smoking when examining the association between active smoking and breast cancer. Previous studies may have failed to find an effect of active smoking, because they did not exclude passive smokers from the unexposed category. The association is not entirely explainable by analogy with the biologic mechanisms involved in established tobacco-related diseases. Additional studies of comparable design are needed to decide whether these intriguing findings are causal or not." [60] "Molecular Epidemiology: Insights into Cancer Susceptibility, Risk Assessment, and Preven- tion," F.P. Perera, Journal of the National Cancer Institute 88: 4_9 _6-509, 1996 "For more than a decade, there has been wide agree- ment that most cancer results from man-made and SHB

A-12 natural environmental exposures (such as tobacco smoke; chemical pollutants in air, water, food, drugs; radiation; dietary constituents; radon; and infectious agents) acting in concert with both genetic and ac- quired characteristics. It has been estimated that without these environmental factors, cancer incidence would be dramatically reduced, by as much as 80%-90%. Cancer risk from these environmental carcinogens is strongly influenced by many factors, including genetics, age, ethnicity, sex, immune function, pre-existing disease, and level of nutrition. Genetic predisposition acting in isolation probably explains no more than 5% of all cancers in the United States." "The counterpoint between the environment and host susceptibility has been elaborated in recent years through molecular epidemiologic studies of biologic markers present in human cells, tissues, and body fluids. Examples of 'biomarkers' are chemical-specific genetic damage in the form of carcinogen-DNA adducts or changes in key oncogenes or tumor suppres- sor genes that either trigger or block cancer development. Others document genetic and acquired susceptibility traits affecting processes such as carcino- gen metabolism, DNA damage, and repair. Analysis of biomarkers is ir...__asingly being incorporated into cross-sectional, retrospective, prospective, or nested case-control studies to gain improved resolution of the risk factors and mechanisms responsible for cancer." "Molecular epidemiology has the advantage of being directly relevant to human risk, unlike animal or other experimental models that require extrapolation to humans. In contrast to traditional epidemiology that relies on cancer incidence or mortality as the end point, molecular epidemiology has the potential to give early warning by flagging the preclinical effects of exposure and increased susceptibility, thus signaling opportuni- ties to avert cancer through timely intervention. Moreover, biomarker data on the distribution of procarcinogenic changes and susceptibility factors in the population can improve estimation of cancer risk from a given exposure." "However, molecular epidemiology is also subject to many of the limitations of epidemiology, such as the vulnerability to confounding factors that can give misleading results.... At the present time, many biomarkers can be useful in assessing exposure, dose, ETS/IAQ REPORT, ISSUE 123 and potential risk for a group or population; most are not, however, sufficiently characterized in terms of their ability to predict disease for use in screening, diagnosis, or quantitative estimation of individual risk. ... Although routine screening for cancer susceptibility is not justified, the substantial body of molecular epidemiologic and other data on susceptibility now in existence can be helpful in shaping cancer risk assess- ment, public health, and environmental policy." "Unfortunately, prevention is not well served by current methods to assess environmental risks. Al- though sometimes characterized as overly conservative, risk assessment methods currently used by government agencies, such as the Environmental Protection Agency, may underestimate the risk of certain environ- mental carcinogens because of the inherent assumption tiiat all individuals in a population have the same biologic response to a specified dose of a cancer-causing agent. The result can be regulatory and health policies aimed at protecting the 'average American,' ignoring the sizable, more vulnerable, fraction of the popula- tion. While the assumption of population homogeneity has long been in question, considerable quantitative information on the range of susceptibility within populations now shows that it is invalid." "This review discusses representative examples of molecular epidemiologic research during the last 10 years into the nature of susceptibility to common environmental carcinogens. These are viewed within the context of related experimental and epidemiologic data on carcinogenesis. A brief summary of recent evidence on molecular mechanisms in carcinogenesis provides a framework for an in-depth discussion of molecular and epidemiologic evidence of the role of the environment in cancer. The sources of variation in individual susceptibility to environmental carcino- gens are then described in detail, with illustrative examples from the recent literature. The final section discusses some of the implications of individual variability for current policies concerning risk assess- ment and cancer prevention." SHB

MAY 10, 1996 REPRODUCTIVE AND DEVELOPMENTAL_ISSUES [61] "Neuroendocrine Cell Expression in Fetal Lungs After Maternal Exposure to Aged and Diluted Sidestream Cigarette Smoke (ADSS)," K.P. Allamneni, C.G. Plopper, and K.E. Pinkerton, The Toxicologist 30(1, Part 2): 235, 1996 "Pulmonary neuroendocrine cells (PNEC) are specialized airway epithelial cells that may be involved in chemoreception and cellular differentiation. These cells are most abundant during the fetal and neonatal stages of development. The purpose of this study was to examine the effects of maternal exposure to ADSS on the expression of PNEC. Timed-pregnant Sprague-Dawley rats were exposed to ADSS for 6 hours/day, 7 days/week, from gestational day (DGA) 5 to the day prior to sacrifice, while control mothers were exposed to filtered air only....(CGRP), a neuroendo- crine marker was used to visualize PNEC immunohistochemically in lung tissues at 14, 18 and 21 DGA. The frequency of positive cells in the airways was measured per mm of basal lamina. At 14 DGA, CGRP positive cells were not detected in the airway epithelium of either group. At 18 DGA, CGRP positive cells were found to be in greater abundance in central airways compared with peripheral airways. Maternal exposure to ADSS resulted in a significant increase in CGRP positive cells at 18 DGA within central and peripheral airways. These differences were also found at 21 DGA in central and peripheral airways. We conclude that PNEC differentiation in the fetal lung is site-specific and that maternal exposure to ADSS at environmentally relevant concentrations significantly increases the number of neuroendocrine cells within airways during cellular differentiation of the fetal lung." OTHER HEALTH ISSUES A- 13 [621 "Risk Factors for Chronic Otitis Media With Effusion in Infancy: Each Acute Otitis Media Episode Induces a High but Transient Risk," O.P. Alho, H. Oja, M. Koivu, and M. Sorri, Archives of Otolaryngology and Head-Neck Surgery 121: 839-843, 1995 "Our current research was conducted to measure the biologic effects of different risk factors on chronic otitis media with effusion." "Our results indicate that previous acute otitis media episodes pose the greatest risk for chronic otitis media with effusion. Each episode induces an increased risk, which is highest immediately after the episode (> 10-fold) and gradually vanishes after 3 months. The number of earlier episodes or an early first episode do not affect the risk directly, ie, the risk associated with acute otitis media episodes is not cumulative, as earlier reports have indicated. It is true retrospectively that the risk for chronic otitis media with effusion is higher if a child has had numerous acute episodes, because tran- sient risk is involved in each of them, but at any fixed point of time, if the child has avoided chronic otitis media with effusion so far, only information about the _ current month and the past 3 months is relevant." "Accumulations of acute episodes proved to be especially risky. This high risk attached to successive episodes decreased rapidly. More aggressive treatment of acute episodes, such as performing a tympanocentesis and prescribing a beta-lactam antibi- otic, did not affect the risk." "The risk introduced by extrinsic factors is markedly lower than that in previous acute episodes. On the other hand, more powerful extrinsic risk variables exist for chronic otitis media than were found for acute otitis media earlier in this series." _ "Attendance at a group day nursery posed a twofold risk, confirming earlier results. Previous screenings have shown a clear seasonal variation in the occurrence of abnormal rympanograms; the risk is markedly higher during spring, autumn, and winter. Children typically have acute otitis media episodes and attend day care outside the home during these months, which affects the figures. The dynamic model showed that the risk estimates for autumn were especially high, but SHB

A-14 those for the spring and winter were similar to the summer figures. The maximum occurrence of chronic otitis media with effusion was at the beginning of the second year, even after adjustment for the other time-dependent risk factors. Male sex also increased the_ risk twofold. Atopy, bottle-feeding, number of siblings, and parental smoking [OR = 1.44, 95% CI 0.86 - 2.41] had an effect only through acute otitis media episodes, and their effect was more modest than reported earlier, probably because of better stand.rdiza- tion of the effect of previous episodes." "The risk of chronic otitis media with ::cfusion is highest for a boy who has just had his first birthday, is attending a day nursery outside the home during the autumn, and has just experienced successive episodes of acute otitis media. Previous acute otitis media episodes were the greatest risk factor, and this investigation adds to our earlier understanding of how this risk is medi- ated; each acute episode induces an increased risk for chronic otitis media with effusion that is highest immediately after the episode and gradually vanishes after 3 months. Successive acute episodes are especially risky, but this high risk similarly decreases rapidly. The number of previous acute episodes or an early first episode do not affect the risk directly, ie, the risk associated with acute otitis media episodes is not cumulative as reported earlier." [63] "Epidemiology in the Assessment of Small Risks," D. Coggon, Transactions of the Institu- tion of Chemical Engineers 73 (Part B, Suppl.): S36-S38, 1995 "Bias occurs when deficiencies in the design or execution of studies cause risks to be systematically underestimated or overestimated.... Some bias is unavoidable, even in the best designed epiderniological studies, and the effects cannot be quantified precisely." "Statistical uncertainty arises because we are limited in the numbers of people we can study ... Uncertainty of this sort can be quantified rather better than that resulting from bias, for example, by calculation of confidence intervals around risk estimates, but again it cannot be eliminated." "Confounding occurs when the people under investi- gation differ not only in their exposure to the hazard_of interest but also in other ways which independently ETS/IAQ REPORT, ISSUE 123 influence their risk of disease....[R]eliable adjustment for confounders depends on the accuracy of their measurement. Furthermore, one can never exclude the possibility of unrecognised confounders." "The uncertainties in the interpretation of epidemio- logical data are most troublesome when relative risks (le the ratios of risk in people with and without exposure to hazards) are small -- less than a 20% elevation say. At this level, it becomes very difficult to distinguish the effects of a hazard from those of bias, chance and confounding." "While the ability of epidemiology to detect effects depends on the relative increase in disease incidence associated with an exposure, risk management is based on the absolute increase in risk and the number of people affected. Uncertain risk estimates may be tolerable when the disease caused is rare and few people are exposed to the hazard." "Difficulties arise when the diseases affected are more common. For example, a 20% excess of lung cancer represents an absolute increase of approximately one case per 100 people over a lifetime. This would be important if it applied to large numbers of people. Some regulatory authorities seek to prevent lifetime risks as low as one per million from environmental carcinogens. Such small increases in the occurrence of common diseases cannot be measured directly." "An alternative, therefore, is to extrapolate from the risks associated with higher exposures. This requires first that exposure-response relationships can be assessed reliably....[E]rrors in the assessment of exposure can seriously distort exposure-response relationships." "A second requirement for the extrapolation of risks to low exposures is that the shape of the exposure-response curve can be predicted reliably outside the range of empirical assessment. Calculations often assume a linear relation between exposure and risk, but this may not always be justified." "Another consideration in the extrapolation of exposure-response relationships is the comparability of the populations from which data are derived and those _ to which the results are then applied. Often exposure-response is assessed in occupational popula- tions from which potentially vulnerable groups such as children and the elderly are excluded." SHB 9314,0339

MAY 10, 1996 "Can anything be done to counter these method- ological problems? One approach which could reduce the uncertainties in extrapc'.ation of exposure-response relations is to examine intermediate endpoints in epidemiological studies as well as looking at clinically manifest disease." - "While developments such as the measurement of DNA adducts may eventually lead to improved assessment of the risks posed by low exposures, many of the problems will persist for the foreseeable future. Thus decisions in risk management will continue to rely on data that are often incomplete and uncertain." [64] "The Epidemiology of Haemophilus influenzae Type b Disease in the Republic of Ireland," J. Fogarty, A.C. Moloney, and J.B. Newell, Epidemiology oflnfectioru 114: 451-463, 1995 "The importance of Haemophilus influenzae type b (Hib) as a cause of serious disease in infants and children is well recognized. Meningitis is the principal clinical disease but other conditions such as epiglottitis, pneumonia, cellulitis, bone and joint infections and septicaemia also occur. The major disease burden occurs in children under 5 years." "The purpc..,., of this study was to document baseline incidence data on Hib disease for the Republic of Ireland (ROI) against which Hib vaccine efficacy could be evaluated after its introduction. A case-control methodology was used to investigate the hypothesis that certain risk factors not previously investigated in the ROI or the United Kingdom (UK), were more common in children with Hib disease than in controls." "The annual incidence of Hib disease in Ireland was similar to that experienced in England and Wales, Scotland and France, lower than that in northern Europe, Australia and New Zealand and American populations of European origin, and substantially lower than rates experienced in native American, aboriginal and African children." "Two significant risk factors for primary Hib disease were identified: attendance at creche or day-care and the presence of chronic illness. A strong relationship between age and risk of Hib disease for creche or day-care attendance was observed with the highest risk experienced by children in the second year of life.... When stratified analysis was carried out for meningitis A-15 and non-meningitic disease, creche attendance emerged as a risk factor for non-meningitic Hib disease but not for meningitis alone." "The presence of chronic illness was another risk factor for Hib disease in Irish children." "No association with risk of Hib disease was observed with such family characteristics as household cigarette smoking, household crowding, presence of school-age siblings or breast-feeding, although many of these factors have been shown to be risk factors (or a protec- tive factor in the case of breast feeding) in other studies. The homogeneity of the Irish population may account for the similarity in distribution of many of these characteristics that have been shown to be risk factors elsewhere. Of the two risk factors identified, creche or day-care attendance may operate as an environmental factor by increasing the likelihood of children's exposure to Hib bacteria and chronic illness would appear to act as a host factor increasing the susceptibility to development of invasive Hib disease." "Until there is evidence that Hib immunization coverage rates reach 95% for eligible children in the ROI, it is essential that children with chronic illness and those who are creche or day-care attendees receive Hib conjugate vaccine as a priority." [65] "Inequality in Income and Mortality in the United States: Analysis of Mortality and Poten- tial Pathways," G.A. Kaplan, E.R. Pamuk, J.W. Lynch, R.D. Cohen, and J.L. Balfour, British Medical Journal312: 999-1003, 1996 "For the most part, socioeconomic level, whether it is measured by income, education, occupation, social class, or other measures, has been conceptualized as a property of the individual. This is not surprising as one's economic resources can determine, to a great extent, the availability and quality of food, housing, medical care, and other necessities. Recent findings, however, suggest that it may also be important to consider the overall distribution of wealth as a charac- teristic of a society or group." "We studied the relation between variations in income distribution between states of the United States and a variety of health outcomes, including variations in mortalities adjusted for age. In addition, we exam- ined some of the potential pathways, possibly reflecting SHB

A-16 investments in human capital and social resources, by which income inequality may be related to health outcomes. Finally, we considered the impact of income inequality and changes in income inequality on mortality trends." "The degree of income inequality, defined as the percentage of total household income received by the less well off 50% of households, and changes in income inequality were calculated for the 50 states in 1980 and 1990. These measures were then examined in relation to all cause mortality adjusted for age for each state, age specific deaths, changes in mortalities, and other health outcomes and potential pathways for 1980, 1990, and 1989-91." "There was a significarit correlation between the percentage of total household income received by the less well off 50% in each state and all cause mortality, unaffected by adjustment for state median incomes. Income inequality was also significantly associated with age specific mortalities and rates of low birth weight, homicide, violent crime, work disability, expenditures on medical care and police protection, smoking, and sedentary activity. Rates of unemployment, imprison- ment, recipients of income assistance and food stamps, lack of medical insurance, and educational outcomes were also worse as income inequality increased. Income inequality was also associated with mortality trends, and there was a suggestion of an impact of inequality trends on mortality trends." [66] "Editorial: Understanding Sociodemographic Differences in Health -- The Role of Funda- mental Social Causes," B.G. Link and J.C. Phelan, American Journal of Public Health 86: 471-473, 1996 "Several articles in this issue of the Journal docu- ment associations between sociodemographic factors and health-related conditions. Consistent readers of the Journal will note that this is not an unusual phenomenon." "From one point of view, this repeated documenta- tion of the association between sociodemographic factors and health belies a distinct lack of progress and indicates a major problem in the field of public health." "But there is an important principle of social epide- miology that suggests that we will never be able to, nor ETS/IAQ REPORT, ISSUE 123 should we try to, turn our attention away from the sociodemographic factors themselves. Put simply, this principle states that societies shape patterns of disease." "From this perspective, our continued attention to sociodemographic factors is not a sign of stalled progress, but rather a simple reflection of the fact that societies continue to shape patterns of disease through time and that it is the job of public health professionals to stay vibrantly attuned to these processes." "[H]istory gives credence to the somewhat startling and counterintuitive notion that social patterns of disease may persist despite effective interventions on potent risk factors. We illustrate with the case of socioeconomic status and health....[B]y the 1960s, many of the factors previously identified as linking socioeconomic status to disease had been addressed, and one might have expected the association to weaken and perhaps disappear altogether. But it has not. Recent studies demonstrate an enduring or even increasing association between socioeconomic status and many disease outcomes." "[T]he comparison of past and present risk factors reveals an important fact: as some risk factors mediat- ing the association between socioeconomic status_and c'..sease were eradicated, others emerged. Consequently, the association between socioeconomic status and disease has endured." "[W]e propose that such enduring associations between sociodemographic factors and disease are predictable and perhaps unavoidable, because many social conditions are what we have called 'fundamental social causes' of disease. As we define it, a fundamental social cause involves resources like knowledge, money, power, prestige, and social connections that strongly influence people's ability to avoid risks and to mini- mize tlie consequences of disease once it occurs. Because of the very general utility of these social and economic resourcz~s, fundamental causes are linked to multiple disease outcomes through multiple risk-factor mechanisms." "In a dynamic system, fundamental causes are likely to emerge. This is because the resources embodied in fundamental causes can be transported from one situation to another. Consequently, as health-related situations change, those with the most resources are best able to avoid diseases and their consequences. SHB 93140341

MAY 10, 1996 Thus, no matter what the profile of diseases and known risks happens to be at any given time, those who have greater access to important social and economic resources will be less afflicted by disease." [67] "Lack of Effect of Long-Term Supplementation with Beta Carotene on the Incidence of Malig- nant Neoplasms and Cardiovascular Disease," C.H. Hennekens, J.E. Buring, J.E. Manson, M. Stampfer, B. Rosner, N.R. Cook, C. Eclanger, F. LaMotte, J.M. Gaziano, P.M. R.idker, W. Willett, and R. Peto, New England journal of Medicine 334: 1145-1149, 1996 "Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large ran- domized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation." "In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smo' ers and 39 percent were former smokers at the beginning of the study in 1982." "This large-scale, randomized trial among appar- ently healthy, well-nourished men demonstrated no statistically significant benefit or harm due to 12 years of beta carotene supplementation in terms of malig- nant neoplasms, cardiovascular disease, or death. Because of the long duration of the trial, these findings are particularly informative, and the large sample and narrow confidence intervals exclude even a small overall benefit or harm due to beta carotene with a high degree of assurance. However, for indi- vidual end points such as stroke, myocardial infarction, and particular types of cancer, the confi- dence intervals are wider and do not preclude the possibility of a small absolute effect. In view of the slow development of many cancers, follow-up in this and the other trials of beta carotene will continue even though treatment has ceased, in case any benefits or hazards become clear later." A-17 "Factors that could, at least in theory, have produced a false finding of no benefit or harm include an inadequate dose of beta carotene or poor compliance with the assigned treatment. The dose of beta carotene used in the trial, however, placed participants in the top few percentiles of the general population with respect to usual intake, while minimizing noticeable yellowing of the skin.... This intake is above the level of dietary beta carotene consumption that is associated with benefit in observational studies and is roughly equivalent in effects on blood levels to about two carrots a day." [68] "Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovas- cular Disease," G.S. Omenn, G.E. Goodman, M.D. Thornquist, J. Balmes, M.R. Cullen, A. Glass, J.P. Keogh, F.L. Meyskens, B. Valanis, J.H. Williams, S. Barnhart, and S. Hammar, New England journal of Medicine 334: 1150-1155, 1996 "We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta-Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo." "This report presents interim efficacy results of the CARET study, which coincided with the announce- ment of the steering committee's decision on January 11, 1996, to stop the trial's active intervention. Follow-up for additional end points is expected to continue for another five years." "The results of the trial are troubling. There was no support for a beneficial effect of beta carotene or vitamin A, in spite of the large advantages inferred from observational epidemiologic comparisons of extreme quintiles or quartiles of dietary intake of fruits and vegetables or of dietary intake or serum levels of beta carotene or vitamin A. With 73,135 person-years of follow-up, the active-treatment group had a 28 percent higher incidence of lung cancer than the placebo group, and the overall mortality rate and the SHB

A-18 rate of death from cardiovascular causes were higher by 17 percent and 26 percent, respectively." "The second interim analysis led our safety and endpoints monitoring committee and steering commit- tee to recognize the extremely limited pros-)ect of a favorable overall effect, as well as the possibility of true adverse effects." "We have no explanation for the possible adverse associations that we have observed to date. There was no evidence of systemic toxicity in any organ from the vitamin A or, except for the expected skin yellowing, the beta carotene." "The results of our study and the ATBC Cancer Prevention Study in populations at high risk for lung cancer and cardiovascular disease and the finding of the Physicians' Health Study of no benefit or harm after 12 years of beta carotene treatment clearly do not support the widely accepted conclusion drawn from observational epidemiologic studies that beta carotene is a primary component responsible for the association of lower risks of cancer and death from cardiovascular causes with high intakes of fruits and vegetables." "Our findings provide important new information with respect to public policy and public health.... [T]hey make it clear that there can be little enthusiasm about the efficacy or safety of supplemental beta carotene or vitamin A in efforts to reduce the burdens of cancer or heart disease in certain populations. However, we still recommend the dietary intake of fruits and vegetables." ETS/IAQ REPORT, iSSUE 123 "Two reports in this issue of the journal should put to rest any remaining hopes that, for adults, beta carotene suppleme-ts may be an effective means of lo,vering the risk of cancer and cardiovascular disease." "The disappointing results of the clinical trial of beta carotene reaffirm the important of solid scientific knowledge as the basis of disease-prevention strategies. Inferences that beta carotene can prevent cancer and cardiovascular disease were drawn largely from observa- tions of a lower risk associated with vegetable and fruit consumption; they lacked strong support from clinical trials or mechanistic studies." "[N]o one should discount the importance of the findings of epidemiologic studies of diet and chronic disease. In most such studies, persons who ate a relatively large quantity of vegetables, fruits, and grains were found to have a profoundly lower risk of death, particularly from cardiovascular disease and cancer. Antioxidant vitamins may not account for all (or even any) of the benefits associated with this dietary pattern, and the myriad other substances in plants should be examined for possible preventive properties." GENOTOXICITY AND MUTAGENICITY [70] "Formation of Tobacco Smoke-Induced Hemo- globin Adducts in Rats," C.G. Gairola, S.R. Myers, M.T. Pinorini-Godly, and S. Subramaniam, The Toxicologist30(1, Part 2): 6 [69] "Antioxidant Vitamins, Cancer, and Cardiovas- 503, 199 cular Disease," E.R. Greenberg and M.B. Sporn, "Hemoglobin adducts have been used as indicators of New EnglandJournal of Medicine 334: cumulative exposure to chemicals. Cigarette smoke, 1189-1190, 1996 "[S]cores of epidemiologic studies have noted a lower risk of cancer and cardiovascular disease among persons whose diets include a relatively large amount of vegetables and fruits.... Beta carotene has received particular attention as a disease-preventing antioxidant, with numerous favorable reports in scientific journals, and sales of supplements have soared....[T]here has been a persistent expectation that larger trials and longer periods of follow-up would ultimately demon- strate the benefits of beta carotene." which is a complex mixture of chemicals, can poten- tially generate electrophiles in vivo and interact with I _moglobin (Hb) to form a variety of adducts. The present study examined the formation of three Hb adducts in a rat model following experimental exposure to tobacco smoke. Sprague Dawley rats were exposed to sidestream cigarette smoke (SS-CS) for 6 hrs for 1 day or 6 hrs each day for 1 and 3 months in a whole body exposure chamber ... Three adducts, one formed by interaction of acrylonitrile with valine residues (AN-Val) and two formed by interaction of 4-aminobiphenyl (ABP-Cys) or benzo(a)pyrene SHB 93140343

MAY 10, 1996 (BP-Cys) with cysteine residues, were identified and measured ... Hb adducts could be detected evern after 1 day of exposure to SS-CS. Daily smoke exposure for 1 month increased the AN-Val, ABP-Cys and BP-tetrol-Cys adducts in exposed animals by about 2, 40 and 8-fold, respectively, in comparison to control levels ... These results support the use of Hb adducts as potential biomarkers of tobacco smoke exposure." [71] "Formation of 8-Hydroxy-2'-Deoxyguanosine in Heart, Liver, and Lung Tissue Due to Environ- mental Tobacco Smoke Exposure," D.J. Howard and C.A. Pritsos, The Toxicologist 30(1, Part 2): 357, 1996 "Environmental tobacco smoke (ETS) is a hotly debated social, political, and scientific issue; pitting smoker's rights against the health and safety of non-smokers. Striking an acceptable balance between the two depends largely on the potential health hazard assessment of ETS. Studies from this laboratory have shown that exposure to ETS contributes to oxidative stress in mouse heart, liver, and lung tissues. This study measures the level of oxidative damage to mouse liver, lung, and heart DNA as a result of this oxidative stress. Adult female Balb/c mice were exposed to a regimen consisting of seque.,ces of a 30 minute exposure followed by a 1.5 hour non-exposure, repeated up to 3 times. Tissues were excised following the exposure and non-exposure periods. DNA was then extracted from the tissues and analyzed for the presence of the oxida- tive product 8-hydroxy-2'-deoxyguanosine (8-OHdG). In all three tissues, the exposure increased the presence of 8-OHdG above the control levels. In some in- stances, the increased levels returned to normal by the end of the non-exposure period, while other tissues showed a further increase following non-exposure. These studies demonstrate that limited exposure to ETS produces measurable DNA oxidative damage." INDOOR AIR QUALITY A-19 [72] "The Impact of Heavy Metals from Environ- mental Tobacco Smoke on Indoor Air Quality as Determined by Compton Suppression Neutron Activation Analysis," S. Landsberger and D. Wu, The Science of the Total Bnviron- ment 173/174: 323-337, 1995 "The objective of this study is to improve neutron activation analysis (NAA) by using epithermal neutron irradiation and Compton suppression techniques for low level metal determination, and to monitor the concentrations of some heavy metals in public places, where ETS is present; for understanding its impact on indoor air quality." "[T]he detection limits of cadmium, arsenic and antimony measurement have been dramatically reduced to 2 ng for Cd, 0.2 ng for As and 0.05 ng for Sb." "Cadmium has been found as an important heavy metal in particulate phase of indoor air from smoking. Other heavy metals, such As, Sb and Zn are also found at elevated levels. Since these elements are classified as potentially toxic substances, long term inhalation of the metals, even at a low level, has a risk for respirable diseases. The accurate assessment of the risk is difficult to determine in a short period. Therefore, it is benefi- cial for general population to prohibit smoking in the indoor public places, or at least to separate smoking area and non-smoking area to decrease the risk of the passive smoking." [731 "Separating the Impact of Exposure and Person- ality in Annoyance Response to Environmental Stressors, Particularly Odors," G. Winneke, M. Neuf, and B. Steinheider, Environment Interna- tional22:73-81, 1996 "Experimental and field studies illustrate the impor- tance of person-related covariates in modulating annoyance responses to environmental stressors, particularly industrial odours. Experimental evidence is presented on trait-aspects of the annoyance-response, using traffic-noise, environmental tobacco-smoke (ETS), and odor (H,S) as controlled environmental stressors: Subjects preclassified as being high or low responders to either traffic noise or industrial odors in SHB

A-20 their everyday living environment exhibited similarly elevated or reduced reactivity to any of the stressors. Furthermore, field studies on exposure-response associations for odor-annoyance in the vicinity of odor-emitting industrial sources reveal that apart from age and perceived health general stress coping-styles modulate the degree of odor-annoyance: Problem-oriented coping activates and avoidance-coping reduces the expression of annoyance to environmental odours. It is concluded that transactions between person-related variables and environmental perceptions need to be considered for a better understanding of psychological responses to environmental stressors in general, and to environmental odors in particular." "In this paper, an effort is made by the authors to critically review certain experimental and epidemiologi- cal studies on annoyance by environmental stressors. Industrial odors are emphasized in order to demon- strate exposure response contingencies for environmental annoyance as well as their modification by person-related factors, namely trait annoyance, coping style, perceived health and age." SMOKING POLICIES AND RELATED ISSUES [74] "Cigarette Smoking in China: Prevalence, Characteristics, and Attitudes in Minhang District," Y.L. Gong, J.P. Koplan, W. Feng, C.H.C. Chen, P. Zheng, and J.R. Harris, Journal of the American Medical Association 274: 1232-1234, 1995 "In this study, we describe the prevalence, pattern, and familial financial implications of smoking and the attitudes toward and knowledge of the health effects of tobacco use in Minhang in 1993." "Of all 7016 male and female respondents, 6202 (88.4%) believed that smoking is harmful for the smoker and 6195 (88.3%) believed smoking is also harmful to those passively exposed to cigarette smoke." "A total of 332 (14.1%) of all 2279 male current smokers wished to quit smoking.... The most common reasons for wanting to quit were concern about their own health (72.4%), economic consider- ETS/IAQ REPORT, ISSUE 123 ations (27.6%)), objections of family members (12.9%), and concerns about the health of others (9.6%)." "This survey reveals a dangerous health situation that in all likelihood will worsen. More than two thirds of --males in Minhang District smoke, a rate comparable with those found in other parts of China (57% to 80%). People in successive age cohorts seem to start smoking at earlier ages. Young smokers prefer and more often smoke imported brands. Smokers are willing to spend a substantial proportion of their income on supporting their habit. There is a low rate -of quitting smoking and a low desire to quit despite high awareness of the detrimental health consequences of tobacco use. In addition, cigarettes sold in China rave higher tar content and are more likely to be unfiltered than those sold in the United States and thus present a greater health risk." "Future prospects could be even grimmer. Females, most of whom generate their own income, represent an untapped market for tobacco interests. Only 2% of females smoke in Minhang.... For the entire popula- tion of China, lung cancer rates are increasing by 4.5% per year." Beyond the personal economic costs of smoking, in China as well as the United States, tobacco as a profitable crop and commodity creates a conflict of interest for a government also responsible for improv- ing its people's health." "Warnings have been issued previously in the medical literature on the health crisis in China due to tobacco use, and some reassurance has been found in regula- tions imposing controts and restrictions on the tobacco industry. However, the warnings have provoked little organized local governmental or international action, and the regulations have been inconsistently enforced." [75] "Resident Smoking in Long-Term Care Facili- ties -- Policies and Ethics," G. Kochersberger and E.C. Clipp, Public Health Reports III: 66-70, 1996 "Concerns about the quality of care for the 1.5 million nursing home residents in this country led to the nursing home reform measures contained in the _ Omnibus Budget Reconciliation Act of 1987. Promo- tion of nursing home residents' rights, including SHB 93140346

MAY 10, 1996 `accommodations of individual needs and preferences,' was an integral part of that legislation. Nursing homes are no different from society as a whole in balancing issues of personal autonomy and the rights of others as they relate to cigarette smoking. In fact, the close living proximity and restricted mobility of must nursing home residents accentuate these conflicts. When smoking is permitted, nonsmoking staff and residents are exposed to secondhand smoke. Also, residents with cognitive impairment and various physical disabilities are often unsafe smokers and present safety risks to themselves and others." "We ... conducted a national survey of Department of Veterans Affairs (VA) Nursing Home Care Units to collect information on the number of smokers among long-term care residents and the problems arising from allowing patients to smoke." "[I] n the facilities for which we received reports, approximately one-quarter (22%) of the residents were reported to be smokers. All responding facilities accommodated smokers. Seventy-six percent had a designated smoking area connected with the nursing home; smokers in the remaining facilities utilized areas designated for smoking for the entire medical center population. Over half (61%) of the nursing home smoking areas were indoors, and the remainder were reported as being separate structures outside the nursing home, for example, a patio. Most administra- tors (91%) reported that residents were never allowed to smoke in their rooms, with 9% of the facilities `seldom or occasionally' allowing this practice." "Most nursing home supervisors ranked patient safety (the risk of fire) as a`major concern.' Seventy-eight percent of respondents ranked health effects to the smokers themselves a`major concern,' while 70% put health effects of smoking to exposed nonsmokers in that category. Less than half (46%) considered damage to the smoking area (burns in rugs and furniture) of major concern. To a follow-up question, 'Should nursing homes provide a designated indoor smoking areas?' 43.7% of respondents answered yes." "The exposure of nonsmokers to passive or 'second- hand' smoke led to at least occasional complaints in 62% of facilities. Frequent complaints were reported in 23% of responding facilities. Smoking areas in nursing homes are often situated so that it is logistically impossible to protect nonsmokers from smoke expo- A-21 sure. Fifty-three percent of respondents reported that nonsmokers as well as smokers use smoking areas in their fucilities. Of the 47 facilities with ir.door smoking areas, 38 (76%) used exhaust fans to vent smoke directly to the outside. Most nursing homes with such an arrangement (95%) reported these fans to be somewhat effective (62% noting them to be moder- ately or very effective), but the differences between the number of complaints in facilities with and without ventilation fans were not statistically significant." "The majority (91%) of the chief nurses or unit supervisors responding to the survey did not smoke themselves. However, there were differences between these smokers and nonsmokers in the concerns they expressed about smoking behavior. For example, a greater proportion of the nonsmokers (95%) than smokers (78%) expressed concern about exposure of nonsmokers to smoke. VA policy continues to allow smoking in nursing homes 'except when patients are a danger to themselves.' Interestingly, the majority (67%) of the respondents reported seeing smoking as a`privilege,' while 59% felt that smoking was a`right' for their patients. Some respondents reported that smoking is both a right and a privilege. Several explained this apparent contradiction by noting that administrative and personal views were at odds on this matter." "The adverse effects of exposure to passive smoke have received increasing attention and have been the impetus behind indoor smoking bans in many public facilities and healthcare institutions. VA policy, which established smoke-free hospitals in 1991, has recently been made less stringent by controversial federal legislation. Smoking bans on hospitalized patients may be viewed as paternalistic acts, but it is believed that the resulting inconvenience is temporary and offset by improved health for deprived smokers and those around them. Clearly, a smoking ban on long-term care residents would be more difficult to impose. The hospitalized smoker, denied his or her cigarettes, will return home in a week or two, free to exercise self determination which may include a resumption of smoking. The nursing home resident is rarely dis- charged to another `home,' making the smoking ban a lifelong imposition." SHB

A-22 STATISTICS AND RISK ASSESSA•fENT [76] "Who's Exaggerating?" A.M. Finkel, Discover May: 48-51, 54, 1996 "Quantitative risk assessment, or QRA, tries to l;ive policymakers the information they need to answer ... questions in a rational way. It tries to determine how many people are likely to get sick or die as a result of a particular hazard, and how much it would cost to save at least some of them." "[T]he version of QRA that many in Congress, academia, and the media have embraced is a repudia- tion of much of what has gone before iri this field. It is reform premised on a myth -- namely, the myth that current assessment methods routinely exaggerate risk, at a huge cost to society. To my mind, risk assessment is in danger of being subverted just as it is coming into its own as a scientific discipline." "Producing either `best' or `most plausible' estimates of risk sounds like a commonsense goal. But is it really? To decide, you need to answer two questions that critics of current QRA tend to duck. First, what is the evidence.. . that risk estimates today are routinely skewed in an overly conservative way? Second, if risk estimates really are skewed, is that a serious social problem and one for which 'best' estimates are the cure?" "Tackling the second question first, let's think about what it would mean to protect the 'average person' from the 'average risk.' Most individuals are not average as far as risks are concerned; they vary greatly in their exposure and susceptibility to pollution, just as they vary in, say, body weight.... If we design our regulations to protect the average person, risk asses- sors reason, we may fail to adequately protect large segments of the population. Would that really be 'good science'?" "Then there is the question of what it would mean to estimate an 'average risk.' All estimates of risk involve uncertainry....[Y]ou can never get a single definite number; if you're honest with yourself, you'll get a range of answers. Picking the average value of that range is no more scientific than any other choice; all choices are value judgments in that they strike some balance between the health and economic costs of underestimating the risk and the costs of overestimat- ETS/IAQ REPnRT, ISSUE 123 ing it. Choosing the average, as 'unbiased' as that may sound, merely implies that those costs are exactly equal which is a strong bias indeed." "Risk assessors traditionally set their sights on the 'reasonable worst case' -- that is, they try to give themselves more than an even chance of overestimating the risk in order to be reasonably sure they won't underestimate it." "If instead of averaging the various risk estimates we simply pick the 'most plausible' among them, we may be even worse off. How do we decide which of. two or more plausible but competing scientific theories is most plausible? By some kind of majority vote among experts?" "So much for the idea that 'best' estimates would naturally lead to 'objective' or commonsense regula- tions. But the great irony of the current debate is the surprising lack of credible evidence that today's risk assessments do in fact tend to be overly conservative." "To be sure, risk assessors do make assumptions that tend to exaggerate risk. For example, they usually assume that subjects are exposed to a suspected car- cinogen 24 hours a day instead of, say, 8. The pending 1P,islation would allow court challences to any regula- tion that uses that assumption, on the grounds that it typically introduces a threefold over-estimate of __ exposure. But dozens of assumptions go into a risk assessment, and critics tend to ignore the ones that cut in the opposite direction." "All in all, no one has yet succeeded in finding a systematic bias in current risk assessment procedures, apart from the desire -- not always fulfilled -- to protect nonaverage people." "To make sensible cost-benefit decisions, obviously, you need to know the costs as well as the benefits of the action you're contemplating. The legislation Congress is now considering prescribes dozens of rules for risk assessment without mentioning problems of cost analysis at all. But figuring out the true cost to the economy of health and environmental regulations is as hard and as fraught with uncertainty as risk assessment itself. And the evidence that•costs are routinely exaggerated is in fact far stronger than the evidence that risks are." SHB 93140347

MAY 10, 1996 "For all these reasons, the direct costs of regulations tend to be overestimated when they are first imposed." "[W]e should not ask of risk assessment more_quan- tity or quality than it can yet deliver. Above all, we should not pretend we are promoting 'good science' when we are really pushing a political ideology -- one that says less government regulation, at least where health and the environment are concerned, is always better than more. It is not that there is anything wrong with value judgments; risk assessment cannot be done without them. It is just that those value judgments should be made explicit and not be allowed to mas- querade as objectivity. Here are my values, the ones that got me into this business in the first place: I believe that risk assessment, as it is now practiced and as it is steadily being improved, can help us protect health and the environment more cheaply and efficiently and prevent unnecessary injuries, illnesses, and deaths. And I believe that whatever society decides about how much it is worth to save a life or protect an ecosystem, the real 'best' risk assessment is one that encourages decision makers to be honest about uncertainty and to make smart -- and humane -- responses to it." SHB

MAY 10, 1996 APPENDIX B UPCOMING SCIENTIFIC MEETINGS • May 10-15, 1996 American Thoracic Society/American Lung Associa- tion 1996 International Conference, Morial Convention Center, New Orleans, Louisiana [Issue 116 item 41] • May 16, 1996 Frontiers in Genetic Toxicology, Hotel Dupont, Wilmington, Delaware, May 16, 1996 [Issue 121 item 46] • May 18-24, 1996 1996 American Industrial Hygiene Conference & Exposition, Washington Convention Center, Wash- ington, D.C. [Issue 119 item 40] • May 19-22, 1996 Fourth International Symposium on Metal Ions in Biology and Medicine, Tarragona, Spain [Issue 119 item 41 ] 9 May 20-21, 1996 Harmonization of State/Federal Approaches to Environmental Risk, Kellogg Center, Michigan State University, East Lansing, Michigan [Issue 118 item 47] • May 20-22, 1996 Issues and Answers to Indoor Air Quality, Falls Church, Virginia [Issue 119 item 37] • June 10-July 5, 1996 New England Epidemiology Summer Program, Boston, Massachusetts [Issue 119 item 42] • June 12-15, 1996 Society for Epidemiologic Research Annual Meeting, Park Plaza Hotel, Boston, Massachusetts [in this issue] • June 20-28, 1996 Air & Waste Management Association 89th Annual Meeting and Exhibition, Nashville, Tennessee [Issue 109 item 28] 9 June 22-26, 1996 ASHRAE Annual Meeting, Marriott River Center, San Antonio, Texas [in this issue] B=1 • July 7-11, 1996 Indoor Air Quality: A Critical Evaluation of the Science and the Art, Johnson State College, Johnson, Vermont [Issue 120 item 35] • July 8-12, 1996 Annual Summer Toxicology Forum, Given Biomedical Institute, Aspen, Colorado [in this issue] • July 17-19, 1996 5th International Conference on Air Distribution in Rooms, Room Vent '96, Yokohama, Japan [Issue 100 item 28] • July 21-26, 1996 Indoor Air '96: The 7th International Conference on Indoor Air Quality and Climate, Nagoya, Japan [Issue 82 item 29] • August 5-9, 1996 Toxicology for the 21st Century, Plaza San Antonio Hotel, San Antonio, Texas [Issue 122 item 39] • August 12-16, 1996 Occupational and Environmental Radiation Protec- tion, Harvard School of Public Health, Boston, Massachusetts [Issue 122 item 40] • August 26-30, 1996 3rd International Course on Sick Building Syndrome in the Office Environment--Measurements and Evaluation, Schaeffergaarden, Copenhagen, Denmark [Issue 112 item 41] • August 26-30, 1996 Inhaled Human Particles VIII: Occupational and Environmental Implications for Human Health, Robinson College, Cambridge, England [Issue 117 item 50] • August 27-30, 1996 The 14th International Scientific Meeting of the International Epidemiological Association: Global Health in a Changing Environment, Nagoya Congress Center, Nagoya, Japan [Issue 121 item 47] SHB

B-2 ETS/IAQ REPORT, ISSUE 123 • September 15-18, 1996 Sixth International Meeting on the Toxicology of Natural and Manmade Fibrous and Non-Fibrous Particles, Hilton Hotel, Lake Placid, New York [Issue 120 item 36] • September 15-20, 1996 25th International Congress on Occupational Health, Stockholm International Fairs, Stockholm, Sweden [Issue 115 item 32] • September 16-18, 1996 The Ninth Annual National Conference on Indoor Air Pollution, Hotel Royal Plaza, Orlando, Florida, September 16-18, 1996 [Issue 121 item 48] • September 16-20, 1996 13th Inte-national Symposium on Contamination Control, The Hague, Netherlands [in this issue] • September 20-22, 1996 Ist International Course on Risk Assessment of Carcinogens, Silja Serenade, Stockholm, Sweden [Issue 113 item 54] • October 6-8, 1996 IAQ'96: Paths to Better Building Environments, Baltimore, Maryland [Issue 110 item 39] • October 6-9, 1996 Carcinogenesis from Environmental Pollution: Assess- ment of Human Risk and Strategies for Prevention, Hotel Gellert, Budapest, Hungary [Issue 120 item 37] • August 24-28, 1997 10th World Conference on Tobacco or Health, Beijing International Convention Center, Beijing, China [Issue 122 item 41] SHB

APPENDIX C PRIVACY LAWS Jurisdiction I Year Enacted I Protects Arizona* 1991 Tobacco Use §36-601.02 Colorado 1990 Lawful Activities §24-34-402.5 Connecticut 1991 Smoking §31-40s Delaware* 1989 Smoking Executive Order Dist of Columbia 1992 Tobacco Use §6-913.3 Illinois 1991 Lawful Product Use Ch. 48, Para. 2855 Indiana 1991 Tobacco Use IC 22-5-4 Kentucky 1990 Smoking 344.040 Louisiai.a 1991 Tobacco Use R.S. 23:966 Maine 1991 Tobacco Use 26 MRSA §597 Minnesota 1992 Lawful Product Use §181.938 Mississippi 1991 Tobacco Use §71-7-33 Missouri 1992 Tobacco (& Alcohol) Use §290.145 Montana 1993 Lawful Product Use §39-2-101 Nevada 1991 Lawful Product Use 613.333 New Hampshire 1991 Smoking §275:36, 37-a, 40 11236144 1

Jurisdiction Year Enacted Protects New Jersey 1991 Smoking 34:6B-1 New Mexico 1991 Tobacco Use §50-11-1, et seq. New York 1992 Lawful Product Use & Some Lawful Labor Law §201-d Activities North Carolina 1992 Lawful Product Use §95-28.2 North Dakota 1991 Lawful Activities §14-02.4-01 through 14-02.4-18 Oklahoma 1991 Tobacco Use §40-500 et seq. Oregon 1989 Smoking §659.380 Rhode Island 1990 Tobacco Use §23-20.7.1-1 South Carolina 1990 Tobacco Use §41-1-85 South Dakota 1991 Tobacco Use §60-4-11 Tennessee 1990 Some Lawful Products §50-1-304 Virginia* 1989 Tobacco Use §15.1-29.18 West Virginia 1992 Tobacco Use §23-3-19 Wisconsin 1992 Lawful Product Use §111.321 Wyoming 1992 Tobacco Use §27-9-105 * Law applies only to public employees. 11236144 ~

ETS/JAQ REPORT FAx COMMUNICATION SHEET NOTE.• If you would like more information on one of the stories in this report, or if you would like a copy of one of our Current Reference Documents, please complete and FAX this form. To: Larry C. Frarey, Esq. Shook, Hardy & Bacon L.L.P FAX 816-421-5547 From: Telephone: Date: I would like additional information that may be available on the articles in Issue numbered as follows [write in the bracketed number next to the article headline]: I I I I I I I I I [ I [ ] [ I [ I [ I [ I [ ] [ ] Address FAX # Overnight Delivery Regular Mail (Ifpreference is not indicated information will be sent by regular mail.) I would like a copy of the following Current Reference Documents: U Chart listing reported incidences of Sick Building Syndrome ~ OSHA's notice to regulate workplace smoking and related materials (contains notice as published in the Federal Register) _ FA Quarterly compilations of synopses and excerpts of scientific articles about ETS and IAQ (prepared in January, April, July and October) ~ Quarterly overview of ETS cases not involving cigarette manufacturers (updated in February, May, August and November) F~ A Review of ETS Battery Claims F-1 Ongoing overview of ETS-related claims filed under the Americans with Disabilities Act D Current status and overview of EPA litigation

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