Tobacco Documents Online

Draft - Do not cite or quote IN•+!RODIICTION In 1986, the Surgeon General and the National Research Col[ncil, the latter under contract to EPA, examined the health ef,`ects of the breathing of Environmental Tobacco Smoke (ETS) by noasmokers (also known as involuntary or passive smoking). They ag'.,eed that passive smoking caused lung cancer in nonsmoking adlilts, caused increased rates of respiratory infections in chLldren, caused acute noxious effects in many nonsmokers, and was a najor contributor to indoor air pollution. Subsequent to the pu')lication of these documents, smoking restrictions began to pr,Dliferate. However, a number of diverse technical questions ar,Dse concerning public attitudes toward smoking restrictions, he=3lth and comfort effects, factors affecting exposure, measuring en,rironmental concentrations of ETS, effects of ventilation on ETS and indoor air quality•, nonsmokers' ul3take of tobacco combustion pr.Dducts, and corporate experience in effective smoking policy, all co,nprise chapters in this compendium. In the interest of providing an=swers to this complex of questions, this technical compendium was co•nmissioned. A brief summary of each chapter follows. Chapter 1 demonstrates that high dose exposures to tobacco• smoke, i.e., the effects of smoking on smokers, are very toxic, caLising cancers, cardiovascular diseases, and respiratory diseases. It is graphically illustrated why cigarette smoking is now rGcognized as the Nation's•single largest cause of premature death an3 disability. Chapter 2 reviews studies of the concentrations of certain ETS constituents observed in homes, offices, and other locations by personal exposure monitors. It is concluded that ETS is the primary contaminant contributing to respirable particulate air pollution, and contributes substantially to other indoor contamininants such as benzene, carbon monoxide, and others. Even in low doses, tobacco smoke contains a wide variety of toxins, including many carcinogens. Chapter 3 treats the methods of assessing nonsmoker's exposure •to environmental tobacco smoke by atmospheric markers, and the measurement of these marker substances in indoor air. It is ccncluded that atmospheric monitoring for respirable particles or nicotine from ETS is critical for assessing exposures and control erforts, and that a number of reliable methods are available for s1ich monitoring. Chapter 4 provides a detailed treatment of the absorption and m--.tabolism of tobacco combustion products by nonsmokers. It shows t-at absorption has been conclusively demonstrated by studies of ni cotine and its metabolite, cotinine, in the body fuids of nrinsmokers, and that such biomarkers represent a reliable specific m=-,thod for assaying the level of uptake of ETS. This exemplifies 6

Draft - Do not citeWor quote TABLE OF CONTEMTS Chapter 1. Effects of Smoking on Smokers. Donald Shopland ..............................................9 Chapter 2. Environmental Concentrations of ETS. John McCarthy, Elizabeth Miesner, and John D. Spengler..................................................... 16 Chapter 3. Measuring Exposure to Environmental Tobacco Smoke. Brian P. Leaderer ............................ :............. 31 Chapter 4. Absorption of Smoke Constituents by Nonsmokers. Dietrich Hoffmann, Klaus D. Brunnemann, and Nancy J. Hatley ........................................... 43 Chapter 5. Environmental Tobacco Smoke and Cancer. Jonathan M. Samet ...........................................67 Chapter 6. Passive Smoking and Heart Disease. Stanton A. Glantz and William W. Parmley .....................81 Chapter 7. Exposure Assessment in.Passive Smoking. James L. Repace ...........................................112 Chapter 8. The Odor and Irritation of Environmental Tobacco Smoke. William S. Cain .................. .'......................... 137 Chapter 9. Passive Smoking -- Beliefs, Attitudes, and Exposures in the United States. Thomas E. Novotny ........................................... 152 Chapter 10. Passive Smoking and Daycare. Glen L. Bennett ............. :.............................. 180 Chapter 11. No Smoking Policies at the Worksite: A look at what companies are doing today. Ruth Behrens ...............................................197. Chapter 11 Appendix: Economic Justification for Worksite Smoking Policies. Ruth Behrens ...............................................219 TIlVIIiT 0029994 5

Draft - Do not cite or quote Mr. James Repace, U.S. Environmental Protection Agency, Washington, DC (Editor) Mr. Donald Shopland, National Cancer Institute, Bethesda, MD (Editor) John Slade, M.D., Dept. of Medicine, St. Peter's Medical Center, Rutgers University, New Brunswick, NJ Dimitri Trichopoulos, M.D., DrPH, Harvard School of Public Health, Boston, MA The editors also acknowledge the comments of the tobacco industry. Mr. Samuel D. Chilcote, Jr., President, The Tobacco Institute, Washington, DC Dr. Thomas Borelli, Phillip Morris USA, Richmond, VA 4 TIMN 0029995

Draft - Do not cite or quote Washington, Dc: (Sponsor) Dr. Lois Biener, Miriam Hospital, Brown University, Providence, RI Ronald Davis, M.D. Office on Smoking & Health, Centers for Disease Control, Rockville, MD (Sponsor) James W. Davis, M.D., Veterans' City, MO Administration Hospital, Kansas Ms. Hildy Dillon, American Lung Association, New York, NY Dr. Cedric Garland, Dept. of Community Medicine, University of California, San Diego, CA Dr. Stanton A. Glantz, Department of Cardiology, University of California Medical School, San Franscisco, CA Dr. Lawrence C,arfinkel, American Cancer Society, New York, NY Dr. Katherine Hammond, Dept. of Family & Community Medicine University of Massachusetts Medical Center, Worcester, MA Dr. Marvin Kristein, State University of New York, Stony Brook, NY State Univ. of New York, Stony Brook Dr. Joellen Lewtas, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, NC Dr. Alfred H. Lowrey, Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC Henry McIntosh, M.D., American College of Cardiology, Washington, DC Dr. Michael McGinnis, Office of Disease Prevention and Health Promotion, Public Health Service, Washington, DC (Sponsor) Matthew Meyer, Esq., Coalition on Smoking or Health, Washington, DC Dr. Gregory Morosco, Health Education Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (Sponsor) Dr. Demetrios Moschandreas, Illinois Institute of Technology Research Institute, Chicago, IL Dr. David Mudarri, U.S. Environmental Protection Agency, Washington, DC Dr. Terry Pechacek, Smoking, Tobacco, and Cancer Program, National Cancer Institute, Bethesda, MD (Sponsor) 3 TIMN 0029996

Draft - Do not cite or quote PREFliCZ This compendium of technical perspectives on Environmental Tobacco Smoke (ETS) is intended to be a useful resource document for a diverse audience, including: decision-makers such as labor and management officials concerned with workplace exposures, public health officials and corporate medical directors who are concerned with making health policy recommendations, educators, industrial hygienists and safety officers, ETS researchers, indoor air pollution investigators, and legislators who are considering legislation to restrict smoking in workplaces, restaurants, and public access buildings. Although the technical level varies, even the more technical treatments do not require a specialist's knowledge for understanding. There are eleven chapters in this compilation, including health effects of active smoking in adults a:zd passive smoking in children and adults, ETS exposure and dosimetry, comfort aspects, ventilation and ETS, public beliefs about the harm of ETS and attitudes toward controls, and effective workplace smoking policies, each of which is aimed at a somewhat different audience. Although not all chapters will appeal equally to such a varied group, it is hoped that the technical information in this document, written by experts in the field, will provide information necessary to allow the public, corporations, government agencies, and legislators to make well-informed choices regarding exposure to ETS. This perspective on ETS reflects the viewpoints and expertise of authors who were selected based upon their publications and recognition as experts on various aspects of ETS. Accordingly, the opinions expressed do not necessarily represent the official policies of the sponsoring agencies. This document is the result of a coordinated effort jointly sponsored and produced by the Environmental Protection Agency (EPA) (chapters 2,3,4,6,7, and 8), the National Cancer Institute (NCI) (chapters 1,5), the Office on Smoking and Health (Centers for Disease Control) (chapter 9), the National Heart, Lung, and Blood Institute (chapter 10), and the Office of Disease Prevention and Health Promotion (Department of Health and Human Services) (chapter 11). The editors acknowledge with gratitude the following distinguished scientists, physicians, and others who lent their support to the development of this document by contributing critical reviews of the various manuscripts, by coordinating manuscript preparation, or assisting in other ways. Mr. Robert Axeirad, U.S. Environmental Protection Agency, 2

ENVIRONMENTAL TOBACCO BMOICE: A COMPENDIUM OF TECHNICAL INFORMATION May 1991 DRAFT DISCLAIMER This document is a preliminary draft. Do not cite or quote. The contents represent only those views of the individual chapter authors. It should not be construed as representing the views or policies of the participating organizations. TIMN 0029998

Draft - Do not cite or quote that low dose exposure to tobacco smoke leads to the absorption of toxins from the smoke in amounts sufficient to potentially cause disease. Chapter 5 discusses the evidence that low dose exposure to tobacco smoke has been observed to increase the risk of lung cancer in nonsmokers, and discusses conclusions of the World Health Organization, the National Research Council, and the U.S. Surgeon General that ETS exposure increases lung cancer incidence in nonsmokers. Chapter 6 discusses the evidence that low dose exposure to tobacco smoke has been observed to increase the risk of heart diseases in nonsmokers, and discusses the epidemiological, biochemical, and biological bases for this inference. It is concluded that the combined epidemiological and physiological evidence suggests that ETS exposure is a cause of heart disease in nonsmokers. Chapter 7 investigates the assessment of nonsmokers' exposures to ETS by mathematical modeling, atmospheric indicators, and biomarkers in body fluids. Exposures assessed by these various methods produce consistent results. Because of the large source strength of tobacco-burning products, exposure to environmental tobacco smoke is inadequately controlled by measures short of physical separation of smokers and nonsmokers on different ventilation systems, making ETS a significant indoor pollutant of buildings. Chapter 8 explores the effects of ventilation on the perception of odor and irritation from ETS in both nonsmokers and smokers, and shows that attempts to control the odor and irritation of ETS through ventilation and air cleaning have significant limitations. Chapter 9 shows through national surveys of trends in public attitudes, that the general public, including both smokers and nonsmokers, believe that tobacco smoke polluted air is harmful and a large majority find it irritating. There is widespread support for restrictions against smoking, particularly in the workplace. Chapter 10 discusses the evidence that smoking both at home and in daycare centers harms children and infants from tobacco- smoke polluted air. This has direct implications for public education of both parents and daycare providers, as well as for state policies and regulations affecting facilities which offer daycare. Chapter 11 points out the common solution to the problem of ETS is source control, and examines features of corporate smoking policies in the workplace, with attention to benefits, incentives, employee and union involvement, and education. Case histories are 7

Draft --Do notwr cite-. or quote discussed involving several major corporations, detailing problems encountered and successes. it is concluded that smoke free workplaces have been achieved in a variety of settings. If thoughtfully implemented, they enjoy widespread support. 8 TIMN 0030000

Draft - Do not cite or quote CHAPTER 1 EFFECTS OF SMOKING ON SMOKERS Donald Shopland Coordinator Smoking and Tobacco Control Program National Cancer Institute, Bethesda, MD Cigarette smoking is the nation's leading cause of premature death and disability. In 1985, smoking caused approximately 390,000 deaths in the tJnited States (Figure 1). By 1991, this number had increased to 440,000. In addition, tens of millions of people suffer from chronic disabling diseases and conditions caused or aggrevated by smoking. Every medical authority and organization who has objectively examined the evidence linking smoking to early death and disability has reached a similar conclusion. The ovidence that smoking is a major health threat is staggering: over 50,000 citations from dozens of cultures are in the scientific literature. Smoking causes or is associated with cancers of the lung and bronchus, larynx, lip and oral cavity, bladder, pancreas, kidney, stomach and cervix, coronary artery disease, cerebrovascular disease (stroke), atherosclerotic aortic aneurysm, atherosclerotic peripheral vascular disease, chronic bronchitis, emphysema, low birth weight babies, and unsuccessful pregnancy. This chapter concentrates on the relationship between active smoking and three diseases caused by ETS -- lung cancer, heart disease, and nonmalignant lung disease. While there are qualitative differences between the mainstream smoke inhaiEd by the smoker and the ETS nonsmokers inhale, both forms of tobacco smoke contain the same carcinogens, irritants, and other toxins. The effects of high doses of smoke on smokers thus provide an indication of what effects low dose exposures of ETS would be expected to have on nonsmokers. This connection is particularly important because the diseases active smoking causes exhibit dose- response relationships, with higher doses producing greater effects. Because no threshold has been demonstrated for the carcinogenic and other effects of tobacco smoke on tr.e body, the existence of a dose-response relationship suggests that ETS would provide similar, but smaller, dangers than active smoking. Cancer Most estimates in the scientific literature indicate that nearly one-third of all U.S. cancer deaths result from cigarette smoking. Of the approximately 136,000 cancer deaths which occurred in 1985 because of smoking, 106,000 are of the lung (Figure 1). Lung cancer alone is responsible for fully one-quarter of all 9 TIMN 0030001

Draft - Do not cite or quote cancer mortality; were it not for the increasing number of deaths from lung cancer produced by smoking, we would be experiencing a substantial decline in the cancer death rate in the United States. Approximately 85 to 90 percent of all lung cancer deaths are smoking related. The evidence linking smoking and excess cancer mortality is so strong that only the tobacco lobby continues to claim that no causative role has been established. An examination of the association between cigarette smoking and lung cancer graphically illustrates smoking's role in the causation of neoplastic diseases. Tobacco smoke contains at least 43 known or suspected human carcinogens (Table 1), several of which are regulated by the federal government as environmental toxins. There is no known threshold for the carcinogenic effects of these agents. A host of epidemiological studies published during the last two decades provides an abundance of data which demonstrate that exposure to these carcinogens because of smoking leads to an increase in cancer deaths. In particular are the major prospective studies on smoking and health. These studies, conducted in the United States, Canada, England, Japan and Sweden represent some of the largest population based studies ever undertaken by medical science (Table 2). They involved enrolling healthy men and women into a study design and then followed these individual over time. Numerous factorr about them were recorded including where they lived, their occupations, dietary habits, whether they used tobacco, accesss to health care, and many other factors. As a group, these eight studies in the United States, the U.S. Veteran's Study and the American Cancer Society (ACS) 25-state Study contained cohorts of 290,000 and 1 million persons respectively. The Veteran's Study continues to this day and this cohort has been followed prospectively for 26 years. These studies convincingly demonstrate that smoking causes cancer. Lung Cancer Lung cancer mortality rates are strongly influenced by the total dose of cigarette smoke received. If one smokes more cigarettes per day,, inhales deeply, if they started smoking at an early age had has smoked for many years, the risk for lung cancer .is increased dramatically. The most often used measure to gauge lung cancer mortality is the number of cigarettes consumed daily. In the ACS 25-state study, for example, among males smoking less than 1/2- pack per day their lung cancer rate was nearly 5 times greater than that of a nonsmoker. With each increase in the number of cigarettes consumed daily, a corresponding increase in lung cancer mortality is observed (Figure 2). For those smokers consuming two or more packs daily, their lung cancer mortality is about 24 times greater than 10 TIMN 0030002

Draft - Do not cite or quote that of the nonsmoker. At the other extreme, even light smokers, who consume only 1-9 cigarettes per day, see a quadrupling of the risk of lung cancer. ~ An inverse dose-response relationship exists between an early age of regular smoking and lung cancer mortality. In the U.S. Veterans Study, those smokers who started smoking in their early teens had substantially higher lung cancer death rates than those who started in their late teens or twenties (Figure 3). Those who began smoking before age 15 experienced a 19-fold greater lung cancer mortality, compared to a slightly greater than 5-fold excess risk for those who initiated their behavior after age 25. These results demonstrate that a dose-response relationship exists for exposure to the carcinogens in cigarette smoke and the risk of death from lung cancer: the greater the lifetime exposure to tobacco smoke, the greater the risk. Further evidence for the' existence of a dose-response relationship comes from follow-up of people who stop smoking and so remove the exposure from the carcinogenic agents in mainstream smoke. When an individual stops smoking, his or her lung cancer risk declines relative to the continuing smoker. After about 15 years off cigarettes the former smoker's lung cancer risk approaches that of the life-long nonsmoker. However, it appears that some excess risk may be carried throughout life. This residual risk is strongly influenced by the individual's total lifetime exposure to the agent and the total number of years of smoking cessation. The presence of a dose-response relationship between smoking and lung cancer, combined with the fact that there are significant elevations in risk associated with even the lowest levels of smoking, demonstrates that there is no threshold for the carcinogenic effects of cigarette smoke. This result from active smokers is consistent with the observed elevations of lung cancer risk among nonsmokers exposed to ETS. Coronary Heart Disease In contrast to cancer, in which.smoking produces the disease through the cumulative effects of long term exposure to the carcinogens and co-carcinogens in the smoke, smoking effects the cardiovascular system immediately as well as over the long term. The carbon monoxide in the smoke reduces the oxygen carrying capacity of the blood by binding to hemoglobin competitively with oxygen. Nicotine is a vasoconstrictor, which increases blood pressure and narrows coronary arteries. Smoking causes release of catecholamine, which increase blood pressure and heart rate. Smoking also increases platelet aggregation and adhesion, which contributes to the development of atherosclerosis. All these 11 TIMN 0030003

Draft - Do not cite or quote effects occur immediately upon smoking and resolve relatively quickly after stopping smoking. As a result, one year after stopping smoking, the excess risk of death from heart disease falls by half; the same drop in risk for lung cancer takes 10 years. As with cancer, these effects exhibit a dose-response relationship, with greater more smoking and smoking in combination with other heart disease risk factors, increasing the risk of death from coronary heart disease. As with cancer, there is no threshold for these effects, so the effects of active smoking on the heart and cardiovascular system support the biological plausibility of the observed effects of ETS on the heart. Coronary heart disease (CHD) continues to be this nation's leading cause of death, and for nearly 20 years, medical research has shown that smoking is one of the maj or independent risk factors or causes of CHD (along with high blood pressure and high cholesterol levels). In the final report of the Pooling Project, an interaction between smoking and other risk factors was observed (Figure 4). Each independent risk factor contributed about the same increased level of- risk, however, when two or more factors were present, the risk of a major CHD event was increased beyond the sum of the independent risk -- thus, synergistic effect was created when two or more risk factors were present. Overall, smokers have a 70% greater CHD death rate, a two- to fourfold greater incidence of CHD, and a two- to fourfold greater risk for sudden death than nonsmokers. Dose-response relationships between cigarette smoking and CHD mortality have been demonstrated for several measures of exposure to cigarettes, including the number of cigarettes smoked per day, the depth of inhalation, age at which smokingtegan, and the number of years of smoking. Smoking cigarettes with reduced yields of tar and nicotine does not reduce CHD risk, probably because these cigarettes do not have reduced yields of carbon monoxide and other combustion products which affect the cardiovascular system. The independent risk of CHD for smoking is greater at the younger age groups although the greatest number of excess CHD deaths due to smoking actually occurs in the older age groups (Figure 5). Smoking has also been shown to increase the risk for other cardiovascular diseases, including peripheral vascular disease, cerebrovascular disease (at younger age groups), and aortic aneurysms. For women, smoking •can interact with oral contraceptives to greatly increase the risk factor for fatal and nonfatal myocardial infarction and subarachnoid hemorrhage. Smokers exhibit more atherosclerosis, both in the aorta and coronary arteries. Cigarette smokers who continue to smoke following transluminal coronary angioplasty appear more likely to require repeat angioplasty than nonsmokers, suggesting that the effects of smoking on atherosclerosis occur quickly. The polycyclic aromatic hydrocarbons which result from the combustion 12 T11~N 0030004

Draft-- Do not cite or quote of the smoking materials contribute to these effects. The increase in platelet adhesion observed in smokers also contributes to the development of atherosclerotic plaque. Cigarette smoking aggravates the conditions of people with CHD. Smokers have a more difficult course following coronary artery bypass surgery. Smokers who experience angina pectoris have a higher risk of death than nonsmokers, a poorer prognosis following non-fatal myocardial infarction, and a greater risk of sudden death. Smoking increases the risk of silent ischemia in patients with stable angina. Many public health estimates place the total number of excess cardiovascular disease (including stroke) deaths due to smoking to be.greater than those due to cancer (Figure 1). Up to 30 percent of all CHD deaths may be due to cigarette smoking and its interaction with other risk factors. These effects all exhibit a dose-response relationship with no threshold in active smokers, with detectable damage even among light smokers. These facts support the biological plausability of 'the evidence linking ETS with heart disease in nonsmokers. ' Nonmalignant Respiratory Diseases in addition to causing lung cancer, smoking causes or aggravates several related nonmalignant respiratory diseases, including emphysema, asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). While the number of smoking-induced deaths classified due to chronic obstructive pulmonary disease (COPD) is smaller than for cancer or cardiovascular disease (Figure 1), COPD afflicts about 12 million Americans. Even if not fatal, COPD and related disorders such as emphysema severely debilitate the victim and represent a substantial number of people who become disabled due to their condition, unable to work or even seek employment. 0 For many years cigarette smoking has been known to increase the risk of developing and dying from COPD. Even the first Surgeon General's Report issued in 1964 identified a causative role between smoking and chronic bronchitis. As with lung cancer, the risk of contracting and dying from COPD is substantially elevated among smokers (Figure 6) and this risk increases with an increased dose of cigarette smoke received; as with the other smoking-induced diseases discussed in this chapter, there is :a positive dose- response relationship. Mortality rations for COPD in smokers versus nonsmokers are very high, exceeding 30 to 1 for heavy smokers (Figure 7). Smoking also has a dramatic effect on lung function. The normal rate of lung function decline with increasing age is accelerated in cigarette smokers (Figure 8). These effects 13 TIMN 0030005

Draft - Do not cite or quote probably reflect damage to the small airways of the lungs as well as a thickening and increased reactivity of the airways in response to chronic exposure to the irritants in cigarette smoke. The volume an individual and exhale in one second of forced expiration (FEVj) is a measure of small airway function. Figure 9 shows that FEVi falls in a dose-dependent manner as the amount of smoking increases. There is no safe level of exposure: there is a measurable decrement in pulmonary function even among light smokers. Stopping smoking partially reverses the nonmalignant effects of the respiratory system (Figure 8). When one stops smoking, the decline in lung function with age resembles that of a nonsmoker, but a permanent decrement in lung function remains, indicating some permanent damage. The amount of this permanent deficit depends on the duration and intensity of smoking. ETS exposure produces similar, but more modest nonmalignant pulmonary effects. FEV1 is reduced in passive smokers among both children and adults to levels similar to that observed in light smokers. Children of parents who smoke develop more asthma, bronchitis and other respiratory problems. The rate of lung development in children exposed to ETS is smaller than that of unexposed children. These effects of ETS are what one would expect based on the effects of active smoking. Conclusions This chapter has reviewed the effects of active smoking in on those cancers, heart disease, and nonmalignant pulmonary diseases which have also been identified with passive smoking. In each case, cigarette smoking significantly increased the risk of disease in smokers in a dose-dependent manner. There is no evidence of a threshold level for adverse effects. Because ETS is similar to (but more toxic than) mainstream smoke, these effects on the smoker help provide evidence for the biological plausibility for the epidemiological evidence linking ETS with lung cancer, heart disease, and nonmalignant respiratory disorders, after accounting for the lower dose the involuntary smoker receives. 1. There is a dose-response relationship between exposure to tobacco smoke and the diseases of smoking. 2. There are no discernable thresholds of exposure for the diseases of smoking. 3. Adverse health effects observed in smokers provide biological plausibility for the occurrence of those diseases in nonsmokers. 14 TIMN 0030006

Draft - Do not cite or quote am" d.wt. • w.. = . _-- . ~ r Rf.pq. Vow r.a.~... ~ _~.._ UWY" ~ „ Men w 0% {005. ,00" ,ti00S 2000% :aOtIS 3000% )• Grnen 3eniw = fanwr IInnwr w.. ~---• LwVIM ;: r...a.. M Women 0s {001 1000% ,s001 ~ Curr.at 3nn..r ~.'. f«m.. ynor« W 200" FZ.rTJIIZ Z• Perasnt incr.asd eaneer morality risk. by sita and y.ndar. in ourrent and form.r smoke. s as d.r'r.•ad fror.a th. Amtriean Canesr Soepr,ty 50-Stat. Study. TIMN 0030007

Draft - Do not cite or quote I krlartalityr Aai;baa 20 1S 10 a © N one All SM 4 10 11-19 20 N o, ci ctgare t tes da11y FIGURE 3. (1989 SURGEON GENERALIS REPORT, p. 49) 21-30 21« TMN 003000g

uZZ) uUdrHS AtzrIDutea tO tirfl. oKing in 198b Source: US Surgeon General, 1989 W O O `O O H

Draft - Do not cite or quote TABLES AND FIGIIRES, CHAPTER 1 1- TIMN 0030010

FIGURE 4. (a 0 -6-b Lung canceO mortality ratios for males, by age began smoking - U.S. Veterans' S tudy 20 15 Nonsmoker 25+ 20-24 15-y 9 18.7 <15 Age began smoking (in years)

200 180 160 0 140 C3 *- 120 ` a 100 ~ ro 80 tr 60 40 20 Major risk factor combinations, 1o-year incidence of first major coronary events, men age 30-59 at entry, Pooling project None of 3 SM Only Risk Factor Status at Entry SM = smoker, C= cholesterol, H= hypertension CorH Only SM&C 'C&H AII3 or (No SM) SM&H e

Coronary heart diseas:e- ~~t'r~athSl S-1 ! 0 K~"i rS-! 9ref t-~ --- Do not cita= or quote n0 smokers Deaths per 100,000 men 996 500 1000 .._.. 422 - 400 _ 800 GMVMAM~ ~ ..~. 1~, ----- 300 ~ 600 542 ~ : ~ 200 150 ~ 400 .~ - ~ 100 ~ ~~ _= 200 ~ o ~ --• ® ~ 0 0 2500, 2000 1500 1000 500 2025 ~ ~ - 1400 = ' Ages 45--54 Ages 55-64 0~ Ages 65-74 =Nonsmokers = Smokers FIGURE 6. 0 TIMN 0030013

COLD deaths Draft - Do not cite or quote smokers vs. nonsmokers Deaths per 100,000 persons 500 400 - 300 - 200 ~ 100, f Nonsmokers 35-44 45-54 55-64 65-74 75-84 Age group FIGURE 7. 0 TIMN 0030014

Draft°- Do not cite.or quote -3.0 -1.0 -1.0 0.3 1.0 2.0 3.4 30 1-20 F+t-TRS 20 tf.W7 x 10 1088.590 0 0.0 1.0 2.0 3.0 30 21-+t0 Pa-TRS r' =o 901539 3b3i 0 -3.0 -2.0 - t.0 0.0 1.0 2.0 3.0 30 41-60 Px-TRS 20 N.S7S Y 10Ro.699 10 Q I rM__ -3.0 -2.0 - 1.0 0.0 1.0 2.0 3.0 30 S1-ae ~tt-TR~ ,~ 20 )o N.la9 11 LL LU.~~ Q -3.0 -2.0 - , I.0 O.0 1.0 2.0 3.0 30 a (a1t_ TRs ~' io ice:o.s)= . T% a 30 $1- rs-TRs ~ 20 118108 10 !OR 96i a 3.0 -2.0 -I.0 0.0 l.0 2.0 3.D MEIL„T AOJU5TE0 FEvt RESIOUAL tLITERS) I FIGURE 10. -Percent distribution of predicted values of forced expiratory voiumein 1-sec(FEY1) in subjects with varyingpadt-yearsofsmok- ing. N07M TnwVe udiesus mean. IQR is uaeiquamk raafe. SOURC'L IIunvw.e aL t 1977). Doekery e aL ! I9ti1. TI1VIN 0030015

m V ~ o 0 FIGURE s. \,z '. T-4 COLD mortality ratios for men and women, ~ ® by number of cigarettes smoked per day, ,~ sicians' Study ~ British Ph U y iO O 0 A i ~, 40 N A W 0 30 cU ~ .~' ~ ~ 20 0 2 1 0. 111111 0 1111111 26.0 F. Nonsmoker 1-14 15-24 M Female 38.0 28.5 25+ Cigarettes per day

Draft - Do not cite or quote TABLE 1. Expect.d Canc.r O.aths Caused by Srnokinp-Llnit.d Stst.s 1989 19~! Garu.r Smakr+0 GaMs Ats7butabl. Sit. Eao.ac.d llwk !%1 Esomat.d DOaths Ow to SmOtwq M.n Buccal cavity andoharymc 5.775 92 5,313 Larynx 3.000 81 2.430 Ltxro 93.000 90 83.700 Esophapus 6.900 78 5.382 8tadd.r 6.900 47 3.243 Kidn.y 6.000 48 2.880 Psnorass 12.500 29 3.625 Total 106.573 Women Buccsl cavny and Pharyn: 2.875 61 1.754 Larynx 700 87 609 luny 49.000 79 38.710 Esooh.qus 2.500 75 1.875 Bladd.r 3.300 37 1.221 Kidn.y 4,000 12 480 Ptncsas 12.500 34 4.250 Total 48.899 Total m.n and women .xp.cs.d to dio of eane.r in 1989 502.000 Pwcant attributed to smoking .31 Total .ac.ss cancer d.aths due to amoicinQ.:oact.d in 1989 155.472 0 TIMN 0030017

---Tumucl&enic pgenls In /pbpecw Iwnd iflbwcca smake Mainsueam Evidence fa IARC evaluauon uf calclnogenicuY Coulpluuda Prucesscd tcehacco Ipei granl) smokc (per e/garerle) in lab animis In humans Aromatic amincs 2-7-uluidlae 30-21K)ng Suffrcicnt InaJequale 2-Naphlhylamine 1-22 ng Sufficient Sufficient 4-Amimlhiphenyl 2-S ng Sufficient Sufficlcnl Aldch)des Pormaldcllyde' 1,6-1.4pg 70-I00N` Sufficient NA Actrahlcl/yJc' 1.4-7.4mg ie-1,400m` Sufficient NA Cruuwaldchyde 0 2-2.4 pg 111-20 Ng NA NA Misccllaneuus organic cumpounds neni,cne 12-4g Ng Suffscicnl Sufficient Acrylaniuilc 3.2-15pg Sufficient l.imiud 1.1-1)imcdlylhydozinc 6(1-147pg Sufficient NA 2-Niuoprupane 0.73-1.21 pg Sufficient NA Elhylcalhamalc 310-375ng 20-3gng Sufficient NA Vinylchloridc 1-16ng Sufficient Sufficicnl Inorganic cornpounds Ilydraiinc 14-Sing 24-Jl3ng Sufficient Inadcyuart Arscnic 51M1-9011ng 40-120ng inadcquale Sufficient Nickel 2.n00-6lNN)ng 0-6flOng Sufficient Linlilcd Chlomium 1,(XNI-2,IM)(Ing 4-70ng Sufficient Sufficient Cadmium 1-31N1-1,6/10ng 41-62ng Sufficient I.imilcd 1-caJ 8-10 pg Sufficient Inadcquate Pulumum-211) 112-1.2p(:i f10)-IOpCi NA NA NI111: NU. w~ Jau: NA. cvaluuun hat na IKCn donc by IAKC. '1 he fuunh RelMUI ad Ihc IakpcnJcnl Scunnlic C/umuwce on "Smul,-ng aud Ileahh'-/19aN1(wldnhcJ valucs hw Ihe Ia kadmg (1 K a`auuei in 19B61S/ 4 pcrunl aJ the madcll nf 2/1- I/IS pshipuue Imcan. 19 pEl lul tonnaWehlJr aa.l St0 I 1 SII pR/. IEa/cluc / mcan. 9111 JIR 116a at clalJchl Jc 1111'It1 I IL.Itm.un+ud 11..1n w p.... 1 e Mainstrcam Evidence tor IARCevalualiun of carcinugcnicil y ~ Compounds Proccssed tobacco (per gram) smuke (pcr ciguetle) In lab animals In hwuans PAII Bcnzia)anlhracene 20-70ng Sufficient NA Benzo(b)tluoranthenc 4-22 ng Sufficient NA Benz(j)tluoranthene 6-21 ng Sufficient NA Benzo(k)Ouoranlhene: 6-12ng Sufficienl NA Bcnzo(a)pyrcnc 0.1-90ng 20-40ng Sutficienl Prubable Chqsene 40-60ng Sufficient NA Dlbenzla,h)a/uluacene 4 ng Sufficient NA Dibenzo(a.i)pyrcne 1.7-3.2ng Sufficient NA Dibcnzofa,4pyrcnc Presenl Sufficient NA Indcno(1.2.3-c.d)pyrene 4-20 ng Sufficient NA S-Atclhykhryscnc 0.6 ng Sufficient NA Aza-arenes Quinoline 1-2 Ng NA NA Ditrcnz(a,h)acndinc 0.1 ng Sufficient NA Dlbenz(a j)acridine 3-10ng Sufficient NA O 71i-Dibenzo(c.g)ca/bazole 0.7 ng Sufficient NA h a N-NUrosamines N-Nitrosodimelhylamine ND 21Sng 0.1-IgOng Sufficient NA rt / N-Nitrosoahyl 3-13 ng Sufficient NA d 0 meth)lamine N-Nitrosodicthylamine ND-25 ng Sufficient NA :J 0 N-Nnrosopyrrulidinc ND-360 ng 1.5-110 ng Sufficient NA frt N-Niuowdiuharwlamilu: ND-6 9110ng ND-36ng Sufficient NA n /-a- ' , ft 4) -Nuruwnumicuuru N 113- 89 pg 012-3.7 pg Sufficient NA 0 4-(Mubyluiuosa/mno)-1- 0 2-7 pg 0.08-0.77 Ng Sufficient NA O-PY(idyl)-1-bulanunc N' Nurnwanabasmc 11(11- 1 911g 0-14-4 6µg I imilcd NA F 0 ',M, NII /!a/1u, ,.d1r n 1.1 It , ft W TIMN 0030018

Dr3ft - Do not cite or quote TAB LE 4. MoRality +tatioI ror M.n and wom.n 3S r..ra and Old.r According to Smoking Stattu at TLe. o# Enrodm.nt ::-::+n stuov 5osut. Sh,dy G.r.nt smokr Fomw smdc.w c~...nt snwY.r Pom,.. , , smok,.• . ~ M.n Lung 11.35 4.96 22.36 9.36 Ora/ 6.33 2.73 27.48 8.80 ESoohaQus 3.82 1.28 7.80 5.83 l.xynx 10.00 8.80 10.48 5.24 Blaoa.r 2.90 1.75 2.86 1.90 P anaaas 2.34 1.30 2.14 1.12 Kidn.y 1.84 1.79 2.95 1.95 wom.n Lung 2.69 2.59 11.94 4.96 Ora/ 1.96 1.89 5.59 2.88 Esophagus 1.94 2.15 10.25 3.16 harynx 3.81 3.10 17.78 11.88 8taddar 2.87 2.31 2.58 1.85 Pana.aa 1.39 1.38 2.33 1.78 KidMy 1.43 1.47 1.41 1.16 Ut.uus 1.18 - - - Oata from th. Surg.on Gan.ral's Aeport. 1989.° TIMN'0030019

TABLE 3. Outline of Eight Major Prospective Studies IN.1. C.d«1o/ Author• NUI Hammond U"n ilkaysrna MM N.mmond Dunn FrlbwQ P+lo Kahn JoN. 1/"n Und.n Ikub.o P1M• RoQo1 Walk.r Or..k" Lorkh 1Aal.a .nd ToW popul.llon ftob*bft Lmal.o o/ Ca1Hom1. .arnpl. d SubJ.c/• 8r1Ush In U.S. 20 h.aMh Canadian Whlte malw mat..ln Ih. doda• 25 v.l.rs" d1.lr/cta In p.nslorwr In v.glou• 8wr.dl.h S/a1.. Japan nlne a/a1.s oocupatlons popul.tlon Popul.llon sli• 40.000 1.000.000 200.000 266.000 92.000 117,000 N,000 66.000 F.m.l.. 6.000 662.611 < ix 1.2.957 14.000 27.700 A0. fian0• 2045 t 36-i1 3S-il 40 30-Y0 60-00 33-N 18-OY and up Y..rol 1951 iObO 1Q54 1006 lOS6 1002 1064 1Yu .nrollmenl 1957 Yean ol 20-22 6-a /ouowup y.ar® 12 y®at® 1® y®u. 13 y..r. • you. 4 ysan ywn 10 y+.n t.porl.d Numb.r o/ 11,140 150,000 101,500 30.100 11.000 12.000 4.700 4,600 deaths P.r.on ys.r• ol 000.000 0,000.000 J•600.000 3.000.000 500.000 070,000 4i0,000 660.000 •Mp•I I~nG~ .e 0 0

Draft:- Do not cite or quote CHAPTER 2 EXPOSURES TO INDOOR PARTICULATE AIR POLLUTANTS John McCarthy PhD, Elizabeth Miesner PhD, John Spengler PhD Department of Environmental Science and Physiology Harvard School of Public Health Boston, Massachusetts 02115 Throughout our lives, we are exposed to gaseous and particulate contaminants in the air. For some airborne contaminants, our exposure is dominated by their occurrence in outdoor air and the time we spend outdoors. However, even for the pollutants that have only outdoor sources, the air that ventilates our homes, offices, and vehicles originate outdoors.. Considering chronic exposure or protection from acute episodic outdoor Pollution events, the time we spend indoors and the protection these indoor environments provide are important considerations. In the presence of indoor sources of contaminants such as unvented combustion, evaporation of solvents, and dispersion of microbiological organisms among others, the time-activity patterns of people in their use of these indoor environments become important considerations in determining exposures. People can have very different exposures to indoor contaminants depending on social,•demographic and economic differences in the population, as well as the physical differences that exist across indoor environments. These differences are characterized by the use of the structure, its volume air flow and air exchange, the efficiency of contaminant removal and, most importantly, the generation rate of the source itself. Thus, concentrations of air pollutants can and do vary depending on location. Outdoor pollutant levels may differ from indoor levels. Different indoor locations like homes, schools or workplace can also register varying pollutant levels. An individual's total exposure to air pollutants therefore depends on the time spent in each of these microenvironments and the various concentrations of air pollutants. Time-Activity Patterns The activity patterns of people determine the duration of exposure and, at times, the intensity of exposure to airborne 16 TIMN 0030021

Draft - Do not cite or quote contaminants. The amount of time a person spends in different microenvironments is influenced by age, sex, occupation, social class, and season. Letz et al. (1984) studied the time-activity patterns of 332 residents of Roane County, Tennessee. The results of study showed that these individuals spent 75% of their time in the home. This figure was higher (84.9%) for housewives, unemployed and retired persons. Overall 10.8% of the participants time was spent: at "work". Full-time employed individuals worked between 21-24% of the time. Of the remaining time, 8.5% was spent in public places, 9% in travel, and 2.8% in various other locations. Quakenboss et al. (1982) studied the time allocation for 66 family members from 19 homes in Portage, WI. Individuals were put into one of five general subgroups which are shown in Table 1. Despite wide variations, each group spent most of the time at home. 'For all participants, total time spent indoors was 85%. More recently, Quakenboss and his colleagues analyzed time- activity data for over 300 individuals in the Portage, WI area. Participants were categorized into three groups: workers, nonworkers, and students. Activity data was collected from both summer and winter seasons and is summarized in Table 2. Again all groups spent the largest percentage of their time in the home. Time spent outdoors decreased from summer to winter. Infants, because they are essentially immobile, spend most of their time in the bedroom according to a recent study by Harlos et al. (1987). The rest of their time is usually spent in the living room, kitchen, or in travel as illustrated in Figure 1. j Knowing an individual's or a population's activity patterns is not sufficient in itself to determine exposure to contaminants. Outdoor pollutants do penetrate indoors and can undergo reactions. Indoor contaminant concentrations vary according to the source rate, air exchange and air flow, and reactions. Characterizing sources indoors will not always lead to accurate estimates of concentrations or exposures. Therefore, depending on the distribution of sources indoors and the degree of mixing, there may be considerable differences in pollutant concentrations across indoor environments. Lebret (1985) examined the respirable suspended particulate (RSP) levels in rooms while participants were smoking or within one-half hour of smoking. He found significant variation between the living room kitchen and bedroom. Ju and Spengler (1981), who studied 24-hour average concentrations of respirable particulates, also found statistically significant variation between some rooms although the absolute differences were relatively small. Monitoring 1 7 TIMN 0030022

Draft - Do not cite or quote There are a number of different instruments available to monitor air pollutants. Often the type of instrument used depends on the exposure of interest. Immediate exposures are most important when studying irritant and acute allergic responses. For this type of exposure, instruments which take short-term or instantaneous readings are often used: the piezobalance or nephelometer are both used to measure particulates, the ecolyzer is used to measure carbon monoxide. One advantage to these types of instruments is their ability to detect peak pollutant levels. For acute effects such as upper or lower respiratory infections, the exposures of interest range from hours to days. For increased prevalence of even a lifetime.(?) To measure these exposures, integrated or time-averaging methods are used. These methods include filters which are used to collect particles over long time periods. EXPOSURE TO AIRBORNE PARTICLES S ize Distribution and Composition of Particulates The distribution of particulates is essentially trimodal with peak diameters at approximately 0.02 µm, 0.5 µm and 10 µm as shown in Figure 2. These size modes reflect the origins of the particles and the physical chemical processes affecting them. The ultrafine fractions are typically fresh combustion emissions of aiken nuclei and condensing vapors. The submicron size (0.1-1 µm) Yias been called the accumulation mode. Again, incomplete combustion adds particles to this size range; however, the oxidation of gases such as S02 and NOZ to form sulfates and nitrates are predominantly found in this range. Particles larger than 1 µm can be of biological origin--fiber frVments, spores, pollens, and bacteria. Bursting bubbles and sea spray can generate condensation nuclei. But it is mostly abrasion and/or erosion that generate larger particles. The fine particle fraction, or <2.5 µm, is produced by combustion or condensation of vapors. At least 75% of the sulfur, zinc, bromide and lead are found in this size range (Dzubay and Stevens, 1975). Particles <2.5 µm are very important for health reasons since these particles can reach the alveolar regions of the lungs. Particles greater than 2.5 µm in diameter, or coarse particles, are usually formed by mechanical processes like grinding, crushing, and abrasion. At least 75% of the silicon, calcium and iron, elements commonly found in soil, appear in this size fraction (Dzubay and Stevens, 1975). Particles from 2.5-10 µm can be inhaled and can become deposited in the tracheobronchial 18 TIMN 0030023

Draft - Do not cite or quote regions. Environmental Tobacco Smoke Environmental tobacco smoke (ETS) is a mixture of exhaled mainstream smoke and sidestream smoke. Sidestream smoke is the smoke that is formed by smoldering between puffs of a tobacco product and is the major source of ETS. Approximately half the tobacco in a cigarette is burned in the sidestream mode. The complex mixture that the smoker inhales with each puff of a cigarette, cigar, or pipe is called mainstream smoke. The portion of mainstream smoke that the smoker exhales and the small amount of vapor diffusing through the wrapping of the cigar or cigarette add little to ETS. ETS consists of fresh and aged sidestream and mainstream smoke. The particle sizes which make up ETS vary due to coagulation (the process where two or more particles collide and combine to form a larger particle), evaporation, and the adhesion of particles to surfaces. The size distribution of particles is also affected by air dilution, relative humidity and temperature. .. Under controlled conditions, several researchers have measured the particle size distribution of sidestream smoke (Keith and Derrick, 1960; Porstendorfer and Schraub, 1972; Hiller et al., 1982; Leaderer et al., 1984; Ingebrethsen and Sears, 1986). Based* on these studies, the mass median diameter of sidestream smoke can be estimated to be between 0.2 µm and 0.4 µm. The mass median diameter is the diameter which divides the mass distribution in half, i.e. one half of the mass is contributed by particles larger than this diameter and one half by particles smaller. Because much of the time the tobacco is burning at substoichiometric conditions, particles are produced in the accumulation size mode. As ETS ages, the processes of coagulation cause particles to grow. This offsets mass loss due to evaporation. Composition of ETS Environmental tobacco smoke is made up of several thousand different chemical compounds. These compounds may be in the gaseous or solid phase or both. The chemical composition of sidestream smoke differs from that of mainstream smoke. Over 2,000 compounds have been.measured in sidestream and mainstream smoke. Some of the constituents in the mainstream smoke of nonfilter cigarettes are listed in Table 3. Also given are ratios of these substances in sidestream smoke compared to mainstream smoke. A ratio of greater than 1.0 means the constituent is found in higher concentrations in sidestream smoke than mainstream smoke. Nicotine, a substantial component of tobacco combustion, is produced mainly in the particulate phase. However, as the ETS mixture dilutes and ages, the nicotine rapidly shifts to vapor phase. Chamber studies by McCarthy (1987) and others have 19 T1MN 0030024

Draft - Do not cite or quote demonstrated that the half-life decay of nicotine is more than twice that of the particulate phase. A number of the constituents listed are carcinogens or suspected carcinogens according to the International Agency for Research on Cancer (IARC). Measurement of ETS The large number of constituents in ETS make it impossible to assess overall exposure based on measurement of each one. Instead most researchers have measured one or more compounds and have used those to estimate the total exposure to ETS. Changes in ETS composition over time and exposure conditions limit the accuracy of this method. This chapter will discuss in detail only a few of the possible measures of ETS: particles, nicotine, cadmium and nitrosamine. Most of the data presented will be from studies involving cigarette smoke since this is a major source of indoor ETS. Little work has been done on pipe or cigar smoke. Exposures to Environmental Tobacco Smoke • According to the U.S. Department of Commerce (1985) about 30% of adults in the U.S. are smokers. 40% of homes nationwide have at least one smoker. In a survey of over 10,000 children in six U.S. cities, the percentage of children living with one or more smoking adults varied from a low of 60% .to a high of 75% (Ferris et al., 1979). Lebowitz and Burrows (1976) reported 541% of children in a study in Tucson had at least one smoker in the home. These data indicate that the potential for exposure to ETS in the home is greater than that inferred from national statistics. In part, this reflects the demographics of smoking where it is adults in their child-raising years that are more likely to be smokers than the overall average. Surveying a new cohort of elementary- age children in six U.S. cities reveals that on average, parental smoking has decreased between 10% to 15% over a decade (mid 1970's to mid 1980's). Smoking between different demographic groups can vary widely and this will modify the exposure of nonsmokers to ETS. Overall, ETS exposure will depend on the proximity of an individual to the source of smoke. Patterns of smoking will be influenced by time, location, and type of activity. MICROENVIRONMENTAL MEASUREMENTS OF CONCENTRATIONS Concentrations of Particles and ETS Numerous studies have been conducted using respirable suspended particulates (RSP) as markers for ETS. Both continuous and integrated measurements methods have been used. Although RSP 20 TIMN 0030025

Draft - Do not cite or quote is not specific for the presence of smokers in the home and other indoor locations, the number of cigarettes smoked have shown to correlate well with RSP. Particulate Concentrations in Homes Spengler et al. (1981) measured 24-hour respirable particulate levels in 55 homes in six U.S. Cities. The mean monthly concentration across cities is presented in Figure 3, with indoor particulate levels similar to the outdoor levels. Table 4 shows the respirable particulate levels in the homes as a function of the number of smokers. The actual amount of smoking in the home was not reported. The researchers concluded that the major source of indoor particulates in smoking homes was cigarette smoke. Each smoker in the home raised the mean respirable particulate level by 20 µg/m3. Further analysis of the data by Dockery and Spengler (1981) showed that each cigarette smoked in the home increased the mean respirable particulate levels by 0.88 µg/m3. In air conditioned homes, the respirable particulate levels increased by 2.11 µg/m3 per cigarette per day. This increase was probably caused by recirculation of indoor air which reduced the cigarette smoke dilution. More recently Spengler and colleagues (1986) analyzed RSP data from over 200 homes in Watertown, MA. Homes with smokers had RSP concentrations of.30 to 35 µg/m3 higher than nonsmoking homes. RSP concentration and the number of cigarettes smoked per week were highly correlated. Models based on this data predict a contribution of 0.77 gg/m3 per cigarette per day. This would mean a pack of cigarettes would increase the indoor RSP concentration by 15.5 µg/m3. Particulate Concentration in Offices Using a piezobalance, Weber and Fischer (1980) monitored 44 workrooms at seven different companies in Switzerland. The workrooms had varying levels of smoking. A number of samples were taken in each room over a two-day period. After subtracting the particulate levels found in an unoccupied room, the mean particulate level for the 492 sam3ples taken was 133 µg/m3 with a standard deviation of 130 µg/m . The maximum concentration measured was 962 µg/m3. Quant et al. (1982) used a piezobalance to monitor three offices. The offices were divided into cubicles with half-wall partitions and contained both smoking and nonsmoking areas. Offices were monitored continuously for one work week. Figure 4 shows the results of continuous monitoring in one of the offices. For the three offices, the ten-hour day averages ranged from 37µg/m3 to 89 µg/m3. 21 TjMN 0030026

Draft - Do not cite or quote Miesner et al. (1988) used both continuous and integrated methods to monitor in five office buildings in metropolitan Boston. Both filters and nephelometer were used to measure in 12 offices, one conference room, and a designated smoking room of a large nonsmoking office. In offices without smoking, concentrations typically ranged from 15 to 10 µg/m3. In offices with smoking, concentrations were higher, ranging from 20 to 80 µg/m3. n designated smoking areas, concentrations were 100 to 500 µg/m~. Short-term concentrations measured with the portable MINIRAM exceeded 1000 µg/m3 in one of the designated smoking areas. Particulate Concentration in Offices Repace and Lowry (1980) measured particulate levels in various indoor public facilities both in the absence and presence of smoking. For nonsmoking locations such as restaurants, libraries, a church, and a bakery, the mean indoor RSP level was less than 60 µg/m3. Measurements taken in public facilities in the presence of smoking are shown on Table. 5. Measurements range from 86µg/m3 to 187 µg/m3 for restaurants and cafes that permit smoking. Other areas where there are likely to be more smokers per area than in restaurants had much higher concentrations of particulate matter, ranging from 200 to 700 µg/m3. Besides monitoring in offices, Miesner et al. (1988) also took continuous and integrated RSP measurements in numerous public facilities including a library, museum, school, subway, bars, and restaurants. They found that for most public buildings where no smoking was p~resent the particulate levels were low usually less than 30 µg/m . Levels in transportation facilities such as the subway and bus stations were slightly higher with a mean integrated measurement of 63 µg/m3. Higher concentrations were found in smoking areas such as bars, restaurants and a public smoking room with a mean integrated measurement of 79 µg/m3 and a standard deviation of 44 µg/m3. Concentration of Other Components of ETS Numerous researchers have looked at other tracers for ETS. Because of its high specificity for tobacco smoke and its presence in high concentration, nicotine is a promising choice. McCarthy et al. (1987) measured indoor nicotine levels in smoking and nonsmoking homes. The home nicotine values ranged from an average of 0.1 µg/m3 in the nonsmoking households to 4.2 µg/m3 in the smoking households. The presence of low nicotine values in some of the nonsmoking households can be accounted for by visitors to the home who were smokers. A number of studies have used integrated readings to determine nicotine levels in offices and public buildings. A selection of these studies are presented in Table 6. 22 Z"IlVIN 0030027

Draft - Do not cite or quote Cigarettes are also known to be a source of cadmium. Lebret et al. (1987) considered cadmium as a useful tracer for ETS. They monitored twenty homes and one outdoor site for fine particulates in Watertown, MA. Particles were analyzed for elemental composition using x-ray fluorescence. At the outdoor site and in homes without smokers, cadmium levels were below the detectable limit. In homes with smokers, indoor cadmium levels were highly correlated with indoor fine particulate measurements. Nitrosamines, some of which have been listed as animal carcinogens by the IARC, have been studied in public facilities and homes (Brunnemann et al., 1978). Using continuous measurements they found mean levels of nitrosamines in public facilities which ranged from 0.01 to 0.24 ng/L. Both homes monitored had levels of less than 0.005 ng/L. Wallace s:t al. (1987) measured the personal exposure and breath levels of benzene and other aromatics in 200 smokers and 322 nonsmokers in New Jersey and California. Benzene is listed as a human carcinogen by the IARC (1986). They found a significant increase in breath concentration with the number of cigarettes smoked. Smokers were found to have up to 10 times the breath concentration of benzene compared to nonsmokers. Nonsmokers who reported smoke exposure at work showed elevated levels for fall and winter but not for spring and summer. The authors concluded that cigarettes were the major source-of benzene for about 50 million U.S. smokers. No single constituent of ETS is sufficient to completely characterize an individual's exposure to ETS., Research on ways to relate these measurements to specific health effects continues to be done. The most prudent course is to measure several of these components in exposure studies. Markers specific to the class of ETS components, or health outcome of interest, could be utilized in epidemiologic studies to enhance precision of the exposure. Personal Exposures Personal monitoring studies have many of the same problems that area monitoring has, such as trying to.measure ETS exposure based on one or more markers. However, personal exposure monitoring has the advantage of including spatial and temporal dimensions to the measurements. It is also possible to use time- activity diaries to link exposure with location and activity. The results of a personal monitoring study by McCarthy et al. (1987) show that the exposure of children to RSP was much higher than that of children from nonsmoking households. The average personal RSP value increased from 29 µg/m3 for children from nonsmoking families to 56 µg/m3 for children from smoking families. The average personal nicotine concentration increased from 0.3 23 TIMN 0030028

Dratt- Do not..cite or quote jcg/m3 to 2.5µg/m3 for children from nonsmoking and smoking families respectively. A child's personal nicotine is highly correlated with the consumption of cigarettes in the home while the personal RSP was not. This implies that although there are multiple sources of RSP, the majority of ETS exposure is from the child's home. Spengler et al. (1985) had 101 nonsmoking volunteers from Kingston/Harriman, Tennessee wear personal respirable suspended particulate monitors for 3 days. Nonsmokers were divided in two groups: those who lived with a smoker and those who did not. Outdoor and indoor particulate levels were taken for comparison. Results showed that personal exposure was not correlated with outdoor concentrations but that ETS significantly increased an individual's personal concentration profile. In Spengler and Tosteson (1981), 45 nonsmoking adults were monitored for RSP for 18 days. They were also divided into two groups: those exposed to ETS and those who were not. Area monitors were also placed inside and outside. Personal exposure was higher than both indoor and outdoor measurements. On average, the individual exposure was increased by 20 µg/m3 among those• who reported exposure to ETS. Cotinine is a major metabolite of nicotine. McCarthy et al. (1987) measured cotinine levels in the urine and saliva of 81 nonsmoking children. Nicotine levels in the air were also monitored as was RSP. They found a high correlation between personal nicotine levels and cotinine indicating a quantitative relationship may exist. They did however find high variability. ~ Coultas et al. (1987) measured cotinine in the saliva of 1360 nonsmoking children and adults. They found an increase with the number of smokers in the home at all ages. However, household variability was wide and even 30% of the nonsmokers living in a nonsmoking home had detectable cotinine levels. 0 Summary 1. Environmental tobacco smoke is the primary contaminant causing elevated RSP levels in enclosed spaces. 2. Environmental tobacco smoke can be a substantial contributor to the level of indoor air pollution concentration of benzene, acrolein, N-nitrosamine, pyrene and carbon monoxide. 3. Measured exposures to respirable suspended particulates are higher for nonsmokers who report exposure to ETS. TIMN 0030029 24

Draft - Do not cite or quote REFERENCES BADRE, R., GUILLERM, R., ABRAN, N., BOUTDIN, M., DUMAB, C. Pollution atmospherique par la fumee de tabac (Atmospheric pollution by smoking). Annales Pharmaceutiques Francaises 36(9/10):443-452, 1978. BRUNNEMANN, X.D., ADAMS, J.D, HO, D.P.S., HOFFMANN, D. The influence of tobacco smoke on indoor atmospheres: 2. Volatile and tobacco-specific nitrosamines in main- and sidestream smoke and their contribution to indoor pollution. Proceedings of the Fourth Joint Conference on Sensing fo Environmental Pollutants, New Orleans, 1977. American Chemical Society, 1978., pp. 876-880. CANO, J.P., CATALIN, J., BADRE, R., DUMAS, C., VIALA, A., GaILLERME, R., Determination de la nicotine par chromatographie en phase gazeuse: 2. Applications (Determination of nicotine by gas- phase chromatography: 2. Applications). Annales Pharmaceutiaues Francaises 28 (11):663-640, 1970/ COULTAS, D.B., HOWARD, C.A., PEARE, G.T., SRIPPER, B.J., SAMET, J.M. Salivary cotinine levels and involuntary tobacco smoke exposure in children and adults in New Mexico. American Rev. Resp. Dis. 136:305-309, 1987. CIIDDEBACX, J.E., DONOVAN, J.R., BURG, W.R. Occupational aspects of passive smoking. American Industrial Hvaiene Association Journal 37 (5) :263-26.7, 1976. DOCICERY, D.W., BPENGLER, J.D. Indoor-outdoor relationships of respirable sulfates and particles. Atmospheric Environment 15(3):335-343, 1981. DUZUBAY, T.G., STEVENS, R.X. Ambient air analysis with dichotomous sampler and x-ray fluorescence spectrometer. Environmenta Science and Technoloay. 9(7):663-668, 1975. ELLIOTT, L.P., ROWE, D.R. Air quality during public gatherings. Journal of the: Air Pollution Control Association 25(6):635-636, 1975. FIRST, M.W. Environmental tobacco smoke measurements: Retrospect and prospect. European Journal of Respiratorv Diseases 65(Supp. 133):369-376, 1984. HARLOS, D.P., MARBURY, M., SAMET, J., SPENGLER, J.D. Relating indoor NOZ levels to infant personal exposures. Atmospheric Environment, 2:1(2):369-376, 1987. HARMSEN, H., EPPENBERGER, E. Tabakrauch in verkehrmitteln, wohn un arbeitsraumen (Tobacco smoke in transportation vehicles, living and working rooms). Archiv fur hyfiene und bakteriologie 141(5):383- 25 TIMN 0030030

400, 1982. Draft - Do not cite or quote HILLER, F.C., MCXUSXER, X.T., MAZUMDER, M.K., WILSON, J.D., BONE, R.C. Deposition of sidestream cigarette smoke in the human respiratory tract. American Review of Resgiratory Disease 125(4):406-408, 1982. HINDB, W.C., FIRST, M.11. Concentrations of nicotine and tobacco smoke in public places. New England Journal of Medicine 292(16):844-845, 1975. HOFFMAN, D., HALEY, N.J., BRIINNEMAN, X.D., ADAMB, J.D., WYNDER, E.L. Cigarette Sidestream Smoke: Formation. Analvsis and Model Studies on the uptake by Nonsmokers. Paper presented at the U.S.- Japan meeting on the new etiology of lung cancer, Honolulu, March 21-23, 1983. INGEBRETHSEN, B.J., SEARS, S.B. Particle Size Distribution of the Sidestream Smoke. Paper presented at the 39th Tobacco Chemists' Research Conference, Montreal, October 2-5, 1986. JU, C., SPENGLER, J.D. Room-to-room variations in concentrations pf respirable particles in residences. Environmental Sciences and Technoloay 15(5):592-596, 1981. JIIST, J., BORXOWSKA, M., MAZIARKA, S. Zanieczyszcenie 'dymen tytoniwym powietrza kawiarn Warszawskich (Tobacco smoke in the air of Warsaw coffee rooms). Roczniki Pantstwowego Zakiadu HYaieny 23 (2) :129-135, 1972, XEITH, C.H., DERRICX, J.C. Measurement of the particles size distribution and concentration of cigarette smoke by the confuge. Journal of Colloid Science 15:340-356, 1960. LUS, J., KIIHN, H. Verteilung verschiedener tabakrauchbestandteile auf haupt-und nebenstromrauch (eine ubersicht) (Distribution of various tobacco smoke components among mainstream and sidestream smoke (a survey). Bietrage zur Tabakforschung International 11(5):229-265, 1982. LEADERER, B.P., CAIN, W.B., ISSEROPP, R. Ventilation requirements in buildings: 2. Particulate matter and carbon monoxide from cigarette smoking. Atmospheric Environment 18(1):99-106, 1984. LEBRET, E. Air Pollution in Dutch Homes, Ph.D. Thesis, Wageningen Agricultural University, The Netherlands, 1985. LEBRET, E., McCARTHY, J., BPENGLER, J.D. A survey of time-activity patterns in Kingston/Harriman. Methods and Support for Modelled Data. Presented at Quality Assurance in Air Pollution Measurements Conferences, Boulder, Colorado, October 14-18, 1984. 2 6 TIMN 0030031

Draft - Do not cite or gv#-y NSCaARTHY, J. Physical and Biological Markers to A- to Environmental Tobacco Smoke. Ph.D. Disse- Public Health, Harvard University, 1987. McCARTHY, J., SPENGLER, J., CHANG, B. A persona~ to assess exposure to environmental tobacco smoke the 4th Interngtiona Conference on In oor Air 4ua. Berlin (West), 17-21 August 1987. MIESNER, E.A., RUDNICX, S.N., PRELLER, L., HU, I J.D., OZRAYNA2C, H., NELSON, W. Report to the U.S. Protection Agency, Cooperative Agreement No. C'A Harvard School of Public Health, 665 Huntington Avern, (1988). MURAMATSU, M., UMEMURA, S., ORADA, T., TOMITA, H. Ea personal exposure to tobacco smoke with a newly develop personal monitor. Environmental Research 35(1):218-22. NEAL, A. D. , WADDEN, R.A. 8. , ROSENBERG, S.H. Evaluation particulate concentration for an urban hospital. industrial Hya,iene Association Journal 39(7):578-582, 19', PORSTENDORFER, J., BCHRAUB, A. Concentration and mean partic of the main and side stream of cigarette smoke. Staub-Rein. 36, 1972. OT g2~~2 DE4 ~ t ~ d C4,tSSo go,~a F+ a 4 1 i9 a~e ~~W g es D QUACXENBO88, J.J., RANAREX, M.S., SPENGLER, J.D., LET2 Personal monitoring for nitrogen dioxide exposure: Methodolot considerations for a community study. Environmental Internati 8(1-6);249-258, 1982. QUACRENBO88, J.J., SPENGLER, J.D., RANARER, M.S., LETZ, R., DUPI C.P. Personal exposure to nitrogen dioxide: relationship indoor/outdoor air quality and activity patterns. Environmenta Science and Technoloqy 20:775-783, 1986. QUANT, P.R., NELSON, P.A. SE, G.J. Experimental measurements of aerosol concentration in offices. Environment International 8:223-227, 1982. REPACE, J.L., LOWREY, A.H. Indoor air pollution, tobacco smoke, -and public health. Science 208:464-472, 1980. REPACE, J.L., LaWREY, A.H. Tobacco smoke, ventilation, and indoor air quality. American Society of Heatina, Refrigerating, and Air- ConditioningEnaineers. Inc., Transactions 88 (part 1):895-914, 1982. SARUMA, H., KUSAMA, M., MUNRARATA, S. OHSUMI, T., SUGAWARA, S. The distribution of cigarette smoke components between mainstream and sidestrea.m smoke: 1. Acidic components. Beitrage zur 27 10, TIMN 0030032

Draft - Do not cite or quote Tabakforschuna 12(2):63-71, 1983. SAKU2+iA, H., KUSAMA, M., YAMAGIICHI, S., MATSIIRI, T., SUGAWARA, S. The distribution of cigarette smoke components between mainstream and sidestream smoke:2. Bases. Beitrage zur Tabakforschung 12(4):199-209, 1984. SAICUMA, H., 1CIISAMA, Ir1. , YAMAGIICHI, K. , SIIGAWARA, T. The distribution of cigarette smoke components between mainstream and sidestream smoke:3. Middle and higher boiling components. Beitrace zur Tabakforschunq 12(5):251-258, 1984. SCHMELTZ, I. dePAOLIS, A., HOFFMANN, D. Phytosterols in tobacco: Quantitative analysis and fate in tobacco combustion. BeitracLe zur Tabakforschuna 8(4):211-218, 1975. SPENGLER, J.D., DOCRERY, D.W., TURNER, W.A., WOLFSON, J.M., FERRIS, B.C. JR. Long-term measurements of respirable sulfates and particles inside and outside homes. Atmospheric Environment 15(1):23-30, 1981. ,¢PEBdGLER, J.D., REED, M.P., LEBRET, E., CHANG, B.H., WARE, J.H., SPEIZER, F.E., FERRIS, B.G. JR. Harvard's indoor air pollution/health study..Paper presented at the 79th Annual Meeting of the Air Pollution Control Association, Minneapolis, Minnesota, June 22-27, 1986. SPENGLER, J.D., TREITMAN, R.D., TOSTESON, T.D., MAGE, D.T., SOCZEX, M.L. Personal exposures to respirable particulates and implications for air pollution epidemiology. Environmental Science and Technology 19(8): 700-707, 1985. SPENGLER, J.D., TOSTESON, T.D. Statistical Models for Personal Exposures Data. Paper presented at Environmetrics 81, Conference of the society for Industrial and Applied Mathematics, Alexandria, Virginia, April 1981. WALLACE, L., PELLIZZARI, E., HARTWELL, T.D., PERRITT, R, ZIEGENFUS, R. Exposures to benzene and other volatile compounds from active and passive smoking. Archives of Environmental Health 42(5):271- 279, 1987. WEBER, A., FISCHER, T. Passive smoking at work. International Archives of' Occupational and Environmental Health 47(3):209-221, 1980. WHITBY, X.T. The physical characteristics of sulfur aerosols. Atmostpheric Environment 12:135-159, 1978) U.S. DEPARTMENT OF HEALTH AND HtJMAN SERVICES. The Health Consequences of Involuntary Smoking. A Report of the Surgeon General. DHHS Publication No. (CDC) 87-8398, 1986. 2 $ TIMN 0030033

Draft - Do not cite or quote U.S. DEPARTMENT OF TRANSPORTATION AND U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. Health Aspects of Smokina in Iransoortation Aircraft. U.S. Department of Health, Education, and Welfare, National Institute for Occupational Safety and Health, December 1971. ' I 29 TIMN 0030034

Draft - Do not cite or quote FIGURES AND TABLES, CHAPTER 2 30 TIMN 0030035

Dratt - Do not cite or quote 0 FIGLIRES AND TABLES, CHAPTER 2 30 T.IMMN 0030036

Draft - Do not cite or quote J02 01 1 1 2 PARTICIE 01A)IETER. RICROIETER ~~ T1pLRS(ENt RuC1EI OR~ ACCtJaRATIOR~ AIttCM wuCLEI RARGE RAIiGE r1R0 KOw DuST EwISSECwS SEA SRR.IT rCL GL+105 KAR PARTICLES KCMAMICALLT GEMERATED AEROSOL RAJK.E 0 iI1K PlRT1CLES COAISt PARTECLtS IGURE 2. Schematic of an atmospheric aerosol surface area distribution showing the three modes, main source of mass for each mode, the princeipal process involved inserting mass into each mode, and the principal removal mechanisms. ource: Whitby (1978) TIMN 0030037

Draft - Do not cite or quote iiov. O.e .i.n hd. lAr. Aqr. Yar dR JN. Aur} Sq oet tyo.. Q~c Ja F.b. Wr. Apr. 197{ 1917 1978 FFIGURE 3. Honthly, Mean Mass Respirable Particulate Concentrations (µg/m3) Across Six Cities Source: Spengler et: al. (1981) TIMN 0030038

Draft - Do not cite or quote ?IGURE 4. Aerosol Mass Concentration in R& D Office :ource: Quant ec al. (1982) TIMN 0030039

Drast - Do not cite or quote TABLB 1. Mean Percent and Standard Deviation of Time Allocation in Various Locations by Nork or School Classification Subgroup Lovtia( 8om.m.k®r 9n+dut Ontdoor v4rk.e OQIa/ S.r.ia. ladusr9.U Cooaruct,iom Toeai, a11 p.rcidpaee.. Ho~ 6991 4f.97 66.74 67?i 61.21 (S.OQI' (13977 (12.?A) q.71) (7.06) (13AO1 Outaid. 6a2 36! 19i1 117 10A1 i.Ot (3.?J) (b= (E.bdl C1.46) (10.7Q (l.07) )totor "biei. 421 f.li 6.67 {.6Y 734 b.bl p.19) W.74 (6.16) Q33) (79Z) ({29) oth.e ladooe. 6.01 23.61 119i 1u.96 tA.60 41.bi (3 27) (10.61) (M (101A) (1Z96) (11.37) C001cia6 4.0 0.31 0.00 2.3Z 092 1.24 (1.661 (0.79) (OA01 (Z.97) (0.66) (196) Ne.r .mA.rs 2.34 690 175 11.73 12.03 6.a9 (4= (7a61 (J.36) (16.19) (10.06) (9.71) Nambrr 1 32 4 12 6 Q6• ~ Nus6.e. la pu.ntbr aim tSo w..eiaer d..i.tSm 'T- ae..*iq.i Partwip.ar wn (sdndd in th. muL but not jt..w a.prnta mlqar7. Sdtfl1'Cg Dus ftr Qu+et.aEoft .1.L (lUfa TIMN 0030040

Draft - Do not cite or quote TABLE 2. :Sean Percent Time Spent in Various Locations for Three Population Groups phase summer winter location home (SD) outside (SD) motor vehicle (SD) work/school. (SD)) other indoors (SD) N home (SD) outside (SD) motor vehicle (SD) work/school (SD) other indoors (SD) N population group workers nonworkers students combined totals 59.3 (11.9) 75.2 (12.1) 68.3 (12.5) 65.4 (13.3) 12.3 (9.1) ' 12.9 (9.9) 15.0 (9.3) 13.7 (9.4) 5.8 (4.2) 4.4 (2.7) 3.3 (4.3) 4.4 (4.3) 15.5 (10.9) 0.2 (0.8) 4.4 (7.8) 8.4 (10.6) 7.0 (6.4) 7.2 (6.4) 9.0 (9.6) 8.1 (8.2) 137 32 177 346 66.1 (11.4) 83.3 (8.4) 66.1 (10.1) 67.5 (11.5) 3.3 (5.35) 1.9 (2.0) 3.9 (3.3) 3.5 (4.2) 5.6 (5.6) 4.3 (2.5) 3.3 (2.61 4.2 (4.1) 18.6 (10.4) 3.0 (7.1) 19.5 (7.5) 17.9 (9.7) 6.4 (6.0) 7.6 (5.3) 7.3 (6.2) 7.0 (6.1) 127 26 176 339 ource: Quackenboss.et al. (1986) 0 TIMN 0030041

Draft - Do not cite or quote TABLE 3. Distribution of Constituents in Mainstream Smoke (aS) and the Ratio of Sidestream Smoke (SS) to MS of Nonfilter Cigarettes ',apar phasw eonatituanu' MS ran6t SSIMS ratio Putieu/atr phaae anatituenta' MS raMa Sg/MS ratio rhat mononde 10-23 m6 23-1.7 Partind.Le matter, a 15-40 mg 1.3-1.9 .faoa dieade 2t1..10 mg Nieotin. 1-2.5 mg 2.6-3.3 :~onyl ailfide µ6 18-42 0.03-0.1~ Anatabine 2-20 µ: <0.1-0.5 ven e' 12-1a 10 PAena1 64-110 pC 1.6.~.0 .uotK 169 µs 6 Gt.ehd 100.7G0 µC 0.6-09 -m.ldthyde 70-100 ys 0.1-a50 Hydrtpuintmt 110-300 la 0.7-03 eolrm 60-i00 µ~ 8-15 Mi1int 360 ng 30 reon. 100-230 µt 2-S 2•Toluiditu 160 n= 19 'tdine 16-40 µ6 6.5-20 2•Naphthylamine' 1.7ng 30 Eathylpyndint 12-16 µs 3-13 4.Aminobiphenyi' /.6nY 31 •°~dpyndlne 11-30 µs 20-40 Henzfa Nnthracene' 20-70 ng 2-4 deagtn q•anedt 100~.00 µi 0.1-0.25 Bensa(a{pyrene' 20-40 ng 25-3.5 srau+ie' 32 ng 3 Choleaterai ZZ mg 0.9 mwe~. ~ 50-130 µs 40-170 Y-Butyrolaetont' 10-22 µs 3.6-3.0 rtiTiamine 11.5-2>!.7 µr 4.2-6.4 Qainolina . 0.5-2 µ~ 8-11 xtitylamne 7.3-10 µi 3.7-0.1 Harman 1.7-0.1 µ6 0.7-1.7 ro~en oxidt 100-600 ps 4-10 N'•Nittoanorekotine' 200-J.000 n= 0.5.1 I~o.odimethylamina' 10-40 ng 20-100 NNK' 100-1.000 ng 1-4 ~iera.opyrt~olidine' i-30 n6 6-70 N•Nitro.odienthanoiamine' 20-70 ng 1.2 mtc aeld 210-d90 ~ 1.4-1.6 Gdmium 100 ng 7.2 9e acid 330••810 µC 1.9-3.6 Niek.l' 20-80 ng 13-J0 Zine 60 nr 6.7 Peionwm•210a 0.04-0.1 pCi 1.0-4.0 &naoie aeid 31-25 u6 0.67-0.95 i.etse aaid 63-174 4 0.5-0.7 Glycvlia aeld 37-126 µt 0.6-095 Suxinia aeid 110-Yf0 µC 0.43-0.62 ' Y.lu.a an U)'R* lw fresh and undaluW MS aM SS. "Nunue eaee7nam dARC 19041. `Suap.eW human umnegan dARC 39ei1. 'Aasmal umnatrn t1ARC 19ei/ -Qt41MCL FJCiolt and Rar./1975t HoRmaee et al. /1961k Klua and Kuhn t3ffZL Sakuent a d. f1%1h. Sakueaa. Ku.eana. Yaana6uehi. Mawks a al. t1964t Skuma. Kuaaen.. Yam.dn.eht _..ae%//961 t Sehm.lta M aL 11f75a TIMN 0030042

Draft - Do not cite or quote 'ABL: 4. Respirable Particulate Levels as a Function of Number of Smokers 3makr saa+. Nnenbw Y..a W/v9 8taodard dtyiatio. IV. Umokars X homu/L1DS ..mpi.r u4 uA 1 rmotw 13 6oma./!8t ump{.r 3" 1" s aokM S+ moot.n s eamar/1ad ..mpiu 4 homaR umpLr 70.4 il.i 4" ltJ 3OUllM- Sp.Kl.r.e aL tifali TIMN 0030043

Draft - Do not cite or quote .d TABLE S. Particulates Measured under Realistic Conditions iYpe ~[ pnmisw oavp.nc~ (aetive ~moksrs prr 100 a') coeksa0 paKw 0.73 Icdge k.iq 1M Su asd p ill L7i Htsbam bingo 2.77 PSaaesa 234 SarlaoeJ[Lail laiags 3.54 GSuroh Diesgo pm. 0.41 Im 0.74 Bo+.iins all.? 1.3,1 Hapita! +vaitiag toos Zli shoQpins pi.:a emaurmt S.mp1a I 0.18 Samq{s 2 0.19 8atbqu" ca"uraat 0.4, sandrieh e,rt.waat A Smotiag "esim oa5 Yoconokiag rtios 0 FaKaad rs.c.nraat 0642 SporL u.ma 0.008 Neishborhood ce.taursot/6.r 140 Houl 6.r 0M Sandw+ch resautaat 8 Smot.iag ..Mion 0.13 Nocamaking ..~. 0 Ro.ddde r.resnraat 1.12 cod.-mom rme as4 D(aaK tb"tr 0.14 Rawpeiom i.8 l.if linp bAll am' ossd Moartardng Lev.L 4.g/a') 4oo®okus4 oooud. (j,`/a 7 V.atiLtios meditioo. (mul M... SD IL.a $a Natuew 1i 261 S 2{ u M.e3.nia.1 M.eba,+iea! M.dn..n+ ao Is is sit s as M x !s 417 s s! eo' 61' Y.e~aoisi 32 414 ~ bt a' YwAaaid 2i 22< t 1~1 504 Yrh.aioi 42 27f 2 1~ 30 M.rbaoiol 12 Z9 t f 224 N.rhaniml 20 = s 1f 49' lf.eitaaid 12 1s7 t 63 66' x.d,.s:w 1s 153 t t si' Yr.h.aivi u 163 t 4 ~' Maebaeiol 10 136 x 11 10' M.ehanfe.l 20 110 i 36 10' I(.ehaaiol 30 st x 6 w Meeh.aiesl a 1a 2 X s+' M...a....o.i is f{ 2 13 6d' M...w,n....l 12 90 S 17 56' 1(.eh.aiul 12 90 2 2 30 1V(.rhaeieai t si 2 7 56 M.r.h.niol MaAanio! (9a .eh') 21 u 307• 30 M.eh.aiea! (4 3 aei') 4 aa , M.rhaeioJ 44 146 t 43 47 s 10 H.eh.aierl 20 301 s 30 32' N.oun1 s 1140 40' M.ch.aie.l (1-3i .eit') • su• 40• wc,.t.w~onr e.r.ueo~s O auas....r...i s.e.~ 1~ pr L.or. .aartuw Wnd s da..rmuad hes moaevaaa w mr.+r.a i.9tCSCE: U.S. Departaaent of Health and Human Services (1°86) TIMN 0030044

Draft - Do not cite or quote TABLE 6. Nicotine Heasured Under Realistic Conditions Nawmilokias t.ml. cudm'1 omada TYp, d prnm;a., oon+vaae.7 Ventitaeio. xoeicoriae 0oeditioes x... Ran" H... Ru+eP a aL a eala. Rmw. Ha.pical lobby 2 tr.in mmp.rtny.nq tyt Vv4.1 Is smokar. 12 so 30 .nokns 2 to 3 pmoksis 3 smokus Not dw. Not pv.. Not si..a Not p.+ Nawral, op.. NaWnlL eloni 60 +.i...opi. 50 mi. "=pl. 60 mis rapi. 50 mis uspl. 50 min n®pit 60 mia nepM 24-dZ 6af 31 X'40 6i 1010 t aL Submarin. 61Re.' 157 e4anetr P•rdsl 94-103 eipnet.r PK day Y.. Yas 32 "/.' 1b-36 PC/a' m aed 'i?aia Not p..a Nadusl, eiarl 30-ib mis 0.7-J.1 :rV1w "MON ,ad FSrR traia Su. Not gives Na pr.. Not p... Not gives 27, hr ..mpl. 2'1, br ..aept.. 0 es Valuu. anc p.w Vatur ooe p... gus waicinY room Na gives Nae gives 2'1, hr ..aeplw 1.0 Valur ooe pv.. Aizline aitiet roes Not gives Not gives 2'/, hr nmplw 11 Vtlw aot pr.r Rertauraet Not [ivs Not Siv.. 2'/, hr rsples 62 valur aot p... Coektil lounp Not pv.. Not pv.. 2'!, hr .rmpi.s 10, valuw mt gives 3tudesc louar. Not gives Na pr.. 2'!, hr ..mpi. 2i V~~ ~ p~ ,W >%.rlwe 44 olfk.. Vari.d Vui.i 140 x 3 hr umq1.. 0.9 z 1! 13d (p.ak) V.Ju.t aoc gives 1 public baiM{at Naeeokaes Y.dbaafmi Not p~w u { yublfs W']diaw 1 eo 6 mokar Naan1 aa1 mr3~.aiaa! Not Si+.. 13.2 17-OA aan .t aL OQSa. Nat `E..r Nd p... Not p..n 1f.{ 1.SS1.~ oBo. Not gi..n Not p... Nat gf..n 211 1lLlL1 LboRtoeY Not gives Not p,.. Nae gi... i.i 114s S aoetn.nar eoom. Not p... Not gives Not gives 2l7 1t,6-62.0 3 ymis. Not p..~ Not p..a Nat p+.. 11.1 7.L.il.i Hospieal lobby 4 Zae.1 lobb;.. Not gives Not p.en Not pw. Nae p+.. Na Q... Nd gives 16 1j -tA 11.2 iA-iil 6 rastausaab Not gives Not gives Not ii+.o 1a.3 7.1-21-S 3 cata.ru. Nac p... Nac p... Not p..w lf.~ 11.~.2 3 Aus aat r.iL.7 Wa+;+al twar Not p..n Noe pw. Nat p+.. 1f.1 10.1~[t { as Nat gives Nat p... Nat p..s {7.7 7.7-ii1 i tr.im Not p.+r Not pPw Not 2i+w. M i.6-7[1 7 airplaew Not p... Not O.w Not p... 1i2 L3-iL3 read 5...1. \aw d." w+boral.i. ,I alu. l.uo.euyW m+o.l A.n b... w+ma.r.i RCE: U.S. Department of Health and Human Services (1986) TIMN 0030045

Draft - Do not cite or quote CHAPTER 4 ABSORPTION OF SMOKE CONSTITUENTS BY NONSMORERS Dietrich Hoffmann PhD, Klaus D. Brunnemann MBc, Nancy J. Haley PhD American Health Foundation 4alhalla, New York 10595 INTRODUCTION Exposure to environmental tobacco smoke (ETS) occurs at the worksite, in public places, and in private homes. ETS is a composite of effluents generated in various ways during the burning of tobacco products. The major source for ETS is sidestream smoke (SS) which is formed during smouldering of cigarettes, cigars and pipes between the taking of puffs. Minor contributions to ETS are made by those pollutants of the mainstream smoke (MS) that are exhaled after inhalation of each puff by the active smoker. The smoke escaping into the air from the burning cone and from the mouthpiece of a tobacco product during and after puff-drawing is another minor contributor, in addition there is some diffusion of MS gas phase components through the cigarette paper into the environment. More information is needed on the relative sources of smoke in the complex mixture of ETS generated from different cigarettes under varying conditions. In the laboratory, MS and SS are generated under standardized conditions by machine smoking (1,2). While these conditions enable us to compare the yields of individual smoke constituents from various brands of cigarettes, cigars and pipe tobacco, they do not fully reflect the patterns of smoking by humans (3,4). The consumer's intensity of puff-drawing and inhaling of the smoke is profoundly influenced by the nicotine content of the MS (4,5), and smoking intensity is highest when cigarettes with perforated filter tips are being smoked (6). The SS release is governed by the velocity of air currents -around the burning cone; thus, higher air flow generates higher yields of most aS components. Even though a major reduction of mainstream smoke yields of the sales-weighted average cigarettes has occurred during the last three decades, (U.S. cigarettes declined from 35.5 mg tar in 1954 to 12 mg tar in 1983; (7)), the SS emissions of smoke constituents were not significantly reduced ( 8, 9). The data in Table 1 emphasize this with a comparison of the yields of a select group of toxic compounds in the MS and SS of four types of U.S. cigarettes. These cigarettes were machine- smoked under identical conditions. Since the consumer of the low- yield filter cigarettes is likely to smoke more intensely, a 4 3 TIMN 0030046

Draft - Do not cite or quote larger portion of the tobacco column is burned during smoking of this type of cigarette than is burned during smoking of nonfilter cigarettes. 'Therefore, a somewhat lower yield of SS is expected from the low-yield cigarette smoked by the consumer than is obtained by its standardized machine smoking. The exposure of nonsmokers to the effluents of burning tobacco products usually occurs after considerable dilution of these air pollutants. This is well substantiated by analyses of the air in enclosed spaces polluted by tobacco smoke (10,11). A. Biological Markers in Physiologi.cal Fluids The exposure of nonsmokers to ETS can be assessed with the help of questionnaires, by estimating the dose from the chemical analysis of smoke-polluted air, by personal monitoring of ETS components and/or by measuring the uptake of individual smoke components in physiological fluids of individuals during or after exposure. The last and most promising method will be discussed in this chapter. The degree of exposure to ETS depends on several factors, including length of time spent in a smoke-polluted area, the number of smokers within this area, the size and nature of the space, the degree of ventilation and the respiratory rate of the exposed individual. Thus, optimal assessment of ETS exposure is achieved by analysis of physiological fluids of exposed individuals as wel.l as by analysis of the respiratory environment. New biochemical methods enable us to quantify exposure to ETS by determining the uptake of certain smoke contstituents (or their metabolites) in biological fluids. An primary requirement for such biochemical measurements is the availability of highly sensitive and specific methods. 1. Nicotine and Cotinine. Disregarding accidental or occupational exposure to tobacco (12,13), or the use of nicotine-containing chewing gum or nicotine aerosol rods as aids for smoking cessation (14), the presence of nicotine and of its major metabolites in physiological fluids is entirely due to the exposure to tobacco, tobacco smoke, or ETS. Low levels of nicotine have been found in other members of the solanaceous variety of plants (14A) but could not be expected to make an impact on the body burden of nicotine which is obtained from tobacco sources. Nicotine and its major metabolite, cotinine, in saliva, blood or urine of active smokers and of passively exposed nonsmokers are primarily determined by gas chromatography (GC) with a nitrogen-sensitive detector, and by radioimmunoassay (RIA) (15-17). An HPLC method which has been developed for quantitation of cotinine in plasma or saliva of smokers (18) has not been applied to urine analysis even though the analysis of this biological fluid appears to have the greatest potential for 4 4 TIMN 0030047

Draft - Do not cita_or quote evaluation of nicotine uptake by nonsmokers. A problem with this HPLC method seems to be an unusually high background of cotinine in persons reporting no exposure to ETS. The possibile co- migration of caffeine with cotinine in this system needs to be excluded. (18A) A recently published, highly sensitive method for determining nicotine in plasma by HPLC with dual electrochemical detection (2 ng/ml) has not as yet been applied to physiological samples of involuntary smokers (19). Another emerging analytical method for the determination of nicotine or cotinine is the enzyme- linked immunosorbent assay (ELISA; 20). Trans-3'-hydroxycotinine has been found to be the most abundant nicotine metabolite in the urine of active smokers (21), however, it is difficult to quantitate. Since the compound is not readily soluble it has to be transformed into a heptafluoro derivative prior to GC, detection (22). The levels of 3'- hydroxycotinine in plasma have been found to be much lower than those of cotinine in the same smokers although the renal excretion of 3'-hydroxycotinine has been reported to be greater (23). Despite its abundance in urine of smokers, this compound has not yet been applied to the analysis of ETS uptake by nonsmokers. The GC and RIA methods are most widely used for assaying nicotine and cotinine in active as well as in passive smokers, primarily because of their specificity and sensitivity, and because the needed instrumentation is available in most modern laboratories. Chromatographic methods, especially those using GC with nitrogen-phosphorus detectors (detection limit 0.1 ng/ ml fluid; 16), or a mass-spectral detection system, offer'greatest specificity and high sensitivity; however, they require expensive instrumentation and technical expertise and they are rather labor intensive. Since the air as well as glassware in laboratories may contain traces of nicotine, the chromatographic methods require the ut:nost precautions to avoid contamination of samples. The RIA techniques are operationally simpler, less expensive and require smaller samples (detection limit 0.35 ng/sample; 17). More than 50 nicotine metabolites and structurally-related molecules have been tested as inhibitors of nicotine and cotinine antigen-antibody reactions; few of them interfere with the RIA (24). Nevertheless, the potential for cross-reactivity with unknown endogenous components exists. ' The fact that, upon analysis, thousands of samples obtained from nonsmokers in the US and UK have been found to be negative, indicates that diets and drugs commonly used in these two countries do not pose problems of interference. There is good correlation between results obtained by GC and RIA analysis for plasma cotinine concentrations (r=0.99; 25). A potential problem in RIA analysis can come from extrapolation to values below the linear range of the standard curve. Care must always be taken to insure proportionality of response. 45 ~'l~T 0030048 __

Draft - Do not cite or quote An interlaboratory comparison of data from 11 laboratories in 6 countries has demonstrated that GC and RIA techniques can reliably quantitate nicotine and cotinine in urine and plasma samples. A good correlation of laboratory methods was observed in plasma samples and in urine samples to which cotinine had been added as a tracer. However, in urine samples without tracer, several RIA values for cotinine were found to be slightly higher than those observed by GC. This could be due to a cross reaction of the antibody with another compound present in urine, or the discrepancy could arise from a loss of urinary cotinine during GC extraction. The former explanation is more likely to apply here although conventional GC extraction techniques have been reported to result in the loss of conjugated metabolites of nicotine. The quantitation of these conjugated compounds by GC methods has recently been reported by Curvall et al. (25a). In addition cross reactivity of various cotinine antibodies with trans- 3'hydroxycotinine has been reported to range from 2% (J.J. Langone, pers. comm.) to 30%; (25b)) All immunoassay methods have led, however, to perfect distinction between nonsmokers and active smokers (26). Table 2 presents data from model studies on the uptake of ETS by nonsmokers under acute exposure conditions (27-30). The main purpose of these assays was to develop the methodology for field studies and to compare the uptake of nicotine from environments with various degrees of pollution and different types of pollutants under controlled conditions. It has been shown that the equilibrium of nicotine between vapor phase and particulate phase of ETS depends greatly on the concentration and pH of the emitted smokestream (31) and, thus, influences the uptake of nicotine by inhalation. After repeated exposure to ETS under controlled conditions, such as twice daily 80-minute exposure on 3 consecutive days to the diluted pollutants of 4 concurrently smoked cigarettes (32), the measurements in 4 nonsmokers have shown that except for nicotine in the saliva, the physiological fluids do not reflect maximal concentrations of nicotine and cotinine until at least 24 hours later. This observation has led to comparisons of the elimination of cotinine in smokers and nonsmokers exposed to ETS (33). The elimination half-life (t1/2) of cotinine from the urine of smokers took 21.9 hours and 32.7 hours for nonsmokers. In a second assay, five cigarette smokers were asked to abstain from tobacco use for 5 days and were then given nicotine gum for three days. After another 8 days of abstinence from nicotine, the volunteers were exposed to sidestream smoke (SS). At this point, the cotinine elimination (t1/2) from urine (ng/ml) by smokers took 15.4 hours, by nicotine gum users 18.2 hours, by 8-day exsmokers 27.5 hours, and by the never-smokers 25.6 hours (33). These findings suggest that the residence times of nicotine, cotinine and other tobacco alkaloids, are likely related to the route of nicotine uptake as well as to possible differences in metabolism between smokers and 4 6 TIMN 0030049

Draft - Do not cite or quote nonsmokers. The longer elimination time for cotinine in nonsmokers has been confirmed by other study groups (35-37), however, the observation has also been challenged (38,39). A longer residence time of nicotine metabolites in nonsmokers could conceivably increase the possibility of endogenous formation of carcinogenic N-nitrosamines (40). Most importantly, differences in the elimination times of cotinine from urine preclude a direct extrapolation to "cigarette equivalents of smoke uptake" by comparing the levels of cotinine excreted by active and passive smokers. This has been discussed by some investigators (10). Table 3 includes comparisons of nicotine and cotinine in physiological fluids of nonsmokers with or without ETS exposure, and of active cigarette smokers in England (41). Data on the uptake of nicotine by involuntary smokers from additional studies are summarized- in Table 4 (29,42-54). Most of these studies demonstrate that nicotine and cotinine levels in physiological fluids of involuntary smokers generally amount to 1 percent and r..each maximally a few percent of the amounts determined in active cigarette smoke:rs. Data by Matsukura et al. from Japan on the other hand, show exceptionally high levels of cotinine in the urine of passive smokE.rs. This may be due to several factors including differences in the design of studies and measurement methods (26). Aside from differences in methodology one cannot rule out that differences in the uptake and metabolism of nicotine which have been observed in various population groups, and diet may be partially responsible for the exceptional data reported in the Japanese study (47). A recent finding indicates that the urinary excretion rates of Japanese smokers were significantly different from those determined in adult cigarette smokers in Europe and North America (55). Additionally, a large epidemiological study in the U.S. has demonstrated significant differences in serum cotinine levels between Black and White smokers after adjustment for cigarettes smoked per day and daily nicotine availability (55a).These differences in nicotine metabolism require further thorough investigation. Survey data on exposure at home, in the workplace and on social occasions were collected from 319 employed subjects and were correlated with levels of cotinine in a random urine sample. Mean urine/cotinine/creatinine levels were higher for women than for men possibly due to differences in creatinine excretion between the sexes. It is also noteworthy that 94% of the women were employed indoors. Higher levels of urinary cotinine were noted in both men and women who lived with a smoker than in those subjects who did not report living with a smoker (13.3+2.4 vs 5.1±0.4 in men and 13.9±1.9 VS. 5.6±0.6 in women). Differences in the prevalence of exposure at home existed between sexes (males 13.5% vs. females 29.2%). Levels of cotinine found across different exposures indicate that home exposure has a more pronounced effect on urine 4 7 TIMN 0030050

Draft - Do not cite or quote cotinine than does workplace exposure (Table 5; 55b). The nicotine uptake by infants due to ETS exposure, caused by smoking mothers or caretakers, appears to be higher than that observed in adult passive smokers. The amount of cotinine excreted in the urine of the infants was correlated with the number of cigarettes smoked by the mother, or caretaker or other persons, during the 24 hours preceding the measurement (33). The primary determinant of urinary cotinine levels has been found to be the smoking behavior of the mother. The finding of relatively high uptake of ETS, as determined by nicotine/cotinine concentrations in the urine of infants, is in line with the observation that infants of smokers have higher rates of respiratory infections than infants in nonsmokers' homes (56). Analytical data on nicotine and cotinine in physiological fluids of nonsmokers can be misleading in a few cases. These pertain to the very light smokers and those nonsmokers who either chew tobacco or use oral snuff. it is possible, though rare, that the very light smoker shows nicotine/cotinine levels approaching those of passive smokers with extremely high ETS exposure. When used in combination with cotinine measurements, COHb analyses can help to differentiate between the two groups. In regular consumers of snuff or chewing tobacco, cotinine levels are comparable to those found in cigarette smokers while thiocyanate levels and COHb values remain low (57). The determination of nicotine and cotinine in hair has been tried in an attempt to differentiate between active and passive smokers. (58). This determination revealed higher nicotine concentrations in the hair of smokers than in the hair of ETS- exposed nonsmokers and documented the absence of cotinine, the major metabolite of nicotine, within the hairshaft of nonsmokers. Hair sampling for determining ETS-exposure of nonsmokers deserves more thorough investigation. In summary, in the hands of experienced biochemists, the determination of nicotine and, especially, of cotinine in saliva, serum and/or urine in involuntary smokers represents a reliable, specific method for assaying the level of uptake of ETS by nonsmokers. The choice of biological fluid for the quantitation of cotinine depends upon the question asked. For the evaluation of changes in smoking behavior, serum or urine are preferred while saliva is sufficient to determine whether or not a subject is a smoker (59). For studies of ETS exposure, it is often impractical to collect serum by venipuncture, and since nicotine concentration in saliva can be extremely high immediately following ETS exposure, several hours must pass before the concentration of cotinine in saliva is stabilized (30). Also, when large numbers of subjects are to be evaluated, it is preferable to avoid invasive procedures which might discourage participation and possibly bias the results. 4 8 TIMN 0030051

Draft - Do not cite or quote Measurements of cotinine in urine and saliva have been successfully used to quantitate ETS exposure in large populations. Cotinine excretion in urine is independent of pH, while nicotine excretion is greatly influenced by it. At values above pH 6.0, resorption of nicotine from the urine occurs especially during longer residence time in the bladder. Cotinine is not subject to resorption and, as far as it has been investigated, 3'- hydroxycotinine, a second major nicotine metabolite, is also not affected (60). Quantitation of cotinine in random urine samples can have methodological problems relative to the volume of urine excreted in any given time period as well as dilution effects. The ideal standard for evaluation of cotinine excretion in urine would be the analysis of a 24-hour urine sample. Since this is impractical in epidemioiog.ical studies, random urine samples are usually collected at the time a questionnaire is administered. In this case, the ratio of cotinine to creatinine in-a given sample is often used to allow for differences in urine dilution. Urinary creatinine excretion is usually constant from day to day for a given individual, but it does vary among individuals. As a reflection of muscle mass it is generally excreted at about 1 g per day (men, 1. 1 to 3. 2 g/day ; women, 0. 9 to 2. 5 g/day) . In older persons, the excretion of creatinine may decrease to 0.5 g/day. Low levels of creatinine may-also be found in dehydrated infants; this necessitates caution in the expression of ng cotinine/mg creatinine in a random sample (35). However, a recent study with pre-school children has shown that cotinine/creatinine ratios'in passively exposed children 'track' over several weeks and reflect questionnaire data on exposure (61). Epidemiological studies in adults have also shown good correlations between self-reported indices of exposure and cotinine/creatinine ratios when data for men and women are analyzed separately.(55b) 2. Carbon Monoxide. Carbon monoxide (CO) is formed during the combustion of organic matter including the burning of a tobacco product. it is also produced in vivo during metabolic processes. Endogenous CO results primarily from the breakdown of heme- containing proteins such as hemoglobin. In nonsmokers who are not exposed to industrial pyrolysis products or vehicle emissions, the baseline levels of CO, present in the bloodstream as -carboxyhemoglobin (COHb), are generally below 1.5% of the total hemoglobin. Persons exposed to heavy vehicle emissions can have COHb levels up to about 2.5%. In cigarette smokers, COHb levels were found to average 5.7% in a study of 450 smokers (62) with little difference being noted between smokers of high- or low-yield products. This value is similar to that of 4.7% found in middle aged men in a study by Wald et al. (63). Carboxyhemoglobin levels are not good indicators of ETS 49 TIMN 0030052

Draft - Do not cite or quote uptake, due to the fact that CO exposure is not limited to tobacco smoke; in addition, the measurement of COHb is relatively insensitive. A study in England did not find significant differences in COHb levels in subjects reporting no exposure, some exposure, or a lot of exposure (64). This was confirmed by others (65) and also by a controlled chamber assay (61) . One study in which significant elevations of COHb were found used controlled exposure to tobacco smoke at a level of 25 ppm CO for 8 hours. This intense exposure resulted in an average increase of COHb levels by 2.5% (85). However, such results are not applicable to free-living situations in field studies (67). 3. Thiocyanate. Hydrogen cyanide, absorbed from tobacco smoke is detoxified in the liver to thiocyanate (SCN-). Measurement of SCN- has been used to differentiate smokers from nonsmokers or, as mentioned earlier, in combination with nicotine-cotinine assays to distinguish smokers from chewers of tobacco. Thiocyanate can also be derived from the diet, cruciferous vegetables being an excellent source (68). The specificity of SCN as a marker of tobacco smoke inhalation is poor and it is generally difficult to distinguish light smokers from nonsmokers. This lack of specificity makes SCN- unsuitable for the evaluation of ETS uptake by nonsmoking subjects. 4. Hydroxypr_oline. Japanese investigators have studied the excretion of hydroxyproline in persons exposed to ETS as well as in active•smokers and in persons exposed to high levels of air pollutants (69). The rationale for these studies is that the inhalation of nitrogen dioxide causes degradation of lung collagen and elastin which results in urinary excretion of hydroxyproline. The investigations of the Japanese group suggested an elevated excretion of hydroxyproline by children of smoking parents as well as by wives of smoking husbands, active smokers,. and individuals exposed to vehicle emissions. Since NOx levels in ETS are relatively low by comparison to mainstream smoke or vehicle emissions (56,70,71), such increased elimination of hydroxyproline in passively exposed persons seemed surprising. In fact, another group of investigators has been unable to confirm this finding (72). 5. N-Nitroso-Amino Acids. The occurrence of endogenous nitrosation reactions in cigarette smokers has been demonstrated in several studies. This phenomenon entails the risk of endogenous formation of carcinogenic N-nitrosamines. Endogenous formation of N-nitrosamines has been proven by urinary excretion of the noncarcinogenic N-nitrosoproline (NPRO), N-nitrosothioproline (NTPRO), and N-nitrosomethylthioproline (NMTPRO). Whereas the• average excretion of NPRO in nonsmokers amounted to 2.0±1.5 ug/24 hrs, cigarette smokers excreted an average of 7.0±4.0 ug/24 hrs (73-77). In the case of NTPRO, the average urinary excretion by nonsmokers (ug/24 hrs) was 5.9, that by cigarette smokers 8.7 and that of NMTPRO was 5.6 and 8.5, respectively (75). Only two studies have explored the possibility that endogenous_f_o_rmation of 5 ° TIMN 0030053

Draft - Do not cite or quote N-nitrosamino acids may also be increased in involuntary smokers (77,78). The data for NPRO in the urine of a limited number of involuntary smokers were not different from NPRO data for nonsmokers without ETS-exposure. A carefully designed study with a larger number of passive smokers may prove that the average value for NPRO or, more likely, for NTPRO is higher in ETS- exposed nonsmokers than in those without ETS-exposure. Controlled long-term exposures at high levels of ETS have not measured NPRO or NTRO and such studies might show a value for NPRO or, more likely, for NTPRO that is higher in ETS-exposed nonsmokers than in those without ETS exposure. However, it is unlikely that the determination of N- nitrosamino acids in urine would ever lead to an assay for personal dosimetry of ETS-exposure in free-living subjects. 6. Aromatic Amines. The sidestream smoke of cigarettes contains significantly larger quantities of aromatic amines than the mainstream smoke. For example, the MS of a nonfilter cigarette contains 0.36 ug aniline and 0.16 ug of 2-toluidine, whereas the SS of the same cigarette releases 10.8 ug of aniline and 4.1±3.2 ug of 2-toluidine (79). The urine of cigarette smokers contains somewhat higher amounts of aromatic amines than the urine of nonsmokers. The 24-hour urine void of cigarette smokers contains 3.1±2.6 ug aniline and 6.3±3.7 ug 2-toluidine, while the urine of nonsmokers contains 2.8±2.5 ug aniline and 4.1±3.2 ug 2-toluidine (80). The levels of metabolites of these aromatic amines are expected to be markedly higher in the urine of smokers than of nonsmokers. Confirmation of the significance of this difference would encouragse the development of analytical dosimetry for evaluation of the impact of ETS-exposure on urinary excretion of the metabolites of aromatic amines. 7. Thioethers in Urine. Cigarette smokers excrete higher amounts of thioethers than do nonsmokers (81). A study of 26 cigarette smokers showed mean urinary thioether values of 4.3+0.4 mmol/mol creatinine compared to an equivalent mean value for 10 nonsmokers of 2.8±0.2 mmol/mol creatinine (82). In another study nonsmokers were placed on a controlled diet and were subjected to 8-hr ETS-exposure at two levels of concentration. Prior to ETS exposure •10 nonsmokers excreted 40.0±15.4 umol thioethers/24 hrs. The levels rose to 53.9±22.8 umol after exposure to ETS dose 1 (10 ppm CO). At a higher dose level (20-22 ppm CO), pre-exposure values were 69.3±36.3 and post- exposure levels 90.7±44.8. The 10 cigarette smokers who smoked 20 cigarettes each during 8 hrs in order to provide the ETS pollution in the chamber showed an increase of thioether excretion from 89.1±24.8 to 136.1±38.9 umol/24 hrs (67). In other words, the urinary thioether excretion of the passive smokers in this study increased up to 45% and, in the case of the active smokers with the same ETS exposure it increased about 50- 65%. These findings 51 TIMN 0030054

Draft - Do not cite or quote require confirnation but they appear to indicate that the thioether analysis of the urine will most likely not be suitable for the determination of the ETS uptake by involuntary smokers due to varying background levels across subjects. B. Genotoxicity of Physiological Fluids Several studies have explored the possibility that physiological fluids of cigarette smokers contain significantly higher amounts of genotoxic agents than those of nonsmokers (81). The most extensive data base in this field has shown significantly higher mutagenicity in the Salmonella thvvhimurium assay of urine of cigarette smokers compared to those of nonsmokers. Since the original study by Yamasaki and Ames in 1977 (83) at least 20 investigations have shown that the urine of cigarette smokers is significantly more mutagenic than the urine of nonsmokers who are not exposed to genotoxic agents in occupational environments. But it has also been shown that the mutagenicity of the urine of smokers can be effected by diet (84). It has further been surmised that exposure of nonsmokers to ETS may lead to increased urinary excretion of mutagens. Of the 6 published studies in which the urine of passive smokers was tested for mutagenicity with the Ames test, 3 showed increased activity and 3 showed no increase or, at the most an insignificant increase in mutagenic activity (81,85- 87). C. Adduct Formation of Carcinogens in Passive Smokers. _ Measurements in physiological fluids of nicotine and its major metabolite, cotinine, have been shown to be objective indicators of 'the uptake of ETS. However, these assays will not reflect an individual's response to specific ETS carcinogens. That '_nformation is best obtained by assessing levels of macromolecular adducts with carcinogens or their metabolites. Development of such assays is based on examining the mechanisms of metabolic activation and detoxification of tobacco smoke carcinogens. 1. Benzo(a)pyrene. In the case of active smokers, adducts of at least 4 types of tobacco carcinogens or procarcinogens have been studied. These adducts are formed by reaction of specific metabolites of tobacco smoke constituents with .DNA and/or hemoglobin. Benzo(a)pyrene (BaP), a carcinogenic representative of the polynuclear aromatic hydrocarbons in tobacco smoke-is known to be metabolized to bay region diol epoxides (e.g. 7,8- dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP). Such diol epoxides can bind to DNA in human tissues and lymphocytes. Antibodies developed against the major BPDE-DNA adduct have been used to assess its presence in surgical specimens of lung tissue, in human placenta, and in peripheral blood lymphocytes (89-91). Evidence for the presence of such adducts in samples from smokers has been ascertained but significant differences between smokers and nonsmokers have not been observed. ---- - 5 2 TIMN 0030055

Draft - Do not cite or quote 2. Aromatic Amines. 4-Aminobiphenyl and 2-naphthylamine are the known tobacco smoke constituents which are most likely to contribute to the increased risk of bladder cancer of cigarette smokers. The mechanisms by which these compounds are metabolically activated and produce DNA adducts in the bladder epithelium have been extensively studied (92). These studies have shown that the corresponding hydroxylamines are key intermediates in DNA and protein modification. The hydroxylamines also react with hemoglobin, in the case of 4-aminobiphenyl, a sulfinic acid amide of the beta-cysteine (93-95). This adduct readily releases 4- aminobiphenyl upon treatment with dilute acid. A method was developed to analyze the released 4-aminobiphenyl by gas chromatography with detection by negative ion chemical ionization mass spectrometry (95). Application of this method to smokers showed that adduct levels were higher than in nonsmokers, and decreased upon smoking cessation. The method may be further refined for assessing the uptake of carcinogenic aromatic amines from ETS by nonsmokers. 3. tE hylene. This volatile unsaturated hydrocarbon is present in both mainstream smoke (200-400 ug/cigarette) and sidestream smoke of cigarettes (96). Cigarette smoke contains also traces_ of the carcinogenic ethylene oxide (7.0 ug/cigarette; 97,98). Upon absorption, ethylene is metabolized to the reactive ethylene oxide. The latter binds to cellular macromolecules and to hemoglobin..The alkylated valine is cleaved off of the isolated hemoglobin and the derivatized hydroxyethylvaline is analyzed by GC-MS. Cigarette smokers showed significantly higher hydroxyethylvaline levels (389±138 pg/g hemoglobin) than nonsmokers (58+25 pg/g; 99). So far the method has not been applied to estimates of exposure of involuntary smokers to the procarcinogen ethylene. 4. Tobacco-Specific N-Nitrosamines. During tobacco processing and during smoking tobacco alkaloids give rise to tobacco-specific N-nitrosamines (TSNA). The nicotine-derived N- nitrosamines N'-,nitrosonornicotine (NNN) and4-(methylnitrosamino)- 1-(3-pyridyl)-1•-butanone (NNK) are powerful carcinogens. They occur in relatively high concentrations in cigarette mainstream smoke (NNN, 0.12-3.7 ug/cigarette; NNK, 0.08-0.77 ug/cigarette) and sidestream smoke (NNN, 0.15-1.7 ug/cigarette; NNK, 0.2-1.4 ug/cigarette; 40). These agents are metabolically activated by alpha-hydroxylation, leading to a highly reactive intermediate which forms DNA adducts and protein adducts (Fig. I). Metabolic activation of NNN and NNK also leads to the formation of hemoglobin adducts. Acid or base hydrolysis of these releases a keto alcohol (compound 5; Fig. I; 100). A highly sensitive GC-MS method has been developed to facilitate the detection of a derivative of compound 5. Refinement towards further increased sensitivity of the method should lead to a dosimetry assay allowing determination of the uptake of the carcinogenic TSNA by passive smokers. 53 ~Il~~T 0030056

Draft - Do not cite or quote FUTURE NEEDS The absorption of tobacco-specific smoke constituents from ETS has been demonstrated through analyses of nicotine and its major metabolite, cotinine in the body fluids of exposed nonsmokers. Less tobacco-specific markers have also been measured in exposed populations; however, the results were ambiguous in regard to the quantitative uptake of ETS. There is a need to provide information about the uptake and disposition of carcinogenic constituents by individuals exposed to ETS in acute and chronic situations. Analyses to be fully developed and applied to passive smokers will include measurements of adducts of genotoxic smoke constituents covalently bound to DNA or hemoglobin. These techniques have been developed for benzo(a)pyrene, 4- aminobiphenyl, ethylene, and tobacco-specific N- nitrosamines. It is not known whether or not all of these methods can be made sufficiently sensitive to monitor the uptake of tobacco-specific components from ETS. Nicotine in ETS is predominantly present in the vapor phase of the smoke rather than bound to the aerosol particles. In order to measure the uptake of carcinogens and toxins residing in the particulate phase of ETS; deposition studies must be developed with specific markers. Particulate phase constituents which could be quantitated include tobacco-specific N- nitrosamines, polyphenols, such as the immunoactive compound rutin, or the tobacco-specific solanesol.(101) However, the levels of these compounds are expected to be low so that development of suitable methodology calls for highly sensitive detection methods. SUMMARY 1. The absorbtion of tobacco-specific smoke constituents from ETS has been demonstrated through analyses of nicotine and its major metabolite, cotinine in the body fluids of exposed nonsmokers. 2. The determination of nicotine or cotinine, in the saliva, serum, or urine of involuntary smokers represents a reliable, specific method for assaying the level of uptake of ETS by nonsmokers. 3. Although cotinine levels in physiological fluids of involuntary smokers generally are of the order of few percent of those of active smokers, differences in the elimination• times of these compounds in active and involuntary smokers preclude a direct extrapolation to "cigarette equivalents of smoke uptake." 4. There is a further need to quantitate uptake and fate of carcinogenic constitutents of ETS-exposed nonsmokers, particularly the measurements of adducts of genotoxic smoke components attached to DNA or hemoglobin. TIMN 0030057 54

Draft - Do not cite or quote ACRNOWLEDGEMEN'I'S We thank Ilse Hoffmann and Bertha Stadler for editorial assistance. Our studies are: supported by Grants No. CA-29580, CA-44377 and CA- 32617 from the National Cancer Institute. TIMN 0030058 55

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Draft - Do not cite or quote 17,1987. 33. Greenberg, R.A., Haley, N.J., Etzel, R.A, and Loda, F.A. Measuring the exposure of infants to tobacco smoke. New Engl. J. Med. 310: 1075-1078, 1984. 34. Haley, N.J., Sepkovic, D.W., Louis, E.T., and Hoffmann, D. Absorption and elimination of nicotine by smokers, nonsmokers and chewers of nicotine gum. In: The Pharmacology of Nicotine, Rand, M.J. and Thurau, K., eds., IRL Press, Washington, DC, 1988, pp. 20- 21. 35. Goldstein, G.M., Collier, A., Etzel, R., Lewtas, J., and Haley, N.J. Elimination of urinary cotinine in children exposed to known levels of sidestream cigarette smoke. Proc. 4th International Conference on Indoor Air Quality and Climate, Berlin, "Indoor Air '87", Volume 2: 61-67, 1987. 36. Etzel, R.A., Greenberg, R.A., Haley, N.J., and Loda, F.A. Urinary Cotinine excretion in neonates exposed to tobacco smoke products in utero. J. Pediatr. 107: 146-148, 1985. 37. Scherer, G., Westphal, K., Sorsa, M., and Adlkofer, F. Quantitative and qualitative differences in tobacco smoke uptake between active and passive smoking. in: "Indoor and Ambient Air Quality", R. Perry and P.W. Kirk, eds., London, 1988. pp 189-194. 38. Benowitz,. N.L., Kuyt, F., Jacob, P., Jones, R.T. III., and Osman, A.-L. Cotinine disposition and effect. Clin. Pharmacol. Ther. 14: 604-611, 1983. 39. Jarvis, M.J., Russell, M.A.H., Benowitz, N.L., and Feyerabend, C. Elimination of cotinine from body fluids. Am. J. Publ. Health 78: 696-698, 1988. 40. Hecht, S.S. and Hoffmann, D. Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 9: 875-884, 1988. 41. Jarvis, M.J., Tunstall-Pedoe, H., Feyerabend, C., Vessey, C., and Saloojee, Y. Biochemical markers of smoke,absorption and self- reported exposure to passive smoking. J. Epidemiol. Comm. Health 38: 335-339, 1984. 42. Feyerabend, Higgenbottam, and Russell, M.A.H. Nicotine concentrations in urine and saliva of smokers and nonsmokers. Brit. Med.J. 284: 1002-1004, 1982. 43. Foliart, D., Benowitz, N.L., and Becker, C.E. Passive absorption of nicotine in airline flight attendants. (Letter) New Engl. J. Med. .308: 1105, 1983. 5 9 TIMN 0030062

Draft - Do not cite or quote 44. Jarvis, M.J., Russell, M.A.H., and Feyerabend, C. Absorp- under natural conditions of exposure. Thorax 38: 829-833, 1983. 45. Wald, N.J., Boreham, A., Bailey, A., Ritchie, C., Haddow, J.E., and Knight, G. Urinary cotinine as marker for breathing other peoples tobacco smoke. Lancet 1: 230-231, 1984. 46. Wald, N.J. and Ritchie, C. Validation of studies on lung cancer in nonsmokers married to smokers. Lancet 1: 1607, 1984. 47. Matsukura, S., Tominato, T., Kitano, H., Seino, Y., Hamada, H., Uchihashi, M., Nakajima, H., and Hirota, Y. Effects of environmental tobacco smoke of urinary cotinine excretion in nonsmokers. New Engl. J. Med. 311: 828-832, 1984. 48. Jarvis, M.J., Russell, M.A.H., Feyerabend, Eiser, J.R., Morgan, P., Gammage, P., and Gray, E.M. Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of nonsmoking school children. Brit. Med. J. Z91: 927-929, 1985. 49. Luck, W. and Nau, H. Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers. J. Pedriatr. 107: 816-820, 1985. 50. Pattishall, E.N., Strope, G.L., Etzel, R.A., Helms, R.W., Haley, N.J., and Denny, F.W. Serum cotinine as a measure of tobacco smoke exposure in children. Am. J. Dis. Children 139:1101- 1104, 1985. 51. Schwart'-z-Bickenbach, Schulte-Hobein, Abt, Plum, C., and Nau, H. Smoking and passive smoking during pregnancy and early infancy: effects an birth weight, lactation period, and cotinine concentrations in mother's milk and infant's urine. Toxicol. Lett. 35: 73-81, 1987. 52. Sepkovic, D.W., Axelrad, C.M., Colosimo, S.G., and Haley, N.J. Measuring tobacco smoke exposure: clinical applications and passive smoking. Presented at the 80th Ann. Mtg. Air Pollution Control Association 1987, New York, NY, Abstr. 87-80-2, 1987. 53. Jarvis, M.J., McNeill, A.D., Russell, M.A.H., W4est, R.J., Bryant, A. and Feyerabend, C. Passive smoking in adolescents: One year stability of exposure in the home. Lancet 1:* 1324-1325, 1987. 54. Coultas, D.B., Howard, C.A., Peake, G.T. Salivary cotinine levels and involuntary tobacco smoke exposure in children and adults in New Mexico. Am. Rev. Resp. Dis. 136: 305-309, 1987. 55. Muranka, H., Higashi, E., Itani, S., and Shimiza, Y. Evaluation of nicotine, cotinine, thiocyanate, carboxyhemoglobin, and expired carbon monoxide as biochemical tobacco smoke uptake 60 TIMN 0030063

Draft - Do not cite or quote aarameters. 2:nt. Arch. Occup. Environ. Health 60: 37-41, 1988. 55a. Wagenknecht, L., Cutler, G., Snook, C., Haley, N.J. Black/White differences in cotinine levels among smokers in the United States. In: The Pharmacology of Nicotine, (W. Thurou and M. Rond, eds.), IRL Press, Washington, DC 1988. 35b. Haley, N.J., Colosimo, S.G., Axelrad, C.M., Harris, R., Sepkovic, D.W. Biochemical validation of self-reported exposure to environmental tobacco smoke. Environ. Res. 49: 127-135, 1989. 56. U.S. Department of Health and Human Services. "The Health Consequences of Involuntary Smoking". A report of the Surgeon ueneral. DHHS (CDC) 87-8398, 1986, 359 p. 57. Palladino, G., Adams, J.D., Brunnemann, K.D., Haley, N.J., Hoffmann, D. Snuff-dipping in college students: a clinical profile. Milit. Med. 151: 342-346, 1986. 58. Haley, 'N.J. and Hoffmann, D. Analysis of nicotine and cotinine in hair to determine cigarette smoker status. Clin. Chem. 31: 1598-1600, 1985. 59. Sepkovic, D.W. and Haley, N.J. Biomedical applications of cotinine quantitation in smoking related research. Am. J. Public Health 75: 663-664, 1985. 60. U.S. Department of Health and Human Services. "The Health Consequences of Smoking - Nicotine Addiction". A report of the Surgeon General, DHHS (CDC) 88-8406, 1988, 618 p. 51. Mumford, J.L., Forehand, L., Burton, R., Lewtas, J., Hammond, S.K., and Haley, N.J. Serum and urine cotinine as quantitative :~easures of passive tobacco smoke exposure in young children. Proc. 4th Internatinal Conference on Indoor Air Quality and Climate, Berlin, "Indoor Air '87", Volume 2: 18-21, 1987. 62. Hill, P., Haley, N.J., and Wynder, E.L. Cigarette smoking: carboxyhemoglobin, plasma nicotine, cotinine and thiocyanate vs. self-reported smoking data and cardiovascular disease. J. Chron. Dis. 36: 439-449, 1983. 63. Wald, N., Idle, M., Smith, P.G., and Bailey, A. Carboxyhemoglobin levels in smokers of filtered and plain cigarettes. Lancet 1: 110-112, 1977. 64. Jarvis, M.J. and Russell, M.A.H. Measurement and estimation of smoke dosage to nonsmokers from environmental tobacco smoke. Eur. J. Respirat. Dis. (Suppl) 133: 68-75, 1984. 65. Jarvis, M.J. Uptake of environmental tobacco smoke. IARC Sci. Publ. 81a 43-58, 1987. 61 TIMN 0030064

Draft - Do not cite or quote 66. Hoffmann, D., Brunnemann, K.D., Adams, J.D., and Haley, N.J. Indoor air pollution by tobacco smoke: model studies on the uptake by nonsmokers. Proc. 3rd International Conference on Indoor Air Quality and Climate, Stockholm, "Indoor Air", Volume 2: 313-338, 1984. 67. Scherer, G., Westphal, K., Hoepfner, I., Adlkofer, F., and Sorsa, M. Biomonitoring of exposure to potentially mutagenic substances from environmental tobacco smoke. Proc. of the 4th International Conference on Indoor Air Quality and Climate, Berlin, "Indoor Air '87", Volume 2: 109-114, 1987. 68. Haley, N.J. Axelrad, C.M., and Tilton, K.A. Validation of self-reported smoking behavior: biochemical analysis of cotinine and thiocyanate. Am. J. Publ. Health 73: 1204-1207, 1983. 69. Kasuga, H., Matsuki, H., Osaka, F., and Inoue, M. The study on the relationship between urinary hydroxyproline and creatinine ratio from the viewpoint of public health. Tokai J. SXp. Clin. Med. 4: 343-351, 1979. 70. Guerin, M.R. Formation and physico-chemical nature of sidestream smoke. IARC Sci. Publ. -81: 11-24, 1987. 71. Repace, J.L., Indoor concentrations of environmental tobacco smoke: field studies. IARC Sci. Publ. 81: 141-162, 1987. 72. Adikofer, F., Scherer, G., and Heller, W.D. Hydroxyproline excretion in urine of smokers and passive smokers. Prev. Med. 13: 670-679, 1984. 73. Hoffmann, D. and Brunnemann, K.D. Endogenous formation of N- nitrosoproline in cigarette smokers. Cancer Res. 43: 5570- 5574, 1983. 74. Ladd, K.F., Newmark, H.L., and Archer, M.C. N-nitrosation in smokers and nonsmokers. J. Natl. Cancer Inst. 73: 83-87, 1984, 75. Tsuda, M., Nutsume, J., Sato, S., Hirayama, F, Kakizoe, T. and Sugimura, T. Increase in the levels of N-nitrosoproline, N- nitrosothioproline, and N-nitroso-2-methylthioproline in human urine by cigarette smoking. Cancer Lett. 30: 117-124, 1986. 76. Lu, S.H., Ohshima, H., Fu, H.M., Tian, Li, F.M., Blettner, M., Wahrendorf, J., and Bartsch, H. Urinary excretion of N- nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C. Cancer Res. 46: 1485-1491, 1986. 77. Scherer , G. and Adlkofer, F. Endogenous formation of N- 6 2 7CIlVIN 0030065

Draft - Do not cite or quote nitrosoproline in smokers and nonsmokers. Banbury Rpt. 23: 137- 147, 1986. 78. Brunnemann, K.D., Scott, J.C., Haley, N.J., and Hoffmann, D. Endogenous formation of N-nitrosoproline upon cigarette smoke inhalation. IARC Sci. Publ. 57: 819-828, 1984. 79. Patrianakos, C. and Hoffmann, D. Chemical studies on tobacco smoke LXIV. On the analysis of aromatic amines in cigarette smoke. J. Anal. Toxicol. 3: 150-154, 1979. 80. El-Bayoumy, K., Donahue, J.M., Hecht, S.S., and Hoffmann, D. Identification and quantitative determination of aniline and toluidine in human urine. Cancer Res. 46: 60646067, 1986. 81. International Agency for Research on Cancer. "Tobacco Smoking, IARC Monogr. 38: 1986, 421 p. 82. Heinonen, T., Kytoniemi, V., Sorsa, M., and Vainio, H. U.rinary excretion of thioethers among low-tar and medium-tar cigarette smokers. Internatl. Arch. Occup. Environ. Health 52: 11-16, 1983. 83. Yamasaki, E. and Ames, B.N. Concentration of mutagens from urine by adsorption with the nonpolar resin CAD-2: cigarette smokers have mutagenic urine. Proc. Natl. Acad. Sci. U.S.A. 74: 3555-3559, 1977. 84. Sasson, I.M., Coleman, D.T., LaVoie, E.J., Hoffmann, D., and Wynder E.L. Mutagens in human urine. Effects of cigarette smoking and diet. Mutat. Res. 158: 149-159, 1985. 85. Scherer, G., Westphal, K., Biber, A., Hoepfner, I., and Adlkofer, F. Urinary mutagenicity after controlled exposure to environmental tobacco smoke (ETS). Toxical. Lett. 35: 135-140, 1987. 86. Mohtashamipur, E., Mueller, G., Norpoth, K., Endrikat, M., and Stuecker, W. Urinary excretion of mutagens in passive smokers. Toxicol. Letters 35: 141-146, 1987. 87. Husgafvel-Pursiainen, K., Sorsa, M., Engstrom, K., and Einistoe, P. Passive smoking at work: biochemical and biological measures of exposure to environmental tobacco smoke. Int. Arch. Occup. Environ. Health 59: 337-345, 1987. 88. Ling, P.I., Lofroth, G., and Lewtas, J. Mutagenic determination of passive smoking. Toxicol. Lett. 35: 147-151, 1987. 89. Harris, C.C., Vahakangas, K., Newman, M.J., Trivers, G.E., Shamsuddin, A., Sinapoli, N., Mann, D., and Wright, W.E. Detection 63 TdMN 0030066

Draft- Do not cite or quote of benzo(a)pyrene diol eaoxide-DNA adducts in peripheral blood lyinphocytes and antibodies to the adducts in serum from coke oven workers. Proc. Natl. Acad. Sci. U.S.A. 82: 6672-6676, 1985. 90. Everson, R.B., Randerath, E., Santella, S.A., Cefalo, R.C., Avitts, T.A., and Randerath, K. Detection of smoking-related covalent DNA adducts in human placenta. Science 231: 54-57, 1986. 91. Perera, F.P., Poirier, M.C., Yuspa, S.H., Nakayama, J., Jaretzki, A., Curnen, M.:2., Knowles, D.M., and Weinstein, I.B. A pilot project in molecular cancer epidemiology: determination of benzo(a)pyrene-DNA adducts in animal and human tissues by immunoassays. Carcinogenesis 3: 1405-1410, 1982. 92. Beland, F.A. and Kadlubar, F.F. Factors involved in the induction of urinary bladder cancer by aromatic amines. Banbury Rpt. 23: 315-326, 1986. 93. Neumann, H.G. Analysis of hemoglobin as a dose monitor for alkylating and arylating agents. Arch. Toxicol. 56: 1-6, 1984. 94. Green, L.C.:;'Skipper, P.L., Juresky, R.J., Bryant, M.S., and Tannenbaum, S.R. In vivo dosimetry of 4-aminobiphenyl in rats via a cystaine adduct in hemoglobin. Cancer Res. 44: 4254-4259, 1984. 95. Bryant, M.S., Skipper, P.L., Tannenbaum, S.R., and Maclure, M. Hemoglobin adducts of 4-aminobiphenyl in smokers and nonsmokers. Cancer Res. 47: 602-608, 1987. 96. Wynder, E.L. and Hoffmann, D. "Tobacco and Tobacco Smoke. Studies in Experimental Tobacco Carcinogenesis." Academic Press, New York, NY, 1967, 730 p. ?7. Binder, H. and Lindner, W. Bestimmung von Aethylenoxyd im Railph garantiert unbegaster Zigaretten. Fachliche Mitt. Oesterr. Tabakregie 13: 215-220, 1972. 98. international Agency for Research on Cancer. "Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs, Volume 1-42." IARC Monogr. Suppl. 7: 1987, 440 p. 99. Tornqvist, M., Osterman-Golkars, S., Kautiainen, A., Jensen, S., Farmer, P.B., and Ehrenberg, L. Tissue doses of ethylene oxide in cigarette smokers determined from adduct levels in hemoglobin. Carcinogenesis 7: 1519-1521, 1986. 100. Hecht, S.S., Carmella, S.G., Trushin, N., Spratt, T.E., Foiles, P.G., and Hoffmann, D. Approaches to the development of assays for interaction of tobacco-specific nitrosamines with hemoglobin and DNA. IARC Sci. Publ. 89: 121- 128, 1988. 101. Benner, C.L., Bayona, J.M., Caka, F.M., Tang, H., Lewis, L., 64 TIIqN 0030067

Draft - Do not cite or quote Crawford, J., Lamb, J.D., Lee, M.L., Lewis, E.A., Hansen, L.D., and Eatough, D.J. Chemical Composition of Tobacco Smoke. 2. Particulate Phase Compounds. Environ. Sci. Technol. 23: 688-699, 1989. TIMN 0030068 65

Draft.-- Do not.cite or quote Figures and Tables for ChaDter 4 TIMN 0030069 66

Draft - Do not cite or quote N•O i ~~CH3 NNK ~ Noo 1 O N-% CH2OH N•O ~ "~° C02E! 3 N 0 - O N-NOM N 4 Figure I. Metabolic activation of 4-(methylnitrosamino)-t-(3- pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) to intermediates which bind to DNA and protein. _ TIMN 0030070

Table 4 continued ... a 1 a Nonsmoker Group Children and adults Number of Nonsmokers 529 males 768 females 12esul ts Cotinine/Saliva (ng/ml) smokers in family [teference Coultas et al. (53)~ none one > two a) <5 years old 0.0 (0.0-2.5) 3.8 (0.0-6.1) 5.4 (3.2-7.7) b) 6-12 years old 0.0 (0.0-2.1) 2.0 (0.0-3.8) 5.2 (1.5-7.0) c) 3-17 years old 0.0 (0.0-2.0) 2.9 (0.0-4.9) 4.1 (2.7-7.6) d) 18-29 years old 0.0 (0.0-2.6) 0.0 (0.0-5.8) 0.0 (0.0-4.4) e) 30-64 years old 0.0 (0.0-2.7) 1.9 (0.0-4.5) 4.4 (1.8-11.0) f) > 65 years old 0.0 (0.0-2.6) 3.6 (0.0-6.5) 0.0 *Numbers in parenthesis median values.

Table 4 continued .. ~ Number of Nonsmoker Group Nonsmokers Results Municipal workers Cotiine/Urine (ng/mg creatinine) I. E'1'S exposure in the a) workplace no exposure b) light expsoure c) moderate exposure d) heavy exposure II. ETS exposure in the home a) no exposure b) light exposure c) moderate exposure d) heavy exposure School girls (11-16 yrs) ETS exposure in the home a) neither parent smokes b) father smokes only c) mother smokes only d) both parents smoke Reference Sepkovic et al. •, ( 52 ) 25 4.5*0.6 126 6.610.6 84 7.2t0.8 32 8.4*1.3 77 6.110.8 83 6.7t0.6 71 7.8f1.1 34 7.611.3 Jarvis et al., (537 104 - 1.1*0.5 76 - 2.010.6 40 3.210.8 110 5.011.0 Continued ...

Table 4 continued .. 0 I /0 Nonsmoker Group Number of Nonsmokers Results Reference Cotinine/Urine (ng/mg creatinine) Neonates and infants No. .. No. Schwartz- exp'd I exp'd II Bicken- a) Mother smokes, bach et. breastfeeds 20 12 (1756) 0 -3520 8 (935) 488-2440 al., T551) b) Mother smokes, ~ feeds bottle 16 4 (47) 0 - 160 12 (107) 0- 341 c) Father smokes 18 10 (0) 8 (0) 0- 308 d) No exposure in the home 15 9 (0) 6 (0)

Table 4 continued ... Nonsmoker Group Number of Nonsmokers Results Reference Neonates and infants Nicotine (n /m creatinine) Cotinine Luck and a) No exposure (4-8 days old) b) Exposure via 10 0 0 - 14 (0 0- 56 Nau, (49) breast feeding (3-8 days old) c) Passive smoking 19 (14) 5 -110 (100) 10-555 (2.5-6 months old) (i) Exposure via breast fee3ing and 10 (35) 4.7-218 (327) 117-780 passive smoking (1-12 months old) 9 (12) 3.0- 42 (550) 225-870 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - infants (age 3-15 months) exposure in the home Black infants a) no exposure b) passive smoking White infants a) no exposure b) passive smoking Cotinine/ Serum (ng/ml) Pattishall et al., 50T- 9 1.0 (1.87;L2.38) Pattishall et al., 1985 15 4.0 (5.27*3.50) (51) d . ~ . K rt 9 0.0 (0.22&0.44) ~ 5 0.4 (0.90f1.30) ~ 0 0 H

Tabl.e 4 continued ... Nonsmoker Group Husbands of a) nonsmokers b) smokers 1 Number of . Nonsmokers Results Reference Cotinine/Urine (ng/ml) Wald and 101 8.5f 1.3 Ritchie, 20 25.2114.6 (46) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Nonsmokers a) nonsmokers at home b) smokers at home Cigarettes smoked day in home of nonsmokers; 1- 9 10-19 20-29 30-39 > 40 unknown Cotinine/Urine (ng/mg creatinine) Matsukura 200 0.5 10.09 et al., 272 0.79f0.1 (47) Cotinine/Urine (u /mg) creatinine) 25 0.3110.08 57 0.42f0.1 99 0.R710.19 38 1.03f0.25 28 1.56t0.57 25 0.56*0.16 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- - - - - - - - - - - - - - - Infants (<10 months, Nico tine/Urine Cotinine/Urine ~ Greenberg d not breastfed) (n m creatinine) ("m ) et al.; - h a) not exposed to ETS 18 0 (0-59 4 0-125 T33T b) exposed to ETS 28 53 (0-370) 351 (41-1,885) rt ~ d 0 School children (11-16 yrs) Cotinine/Saliva (ng/m1) :3 a) Neither parent smoked 269 0.4410.68 Jarvis et 0 rt b) Only father smoked 96 1.3111.21 al., (48j 0 c) Only mother smoked 76 1.9511.71 P- d) Both parents smoked 128 45 3.38f2 rt . 0 0 TIIYIl~T 0030075 Continued .. h ~ ~

FPabl.@ q , Uptake of nicotine by nonsmokers exposed to ETS under daily life conditions Number of Nonsmoker Group Nonsmokers Hospital personnel 14 (78 min in smoke- 13 filled room) Hospital personnel and outpatients a) no exposure to ETS 26 b) exposed to ETS 30 Results Reference Nicotine/Urine (ng/ml) 12.4f16.9 Russell and Fey-erabend 8.919.1 (29) Nicotine/Saliva (ng/ml) 5.9 7.5 Feyerabend 10.1 21.6 et al. (42) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Flight attendants Nicotine/Serum (ng/ml) 6 pre flight: 1.610.8 Foliart et al.' post flight: 3.211.0 (43) ~ Office workers 7 Content/ml Nicotine (ng) Cotinine (n ) Jarvis et al. a) 11:30 a.m. sample saliva a 1.90 b 43.63 a 1.50 b 8.04 (44) r~ b) 7:45 p.m. sample serum 0.76 2.49 1.07 7.33 after 2 hr stay urine 10.57 92.63 4.80 12.94 in pub - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Hospital staff and Cotinine/Urine (ng/ml) Wald et al. outpations (45) a) no exposure to ETS 22 2.0 (0.0 - 9.3 b) exposed to ETS 190 6.0 (1.4 -22.0) Continued ... TIMN 0030076 I

i 0 f Table 3. Approximate Relations of Nicotine as a Parameter Between Nonsmokers, Passive Smokers, and Active Smokersa (41) Nonsmokers without ETS Exposure No. = 46 Nonsmo ers w th ETS Exposure No. = 54 Active Smokers No. = 94 Nicotine/Cotin % of ine Mean Value Active Smokers' Value % o Mean Value Active Smokers' Value Mean Value Nicotine (ng/m l) in plasma 1.0 7 0.8 5.5 14.8 in sal iva 3.8 0.6 5.5 0.8 673 in urine 3.9 0.2 12.1* 0.7 1,750 Cotinine (ng/m in plasma l) 0.8 0.3 2.0* 0.7 275 in saliva 0.7 0.2 2.5** 0.8 310 in urine 1.6 0.1 7.7** 0.6 1,390 aDifferences between nonsmokers exposed to ETS compared with nonsmokers without exposure: *p<0.01; ** p<0.001. MIN 0030077

Table 2 continued. No. of ETS-Conditions Passive Smokers Room - 16 m3 4 cigarettes con- currently and con- tinuously smoked for 80 min; 6 air exch./hr. (200 g nicotine/m3; 20 ppm CO) 6 Results Investigators Time during exposure Nicotine Cotinine Hoffmann et al., 1984 (ng/ml ng m (30) 0 Saliva 3 1.0 Plasma 0.2 0.9 Urine 17 14 80 min. Saliva 730 1.4 Pl asma 0.5 1.3 Urine 84 28 Time followin ex osure 30 min. Sa iva 148 1.7 Plasma 0.4 1.8 150 " Saliva 17 3.1 Plasma 0.7 2.9 Urine 100 45 300 " Saliva 7 3.5 Plasma 0.6 3.2 Urine 48 55 *Nicotine and cotinine were measured in urine as ng/mg creatinine. i TIMN 0030078

n f Table 2. a Uptake of nicotine by nonsmokers exposed to B'1'S under controlled conditions ETS-Conditions No. of Passive Smokers Results Investigator(s) r•--- Room - 170 m3 (11 smokers) •Urinar excretion a 100 cigarettes were smoked during 2 hrs; no ventilation 7 Nicotine: 10*6.8 ug 6 hrs. Cotinine: 35#34.5 pq/6 hrs. (30 ppm CO) (b) same conditions as above (a) but with ventilation 7 Nicotine: 18t7 pg/6 hrs. Continine: 19#9.4 Ng/6 hrs. (5 ppm CO) Room - 66 m3 (4 cigarette smokers) (a) Day 1, nonsmoking 2 " 2, 98 cig's smoked n N W 3 21 , 1 4, 98 5, 88 m m N m (b) Day 1, 97 " " 2 " 2, 96 m m 3, 94 4, 103 ~ m W m ® Room - 43 m3 9 smocers consumed 12 80 cigarettes + 2 cigars no ventilation (38 ppm CO) Nicotine/Urine (ug/24 hrs) Cano et al. (28) r 0 - 0 35 - 44 50 - 61 62 5 - 70 b . 47 - 50 H w 23 - 34 H ft 22.5 - 58 47.5 - 69 I 32 - 65 g :3 Nicotine/Plasma (u /ml) Russell and 0 Be ore exposure: 0.7311.6 Feyerabend rt After 78 min. exposure: 0.91 0.29 Nicotine/Urine (ng/ml) (29) n N- rt 15 min. after exposure: 80.0158.7 M 0 continued H TEWN 0030079

DrSft - Do not cite or quote Table 1. Toxic and tumorigenic agents in MS and SS Cigarette Smoke Smoke Constituent streama A (NF) B(F) C (F) D(PF) Tar MS 20.1 15.6 6.8 0.9 (mg) SS 22.6 24.4 20.0 14.1 --------------------------------------------- Nicotine MS 2.04 1.50 0.81 0.15 ~ (mg) SS 4.62 4.14 3.54 3.16 --------------------------------------------- CO MS 13.2 13.7 9.5 1.8 (mg) SS 28.3 36.6 33.2 26.8 --------------------------------------------- Catechol MS 41.9 71.2 26.9 9.1 (ug) SS 58.2 89.9 69.5 117 ---- ---- ---- --- BaP MS 26.2 17.8 12.2 2.2 ~ (ng) SS 67.0 45.7 51.7 44.8 -------- i ------------------•• -------------- --- Ammonia MS 76.0 19.4 34.0 40.4 (µg) SS 524 893 213 236 --------------------------------------------- NDMA MS 31.1 4.3 12.1 4.1 (ng) SS 735 597 611 685 --------------------------------------------- NPYR MS 64.5 10.2 32.7 13.2 (mg) SS 117 139 233 234 --------------------------------------------- NNN MS 1007 488 273 66.3 (ng) SS 857 3G7 185 338 --------------------------------------------- NNK MS 425 180 56.2 17.3 (ng) SS 1444 752 430. 386* a Abbreviations: NF, nonfilter cigarette; F, filter ciga- rette; PF, cigarette with perforated filter tip; BaP, benzo- (a)pyrene; NDMA, N-nitrosodimethylamine; NPYR, N-nitrosopyr- rolidine; NNN, N'-nitrosonornicotine; NNK, 4-(methylnitros- amino)-1-(3-pyridyl)-1-butanone. L TI4N®030080

Draft - Do not cite or quote CHAPTER 5 ENVIRONMENTAL TOBACCO SMOKE AND CANCER Jonathan M. Samet, M.D. Pulmonary Division Department of Medicine University of New Mexico Albuquerque, NM 87131 Introduction Lung cancer, an uncommon malignancy at the start of the century, has become the leading cause of cancer death in the United States (U.S. DHHS 1982). The American Cancer Society estimates that approximately 157,000 lung cancer cases will occur in the United gtates in 1990. Most cases are rapidly fatal and only a small proportion are cured by surgery or chemotherapy; five-year survival following diagnosis is less than 10 percent. Most lung cancers arise in the larger airways of the lung, the predominant site of deposition of inhaled particles in the size range of 0.5 to 3.0 microns in aerodynamic diameter. Primary cancer of the lung occurs in multiple histopathological patterns that are generally distinct and classifiable by conventional light microscopy. The principal types of lung cancer are squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and large cell carcinoma; in the general population, these four types account for approximately 30 percent, 20 percent, 25 percent, and 15 percent, respectively, of all lung cancers (Butler et al. 1987). Bronchioloalveolar cell carcinoma represents about 5 percent of all lung cancers. The cellular origins of the various cell types have not been established, and controversy remains concerning the specificity of associations between certain cell types and specific etiologic agents. However, in nonsmokers, adenocarcinoma is the predominant type and small cell cancers occur only rarely. The epidemic rise of lung cancer during this century stimulated laboratory and epidemiological investigation of its causes. Most of the early epidemiological evidence indicated that tobacco smoke was a potent respiratory carcinogen, and in 1964 the Advisory Committee to the Surgeon General of the U.S. Public Health Service concluded that cigarette smoking is a cause of lung cancer (U.S. PHS 1964). The numerous investigations performed subsequently have been consistent with this conclusion. The association of lung cancer with cigarette smoking is strongest for squamous cell and small cell cancers, but the other major types are also caused by cigarette smoking. In active cigarette smokers, the risk of lung cancer increases with both the amount smoked on a daily basis and 67 TIMN 0030081

Draft ® Do not cite or quote .:i the duration of smoking (U.S. DHHS 1982; Doll and Peto 1973; -hak et al. 1986). A threshold level of smoking that must be ~eeded to cause lung cancer has never been demonstrated; any ;arette smoking is considered to increase lung cancer risk beyond :t of the lifelong nonsmoker. In former smokers, the relative k of lung cancer declines exponentially in comparison with those continue to smoke. Agents other than tobacco smoke may also cause lung cancer, and as occur in lifelong nonsmokers. A recent study in New Mexico ;wed that the lifetime risks of lung cancer were 0.5 percent and percent in female and male nonsmokers, respectively (Samet at 1988). Occupational exposures to arsenic, asbestos, oromethyl ethers, chromium, coke oven fumes, nickel, and radon .ghters have been linked to increased lung cancer risk, and many .er occupational agents are suspect respiratory carcinogens. A ;:ily history of lung cancer is also associated with increased Ig cancer risk, although a clear -pattern of genetic rceptibility to lung cancer has not been demonstrated. Outdoor - pollution may contain carcinogens and indoor air may have high els of radon, which causes cancer in exposed underground miners. `_mal and human studies suggest that low consumption of vitamin or its precursor, beta-carotene, may also increase lung cancer sk. ! While studies linking active smoking to lung cancer were first ,lished in the late 1940s and early 1950s (U.S. PHS 1964), ioluntary exposure of nonsmokers to tobacco smoke was not isidered as a cause of lung cancer in nonsmokers until 1981, when 'a first two scientific papers on this subject were published. bsequently, many additional reports have addressed involuntary oking as a cause of :Lung cancer in nonsmokers. The World Health gani zation (1986), the U. S. Surgeon General (U. S. DHHS 1986), and s National Research Council (1986) have reviewed the evidence on voluntary smoking and lung cancer from human populations and dged it sufficient to support the conclusion that involuntary halation of tobacco smoke by nonsmokers causes cancer. This apter reviews that evidence and the conclusions of the research ganizations. The chapter also addressess the more limited idence on involuntary smoking and cancer at sites other than the .ng. .e Eoi,demiolog,ical Apgroach Epidemiology is the scientific method used to describe the ,currence of disease in. human populations and to determine the :uses of disease by studying populations. Descriptive measures ` disease occurrence include the incidence rate, which is the rate : which new cases of disease develop; the mortality rate, or rate ` death; and the prevalence rate, which is the proportion of the )pulation with disease. To identify the causes of disease, Didemiologists generally perform either cohort or case-control 68 TI1VIN 0030082

Draft=- - Do_ not-cite or quote studies. °ach t~~~e of study provides an estimate of relative risk as a measure of tae association between exposure and disease. The relative risk describes the comparative occurrence of disease in exposed compared with nonexposed persons. In a cohort study, the subj ects are selected on the basis of their exposure history and followed'over time for the development of disease. For example, a study of involuntary smoking and lung cancer might be performed by enrolling nonsmokers married to smokers and another group of nonsmokers married to nonsmokers. The lung cancer risk associated with marriage to a smoker would be estimated by comparing incidence of or mortality from lung cancer in the two groups. In a case-control study, cases with the disease of interest and controls without the disease are identified and their past exposures to factors of interest are assessed, often by interview. For example, a case-control study of lung cancer and involuntary smoking might be conducted by identifying nonsmokers with lung cancer and a suitable control group, and then interviewing the subjects concerning the smoking habits of their spouses, other household members, and colleagues at work. Each type of study has advantages and disadvantages, and the results of both types may be distorted by bias. Misclassification of exposure is of particular concern in studying lung cancer and involuntary smoking. Misclassification of exposure refers to the incorrect categorization of actually exposed subjects as nonexposed and of nonexposed as exposed. When misclassification occurs randomly, it tends to bias studies towards no association, that is showing negative results; if nonrandom, it may exaggerate or reduce the apparent effect of an exposure. With regard to involuntary smoking and lung cancer, two types of misclassification are of concern. Subjects classified as nonsmokers may have actually been active smokers and the degree of exposure of nonsmokers to the smoking of others may not be accurately classified. Misclassification of both types is discussed below in relation to specific studies. The diagnosis of lung cancer is also subject to misc.as- sification; a cancer that originated at another primary site and then spread to the lung may be incorrectly diagnosed as a primary cancer of the lung. For example, in the case-control study reported by Garfinkel and colleagues (Garfinkel et al. 1985), 13 percent of cases originally diagnosed as lung cancer were reclas- sified to other sites after histological review: With regard to exposure misclassification in this study, 40 percent of the cases initially classified as nonsmokers on the ba.sis of information in medical charts were found to be smokers on interview. Confounding refers to bias that occurs when the effect of another risk factor is mixed with the effect of the exposure of interest; thus a confounding factor is a risk factor for disease that is associated 6 9 T.ININ 0030083

Draft - Do not cite or quote with the exposure under investigation. For lung cancer in nonsmokers, potential confounding factors include indoor air :.ollution by radon and combustion products other than environmental Lobacco s:aoke, ambient air pollution, and occupational exposures. Although confounding always merits consideration as an explanation for association, the diversity of the populations in which passive smoking and lung cancer have been associated argues strongly against confounding as the source of the association. Although individual studies may be affected by one or more biases, the totality of the epidemiological evidence as well as other relevant research are considered in judging whether an exposure adversely affects health. A bias potentially important in one study may be unimportant or adequately controlled in another. Thus review of all pertinent literature may show that bias cannot satisfactorily explain an association between exposure and disease. Enidemiological Evidence on Involuntary Smokinct and Lung Cancer Evidence concerning involuntary smoking and lung cancer has been sought indirectly in descriptive data on mortality rates and directly with case-control and cohort studies. Time trends of lung cancer mortality across this century in nonsmokers have been examined with the rationale that temporally increasing exposure to environmental tobacco smoke should be paralleled by increasing mortality rates (Enstrom 1979; Garfinkel 1981). These data can only provide indirect evidence on the lung cancer risk associated with involuntary exposure to tobacco smoke. Enstrom (1979) cal-- culated lung cancer mortality rates from various nationwide sources for the period 1914-1968 and concluded that'a real increase had occurred among nonsmoking males after 1935. In contrast, Garfinkel (1981) found no time, trends of lung cancer mortality in nonsmoking participants in two cohort studies, the Dorn Study of U.S. veterans, 1954-1969, and the American Cancer Society study, 1960- 1972. Most of the case-control and the cohort studies indicate in- creased lung cancer risk in nonsmokers married to smokers, but these studies do not uniformly show increased risk for sources of exposure other than smoking by the spouse (Tables 1 and 2). The first two major epidemiological studies were reported in 1981 by Hirayama and Trichopoulos and colleagues (Tables 1 and 2). Hirayama conducted a cohort study of 91,540 nonsmoking women in Japan. Mortality in these women was assessed over a 14-year follow-up period. The ratio of the observed to expected numbers of lung cancer deaths increased in a statistically significant pattern with the amount smoked by the husbands. The findings could not be explained by other factors, such as age and occupation of the husband, and were unchanged when the follow-up was extended by several years (Hirayama 1984). After its publication, the report of this study received intensive scrutiny, and correspondence in the British Medical Journal, which had published it, raised concern 70 T]A1N 0030084

Draft - Do not cite or quote about various aspects of the study's methods and findings. In his responses to the correspondence, Hirayama satisfactorily answered most of the criticisms, although he could not eliminate the possibility of unreported smoking by women classified as nonsmokers. If self-reported nonsmokers married to smokers were actually more likely to be smokers, then the resulting bias would tend to indicate an increased risk from marriage to a smoker. Based on the same population, Hirayama has also reported significantly increased risk of lung cancer for nonsmoking married men whose wives smoke (Hirayama 1984). In 1981, Trichopoulos and coworkers (1981) also reported in- creased lung cancer risk in nonsmoking women married to cigarette smokers (Table 2). These investigators conducted a case-control study in Athens, Greece, that included selected histological types of lung cancer and control subjects ascertained at a hospital for orthopedic disorders. The finding of increased risk was unchanged when the case and control series.were enlarged (Trichopoulos et al. 1983). S The results of subsequently reported case-control studies have also demonstrate& significantly increased risk of lung cancer in nonsmokers exposed to environmental tobacco smoke (Table 2). The findings from the more recent reports based on studies throughout the world greatly strengthen the evidence from the earlier studies. Several of the newer studies included relatively large numbers of nonsmokers (Garfinkel et al. 1985; Akiba et al. 1986; Dalager et al. 1986; Lam et al. 1987; Gao et al. 1987). Furthermore, in most of the newer studies, involuntary smoking was assessed in greater detail than in the earlier reports. The results of two other investigations have also been interpreted as showing an increased lung cancer risk associated with involuntary smoking, but both of these studies have limitations. Knoth and coworkers (1983), in Germany, described 59 lung cancer cases in females of whom 39 were nonsmokers. Based on census data, these investigators proj ected that a much greater than expected proportion of the nonsmokers had lived in households with smokers. In another report, Gillis et al. (1984) described the preliminary results of a cohort study of 16,171 males and females in western Scotland (Table 1); exposure to tobacco smoke in the home increased the lung cancer risk for nonsmoking men but not for nonsmoking women. This observation was based on••only 16 cases of lung cancer in nonsmokers, however. Other investigations indicate lesser or no effects of exposure to environmental tobacco smoke on lung cancer risk (Tables 1 and 2). In these studies, however, the statistical uncertainty is large because of the relatively small numbers of subjects; ac- cordingly, the apparently negative findings are statistically compatible with the findings of those studies judged as positive. Two separate case-control studies in Hong Kong, where lung cancer 71 TIMN 0030085

Draft - Do not cite or quote incidence rates in females are particularly high, did not indicate excess risk from involuntary smoking (Chan et al. 1979; Chan and Fung 1982; Koo et al. 1984; 1985; 1987). In the more recent of the two studies, the investigators comprehensively assessed cumulative exposure from home and workplace sources, but misclassification of exposure may have biased towards the negative results. A subsequent study in Hong Kong did find a significant association of spouse smoking and lung cancer risk (Lam et al. 1987). Lee and coworkers (Lee et al. 1986) in England reported a small case- control study with negative findings, but the statistical power of that study is limited. Another recent hospital-based case-control study, conducted in Japan, also failed to show an association be- tween lung cancer risk and spouse smoking (Shimizu et al. 1988). The results of' the American Cancer Society's cohort study of lung cancer mortality in 176,139 nonsmoking women have also been considered by many as not showing an increased risk in those par- ticipants married to smokers (Garfinkel 1981). However, the risks for the nonsmoking women with smoking husbands were increased somewhat, but the increase was not statistically significant. Misclassification of exposure from active and involuntary smoking may have affected the results of this study. Preliminary resul-s from a nationwide case-control study also did not demonstrate increased lung cancer risk from domestic exposure to tobacco smoke (Kabat and Wynder 1984), but the number of subj ects was small. Two case-control studies of nonsmokers and smokers with selected histological types of lung cancer did not provide strong evidence for increased risk from involuntary smoking (Wu et al. 1985; Brownson et al. 1987). However, both studies included only small numbers of nonsmokers. Conclusions on Involuntarv Smoking and Luna Cancer Scientists draw on a wide range of evidence in judging whether an agent, such as environmental tobacco smoke, causes disease. In addition to epidemiological data, the findings of laboratory studies involving in-vitro systems and of animal studies involving exposure to the agent are often relevant. Criteria have been developed for guidance in making judgments on the causality of exposure-disease relationships, but these criteria only provide guidelines, not strict rules of evidence (U.S. PHS 1964; Rothman 1986). Interpretation of the evidence on particular exposure- disease relationships often requires review by multidisciplinary panels of scientists who are instructed to reach a consensus, often in a setting of substantial uncertainty. For example, the World Health Organization regularly convenes panels of scientists to address the carcinogenicity of environmental agents. For environmental tobacco smoke and lung cancer, the evidence has been considered by scientists convened by the International 72 TIMN 0030086

Draft=- Do not cite or quote Agency for Research on Cancer of the World Health Organization, the National Research Council, and the U.S. Surgeon General (Table 3). All three groups concluded that environmental tobacco smoke causes lung cancer among nonsmokers, although the approach used by each group was different. Consensus among the three groups, in spite of differing methodology, strengthens the determination that involuntary smoking causes lung cancer. For all three types, the biological plausibility of this association was supported by the evidence on active smoking and lung cancer, knowledge of the constituents of environmental tobacco smoke, and data demonstrating the uptake of tobacco smoke by nonsmokers. The International Agency for Research on Cancer of the World Health Organization (1986) reviewed the evidence available through the end of 1984. It reached its conclusion concerning involuntary smoking and lung cancer largely on the basis of biological plausibility. The agency cited the characteristics of sidestream and mainstream smoke, the absorption of tobacco smoke materials during involuntary smoking, and the nature of dose-response relationships for carcinogenesis, which project some risk for any .level of exposure. In reaching its conclusion, the National Re.search Council committee considered the biological plausibility of an association between environmental tobacco smoke exposure and lung cancer and the supporting epidemiological evidence, available through mid- 1986. The committee carefully considered the sources of bias that may have affected the epidemiological studies and concluded that the association documented in the studies could not be attributed solely to bias. 3ased on a pooled analysis of the epidemiological data and adjust:nent for bias, the report's authors concluded that the best estimate ior the excess risk of lung cancer in nonsmokers married :o smokers was 25%. The 1986 report of the U.S. Surgeon General also characterized involuntary smoking as a cause of lung cancer in nonsmokers. This conclusion was based on the extensive information already available on the carcinogenicity of active smoking, on the qualitative similarities between environmental tobacco smoke and mainstream smoke, and on the epidemiologic data on involuntary smoking. The extent of the lung cancer hazard associated with involuntary smoking in the United States has appeared uncertain. (U.S. DHHS 1986; Weiss 1986). The epidemiological studies provide varying and imprecise measures of the risk (Tables 1 and 2), and exposures to environmental tobacco smoke have not been characterized for large and representative population samples. Thus, any risk assessments for involuntary smoking and lung cancer are subject to substantial uncertainty. Nevertheless, risk assessment can provide insight into the magnitude of the lung cancer problem posed by involuntary smoking. 73 TIMN 0030087

Draft - Do not cite or quote Repace and Lowrey (1985) used data on'lung cancer mortality in Seventh Day Adventists, a nonsmoking group, to estimate the effect of exposure to environmental tobacco smoke in increasing lung cancer risk. Their analysis led to an estimate of 4,666 lung cancer deaths per year attributable to environmental tobacco smoke exposure. A later estimate gave 3,450 female lung cancer deaths and 1,440 male lung cancer deaths per year.(Repace and Lowrey, 1986) An appendix to the National Research Council's 1986 report provides estimates of the numbers of lung cancer deaths attributable to passive smoking. For the year 1985, the risk assessment projects approximately 1,000 lung cancer deaths in males and 2,000 to 3,000 lung cancer deaths in females attributable to environmental tobacco smoke. 'Wells (1988) attributed 3,000 lung cancer cases annually in the U.S. to involuntary smoking. A recent review of 9 published risk assessments of environmental tobacco smoke and lung cancer found they averaged about 4,500 + 2,800 lung cancer deaths per year (Repaca & Lowrey, 1990). Further epidemiological studies of involuntary smoking and lung cancer are in progress. These studies should refine our understanding of exposure-response relationships for lung cancer and exposure to environmental tobacco smoke. Other investigations are addressing the characteristics and toxicity of environmental tobacco smoke and patterns of exposure to environmental tobacco smoke. While the results of these new studies will provide needed information for scientific purposes, the available -data and the conclusions of the scientific community already provide a compelling rationale for reducing involuntary exposure to environmental tobacco smoke. :nvoluntarv Smok~na and Cancer at Sites Other Than the Lun Several reports have suggested that exposure to environmental tobacco smoke may increase risk of cancer at sites other than the lung. One study found that in children, maternal exposure to environmental tobacco smoke during pregnancy was associated with increased risk of brain tumors (Preston-Martin et al. 1982), and in another study paternal but not maternal smoking increased the risk of childhood rhabdomyosarcoma, a cancer of the soft tissues (Grufferman et al. 1982). in adults, involuntary smoking has been linked to a generally increased risk of malignancy (Miller 1984). Several studies have examined excess risk at specific sites. Sandler and colleagues (Sandl•er, Everson, and Wilcox 1985a; 1985b; Sandier, Wilcox, and Everson 1985) conducted a case-control study on the effects of exposures to environmental tobacco smoke during childhood and adulthood on the risk of cancer. The cases included cancers of all types other than usual forms of skin cancer. For all sites combined, a statistically significant increase in risk was found - for exposure to smoking by a parent (crude relative risk = 1.6) and 74 TVqN 0030088

Draft - Do not cite or quote by a spouse (crude relative risk = 1.5); the effects of these two sources of exposure were independent (Sandler, Wilcox, and Everson 1985). Statistically significant associations were also found for some individual sites. These provocative findings will require replication in additional studies. In a case-control study, such as reported by Sandler and colleagues, biased information on exposure to environmental tobacco smoke is of particular concern. In the cohort study in Japan, Hirayama (1984) found significantly increased mortality from nasal sinus cancers and from brain tumors in nonsmoking women married to smokers. In a case-control study of bladder cancer, involuntary smoking at home and at work did not increase risk (Kabat et al. 1986). Cervical cancer, which has been linked to active smoking, was associated with duration of involuntary smoking in a case-control study in Utah (Slattery et al. 1989) This unconfirmed finding needs additional investigation. These associations of involuntary smoking with cancer at diverse sites other than the lung cannot be readily supported with arguments for biological plausibility based on evidence from active smokers. Increased risks at some of the sites, e.g., cancer of the nasal sinus and female breast cancer, have not been found in active c;nokers (U.S. DHHS 1982). In fact, the International Agency for Research on Cancer (WHO 1986) has concluded that effects would not be produced in involuntary smokers that would not be produced to a larger extent'in active smokers. SUNMARY 1. For exposure to environmental tobacco smoke and lung cancer, the evidence has been considered by scientists convened by the International Agency for Research on Cancer of the World Health Organization, the National Research Council, and the U.S. Surgeon General. All three groups concluded that environmental tobacco smoke causes lung cancer among nonsmokers. 2. Further research in involuntary smoking and lung cancer will refine our understanding and are scientifically necessary; however, existing scientific conclusions already provide a compelling rationale for reducing involuntary exposure to environmental tobacco smoke. References Akiba S, Kato H, Blot WJ. Passive smoking and lung cancer among Japanese women. Cancer Res 1986; 46:4804-7. Brownson RC, Reif JS, Keefe TJ, Ferguson SW, Pritzl JA. Risk factors for adenocarcinoma of the lung. Am J Epidemiol 1987; 125:25-34. 7 5 TIMN 0030089

Draft - Do not cite or quote Butler C, Samet J, Humble CG, Sweeney ES. The histopathology of lung cancer in New Mexico, 1970-1972 and 1980-1981. J Natl Cancer Inst 1987; 78:85-90. Chan WC, Colbourne MJ, Fung SC, Ho HC. Bronchial cancer in Hong Kong 1976-1977. Br J Cancer 1979; 39:182-192. Chan WC, Fung SC. Lung Cancer in nonsmokers in Hong Kong. In: Grundmann E, ed. Cancer Campaign. Vol. 6, Cancer Epidemiology. Stuttgart: Gustave Fischer Verlag, 1982; 6:199-202. Correa P, Pickle LW, Fontham E, Lin Y, Haenszel W. Passive smoking and lung cancer. Lancet 1983; 2:595-7. Dalager NA, Pickle LW, Mason TJ, Correa P, Fontham E, Stemhagen A, Buffler PA, Ziegler RG, Fraumeni JF Jr. The relation of passive smoking to lung cancer. Cancer Res 1986; 46:4808-11. Doll R, Peto R. Cigarette smoking and bronchial carcinoma: Dose and time relationships among regular smokers and lifelong non- smokers. J Epidemiol Community Health 1978; 32:303-13. Enstrom JE. Rising lung cancer mortality among non-smokers. J Natl Cancer Inst 1979; 62:755-60. Gao YT, Blot WJ, Zheng W, Ershow AG, Hsu CW, Levin LI, Zhang R, Fraumeni JF Jr. Lung cancer among Chinese women. Int J Cancer 1987; 40:604-9. 1 Garfinkel L. Time trends in lung cancer mortality among nonsmokers and a note on passive smoking. J Natl Cancer Inst 1981; 66:1061- 6. Garfinkel L, Auerbach 0, Joubert L. Involuntary smoking and lung cancer: a case-control study. J Natl Cancer Inst 1985; 75:463- 9. Geng GY, Liang ZH, Zhang AY, Wu GL. On the relationship between smoking and female lung cancer. In: Aoki M, Hisamichi S, Tominaga S, eds. Smoking and Health 1987. Amsterdam: Excerpta Medica, 1988; 483-6. Gillis CR, Hole DJ, Hawthorne VM, Boyle P. - The effect of environmental tobacco smoke in two urban communities in the west of Scotland. Eur J Respir Dis 1984; 65(suppl 133): 121-6. Grufferman S, Wang HH, DeLong ER, Kimm SY, Delzell ES, Falletta JM. Environmental factors in the etiology of rhabdomyosarcoma in childhood. J Natl Cancer Inst 1982; 68:107-13. Hirayama T. Non-smoking wives of heavy smokers have a higher risk 76 TIMN 0030090

Draft- Do not cite or quote of lung =ancer: a study from Japan. Br Med J 1981; 282:183- 5. Hirayama T. Cancer mortality in nonsmoking women with smoking husbands based on a large-scale cohort study in Japan. Prev Med 1984; 13:630-90. Humble CG, Samet JM, Pathak DR. Marriage to a smoker and lung cancer risk in New Mexico. Am J Public Health 1987; 71:598-602. Inoue R, Hirayama T. Passive smoking and lung cancer in women. In: Aoki M, Hisamichi S, Tominaga S, eds. Smoking and Health 1987. Amsterdam: Excerpta Medica, 1988; 283-5. Kabat GC, Wydner iL. Lung cancer in nonsmokers. Cancer 1984; 53:1214-21. Kabat GC, Dieck GS, Wynder EL. Bladder cancer in nonsmokers. Cancer 1986; 2:362-7. Nnoth A, Bohn H, Schmidt F. Passivrauchen als lung enkrebsursache pei nichtraucherinnen. Med Klin 1983; 2:66-9. Koo LC, Ho JH, Lee N. An analysis of some risk factors for lung cancer in Hong Kong. Int J Cancer 1985; 35:149-55. Koo LC, Ho JH, Saw D. Is passive smoking an added risk factor for lung cancer in Chinese women? J Exp Clin Cancer Res 1984; 3:277- 8Z. Koo LC, Ho JH, Saw D, Ho C. Measurements of passive smoking and estimates of lung cancer risk among nonsmoking Chinese females. int J Cancer 1987; 39:162-9. Lam'* Tx, Kung ITM, Wang CM, Lam WK, Kleevens JWL, Saw D, Hsu C, Seneviratne S, Lam SY, Lo KK, Chan WC. Smoking, passive smoking and histological types in lung cancer in Hong Kong Chinese women. Br J Cancer 1987; 56:673-8. Lee PN, Chamberlain J, Alderson MR. Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases. Br J Cancer 1986; 54:97-105. Miller GH. Cancer, passive smoking and nonemployed and employed wives. West J Med 1984; 140:632-5. National Research Council, Committee on Passive Smoking. Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects. Washington, D.C.: National Academy Press, 1986. Pathak DR, Samet JM, Humble CG, Skipper BJ. Determinants of lung 77 TIMN 0030091

Draft - Do not cite or quote cancer risk in cigarette smokers in New Mexico. J 1986; 76:597-6C4. Natl Cancer Inst Pershagen G, Hrubec Z, Svensson C. Passive smoking and lung cancer in Swedish women. Am J Epidemiol 1987; 125:17-24. Preson-Martin S, Yu MC, Benton B, Henderson BE. N-nitroso compounds and childhood brain tumors: a case-control study. Cancer Res 1982; 42:5240-5. Repace, JL, Lowrey AH. A quantitative estimate of nonsmokers' lung cancer risk from passive smoking. Environ Int 1985; 11:3-22. Repace, JL, Lowrey AH. A rebuttal to criticism of the phenomenologicail model of nonsmokers' lung cancer risk from passive smoking. Environ. Carcino. Revs. (J. Environ. Sci. Health) 1986; C4(2):225-35. Repace, JL, Lowrey AH. Risk assessment methodologies for passive- smoking-induced lung cancer. Risk Analyis 1990; 10:27-37. Rothman KJ. Modern Epidemiology. Boston, Little, Brown and Company, 1986, pp 7-21. Samet JM, Wiggins CL, Humble CG, Pathak DR. Cigarette smoking and lung cancer in New Mexico. Am Rev Respir Dis 1988; 137:1110-13. Sandler DP, Wilcox AJ, Everson RB. Cumulative effects of lifetime passive smoking on cancer risk. Lancet 1985a; 1: 312-15. Sandler DP, Everson RB, Wilcox AJ, Browder JP. Cancer risk in adulthood from early life exposure to parents' smoking. Am J P~.iblic Health :L985b; 75: 487-92. Sandler DP, Everson RB, Wilcox AJ. Passive smoking in adulthood and cancer risk. Am J Epidemiol 1985a; 121:37-48. Shimizu H, Morishita M, Mizuno K, Masuda T, Ogura Y, Santo M, et al. A case-control study of lung cancer in nonsmoking women. Tokohu J Exp Med 1988; 154:389-97. Slattery ML, Robison LM, Schuman KL, French TK, Abbott TM, Overall JC, Gardner JW. Cigarette smoking and exposure to passive smoking are risk facto:rs for cervical cancer. JAMA 1989; 261: 1593-98. Trichopoulos D, Kalandidi A, Sparros L. Lung cancer and passive smoking: conclusion of Greek study (Letter). Lancet 1983; 2:677- 8. Trichopoulos D, Kalandidi A, Sparros L, MacMahon B. Lung cancer and passive smoking. Int J Cancer 1981; 27:1-4. 7 8 ~ 'd ~ ®03®®92

Draft - Do not cite or quote United States Department of Health` and Human Services, Public Health Service. The health consequences of smoking. A report of the Surgeon General. Washington, D.C.: U.S. Government Printing Office, 1982. DHHS (PHS) publication no. 82-50179. United States Department of Health and Human Services, Public Health Service. The Health consequences of involuntary smoking. Washington, D.C.: U.S. Government Printing Office, 1986. DHHS (PHS) publication no. (CDC) 87-8398. United States Public Health Service. Smoking and health. Report of the Advisory Committee to the Surgeon General. Washington D.C.: U.S. Government Printing Office, 1964. PHS publication no. 1103. Wells AJ. An estimate of adult mortality in the United States from passive smoking. Environ Int 1988; 14:249-65. Weiss ST. Passive smoking and lung cancer. What is the risk? (editorial). Am Rev Respir Dis 1986, 133:1-3. World Health Organization. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Tobacco smoking, Vol. 38. Lyon, France, World Health Organization, IARC, 1986. Wu AH, Henderson BE, Pike MC, Yu MC. Smoking and other risk factors for lung cancer in women. J Natl Cancer Inst 1985; 4:747- 51. TIMN 0030093 79

Draft - Do not cite or quote FIGiTREB AND TABLES, CHAPTER 5 TIMN 0030094

Draft= - Do not cite or quote. TABLE I Cohort Studies of Involuntary Smoking and Lung Cancer Study - Findings Comments 91,540 nonsmoking females, 1966-1981, ~ apan (Hirayama 1981). !76,139 nonsmoking females, 1960-1972, U.S. (Garfinkel ? 981) . 8,128 males and females, 1972-1982, Scotland (Gillis et al. 1984). Age-cicupation adjust- ed RR by husbands' smoking: Nonsmokers - 1.00~ Exsmokers - 1.36 Current smokers < 20/day - 1.45 >_ 20/day - 1.91 Aqe-adjusted RR by husbands' smoking: Nonsmokers - 1.00+ Current smokers f < 20/day - 1.27 >_ 20/day - 1.10 Age-adjusted RR for exposure to a tobacco smoker in the home: Males - 3.25 Females - 1.00 Trend statistically significant. All histological types of lung cancer. All histologies. Effect of husbands' smoking not stat- istically signifi- cant. Preliminary, small numbers of cases. *RR = relative risk, as estimated by the ratio of observed to expected number of lung cancer deaths. reference category, risk arbitrarily set to unity as the reference point for comparison. TIMN 0030095

TABLE 2 Draft Case-contr,zl Studies of Involuntary Smoking S tudy. 40 nonsmoking female cases, 149 controls, :973-1980, Greece ('_'richopoulos et a?.. 1981). 34 iemale cases and :39 controls, 1976-, 1977, Hong Kong ; C::an et a1. 1979 ; C:an and Fung 1982). 1 22 ~emale and 8 male nonsmoking cases, 133 'emale and 180 male controls, U.S. (Correa et al. 1983). male and 94 19 female nonsmoking cases and 110 male and 270 female non- smoking controls, Japan (Akiba et al. :986) . 39 nonsmoking cases =nd .36 controls, cuisiana, Texas, i :7 w J D 1 e ~ ersey ( a ager 28 nonsmokinq _ant:rols, New Mexico (?Iumble et al. 1987) . '7 nonsmoking cases, 2 matched control ;eri.es, Sweden ;Pershagen et al. :987). - Do not cite..or.quote and Lung Cancer Findings Comments RR* by husband smoking: Trend statistically Nonsmokers - 1.0 Exsmokers - 1.8 significant. tologies other His- than Current smokers adenocarcinoma and < 20/day - 2.4 >_ 20/day - 3.4 bronchioloalveolar carcinoma. : RR of 0.75 associated with smoking spouse, compared to 1.0 for a nonsmoking spouse. RR by spouse smoking: Ir Nonsmokers - 1.00 < 40 pack years - 1.48 >_ 41 pack years - 3.11 For females, RR of 1.5 if husband smoked; for males, RR of 1.8 if wife smoked. All histologies. Two reports are inconsistent on the exposure variable. Significant increase for >_ 41 pack years. Bronchioloalveolar carcinoma excluded. Clinical or radio- logical diagnosis for 43%. All types of lung cancer. I RR for marriage to a smoking spouse was 1.5 Nearly 1001 histo- logical confirma- tion. All types of lung cancer. RR for marriage to a smoking spouse was 3.2 No effect in active smokers. RR for marriage to a smoker was 3.3 for squamous small cell carcinomas. All types other than bronchiolo- alveolar carcinoma. No effect of expo- sure for other types. Study based within a cohort. TIMN 0030096

Draft - Do not cite or quote TABLE 2 (continued) Case-control Studies of Involuntary Smoking and Lung Cancer Study,__ Findings Comments 102 adenocarcinoma cases, 50 males and females, and 131 controls, Colorado (Brownson et al. 1987). 25 male and 53 female nonsmoking cases with matched controls, 1971-1980, U.S. (Kabat and Wynder 1984). t 88 nonsmoking femal.e cases, 1981-1982,- Hong Kong (Koo et al., 1984, and 1985). 31 nonsmoking and 189 smoking female cases, U.S. (Wu et al. 1985). 0 134 nonsmoking female cases,.U.S. (Garfinkel et al. 1985). 15 male and 32 female nonsmoking cases, and 30 male and 66 female non- smokinQ controls, England (Lee et al. 1986). No effect in entire group. in nonsmoking women, RR of 1.7 for exposure >_ 4 hrs/day, versus 1.0 for <3 hrs/day. RR not significantly increased for current exposure at home: Males - 1.26 Females - 0.92 RR of 1.24 (not stat- istically significant) for combined home and workplace exposure ver- sus 1.0 for nonexposed. No association with cumulative hours of exposure. No significant effects of exposure from par- ents, spouse, or work- place in smokers and nonsmokers. husband. Nonsignificant RR of 1.22 if husband smoked. Significantly increased RR of 2.11 if husband smoked 20 or more cig- arettes daily at home. Significant trend of RR with number of cigarettes smoked at home by the Overall RR for spouse smoking of 1.1. Involuntary smoking effect not signifi- cant in nonsmoking women, but only 19 such cases included. All types. Findings negative for spouse smoking variable as well. All types of lung cancer. Adenocarcinoma and squamous cell carci- noma only. All types of lung cancer. Careful ex- clusion of smokers from the case group. Hospital-based study. TIMN 0030097 *RR = relative risk as estimated by the odds ratio.

Draft - Do not cite or quote TABLE 3 Conclusions of the World Health Organization, Nationa]. Research Council and U.S. Surgeon General or.i Involuntary Smoking and Lung Cancer World Health Organization "Knowledge of the nature of sidestream and mainstream smoke, of the materials absorbed during "passive" smoking, and of the quantitative relationships between dose and.effect that are commonly observed from exposure to carcinogens, however, leads to the conclusion that passive smoking gives rise to some risk of cancere" National Research Council "The weight of evidence derived from epidemiologic studies shows an association between ETS exposure of nonsmokers and lung cancer that, taken as a whole, is unlikely to be due to chance or systematic bias. The observed estimate of increased risk is 34%, largely for spouses of smokers compared with spouses of nonsmokers." U.S. Surgeon General "Tnvoiuntary smoking can cause lung cancer in nonsmokers." "The absence of a threshold for respiratory carcinogenesis in active smoking, the presence of the same carcinogens in mainstream and sidestream smoke, the demonstrated uptake of tobacco smoke constituents by involuntary smokers, and ths demonstration of an increased lung cancer risk in some populations with exposures to ETS leads to the conclusion that involuntary smoking is a cause of lung cancer." TIMN 0030098

Draft - Do not°cite or quote CHAPTER 6 PASSIVE SMORING AND HEART DISEASE: EPIDEMIOLOGY, PHYSIOLOGY, AND BIOCHEMISTRYI Stanton A. Glanta PhD William W. Parmley M.D. Division of Cardiology School of Medicine University of California San Francisco, CA 94143 Introduction The first disease linked to active smoking was lung cancer. It ,s, therefore, not surprising that the first disease linked to passive smoking was also lung cancer (USPHS, 1986). Before the advent of mass marketed cigarettes, lung cancer was a rare disease. The fact that smoking is the major identifiable cause of lung cancer :nade identifying this link -- for both active and passive smoking -- relatively straightforward. This situation contrasts with heart disease, which has many risk factors, so it is not surprising that it took longer for the scientific community to conclude that active smoking caused heart disease (USPHS, 1983). Once the link between smoking and heart disease was established, it became clear that smoking accounted for more heart disease deaths than lung (and other) cancers because of the high prevalence of heart diseasa. Similarly, smoking is the most important preventable cause of coronary disease. Given this history, it is not surprising that exposure to environmental tobacco smoke (ETS) has now been linked to heart disease in nonsmokers (Wells, 1988; Kristansen, 1989) and may result in a substantial number of annecessary coronary heart disease deaths in nonsmokers. Most of the evidence linking ETS and coronary heart disease has appeared since the US Surgeon General (USPHS, 1986) and National Academy of Sciences (NRC, 1986) last reviewed the evidence on the health effects of ETS. Based on the information available as of early 1986, both these reports concluded that the evidence linking ETS and heart disease was equivocal and that more research was necessary before any definitive statements could be made. These conclusions were reasonable at the time they were made. In the four years since these reports were written, considerable information on both the epidemiology and biological mechanisms by which ETS may cause heart disease has accumulated from several areas of scientific investigation. In fact, most of the results IThis chapter is an adaptation of a peer-reviewed manuscript of the same title (Glantz and Parmley, 1990). 80 TIMN 0030099

Draft - Do-not cite-orm quote presentad in _his; chapter were published after the 1986 Surgeon General and National Academy of Science reports. First, there are now 11 epidemiological studies on the relationship betxeen exposure to environmental tobacco smoke in the home and the risk of heart disease in the nonsmoking spouse of a smoker. All but one of these studies yielded a relative risk greater than 1.0. There are several lines of biologic evidence which make this association plausible. There is evidence that exposure to ETS reduces exercise tolerance of healthy individuals as well as people with existing coronary artery disease. Such reduced exercise capability is one of the landmarks of acute compromises to the coronary circulation. There is evidence, from both human and animal studies, that exposure to tobacco smoke, including passive smoking, increases aggregation of blood platelets. Such increases in platelet aggregation are an important stap in the genesis of atherosclerosis. In addition, increasing platelet aggregation contributes to coronary thrombosis, the cause of acute myocardial infarction. Finally, carcinogenic agents in ETS, including benzo(a]pyrene have been shown to produce injuries to the endothelia.l cells which line arteries. Such injuries are the :irst step in the development of atherosclerosis. Thus, exposure to ETS can contribute to both short term and long term insults to the coronary circulation and the heart. Effects of PrimartirSmokina Before reviewing the evidence linking ETS with coronary artery disease, it is worth summarizing the evidence linking active smoking with coronary artery disease. This evidence was summarized in the 1983 Surgeon General's Report, which was devoted entirely to cardiovascular disease (USPHS, 1983); it concluded: In 1980, diseases of the circulatory' system were responsible ~ar approximately one-half of the total U.S. mortality. CHD was the singl_e most important cause of death, accounting for approximately 30 percent of all U.S. deaths. Cigarette smoking is one of the three major independent CHD risk factors. The magnitude of the risk associated with cigarette smoking is similar to that associated with the other two major CHD risk factors, hypertension and hypercholesterolemia; however, because cigarette smoking is present in a larger percentage of the U.S. population than either hypertension or hypercholesterolemia, cigarette smoking ranks as the largest preventable cause of CHD in the United States. Cigarette smoking also acts synergistically with the other major risk factors to greatly increase the risk for CHD. Arteriosclerosis is the predominant underlying cause of cardiovascular disease, and atherosclerosis is the form of 81 TIMN 0030100

Draft~ - Do not cite or quote arteriosclerosis that most frequently causes clinically significant disease, including CHD, atherothrombic brain infarction, atherosclerotic aortic disease, and atherosclerotic peripheral vascular disease. Cigarette smoking contributes both to the development of atherosclerotic lesions and to the clinical manifestations of atherosclerotic vascular disease, including sudden death. Although the precise pathophysiologic basis of these clinical manifestations is not understood, it may be related to several deleterious cardiovascular effects of cigarette smoking, including production of an imbalance between myocardial oxygen supply and demand, a decrease in threshold for ventricular fibrillation, and an increase in platelet aggregation. Nicotine and carbon monoxide are the tobacco smoke constituents most closely associated with these adverse effects; other cigarette smoke constituents such as hydrogen cyanide, oxides of nitrogen, and carbon disulfide are being studied for possible pathologic cardiovascular effects. Since 1983, evidence has also mounted that the polycyclic aromatic hydrocarbons in cigarette smoke can injure the arterial endothelium and initiate the atherosclerotic process. A11 the compounds implicated as damaging to the cardiovascular system of smokers have been identified in ETS (USPHS, 1986; NRC, 1986). d and Heart Disease Since 1984, the epidemiological evidence linking exposure to ETS with heart disease has rapidly accumulated. The results of the eleven published studies are summarized in Table 1 and Figure 1; four studies present data on men, nine on women, and one on both sexes combined. Despite minor differences in methodology or end points (some used death from ischemic heart disease of any origin and some were limited to death from myocardial infarction), the results of these studies are remarkably consistent. A11 the studies on men yielded•relative risks of death from heart disease exceeding 1 for nonsmoking men married to smokers, with a median risk of 1.2. All but one of the studies on women (Lee et al, 1986) yielded relative risks exceeding 1, with a median relative risk of 1.4. Several studies also suggested an increase in the risk of nonfatal coronary symptoms (Svendsen et al, 1987; Palmer et al, 1988; Hole et al, 1989; Dobson et al, 1990); quantitative results in Table 1 only reflect risk of death, not coronary symptoms. Consistency of an observation across different studies increases the confidence one can have in the belief that an association is causal, unless all studies have the same bias. When interpreting the results of such epidemiological studies, it is always important to consider biological plausibility and potential confounding variables which could explain the results. .82 TIMN 0030101

Draft - Do not cite or quote Aside from noting that the compounds in mainstream smoke that have been implicated in heart disease are in ETS, we will defer the discussion of biological plausibility until later in this chapter, when we discuss the effects of ETS on platelets and the atherogenic agents in ETS. For now, we will concentrate on potential confounding variables. These are particularly important in a disease like heart disease, because it is known to be caused by multiple risk factors. A11 of the studies controlled for the most important confounding variable, age, and several (Garland et al, 1985; Svedsen et al, 1987; He, 1989; Hole et al, 1989; Humble et al, 1990) controlled for several known risk factors for coronary artery disease, in particular levels of cholesterol, blood pressure and weight (or body mass or body mass index). Most of the studies also included one or more measures of socioeconomic status, such as the nature of the housing or amount of education. Lee (1988, 19139, 1990) has suggested that the elevated risk of heart (and other) disease with passive smoking could be due to misclassification of nonsmokers who are really smokers. In addition, Wald (1986) has noted that some people who say they live With nonsmokers-liave detectable levels of the nicotine metabolite cotinine in their blood, indicating that they are actually exposed to ETS, either at work or at home. The former type of. misclassification will tend to lead to an overestimate of the risks associated with ETS and the latter will lead to an underestimate of the risk. Careful analysis of the question of misclassification -- which applies generally to studies of ETS and not just heart disease -- have demonstrated that the observed risks cannot be explained by this technical problem (Wald, 1986; Wells, 1986, 1988, 1990; Kawachi and Pearce, 1989; Reinken, 1989). In addition, both the Surgeon General (USPHS, 1986) and the National Academy of Sciences (NRC, 1986) were presented with the argument that misclassification errors accounted for the link between ETS and lung cancer and concluded that ETS caused lung cancer in healthy nonsmokers. To date, no compelling case has been made that this technical error explains consistent findings linking ETS with heart (or lung) disease. Indeed, the net effect of these two types of misclassification errors is to lead to an underestimate of the effects of passive smoking for lung cancer. There is always the possibility that there is some other confounding variable relating to cultural factors, such as the nature of housing or employment or the nature of time spent outside the home. Most studies look only at a crude measure of exposure-spouse smoking-and it is possible that this is an indicator variable for other things, such as poor diet, risky lifestyle, or stress. The fact that results are similar from all over the world in widely varying cultural settings -- including several regions in the United States, the United Kingdom, Japan, and China -- argues against this concern. 83 TIMN 0030102

Draft - Do not cite or quote Several authors also observed a dose-response relationship (Table 1) between increasing amounts of smoking by the spouse and the risk of heart disease in the nonsmoking spouse (Helsing et al, 1988 (statistically significant in women, but not men); Hole et al, 1989; Garland et al, 1985 (although not statistically significant); Humble et al, 1990; He, 1989; Hirayama, 1984). The presence of such dose-response effects across multiple studies, done in different locations with different criteria supports the hypothesis that the epidemiology is revealing a real effect of ETS on heart disease in nonsmokers. While all but one of the studies in Table I and Figure 1 yielded relative risks greater than 1, the fact remains that 3 of the studies in men and 4 of the studies in women had 95% confidence intervals for the relative risk of passive smoking for heart disease that fell below 1.0, meaning that the risk was not statistically significantly elevated above 1.0 (with P<.05). It is important to note that the 95% confidence intervals do not lie symmetrically about 1.0, but rather are skewed towards higher risks. To avoid false negative conclusions, Rothman (1978) suggested examining the confidence interval, as we have done, in concluding the exposure to ETS elevates the risk of heart disease. One can assess formally how confident one can be in reaching a negative conclusion by computing the power of the study to detect an effect of specified size (Friedman et al, 1978). Table 1 shows estimates of the power of each of the studies to detect a 20% increase in risk•of heart disease (i.e., a relative risk of 1.2) with the available samples. The power was computed as described in Muhm and Olshan (1989), using a two-sided test for the relative risk with a Type I risk of 5% (i.e., requiring the 95% confidence interval for the relative risk to exclude 1.0 before concluding a statistically significant elevation in risk in an individual study). Most of the studies have low to moderate power. The two (Helsing et al, 1988; Hole et al, 1989) that have power above the desirable level of 80% both identified significant increases of heart disease risk with ETS exposure. Interestingly, the study by Lee (1986) which was the only one with a relative risk below 1, also had the lowest power to detect an effect, only 3t. It is possible to combine the results of these studies in a formal analysis to derive a global estimate of the relative risk and associated 95% confidence interval. By combining the studies, the sample size and so the power to detect an effect increases. Pooling the studies in Table 1 yields an estimate of the relative risk of death from heart disease of 1.3 (95% CI 1.1-1.6) for men and 1.3 (95% CI 1.2-1.4) for women. These results are consistent with those reported by Wells (1988) who used the studies by Gillis et al (1984), Lee et al (1986), and Helsing et al (1987) to compute a pooled relative risk of 1.3 (with a 95% confidence interval from 1.1 to 1.6) for men and the studies by Hirayama (1984), Gillis et 84 TIMN 0030103

Draft - Do not cite or quote al (1984), Garland et al (1985), Helsing et al (1988), Lee et al (1986), and Martin et al (1986) to compute a pooled relative risk of 1.2 (with a 95% confidence interval from 1.1 to 1.4) for women. Exposure to ETS significantly (p < 0.001) increases the risk of death from heart disease in nonsmokers. Finally, it is worth noting that all these studies are based on the smoking habits of the nonsmoker's spouse, and so exposure to ETS at home. Household exposures to ETS at home are generally much smaller than exposures at work, where the density of smokers is generally higher (Repace and Lowrey, 1985,1987). As a result, these studies will generally underestimate the risk and attendant public health burden due to ETS-induced heart disease if a substantial proportion of the controls are exposed at work. Kawachi et al (1989) have adjusted Wells' (1988) relative risks to account for workplace exposures to ETS and found that the relative risks increase to 2.3 (95% CI 1.4 - 3.4) for men and 1.9 (95% CI 1.4 - 2.5) for women. In addition, Wells (1988) and Kawachi et al (1989) indicate that the number of heart disease deaths due to passive smoking is an order of magnitude greater than the number of lung cancer deaths due to passive smoking. These epidemiological studies demonstrate a connection between ETS exposure and death from heart disease. We now turn our attention to possible physiological and biochemical mechanisms which could explain these observations. Acute Effects of ETS Exposure Chronic exposure to ETS exerts carcinogenic effects by increasing the cumulative risk of a molecule of one of the carcinogens in the ETS damaging the DNA in a cell and initiating or promoting the carcinogenic process. To date, no one has `_dentified any effects of acute exposure to ETS (or, for that matter, any other carcinogen) on cancer. The situation with heart disease is different. In heart disease there are both important chronic changes (i.e., the development of atherosclerotic lesions) and acute changes. The latter include an increase in myocardial oxygen demand which may outstrip the oxygen supply and produce ischemia, and increased platelet aggregation which can lead to coronary thrombosis and acute myocardial infarction. When the coronary circulation cannot provide enough oxygen to the myocardium to meet the demand, the result is ischemia which can be silent or result in anginal chest pain. Earlier onset of angina or hypotension during exercise is a reflection of more severe heart disease. Oxygen supply can be reduced by atherosclerotic narrowing or vasoconstriction of the coronaries or by reducing the oxygen carrying capacity of the blood by forming carboxyhemoglobin. Khalfen and Klochkov (1987) confirmed earlier work by Aronow (1978) demonstrating that exposure to ETS significantly reduced exercise ability in patients with coronary artery disease and the rate 85 TIMN 0030104

Draft - Do not cite or quota pressure product (heart rate times systolic blood pressure). In both studies, patients were exposed to realistic levels of ETS by simply sitting in a waiting room while someone was smoking. These effects were present in both smokers and nonsmokers (HIhalfen and Klochkov, 1987) and regardless of whether or not the room was ventilated (Aronow, 1978; HIhalfen and Klochkov, 1987). Exposure to ETS also increased resting heart rate and systolic and diastolic blood pressure, and resulted in a lower heart rate at the onset of angina (Aronow, 1978). Blood carboxyhemoglobin was increased by about 1% after exposure to ETS (Aronow, 1978). Sheps et al (1987) found no change in cardiovascular function in subjects with angina in response to mild elevation in blood carbon monoxide similar to that experienced in passive smokers when they exposed their subjects to pure carbon monoxide. In contrast, Allred et al (1989) found a significant dose-response relation between carboxyhemoglobin level and the change in the length of time to both electrocardiographic and symptom manifestation in men with angina pectoris exercising after exposure to CO. Even a small increase in the carboxyhemoglobin level, representing a seemingly minor reduction in the oxygen-carrying capacity of hemoglobin, was associated with the statistically significant effects. Acute exposure to ETS leads to an imbalance between myocardial oxygen supply and demand during exercise in patients with coronary artery disease. While this discussion has concentrated on the carbon monoxide in ETS as the active agent, it is likely that some other component of the ETS is also contributing to this effect. The effects of ETS on cardiac performance are, in fact, severe enough to affect exercise performance in young healthy subjects with no evidence of heart disease. McMurray et al (1985) blindly exposed young healthy women to pure air and air contaminated with ETS while they exercised on a treadmill. The results were similar to those observed in patients with coronary artery disease. Resting heart rate was increased during exposure to ETS, which increased blood carboxyhemoglobin by about 1%. Exposure to ETS significantly reduced maximum oxygen uptake (by 0.251/min and time to exhaustion (by 2.1 min). Exposure to ETS also increased the perceived level of exertion during exercise, maximum heart rate, and COZ output. It also significantly increased levels of lactate in venous blood (from a mean of 5.5 mM during control period to 6.8 mM after exposure to ETS). This greater lactate at a lower oxygen consumption during the passive smoking trials indicates a greater reliance on anaerobic metabolism. The combined effect of the reduced oxygen carrying capacity and increased lactate resulted in a reduction in maximal aerobic power and 'the duration of exercise. Thus, even in healthy subjects, exposure to ETS adversely affects exercise performance. The acute effects of CO and direct tobacco smoke• on exercise performance are well documented in the literature. Exposure to CO (or CO in tobacco smoke), and the subsequent elevation of blood carboxyhemoglobin levels to ca. 3%, has been shown to decrease 86 TIMN 0030105

Draft - Do not cite or quote exercise duration in patients with ischemic heart disease and decrease short-term maximal exercise duration in young healthy men. It is conceivable, therefore, that elevations in COHb due to ETS could have similar effects. While the association between active smoking and cardiovascular disease is well known (USPHS, 1983), little is known about the relative importance of each component of tobacco smoke that may be responsible for this relationship. Most experts agree, however, that both CO and nicotine are important, and other constituents of the smoke may play a role as well. Active smoking clearly aggravates the decrease in 02 capacity induced by CO through an increase in the 0. demand of the heart (Deanfield et al, 1986). Passive smoking exposes an individual to all components in the cigarette smoke, but the CO component dominates heavily because only 1% or less of the nicotine is absorbed from passive smoking compared to 100% in an active smoker (Wall et al, 1988; Jarvis, 1987). Currently available information indicates that acute exposure (1 to 2 h) to passive smoke will increase a nonsmoker's COHb level by about 1% (Jarvis, 1987). This small incremental increase in COHb due to ETS alone may not be enough to trigger aLcute cardiovascular effects unless combined with other sources of CO or with other components of ETS having a similar effect (e.g., nicotine). Lamb (1984) has suggested that at maximal exertion levels, up to 90% of the oxygen carrying capacity of the blood may be needed. Because of the carbon monoxide, and perhaps other constituents, ETS reduces this capacity, so the muscle cannot maintain its high rate of aerobic metabolism unless cardiac output is further increased; people with heart disease and reduced ventricular reserve have difficulty meeting this demand. In sum, exposure to ETS increases the demands on the heart during exercise and reduces the capacity of the heart to respond. This imbalance increases the ischemic stress of exercise in patients with existing coronary artery disease and can acutely precipitate symptoms. Moskowitz et al (1990) found evidence that adolescent children of parents who smoked may suffer from chronic tissue hypoxia such as that observed in anemia, chronic pulmonary disease, cyanotic heart disease or high altitude. These children had significantly elevated levels o:f 2,3-diphosphoglycerate (DPG), which suggests that the body is attempting to compensate for hypoxia by increasing DPG level in blood to meet tissue oxygen requirements, even after correcting for age, weight, height and sex. These changes were dose-dependent; the greater the exposure to ETS (measured both in terms of parental smoking and serum thiocyanate in the children), the greater the increase in DPG. There is also evidence that acute exposure to ETS directly affects the myocardial muscle at a cellular level. Gvozdjakova et al (1984) exposed rabbits in a 50 liter child's incubator to the smoke of three burning cigarettes smoked over a 30 minute period and measured several variables related to the metabolism of cardiac 87 TIMN 0030106

Draft - Do not cite or quote mitocznondria. (Mitochondria are the subcellular elements that control cellular respiration; they convert oxygen into usable energy in the form of ATP.) They had three groups of rabbits: one group exposed to a single dose of ETS, one group exposed to 30 min of ETS twice daily for two weeks, and one group exposed to 30 minutes of ETS twice a day for eight weeks. They measured mitochondrial respiration (QO2) as the consumption of oxygen after adding ADP to a vessel containing mitochondrial fragments. Using pyruvate as a substrate, mitochondrial respiration QO was reduced significantly compared to control (pure air) for all hses of ETS, even a single exposure (Figure 2) , to about half the control. value. The oxidative phosphorylation rate was also reduced significantly at all exposures by about one-third. There were no significant changes in the coefficient of oxidative phosphorylation (ADP:OZ) with ETS exaosure. Gvozdjakova et al concluded that pyruvate as a substrate was a sensitive indicator of the toxic action of the ETS on the oxidative process. Later, to further isolate where in the process of mitochondrial respiration, the ETS acted, Gvozdjak et al (1985, 1987) reported data on succinate, NADH, and cytochrome oxidase activity in the mitochondria in the four groups of rabbits. Figure 2 shows the iFesults of exposure to ETS on the activity of NADH oxidase, succinate oxidase and cytochrome oxidase of myocardial mitochondria. The activity of the first two oxidases exhibited no changes compared with the control group -- neither after a single exposure to ETS or following exposures up to 2 weeks. Cytochrome oxidase activity decreased both after a single exposure to ETS and over time, with increasing effects as the duration of exposure to ETS is extended. The observation that cytochrome oxidase and not NADH or succinate oxidase activity was affected by ETS suggests that the deleterious effects of ETS on myocardial mitochondrial respiration occur at the terminal segment of the mitochondrial respiration process. Prolonged exposure to carbon monoxide has been shown in some studies to induce ultrastructural changes in myocardium (Kjeldsen et al, 1974; Thomsen and Kjeldsen, 1974; Lough, 1978). Later, Kjeldsen and co-workers (Hugod et al, 1978), using a blind technique and the same criteria to assess morphological myocardial damage found no significant changes in the coronary arteries or aorta in normocholesterolemic rabbits exposed to CO at concentrations from 200 to 4000 ppm for' up to 12 weeks. They suggested that the positive results obtained earlier were due to the non-blind evaluation techniques and the small number of animals used in these studies. Later, Hugod (1981) : confirmed these negative results using electron microscopy. In. addition, the earlier studies were conducted at "moderate" levels of CO (100 to 150 ppm) which are considerably higher than levels of CO found in smoke-polluted environments (reported to be as high as 40-50 ppm, but more typically are around 10 ppm) (NRC, 1986). These negative studies only argue against an effect of CO in inducing coronary 8 $ TIMN 0030107

Draft. -m Dot not cite or quote atherosclerosis, and not a direct effect of CO on myocardial oxygen supply and demand (Deanfield et al, 1986). Acute exposure to ETS not only increases the demand and compromises the supply of oxygen to the heart as a whole, but also reduces the myocardium's ability to use this oxygen to create ATP to provide energy to support the heart's pumping activity. This effect probably results from several of the compounds in ETS acting simultaneously on the cardiovascular system. Effects on Plate: et The action of ETS to increase platelet aggregation is another way in which ETS can acutely increase the risk of a coronary event. When blood platelets aggregate inappropriately and form a thrombus (blood clot), this clot can form in a fissured plaque in the coronary circulation and precipitate a myocardial infarction. Piatelets are important for the normal body process of hemostasis, to prevent blood loss after an injury. Hemostasis depends on complex interactions among the dynamics of blood flow, components of the vessel wall, blood platelets and plasma proteins. A thrombus can be considered as an inappropriate form of hemostasis and is composed•of a mass of cellular material held together by a network of fribrin. Definitive evidence has confirmed that platelets play a major role in thrombus formation and embolization, especially in the arterial system. In addition, increasing evidence has shown that platelet deposition and thrombus formation can contribute to the growth and progression of atherosclerotic plaques (Fuster and Chesebra, 19811 Ross, 1986). An arterial thrombus appears to develop in three phases: platelet adhesion, platelet aggregation, and activating of clotting mechanisms. Passive smoking increases platelet aggregation and so increases the likelihood of thrombus formation and myocardial infarction. Table 2 summarizes the results of three studies (Davis et al, 1985a, 1986, 1989) on the effects of cigarette smoke on platelet aggregation and damage to the arterial endothelium (lining). (We will discuss the effects on the endothelium below.) Davis et al (1989) also measured platelet aggregate ratios and endothelial cell counts in nonsmokers before and after being exposed to 20 minutes of ETS while sitting in a hospital atrium. Mean values before and after passive smoking were 0.87 and 0.78 (P=.0o2) for platelet aggregate ratios and 2.8 and 3.7 (P=.002) for counts- of anuclear endothelial cell carcasses in venous blood. These changes are in between the effects observed after nonsmokers smoked two tobacco cigarettes and the effects observed after smoking two non-tobacco cigarettes (Davis et al, 1985a) and similar to the values observed in nonsmokers who smoked two cigarettes while trying not to inhale (Davis et al, 1986). These effects were not correlated with the level of nicotine in the blood of the experimental subjects in any of these or other (Davis et al, 1985, 1987), related studies on how drugs modify platelet aggregation and endothelial cell counts. In 89 TIMN 0030108

Draft - Do not cite or quota particular, the effects observed in nonsmokers smoking without inhaling were similar to the effects on smokers smoking two cigarettes, despite the fact that the plasma nicotine levels in the nonsmokers were a factor of 5 smaller than those observed in the smokers (Davis et al, 1986). Other work in the same laboratory comparing smoking with snuff use revealed similar changes in platelet function in response to these two forms of tobacco use (Davis et al, 1990). This result, combined with the finding that smoking non-tobacco cigarettes (Davis et al, 1985a) failed to produce changes in platelet function as large as observed with tobacco cigarettes, suggests that nicotine is an important acti-,;a agent. Since non-tobacco cigarettes also affected platelet aggregation somewhat, however, it is possible that carbon monoxide or other combustion products are also influencing the platelets. Sinzinger and Kefalides (1982) measured platelet sensitivity to antiaggregatory prostaglandins (El, IZ, and DZ) before, during and after 15 minutes of exposure to ETS in healthy nonsmokers and smokers (Table 3). Passive smoking reduced platelet sensitivity to the antiaggregatory prostaglandins 1, and EZ significantly (P<.01) by a factor of about 2 by the end of 15 minutes exposure to ETS among nonsmokers. This effect persisted at 20 minutes after the end of exposure, and was gone by 40 minutes. Platelet response to prostaglandin Dz changed modestly in a similar pattern, but did not reach statistical significance. Among smokers, the control level of platelet aggregation was higher (P<.01) and the prostaglandins had no significant effects on platelet aggregation over time during or following exposure to ETS. Sinzinger and Virgolini (1989) also showed that repeated exposure to ETS for one hour per day for ten days produced lasting changes in platelet function in nonsmokers similar to that observed in smokers. Thus, nonsmokers' platelets seem much more sensitive to a single exposure to ETS than do smokers' platelets, with platelet sensitivity to disaggregating prostaglandins having similar effects in nonsmokers acutely exposed to ETS as it does on the chronic levels of platelet aggregation observed in long-term smokers. Further evidence from the same laboratory that passive smoking increases platelet aggregation comes from work by Burghuber at al (1986), who had smokers and nonsmokers smoke two cigarettes and also ex3osed a different group of smokers and nonsmokers to ETS in an 18 m room in which 30 cigarettes had been smoked just before exposing the nonsmokers. They measured the sensitivity' of platelets to the disaggregating substance prostaglandin 1, (PGIZ), which is released by endothelium and inhibits platelet aggregation. (PGI2 is also called prostacyclin.) Figure 3 shows the results of this experiment. In smokers, neither smoking nor passive smoking affected the sensitivity of the platelets to the disaggregating effect of prostaglandin Iz. The sensitivity of platelets in smokers was also significantly lower than nonsmokers. In contrast, platelets were more sensitive to prostaglandin Iz in nonsmokers, with both smoking and passive smoking producing similar reduction 9 0 TIMN 0030109

Draft - Do not cite or quote in platelet sensitivity to prostaglandin 12. These rssults suggest that the platelets of smokers are already desensitized to the anti-aggregatory substance prostaglandin Iz, so that no further decrease in aggregation is seen. The significant decrease in platelet sensitivity to PGI2 after acute exposure to ETS suggests that after ETS exposure platelets are more likely to aggregate, with the adverse consequences described above. Earlier work by Saba and Mason (1975) also indicated that nicotine increased a variety of measures of platelet aggregation in nonsmokers a.nd smokers. While the effects of nicotine on platelets from smokers was greater than in nonsmokers, the effect generally did not vary with dose (between 2x10.9 and 2x10.4 molar), suggesting that the effects of nicotine on platelets occur at low doses and that the system saturates quickly. This observation may explain why passive and active smoking have such similar effects on platelets (Sinzinger and Kefalides, 1982; Burghuber et al, 1986; Davis et al, 1989). The probable link between nicotine and adverse physiologic effects is nicotine-induced release of catecholamines. Catecholamines are then responsible for increased platelet aggregation. This reasoning suggests that beta blockers might provide some protection in smokers. This premise is borne out by the MAPHY trial --a trial comparing the effects of the beta blocker metoprolol to a thiazide diuretic in the control of moderate hypertension (Wilkstrand, et al, 1988). For the same reduction in blood pressure, the metoprolol treated group had a lower mortality than the thiazide treated group. Virtually all of this reduction in mortality, however, was seen in smokers, and not non-smokers. This study provides evidence that blocking the effects of catecholamines (released by nicotine) was the cause of the reduced mortality in smokers who were receiving metoprolol. in sum, passive smoking has significant effects on platelet aggregation, of a magnitude similar to that observed in active smoking. Moreover, the response of nonsmokers to both active and passive smoking appears to be different from smokers, with nonsmokers being more sensitive to low exposures to cigarette smoke than smokers. '.Chis observation suggests that the pharmacology of ETS in nonsmokers may be different than in smokers, with nonsmokers being more sensitive to low doses of ETS. In particular, it invalidates attempts to estimate "cigarette equivalent" doses of ETS in nonsmokers or extrapolating from risks of smoking in smokers to effects of ETS on nonsmokers. The resulting increase in platelet aggregation can contribute to acute thrombus formation and myocardial infarction. In addition to the role of platelets in acute thrombus formation, platelets are also important in the development of atherosclerosis (Ross, 1986). Once there is damage to the arterial endothelium, either through mechanical or chemical factors, 91 TIMN 0030110

Draft - Do not citz or quote olateiets interac-_ with or adhere to subendothelial connective tissue and initiate a sequence which leads to atherosclerotic plaque. When platelets interact with or adhere to subendocardial connective tissue, they are stimulated to release their granule contents. Endothelial cells normally prevent platelet adherence because of the nonthrombogenic character of their surface and their capacity to form antithrombotic substances such as prostacyclin. Once the endothelial cells have been damaged, the platelets can stick to them. Once the platelets are bound to the endothelium, they release mitogens such as platelet-derived growth factor (PDGF), which encourage migration and proliferation of smooth muscle cells in the region of the endothelial injury (Fox and DiCorleto, 1984). If platelet aggregation is increased because of exposure to ETS, the chances of platelets building up at an endothelial injury will also be increased. Thus, in addition to contributing to acute effects through increasing the likelihood of thrombus formation, the effects of ETS on platelets also increase the chances that endothelial injury will lead to arterial plaque. ETS also plays a role in causing damage to the endothelium and initiating the atherosclerotic process. As discussed above, Davis et al (1989, 1986, 1985, 1987, 1985b, 1990) found that acute exposure to ETS (1989), like active smoking (1986, 1985a, 1987, 1985b) and use of chewing tobacco (1990), lead to a significant increase (P<.002) in the appearance of anuClear endothelial cell carcasses in the blood of people exposed to ETS (or tobacco or tobacco smoke) constituents. The appearance of these cell carcasses indicates damage to the endothelium, which is the initiating step in the atherosclerotic process. As noted above, in nonsmokers the appearance of endothelial cells following passive smoking is almost as great as following primary smoking (Table 2). The process by which endothelial injury leads to the development of an atherosclerotic plaque, including the role of platelets, is described in Figure 4. Based on the information presented so far, exposure to ETS appears to produce injuries similar to those observed with exposure to primary smoke and also affects platelets in a way that increases the chances that they will bind to the injured area and promote growth of smooth muscle cells. The Role of the Po lvcyclic Aromatic Hydrocarbons in ETS Many atherosclerotic plaques in humans are either monoclonal or possess a predominantly monoclonal component (Benditt and Benditt, 1973), which indicates that the smooth muscle cells of each plaque have a predominant cell type. Several animal studies have also shown that injections of polycyclic aromatic hydrocarbons (PAHs), in particular 7,12-dimethylbenz(a,h)anthracene (DMBA), benzo(a)pyrene (Albert at al, 1977; Revis, et al 1984.; Penn et al, 1981; Penn et al, 1986; Majesky et al, 1983) accelerate the development of atherosclerosis. Others (Rogers et al, 1980, 1988) failed to find an effect of active smoking or the extent of fatty 9 2 TIMN 0030111

Drait - Do not cite or quote deposits in the coronary arteries of baboons. (There was a significant effect on the carotid arteries.) Benzo(a)pyrene is an important element in ETS (USPHS, 1986). The effects of PAHs or other carcinogenic or mutagenic elements in ETS (Remmer, 1987) relates directly to the response to injury theory of atherogenesis discussed above (Ross, 1986). Changes in the underlying smooth muscle stimulated by these agents could then initiate the "injury" that leads to platelet aggregation and plaque formation. Thus, chronic exposure to ETS could have effects on plaque formation through mechanisms similar to that by which long term exposures produce cancer in other organs. Albert et al (1977) gave chickens weekly intramuscular injections of DBMA and benzo(a)pyrene for up to 22 weeks, then killed the chickens at various times beginning after 13 weeks and measured the plaque volume in the chickens' aortas. They found that both DBMA and benzo(a)pyrene significantly increased the volume of plaque:compared to control chickens who had just received injections of the solvent used to carry these agents. This study provided the first evidence that known carcinogenic chemicals could be atherogenic as well. Penn et al (1981) extended this result in a similar experiment by showing that the effects of DBMA on the extent of plaque buildup in chickens was dose-dependent. The median cross-sectional area of plaques on individual aortic segments and the plaque volume index (an approximate measure of the total volume of plaque per aorta) increased in a nearly linear fashion with DBMA dose. In contrast to the marked increase in plaque area in the DBMA-treated animals, there was only a slight increase in the percentage of aortic sections with plaques in carcinogen-treated animals than in controls. Plaques with a small cross sectional area were present 4n all animals. Lesions of widely differing cross sectional areas appeared to be similar histologically under the light microscope. Together, these data suggest that a major effect of chronic DBMA exposure is to increase the size of spontaneous aortic lesions. Rather than inducing some sort of cancer-like change in an individual cell that begins the process which ultimately leads to formation of a plaque, Penn et al suggested that chronic DBMA exposure cause:; preferential division of individual cells or patches of cells; within the preexisting spontaneous lesions. From this perspective, DBMA and other exogenous compounds would be acting as a mitogen, similar to that released by activated platelets, to stimulate division of aortic smooth muscle. Revis et al (1984) found similar results in White Carneau pigeons injected with DMBA and benzo(a)pyrene weekly for 6 months, beginning when the pigeons were 3 months old. Compared with the work described above, they found a greater effect on atherogenesis of benzo(a)pyrene than DBMA, and also failed to observe a dose- response relationship between the dose given and the amount of aortic plaque. These differences from the work just described may 93 TIMN 0030112

Draft - Do not cite or quote be related to species differences, differences in the carrier used to inject the PAHs (DMSO in the previous studies vs. corn oil in this one) or differences in the age of the pigeons or dosing schedule. They also found an increase in aortic plaques in pigeons treated with the PAFi 3-methylcholanthrene, but not the carcinogen 2,4,6-trichlorophenol or the PAH benzo(e)pyrene, which is not considered a carcinogen. This result suggests that carcinogenic PAHs, rather than carcinogens or PAHs in general, are implicated in the atherosclerotic process. Revis et al also studied the distribution of these compounds after they had been radiolabelled. Forty-eight hours after the injection of PAHs, radioactivity in the liver, aorta and lung accounted for 75% of the injected dose, whereas in animals injected with 2,4,6-trichlorophenol, radioactivity in the liver and kidney accounted for 80% of the dose. In addition, 80% of the radioactivity observed in the plasma immediately following inj ection of radiolabelled PAHs was associated with the LDL and HDL cholesterol fractions, compared with only 24% of the 2,3,6- trichlorophenol, suggesting that plasma lipoproteins are an important vehicle for transporting PAHs to their sites of activation in the arteries. There is also some evidence that ETS directly affects plasma lipoproteins. Moskowitz et al (1990) showed that adolescent children whose parents smoked had elevated levels of cholesterol and depressed levels of HDL, even after correcting for age, weight, height and sex. These effects were dose dependent; the greater the exposure to ETS, the greater the changes in these variables. High cholesterol and low HDL are important for the development of plaque. Data on cholesterol and HDL from adults married to smokers, however, do not show similar differences (Garland et al, 1985; Svendsen et al, 1987). To further elucidate the possible mechanisms by which PAHs induce atherosclerotic changes, Majesky et al (1983) gave White Carneau and Show Racer pigeons a single injection of benzo(a)pyrene, then looked for metabolites of the benzo(a)pyrene in aortic and hepatic tissues 48 hours later. White Carneau pigeons develop severe atherosclerosis by the time they are 3 years old, whereas Show Racer pigeons are relatively resistant to aortic atherosclerosis. Aortic preparations of the White Carneau strain exhibited a much greater inducibility of the microsomal monooxygenase system than did those of the Show Racer strain, particularly in young pigeons. Aortic tissues from White Carneau pigeons aged 6-12 months exhibited a 3-12 fold inducibility whereas aortic tissues from the same strain at 2-5 years of age exhibited only minor (maximum of 3.3 fold) and, for the most part, statistically insignificant increases. No age differences in inducibility could be detected in the Show Racer strain. Interestingly, the differences in inducibility manifest in aortic tissues were greater in aortic tissues than in hepatic tissues from 94 ~ - TIMN 0030113

Draft - Do not cite or quote the same birds. Thus, the PAHs seem to accelerate any preexisting tendency to deve.lop atherosclerosis. Regardless of the ultimate mechanism by which PAHs exhibit atherogenic effects, it seems logical to suppose that the reactive intermediary metabolites of these chemicals are the proximate atherogenic or co-atherogenic agents since the parent compounds are relatively inert both chemically and biologically. Thus, bioactivation and inactivation. (and regulatory control of these processes) may 'be presumed to play extremely important roles in their atherogenic properties. Bioactivated chemicals vary in their stability/reactivity according to four general categories: (i) those which are extremely unstable and persist only at the immediate site (enzyme) of bioactivation, (ii) those which persist only within cells in which bioactivation occurs, (iii) those which persist primarily only within tissues in which bioactivation occurs, and (iv) those capable of being transferred in the circulation from one organ to another. For the first three of these four categories, biotransformation in the aorta per se (target tissue activation) would be of prime interest and importance. Thus, it appears that PAHs could be playing either a tautagenic or mitogenic role in beginning the atherosclerotic process in suscpptible cells or individuals, depending on how the PAHs in ETS are metabolized in the aorta. The finding that enzymes that metabolize DMBA and benzo (a) pyrene are in the artery wall led Penn et al (1986) to search for specific molecular events in plaque cells that would lead to DNA changes similar to those previously found in tumors. Identification of stich processes would be supportive of the monoclonal hypothesis of atherogenesis. They obtained human DNA samples from coronary artery plaques as well as DNA from normal sections of the coronary arteries at surgery to remove the plaque. These DNA samples were tested with the NIH 3T3 cell transection assay. Foci arose in cells transfected with each of the DNA samples obtained from the huiwn coronary plaque, with an efficiency (number of foci per µg of DNA) ranging from 0.016 to 0.060 (mean 0.036). The transfection efficiencies for DNA's from normal coronary artery, liver, spleen, lung, kidney and trachea were all below 0.00.8. The transformed cells were also injected into the scalps of nude mice, where they developed tumors. These results provide direct evidence for similarities on the molecular level in the development of plaques and tumors. Human coronary artery plaque DNA contains sequences capable of transforming NIH 3T3 cells and these transformed cells can cause tumors after injection into nude mice. Control experiments verified that the transforming cells did indeed contain human DNA and that the tumorigenic (or transforming) activity was not due to the z~~as.oncogene family. Although these results clearly demonstrate that human plaque DNA has transforming ability, the temporal expression of this activity in vivo is not known. The plaques were taken from adult patients in late stages of vascular disease. Thus, we cannot determine from these samples whether the 95 TIMN 0030114

Draft - Do not cit2 or quota manifestation of transformation is a relatively late event in plaque development or an early but stable event. oncogene activation and expression is an important early event- in transfor:aation and tumor genesis. These results identify specific molecular events that may underlie the proliferation of smooth muscle cells that is a hallmark of atherosclerotic plaque development and demonstrates that plaque cells exhibit molecular alterations that had previously only been thought to be present in cancer-cell transformation and tumorigenesis. These results provide direct support for the monoclonal hypothesis. Randerath et al (1988) also demonstrated that constituents of cigarette "tar," including benzo(a)pyrene, are preferentially attracted to the heart and damage DNA there. They studied molecular mechanisms of smoking-related carcinogenesis by examining the induction and distribution of covalent DNA damage in internal organs of the mouse following topic application of cigarette smoke condensate daily for 1, 3, or 6 days then killed 24 hr later. DNA samples were obtained from skin, lung, heart, kidney liver, and spleen. Adducts containing benzo(a)pyrene-derived moieties were identified, together with others. At all three times, the number of adducts in heart and lung DNA was about five times higher than that in liver and slightly higher than that in skin. Covalent DNA damage was estimated to be 6.2, 5.7, 3.9, and 1.9 times higher, respectively, in lung, heart, skin and kidney than in liver, ranging from approximately 1 adduct in 5.4x106 DNA nucleotides in lung to 1 adduct in 3.3x10~ DNA nucleotides in liver. Spleen DNA was virtually adduct free. While the DNA adduct profiles resembled each other qualitatively among the different tissues, there were major quantitative differences between the different•tissues, with the highest DNA binding occurring in the lung and heart. The reasons for the high incidence of DNA adducts in the heart are not known, but may be related to the role of plasma lipids in transaor;.ing ?AHs such as benzo(a)pyrene and preferential binding of these ?ipids to cardiac tissue, as discussed earlier. In sum, there is a growing body of evidence at a molecular level supporting the monoclonal hypothesis of atherogenesis, with compounds in tobacco smoke and ETS strongly implicated as agents which stimulate the devel'opment of coronary lesions. Regardless of whether the monoclonal hypothesis proves to be true (or, more likely, one of several initiators of the atherosclerotic process), the fact is that there is clear evidence that components of ETS, in particular PAHs such as benzo(a)pyrene, initiate or accelerate the development of plaque. These biochemical findings are consistent with the epidemiological finding that chimney sweeps, which are exposed to high levels of PAHs in soot, have an increased risk of heart disease (as well as cancer) and tend to develop these diseases younger than other, comparable, occupations which avoid exposure to PAHs (Hansen, 1983). Summary T'1'IN 0030115 96

Draft mDo cite or quoue There are eleven epidemiological studies, done in a variety of locations, which reflect a 30% increase in risk of death from ischemic heart disease or myocardial infarction among nonsmokers living with smokers. The larger studies also demonstrate a statistically significant dose-response effect, with larger exposure to ETS being associated with greater risks of death from heart disease. These epidemiological studies are complemented by a variety of physiological and biochemical data from human studies which suggest that ETS may adversely affect platelet function and damage arterial endothelium in a way that increases the risk of heart disease. Moreover, ETS, in realistic exposures, also exerts significant effects on exercise capability of both normal people and people with heart disease by affecting the body's ability to deliver and utilize oxygen. In animal experiments, ETS also depresses cellular respiration at the level of mitochondria. The polycyclic aromatic hydrocarbons in ETS also accelerate, and may initiate, the development of atherosclerotic plaque. It is also important to note that the cardiovascular effects of ETS appear to be different in nonsmokers and smokers. Nonsmokers appear to be more sensitive to ETS than smokers, perhaps because some of the affected systems are sensitive to low doses of the compounds in ETS, then saturate and also perhaps because of physiological adaptions smokers undergo as a result of chronic exposure to the toxins in cigarette smoke. In any event, these findings indicate that, in terms of cardiovascular disease, it is unreliable to compute "cigarette equivalents" for passive exposure to ETS, then t:ry to extrapolate the effects of this exposure on nonsmokers from the effects of direct smoking on smokers. These results combine to suggest that heart disease is an important consequence of exposure to ETS. The combination of epidemiological,studies with demonstration of physiological changes with exposure to ETS, together with biochemical evidence that elements of ETS have significant effects on the cardiovascular system, lead to the conclusion that ETS causes heart disease. This increase in risk translates into about 10 times as many deaths from ETS-induced heart disease as lung cancer, and contributes 37,000 to the estimated 53,000 deaths annually from passive smoking (Wells, 1988). This toll makes passive smoking the third leading preventable cause of death in the United States today, behind active smoking and alcohol. TV_N 0030116 97

Draft - Do not cite or quote References Albert R, Vanderlaan F, Nishizumi M (1977) Effect of carcinogens on chicken atherosclerosis. Cancer Res. 37: 2232-2235. Allred EN, Bleecker ER, Chaitman BR, Dahms TE, Gottlieb SO, Hackney JD, Pagano M, Selvester RH, Walden SM, Warren J(1989) Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease. N. Engl. J. Med._321: 1426- 32. Aronow W (1978) Effect of passive smoking on angina pectoris. N. Engl. J. Med. 299: 21-24. Bardford-Hill A (1984) A Short Textbook of Medical Statistics London: Hodder and Stoughton (11 ed.) Barrett T, Gajdusek C, Schwartz S, McDougall J, Benditt E (1984) Expression of the sis gene by endothelial cells in culture and in viv4. Proc. Nat. Acad. Sci. 81: 6772-6774. Benditt E, Benditt J (1973) Evidence for a monoclonal origin of human atherosclerotic plaques. Proc. Nat. Acad. Sci. 70: 1753- 1756. Burghuber 0, Punzengruber C, Sinzinger H, Haber P, Silberbauer (1986) Platelet sensitivity to prostacyclin in smokers and non- smokers. Chest 90: 34-38. Butler T (1990) The relationship of passive smoking to various health outcomes among Seventh-Day Adventists in California. Seventh World Conference on Tobacco and Health, 316 (abstract). Davis J, Hartman C, Lewis H Jr, Shelton L, Eigenberg D, Hassanein K, Hignite C, Ruttinger H(1985b), Cigarette smoking-induced enhancement of platelet function: Lack of prevention by aspirin in men with coronary artery disease. J. Lab. Clin. Med. 105: 479- 483. Davis J, Shelton L, Eigenberg D, Hignite C, Watanabe I(1985) Effects of tobacco and non-tobacco cigarette smoking on endothelium .and platelets. Clin. Pharmacol. Ther. 37: 529-533. Davis J, Shelton L, Eigenberg D, Hignite C (1987) Lack of effect of aspirin on cigarette smoke-induced increase in circulating endothelial cells. Haemostasis 7: 66-69. Davis J, Shelton L, Hartman C, Eigenberg D, Ruttinger H (1986) Smoking-induced changes in endothelium and platelets are not affected by hydroxyethylrutosides. Br. J. Exn. Path. 67: 765-771. Davis J, Shelton L, Watanabe I, Arnold J (1989) Passive smoking 9 $ TIMN 0030117

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Draft - Do not cite or quote Hansen E(1983) Mortality from cancer and ischemic heart disease in Danish chimney sweeps: A five-year follow-up. Am. J. Eoidemiol. 117: 160-164. Hartman P (1983) Mutagens: Some possible health impacts beyond carcinogenesis. Environ. Mutaaen. 5: 139-152. He Y (1989) Women's passive smoking and coronary heart disease. Chuna-Hua-Yu-Fana-I-Hsueh-Tsa-Chin 23: 19-22. (English translation of entire article.) Helsing K, Sandler D, Comstock G, Chee E (1988) Heart disease mortality in nonsmokers living with smokers. Am. J. Eoidemio_1. 127: 915-922. Hirayama T (1984) Lung cancer in Japan: Effects of nutrition and passive smoking. In Lung Cancer: Causes and Prevention M. Mizell and P Correa eds, pp 175-195. Verlag Chemie International, New York. Hole D, Gillis C, Chopra C, Hawthorne V (1989) Passive smoking and cardiorespiratory health in a general population in the west of Scotland. Br. Med. J. 299: 423-427. Hugod C, Hawkins LH, Kjeldsen K, Thomsen HK, Astrup P (1978) Effect of carbon monoxide on aortic and coronary intimal morphology in the rabbit. Atherosclerosis 30: 333-342. Hugod C (1981) Myocardial morphology in rabbits exposed to various gas-phase constituents of tobacco smoke. Atherosclerosis 40: 181- 190. Humble C, Croft J, Gerber A, Casper M, Hames C, Tyroler H (1990) Passive smoking and twenty year cardiovascular disease mortality among nonsmoking wives in Evans County, Georgia. Am. J. Pub. Health 80: 599-601. Jarvis MJ (1987) Uptake of environmental tobacco smoke. in Environmental carcinogens: methods of analysis and exposure measurement: Vol 9: Passive Smoking O'Neill I, Bronnemann KD, Dodet B, Hoffman D(eds), Lyon France: IARC, pp. 43-58. Kawachi I, Pearce N (1989) Passive smoking in New Zealand (letter). N. Zeal. Med. J. 102: 479. Kawachi I, Pearce N, Jackson R (1989) Deaths from lung cancer and ischaemic heart disease due to passive smoking in New,Zealand. N, Zeal. Med. J. 102:337-340. Khalfen E, Klochkov V (1987) Effect of passive smoking on physical tolerance of ischemic heart disease patients. Ter. Arkh. 59: 112- 115. 100 TIMN 0030119

Draft - Do not cite or quote Kjeldsen K, Thomsen H, Astrup P(1974) Effects of carbon monoxide on myocardium: Ultrastructural changes in rabbits after moderate, chronic exposure. Circ. Res. 34: 399-348. Kristensen T (1989) Cardiovascular diseases and the work environment: A critical review of the epidemiologic literature on chemical factor.-s. Scand J Work Environ Health 15:245-264. Lamb D(1984) ]?hysioloay of exercise: Responses and adaptation. MacMillan Publishing Co.: New York. Lee P (1988) Misclassification of smoking habits and oassive smoking. A review of the evidence. International Archives of Occupational and Environmental Health. Berlin: Springer-Verlag. Lee P (1989) Deaths from lung cancer and ischaemic heart disease due to passive smoking in New Zealand (letter). N. Zeal. Med. J. 102: 448. Lee P (1990) An estimate of adult mortality in the United States from passive smoking: A response (letter). Environ. Int. 16:179- 181. Lee P, Chamberlain J, Alderson M (1986) Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases. Br. J. Cancer 54: 97-105. Lough J(1978) Cardiomyopathy produced by cigarette smoke. Arch. Pathol. Lab. Med. 102: 377-380. Majesky 1.4, Yang H, Benditt E (1983) Carcinogenesis and atherogenesis: Differences in monoxygenase inducibility and bioactivation of benzo[a]pyrene in aortic and hepatic tissues of atherosclerosis-susceptible versus resistant pigeons. Car.cinoaenesis 4: 647-652. Martin M, Hunt S, Williams R (1986) Increased incidence of heart attacks in nonsmoking women married to smokers. Paper presented at annual meeting of APHA, October. McMurray R, Hicks L, Thompson D (1985) The effects of passive inhalation of cigarette smoke on exercise performance. Eur. J. A_pml. Physiol. 54: 196-200. Moskowitz W, Mosteller M, Schieken R, Bossano R, Hewitt J, Bodurtha J, Segrest J(1990) Lipoprotein and oxygen transport alterations in passive smoking preadolescent children: The MCV twin study. Circulation 81: 586-592. Muhm J, Olshan A (1989) A program to calculate sample size, power, and least detectable relative risk using a programmable calculator. 101 - _ 7CIMN 0030120

Draft - Do not}cite or quote Am. J. Epidemiol. 129: 205-11. NRC (1986) Environmental Tobacco Smoke: Measuring Exposure and Assessing Health Effects. Washington DC: National Academy Press. Palmer J, Rosenberg L, Shapiro S (1988) Passive smoking and myocardial infarction. CVD Epid. Newsletter 43: 29, 1988 (abstract) Penn A, Batastini G, Soloman J, Burns F, Albert R (1981) Dose- dependent size increases of aortic lesions following chronic exposure to 7,12-Dimethylbenz(a)anthracene. Cancer Res. 41: 588- 592. Penn A, Garte S, Warren L, Nesta D, Mindich B (1986) Transforming gene is human atherosclerotic plaque DNA. Proc. Nat. Acad. Sci. 83: 7951-7955. Pittilo R, Mackie I, Rowles P, Machin S, Woolf N (1982) Effects of cigarette smoking on the ultrastructure of rat thoracic aorta and its ability to produce prostacyclin. Thromb. Haemostas 48: 173-176. Randerath E', Mittal D, Randerath K(1988) Tissue distribution of covalent DNA damage in mice treated dermally with cigarette 'tar': preference for lung and heart DNA. Carcinoaenesis 9: 75-80. Reinken J (1989) Passive smoking in New Zealand (letter). N. Zeal. Med. J. 102: 515. Remmer H (1987) Passively inhaled tobacco smoke: A challenge to toxicology and preventive medicine. Arch. Toxicol. 61: 89-104. Repace J, Lowrey A (1985) A quantitative estimate of nonsmokers' lung cancer risk from passive smoking. Environ. Int. 11: 3-22. Repace J, Lowrey A (1987) Predicting the lung cancer risk of domestic passive smoking. Am. Rev. Resp. Dis. 136: 1308. Revis N, Bull R, Laurie D, Schiller C (1984) The effectiveness of chemical carcinogens to induce atherosclerosis in the white carneau pigeon. Toxicology 32: 215-227. Rogers WR, Bass RL III, Johnson DE, Kroski AW, McMahan CA, Montiel MM, Mott GE, Wilbur RL, McGill HC Jr (1980) Atherosclerosis-related response to cigarette smoking in the baboon. Circulation 61: 1188- 1193. Rogers WR, Carey KD, McMahan CA, Montiel MM, Mott GE, Wigodsky HS, McGill HC Jr (1988) Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon. Expt. Molec. Path. 48: 135-151. 102 TIMN 0030121

Draft m Do not cite or quote Ross R (1986) The pathology of atherosclerosis -- An Update. N. Engl. J. Med. 314: 488-500. Rothman K(1978) A show of confidence. N. Enai. J. Med. 299: 1362-1363. Saba S, Mason R (1975) Some effects of nicotine on platelets. Throm. Res. 7: 819-824. Serabjit-Singh C, Bend J, Philpot R (1985) Cytochrome P-450 monooxygenase system: Localization in smooth muscle of rabbit aorta. Mo ec. Pharmacol. 28: 72-79. Sheps D, Adams K Jr, Brombarg P, Goldstein G, O'Neil J, Horstman D (1987) Lack of effect of low levels of carboxyhemoglobin on cardiovascular function in patients with ischemic heart disease. Arch. Env. Hea:Lth 42: 108-116. Sinzinger H, Kefalides A (1982) Passive smoking severely decreases platelet sensitivity to antiaggreatory prostaglandins. Lancet 2(8294): 392-393. Sinzinger H, Wirgolini I(1989) Are passive smokers at greater risk of thrombosis? Wiener klinische Wochenschrift 20: 694-698. Svendsen K, Kuller L, Martin M, Ockene J (1987) Effects of Passive Smoking in the Multiple Risk Factor Intervention Trial. Am. J. Egidezaiol._ 126: 783-795. Thomsen H, Kjeldsen K (1974) Threshold limit for carbon monoxide- induced myocardial damage. Arch. Environ. Health 29: 73-78. USPHS (1983) 'I'he Health Conseauences of Smoking: Cardiovascular Disease: A reriort of the Surgeon General. DHHS(PHS) 84-50204. USPHS (1986) The Health Conseauences of Involuntarv Smokinc: A report of the Surgeon General. DHS(CDC)87-8398. Wald N (1986) Does breathing other people's tobacco smoke cause lung cancer? Br. Med. J. 293: 1217-1222. Wall MA, Johnson J, Jacob P, Benowitz NL (1988) Cotinine in the serum, saliva, and urine of nonsmokers, passive smokers, and active smokers. A3_._ J. Pub. Health 78: 699-701. Wells A (1986) Misclassification as a factor in passive smoking risk. Lancet ii: 638. Wells A (1988) An estimate of adult mortality in the United States from passive smoking. Environ. Int. 14: 249-265. 103 TIMN 0030122

Draft - Do not cite or c:ttote L'zssis Smoking and Ileart Disea.e: EPidemiology, Physiolo, and Biochemistry CR900223R3 TABLE 1. - ---- -- - - tabie I ~ Eaidemiotogieat Studies of €nvirormentat Tobacco Smoke and Coronary Hesrt Oisease 0eath C f Ausisqe• Typ.a Looation Deaths Relativ. 9SX Oosa Power° ControllirN for: or Risk Confid.ncs ResponsefD Cases Intervai Wes Giltis at ala P Seattand 32 1.3 0.7 - 2.6 - 5% age ! (1984) Lee at als C United 41 1.2 0.6 - 2.6 - 4% a4e, maritai status I , (1986) Kinqdan~ Svendsen at P United States 13 2.1 0.7 - 6.5 Yes 3% I age, blood pressure, ; al'o (1987)° sarum etlolast.rol, ~ wight, eaucation, ateohol 0 Hetsinq et P Marytard 370 1.3 1.1 • 1.6 No 40% age, m.rital status, ; att' (1988) '+ousing edJcation Poat w' 1.3 1.1 - 1.6 Fe..la~ Hfrsyaau 12 P Japan 494 1.2 0.9 - 1.4 Yes 40% age, diet I (t9aL) Gittis at ala P ScotLand 21 3.6 0.9 -13.E - 2% aao (19EL) ~ Garlard at P Catifornia 19 2.7 0.9 -13.6 - 22 age, blood pressure, ~ at'3 (1985) ptasma chotesterol, reight years of marriage ' Le. at at° C I united 77 0.9 0.5 • 1.6 - 6% i age, aarital status t (1986) Kfngdam Martfn at a(" C Utah 23 2.6 1.2 • 5.7 - 3% a9a, family history of C1486) CNO, hypertension, diabetes, wight, aicohol, exereist Hetsinq at P Marytand 988 1.2 1.1 - 1.4 Yes 92% age, housinq, erritai ~ at" (1968) status education ' He (1989)'s C Chin. 34 1.5 1.3 • 1.3 Yes 3% aQe, race, residence, oceupation, hypertension, faoily history of hypertension or CNO, . atcohol, exercise, h rlfpidasia Huabte et at1e P Georgia 76 1.6 1.0 • 2.6 Yes 8% age, serua chotesterot, ~ (1990) blood oressure weight eutter'a P Caiifornia 64 1.4 0.5 - 3.3 - 4% age (1990) - Pooted --T 1.3 i 1.2 - 1.4 -i i i TIMN 0030123 .~Wmanu~,~:s,~~.dix

Draft ° DO not ci-ce or cuaLe ing and Hmrt D6seasc Epademiology, Physiolo~,, and Btocfiemistry CR9O02liR3 Type& Location Oeaichs Retativf 95% Oose Aowr° Ccntrottinq tar; ~ or Risk Contidusee Respons.?s ~ Casas Intarvat ~ o.bined . P ~. ~~. Scottand 3b 2.a 1.2 - 3.10 - 10Z ~ lqe, sax, soeist etsas, ~ btood pr*ssur., ~ elio(estarot, weignt ± I 1.3 1.2 - 1.6 iw cohart, Ca Case control M s coluan indicates no comwnt on the presame or sbsar+cs of dose-respanse rststior>shfp et retative risk of 1.2 with 95X confid.nes sutation; nrntaars of NRftT trist °ve risk cortouted as R= exif CT ti, ln 1~ /mw~) s+her* +y •<Z/in R,)= s a Later follow-up of the poputnticn reportad in Gittis .t sl~ :~rroin.d without regard for s.x, with Gitlis et ata exetud.d beeaus~e Mote et al~~ r:oort Later fotlor-~ja on :he TIMN 0030124 Tabie 1 £pidemiotoqicat Studies of Enviran+rntal Tooscco Smoko ar.i Coronary Meart Oisease 0eath I DILQoC

Draft - Do not cite or quote -'assive Smoking and Heart Diseasc::E:)idemioIogy,,Physiolo, and:Btoc3iesaaistry- CR900213R3 Tabi• 2 I "cffec: of Pessive and Active Smoking on Plstsiet Aggregstion and EMothelial Call Oam.q ie- ~ Platelet Aqgrr9ate Ratio Endotheliat Call Count ~ n I Bafor* After Chang. Bafors After ~ Change ~ @ Passiv. S.okinp .37 .7a -.09 2.3 3.7 0.9 I 10 ~ (nonsrtcker) . ' Tobaccc (r~on.aio~ter) ~ .?A .65 -.15 2.3 4.3 2.5 20 E vs. f Non-tt,b.eeo .aT .7a -.03 2.5 3.0 0.5 cigarette e (nOnsimDKer) ~ t ' inhsl* cigarette I .31 .68 -.13 4.0 5.4 1.4 24 (smoker) vs. tlot innate cigarstte ~ .32 .73 -.09 3.3 4.7 1.4 22 rnonsmoKer) I f Smoke (smousr) vs. ~ .35 .:0 I •.1S ~ 4.4 I 6.4 2.0 ' 17 I I Snuff ~smocer .32 .76 3.9 4.7 I 0.8 ' I NOUN yotas: ALL studies are paired and reflect significant differences (P<.005). Placalet ag9regate ratio is the ratio of platelet count of pistelet•rich plasme, prepared in+rdiately after venipuncture with a solution containing edetic acid and formeldehyde, to that of platelet-rich plasm. prep.rsa in the sanr oarner, except for the absanes of forraeldehydi. A deeraase in the platalet aQpregate ratio reflects an increasad formation of platelet aggregates. Endotheliat call count is mean nuab.r of anuctear call carcasses in 0.9 icL chambers. Source: Oavis et al47'y'bt,U TIMN 0030125 `.t,iantzmana=\eucols.tloc

oraft - oo not cite- or quote Tabi• 3 ~ Plata! a Sensitivity to Prastaqlardins S.fors and After Pfssive Saro/cirq (nq PG/ml p(atetet rieh p(asar) ~ ~Orostaqlandin I Siefora , After I 20 min ~ 60 min I Yoresacears I 1.26s0.11 2.16t0.21' 1.76s0.21' 1.35*0.19 €z 1a.7s3.1 32.ss6.2' 2a.2s6.1° 2i.7s2.a q„ 42„7s3,a 55.6:5.3 51.3*4.2 ".bs4.1 ~ s'mahsra f ! 1.79t0.2b 2.0as0.16 2.06s0.15 1.93*0.23 ~ ILI 27.Dt2.3 30.6*3.5 31.0*4.1 29.1s2.9 ~ ~.9:4.1 43.624.3 4,9.4s3.7 45.2s3.a ~ I a<.01 coawred to eontrol. Usutts are mean s SE)/. Sourca: Sinzing.r and K.fatidas (1982) a' gian czlmanuscnlepa3.doc TIMN 0030126

Draft - Do not cita or quote Wells A (1990) An estimate of adult mortality in the United States from passive smoking: A response to criticism. Environ. Int. 16: 187-193. Wikstrand J, Warnold I, Olsson G, , Tvomilehto J, Elmfeldt D, Berglund G (1988) Primary prevention with metoprolol in patients with hypertension: Mortality results from the MAPHY trial. aAMA 259: 1976-1982. TIMN 0030127 104

Draft - Do not cite or quote FIGIIRES AND TABLES, CHAPTER 6 105 TIlVjN 0030128

Draft~- Do not cite or quote P:zssi,e-Sraoking and I3eart Disr.ase: Epidemiology, Physiologr, and Biochemistry CR900213R3 TABLE 1. Table 1 i Eaidemio(ogical Studies of Envirormental Tobacco Smoke and Coronary Heart Oiseese Dest 'h Author Types Location Deaths Relatiw 9Sx Oose Power° Controltin4 for: or Risk Confidenee Response?D Cases Interval i ~ Maies ~ Gittis at ala P Scottand 32 1.3 0.7 - 2.6 - 5% age I C1984) Lee at at° C United 41 1.2 0.6 - 2.6 - 4% age, arrital status (1986) KKingdom Svendsen at P United States 13 2.1 0.7 - 6.5 Tes 3% age, blood pressure, ~ atso (19a7)d serum cholesterol, s weight, education, I alcohol ~ Hetsing et P Maryland 370 1.3 1.1 - 1.6 Mo 40% age, merital status, I at " (1988) housing edueati ion S Paoted' 1.3 1.6 j Few.l es Hirayama12 P Japan 494 1.2 0.9 - 1.4 Yes 40% age, diet (19lu.) Gittis at ata P Scottand 21 3.6 0.9 -13.3 - 2% aQe C1984) Garland et P California 19 2.7 0.9 -13.6 - 2% age, blood pressure, ~ ~ at1o (1985) p(asma cholesterot, weight years of marriage C Lee et ala C United 77 0.9 0.5 - 1.6 - 6% age, marital status ~ ~ (1986) Kingdom ~ Martin et a114 C Utah 23 2.6 1.2 - 5.7 - 3% age, family history of C1966) CHO, hypertension, diabetes, weight, aleohot, exereise Helsing et P Naryland 9W 1.2 1.1 - 1.4 Yes 92% age, housing, marital attt (1988) status education He C1989)iS C Chin. 34 1.5 1.3 - 1.3 Yes 3% ag., race, residence, oceupetion, hypertension, fami ly history of hypertension or CNO, aicohol, exercise, h rtipidemia Humble et at'e P Georgia 76 1.6 1.0 - 2.6 Yes 8% age, serum eholesterol, (1990) biood pressure weight Butterte P California 64 1.4 0.5 - 3.3 - 4% age (1990) Pooled 1.3 1.2 - 1.4 TIMN 0030129 e'y;1anWmanuscn*\etscois.doc

Draft e Do not cita or qu ote hui.re Smoicing and Heart Diseo:m Epideaaiology, Physioloo and Bioc3iemistry, CR9002liR3 - _.~. Tabie 1 Death Epide+niotogicai, Studies of Erniron+rntat Tobacco Smok• and Coronary keart Disease I .Author Typea Location Deaths Reiative 95% Dosa Power° Ccntrollinq for: or Risk Confidence Response?a Cases intervai Rotlt sexes cambined Not• at al'T P Scotlaroi 84 2.0 1.2 • 3.4 • 10% aae, sax, sociaL ciass, Ct4d91 t blood pressure, eholesteroi, weight aoele~ 1.3 1.2 • 1.4 `P = Prospective cohort, C= Gae control Na entry in this coluan indicatiis no coament on the presance or absenc: of dosa-respossse reiationship `?ores° to detect retative risk of 1.2 with 95% confidencs ~iiglt risk population; monbers oi' MRfIT triaL 'Poolad relative risk computed as R= exp (Z w~ ln R, /Z6~) where w, (Z/tn RI)s ~Tltis report is a Later follor•up of the poputation reported in Gillis et ala ';1t[t studies cambined without resiard for sex, with Giltis et ala excluded beswse Hole et al'? report later follow•up on the sawe pooote- r TIlVIN 0030130

Draft - Do not cite or quote PUsive Smoking 2nd Heart Disease: Epidemioiogy, Physiology, and Btociumis~ CR900213R3 ( Table 2 _ffect of Passive and Active Smoking on Ptatelet Aggregation and Endothelial Catt Damage ~ ( i Platetet Aggregate Ratio Endothetial Cstl Count n Before After Change Before After Change Passive Saiokinp .87 .73 -.09 2.3 3.7 0.9 10 (nonsmaker) Tobacco (nonsmoksr) I .30 .65 -.15 2.3 4.8 2.5 20 vs. Nan-tob.cca .81 .73 -.03 2.5 }.0 0.5 cigarette (nonsmoker) f ° Inhate cigarette ~ .81 .68 -.13 4.0 5.4 1.4 24 ! (smoker) vs. Not inhate cigarette ~ .32 .73 -.09 3.3 4.7 1.4 22 (nonsmoker) ~ Smoke (smok.r) vs. ( ! .35 .70 -.15 4.4 6.4 2.0 I 17 Snuff (smoxer) EEE .32 ..'6 -.06 3.9 4.7 0.8 Notes: ALL studies are paired and reflect significant differences (P<.005). Placelet aggregate ratio is the ratio of ptatelet count of piatelet-rich plasma, prepared inmediately after venipuncture with a solution containing edetic acid and formaldehyde, to that of ptatetet-rich plssms prepared in the same marner, except for the absetxe of formaldehyde. A decrease in the piatelet aggregate ratio reftects an increased formation of ptatelet aggregates. Endothelial call count is mean number of anxlesr cell carcasses in 0.9 ut chambers. Source: Davis et at~~'~ st'~ TM'IN 0030131 cl4iantxitstanttscn\atscolsdoc

Draft - Do not cite or quote Table 3 Ptatelet Sensitivity ta Prosta9tarsiins Before and After Passive Smoking (ng PGlml ptateiet rich ptasms) Prostagiandin I 8efore ' After ( 20 min ~ 60 min I WACIMMIMIM yonsookers I 1.26s0.11 2.16s0.21' 1.T6s0.21' 1.35*0.19 ta.Ts3.1 32.Ss4.2' 28.224.1 ~ 2t.Ts2.3 0 42.T33.3 55.6:.5.3 51.3t4.2 44.6s4.1 Satshers I 1.75*0.26 2.0as0.16 2.06*0.15 1.93t0.23 Z7.as2.3 30.6s3.S 31.0s4.1 29.1s2.9 p2 44.9t4.1 4E.6s4.3 49.8*3.7 45.2:3.E Pe,01 coaaared t® controt. Results are mean t SE?1. Soures: Sinzinger and Kefatides (1982) G1glanuVnanuscnlepa3.doc 'I'IMN 0030132

Draft - Do not cite or quote FIGURE CAPTIONS Figure 1: Relative risk in epidemiological studies of the risk of death from coronary heart disease or myocardial infarction among nonsmokers living with smokers compared with nonsmokers living with nonsmokers. Lines indicate 95% confidence intervals. (Note that two studies have upper bounds to confidence interval off the scale of the graph.) Figure 2: Effect of passive smoking on myocardial mitochondrial respiration. Q02(S3) = oxygen consumption in mitochondria in the presence of the substrate and ADP; QOZ (S4) = capacity of respiratory chain without ADP added; OPR = oxidation phosphorylation rate; ADP:O = oxidation phosphorylation coefficient; RCI = respiratory control index. Source: Gvozdjak et al (1987) Figures 1 and 2. Figure 3: Effect of active (left) and passive (right) smoking on platelet aggregation in smokers and nonsmokers. The sensitivity index, SIpGiZ, is defined as the inverse of the concentration of prostaglandin 12 necessary to inhibit ADP-induced platelet aggregation by 50 0. Lower values of SIpG12 indicate greater platelet aggregation. Source: Burghuber et al (1986) Figures 3 and 4. Figure 4: Advanced intimal lesions of atherosclerosis may occur by at least two pathways. The pathway demonstrated by the clockwise (long) arrows to the right has been observed in experimentally induced hypercholesterolemia. Injury to the endothelium (A) may induce growth factor secretion (short arrow). Monocytes attach to endothelium (B), which may continue to secrete growth factors (short arrow). Subendothelial migration of monocytes (C) may lead to fatty-streak formation and release of growth factors such as platelet-derived growth factor (PDGF) (short arrow). Fatty streaks may become directly converted to fibrous plaques (long arrow from C to F) through release of growth factors from macrophages or endothelial cells or both. Macrophages may also stimulate or injure the overlying endothelium. In some cases, macrophages may loose lose their endothelial cover and platelet attachment may occur (D), providing three possible sources of growth factors -- platelets, macrophages, and endothelium (short arrows). Some of the smooth-muscle cells in the possible lesion itself (F) may form and secrete growth factors such as PDGF (short arrows). An alternative pathway for the development of advanced lesions of .atherosclerosis is shown by the arrows from A to E to F. In this case, the endothelium may be injured but remain intact. Increased endothelial turnover may result in growth-factor formation by endothelial cells (A). This may stimulate migration of smooth- muscle as well as growth factor secretion from the "injured" endothelial cells (E). These interactions could then lead to fibrous-plaque formation and further lesion progression (F). The PAHs in ETS probably act by the second pathway. Source: Ross (1986) Figure 6. TIMN 0030133 110

Draft °' DO IiotC1'ts., Or qt10tE,.' FIGi7R£S AND TABLES. CHAPTER 6 111 --- TMN 0030134

Draft - Do not cite or quote pauiqwoo sapnis IIy + (686 L ) aloH ~ x a) U) s ~ 0 m (066 1.) alqWnH ) jalin8 (066 1 . (686 1.) aH (886 L ) 6uisiaH -+ ~ ~ ~ .; m (886 1.) aa-I -.- ~ I ~ ca ~ ~ ~a (S8(5 1.) puePeE) 5L. (It786 L ) SIII!S •+1 -I - eweAea' H } (r86 L ) (88(5 L ) 6uislaH -}- ~ _ _ _ ---------- (L8(5 1,) uaspuans i i (886 L ) aa~ E Q) LL i i (t~86 L ) S~II~`J ~ i ~ I` ~U LO (D anI;21% TIMN 0030135

= IGIJRE 3 e Lo St PGi2 , Draft --_ q- Pc.01 0.50 , 0 0 , BEFORE 0 BEFORE AFTER

Draft - Do not cite or quote A Nuuar -1 (m.ansnieal. LJL. homocgrstsine. fmmuno/aqte. to:ina. virusas aa) FIGURE 4. TIMN 0030137

Deaths from Passive Smoking Total Deaths: 53,000 Heart Disease 0 n Source: Welis, 1988

Draft - Do not cite or quote CHAPTER 7 EXPOSURE ASSESSMENT IN PASSIVE SMOKING James L. Repace, MSc Indoor Air Division Office of Air & Radiation U.S. Environmental Protection Agency Washington, DC 20460 Introduction This chapter will discuss some of the factors involved in the assessment of exposure to indoor air pollution from tobacco smoke. Exposures to environmental tobacco smoke (ETS) have been assessed by questionnaires, personal air contaminant monitoring of ETS constituents, modeling of concentrations, and biological markers. (NRC, 1986) Most of the epidemiological studies of passive smoking and disease have relied on questionnaires relating to the presence or absence of a smoker at home, and have assumed that this is a good surrogate for total exposure to ETS. To the extent that nonsmokers are heavily exposed outside the home, e.g., the workplace, this surrogate exposure variable will not differentiate well between a more exposed and less exposed group, and tend to cause epidemiologic studies of passive smoking and disease to find no effect or to lack statistical significance. (Repace & Lowrey, 1990) For this reason, several workers, in assessing risk from passive smoking, have attempted to correct for exposures outside the home by adjusting for the finite urinary cotinine concentrations in those who have reported "no exposure" to ETS. (NRC, 1986; Wells, 1990) No studies have yet been performed which yield a national probability sample of exposures to ETS. Thus, all attempts to assess exposure in individual epidemiological studies and otherwise have relied on some assumed paradigm of exposure. This chapter will discuss the evidence for exposure, and emphasize the insights which derive from a modeling approach. Exposure to ETS occurs when an individual occupies a microenvironment which possesses an ETS concentration. A dose is ,said to occur when the individual breathes the concentration. An individual's total exposure to ETS is the time-weighted sum of the individual microenvironmental ETS exposures encountered during the day's activities. (Repace et al., 1980). The dose of ETS will be affected by the individual's respiration rate during the exposures. The dose of various ETS constituents to the body will be determined by their relative rates of absorption and removal. The amount of ETS inhaled is given by the product of the individual's respiration rate during exposure, the ETS concentration in the building, and the duration of the individual's stay in that microenvironment. In 112 - TIlMN 0030139

Draft7- Do not cite or quote equilibrium, the ETS concentration is directly proportional to the product of number of smokers, smoking rate, and emissions per cigarette, pipe, or cigar, and is inversely proportional to the product of space volume and removal rate. (Repace, IARC, 1987) In the epidemiologic studies of passive smoking and lung cancer, exposures are typically estimated on the basis of a questionnaire which assesses smoking status, and typically ask simple questions of the sort: '® if you are a nonsmoker, do you live with, or work with, or have regular contact with persons who are nonsmokers?" (NRC, 1986) Some studies assess past exposure history and spouses' smoking rate as well. This kind of question, though useful, is not likely to be fully reliable or precise, particularly for non- domestic exposures. (NRC, 1986; IARC, 1987) On the other hand, it has been shown that those nonsmokers who report exposure to ETS at home tend to have higher non-domestic exposures as well. (NRC, 1986; Wald, 1986) Those individuals who have exposures both at home and at work appear to have higher exposures than those who are exposed at home only or at work only, as reflected by their urinary cotinine excretion. (Riboli, et al., 1990) Riboli et al. (1990) report data from a ten-country study of 1369 women, showing that when appropriately questioned, nonsmoking women can provide a 'reasonably accurate description of ETS exposure. Ideally, the health effects of ETS might be assessed by quantifying the time-dependent exposures for each of the several thousand compounds in tobacco smoke and defining dose-response relationships for these compounds in producing disease, both as isolated compounds and in various combinations. However, the enormity of this task has led to simpler approaches which attempt to use measures of exposure to individual smoke constituents as estimates of whole smoke exposure. For this reason, exposures to ETS are often assessed using markers of the vapor phase or particulate phase. Although biological markers show promise as measures of exposure (and dose), they also have limitations. Another consideration is duration of exposure. For chronic diseases such as cancer, average exposures occuring over a year or lifetime are of greater importance than short-term exposures.(SG, 1986) The two most promising atmospheric markers for ETS are respirable suspended particles in the size range <3 um (RSP) and nicotine.(NRC,1986; SG,1986; IARC,1987) A majority of field studies have used RSP as an indicator of exposure to ETS because of the substantial emission of RSP in indoor spaces from tobacco combustion. ETS is the dominant contributor to the indoor levels of RSP. The total RSP, as measured by personal monitors, has been found to be substantially elevated for those who report exposure to ETS relative to those who report no exposure. Both air monitoring and modeling clearly indicate that RSP concentrations will be elevated over background levels in indoor spaces when even low smoking rates occur.(NRC, 1986) Although lacking specificity 113 Tg1N 0030140

Draft - Do not cite or qtoz e for tobacco smoke, the prevalence and number of smokers correlates well with RSP levels in homes and other enclosed areas. (SG, 198 6) RSP is the single largest component of ETS by weight, and RSP is currently the best and most-utilized general category of air contaminants to represent ETS.(NRC,1986) A recent study of week- long averages of RSP and nicotine in about 100 homes with smokers in New York State showed an RSP-to-nicotine ratio of about 11:1, above a background of about 20 ug/m3. (Leaderer, 1990) Similar results were obtained in a survey of 21 commercial buildings by Miesner, et al. (1989), who found a RSP-to-nicotine ratio of about 10:1 for workday averages, above a background of about 23 ug/m3. Biological markers in body fluids have also been used for validating self-reports of exposures to ETS. For example, Haley et al. (1989) and Cummings et al. (1990) found that cotinine levels in the urine of those who reported exposure to ETS were more than twice as high as those who denied having been exposed. Nicotine and its metabolite cotinine, which derive exclusively from tobacco products, are the most important markers. Almost all nicotine shifts from the particulate phase in mainstream and fresh sidestream smoke to the vapor phase in ETS. Nicotine and cotinine can be quantified in saliva, blood, and urine. Generally, the mean concentrations of nicotine and cotinine in plasma or urine of nonsmokers exposed to ETS under natural conditions is about 1 percent of the mean values in smokers, (NRC,1986) reflecting the fact that smokers are present in nearly all environments, including most workplaces, restaurants, and even in many vehicles, making it almost impossible for nonsmokers to avoid exposure to ETS. (SG, 1986) A. Sources of ETS I In 1986, an estimated 50 million US smokers aged _>17 yrs smoked about 584 billion cigarettes annually. (NRC, 1986; Tobacco Institute, 1987) They consumed an additional 3.2 billion cigars, as well as an estimated 24.4 million pounds of tobacco for pipes and hand-rolled cigarettes.(NRC, 1986) The average US cigarette smoker smokes 32 cigarettes per day at a rate of 2 cigarettes per hour and emits about 22 mg of RSP per cigarette. (Repace, IARC, 1987) Since the average person spends about 90% of the time indoors, an estimated 12,000 metric tons of RSP are emitted into US indoor microenvironments each year from cigarette smoking alone. Assuming cigars produce 3 times as much RSP as cigarettes and that pipes produce as much RSP as a cigarette, (Repace and Lowrey, 1982) where pipes and hand-rolled cigarettes are assumed to contain 1 g of tobacco, then all cigars are estimated to contribute as much RSP indoors as 11 billion cigarettes, while all pipes and hand-rolled cigarettes are estimated to contribute as much as 15 billion regular cigarettes. This increases the estimated total RSP generated in US indoor microenvironments from all cigarettes, pipes, and cigars to nearly 13,000 metric tons per year. As exemplified by data from EPA's TEAM study, ETS predominates over 114 TIMN 0030141

Draft-- Do not cita or quote other sources of RSP indoors (see Fig. 1.) Although the percentage of the population that smokes has declined from nearly 50% in the 1960's to about 30% presently (OSH,1988), the percent of smokers who are heavy smokers has increased steadily over the past 30 years; thus although the percentage of smokers has gone down, the increase in smoking rate may tend to offset that trend towards lowering nonsmoker exposure to ETS.(NRC,1986). B. Indoor air transport of ETS Nonsmokers are exposed to ETS in indoor spaces. The determinants of these enclosed-space exposures include smoking occupancy, source air-contaminant emission characteristics, source use, building characteristics, space volume, infiltration or ventilation rates, efficiency of air mixing, surface sorption, chemical transformation, and the efficiency of air cleaning equipment. The interaction of these variables in determining the resultant concentrations of ETS has been evaluated in both eontrolled laboratory settings and in field studies within.the theoretical framework of the mass-balance equation. The mass- balance equation--may be applied to tobacco smoke either as an equilibrium model (time-independent) or as a dynamic model (time- dependent). Dynamic and equilibrium models are useful in laboratory studies; equilibrium models are best suited to evaluating and predicting ETS concentrations in field studies, particularly when average concentrations over a period of a workday or longer are of interest. (NRC,1986) Laboratory and field studies typically utilize some form of a single-compartment equilibrium model to evaluate the input parameters of the mass-balance equation, to evaluate field study data, and to project RSP concentrations from ETS indoors. These studies have reduced the general single-compartment mass-balance equation to the following simplified form: ~ C4M = G[m(N. + Ns)V]` (1), where Ceq is the equilibrium concentration of ETS-generated RSP3in a space, expressed in units of micrograms per cubic meter (ug/m ), G is the RSP generation rate from tobacco combustion in units of micrograms per hour (ug/hr), N„ is the ventilation or infiltration rate in units of airchanges per hour (ach), NS is. the loss rate of RSP due to surface removal in a space in air changes per hour, V is the volume of the space in cubic meters (m3), and m is the mixing rate (Repace, IARC, 1987) expressed as a fraction. The above model assumes no air-cleaning devices, either in the space or recirculated air; Leaderer (1984) has given a detailed review of this model. Under laboratory conditions, these input parameters can be controlled and evaluated. In conducting field studies or in estimating past RSP levels indoors, the values on the right side 115 TIMN 0030142

Draft - Do not cite or quote of eq.l have to be determined from available data. This equation assumes equilbrium conditions, and to the extent that any of the generation or removal terms are intermittent (e.g. smoking rate) or variable (e.g. ventilation rate), errors are introduced. (NRC,1986) According to the National Research Council (1986) the most extensive use of the mass-balance equation for assessing RSP levels due to ETS in occupied spaces has been by Repace and Lowrey (1980), who proposed and applied in field observations a condensed version of the mass-balance equation for estimating RSP exposures due to ETS in a variety of indoor microenvironments. Their model is: C*q = 650 Ds/N, (2), where C is the equilibrium concentration of RSP due to ETS in units of micrograms per cubic meter, D is the density of active smokers (burning cigarettes) observed in a space per 100 m3 over the sampling time, and N. is the ventilation or infiltration rate in ach. (NRC, 19 8 6) The constant term (650) is calculated from a standard set of assumed conditions for smoking rates, RSP emission rates, mixing factors, ventilation rates, and sink rates. These standard sets of conditions are derived largely from experimental data and building standards. In applying equilbrium mass balance models such as eq.(2), gathering data on "easily measured input. parameters such as smoking rates or volume can substantially reduce the variablity of the estimated RSP levels.(NRC,1986) Eq. 2 was validated under controlled experimental conditions in real world settings, and was found to predict the equilibrium values of ETS within a high degree of accuracy in exposure chambers using real smokers.(Repace & Lowrey,1980, 1982, Repace, IARC, 1987) Further, the predictions of the model were found to be consistent with RSP levels from ETS measured in the field. However, the NRC stated that additional field testing of eq.{2} as well as a better understanding of the variability of the input parameters was needed.(NRC,1986) In 1987, Rickert et al.(1987) tested a key theoretical assumption regarding the ratio between the effective and ventilatory air exchange rates in the constant term in eq. 2 (Repace, IARC, 1987) and found that the model explained 87% of the variation between observed and predicted values for RSP concentrations from ETS in their experiments. More recently, Repace(IARC,1987) has published a derivative of eq.2 which incorporate advances in understanding. Eq.{2} assumes a steady generation of tobacco smoke, which is generally only valid when 3 or more smokers are present in a space. For less than 3 smokers, it represents an upper bound. It is also Limited for modeling purposes by being based on the room density of active smokers. The derivative equation is based on the room density of habitual smokers (number of habitual smokers per unit space volume). Thus, the presence of an archetypical "habitual" smoker (i.e., one who is assumed to smoke at an average_ rate of 2 116 TIlVIN 0030143

Draft - Do not cite or quote cigarettes per hour at 10 minutes per cigarette, with an emission factor of about 22 mg of SS RSP per cigarette) is the modeling parameter rather than the room density of burning cigarettes. (IARC, 1987) This derivative equation is given as follows: Ceq - 217 Dhs/N1 (3), where C., is the equilibrium concentration in units of micrograms per cubic meter, Dh is the number of habitual smokers per 100 cubic meters of space volume, and N. is the number of space air changes per hour. Eq. 3 assumes that tobacco smoke concentration is in equilibrium, which occurs when the rate of generation equals the rate of remova]., and the concentration is in a steady state. This assumption presumes three or more smokers, since the average smoker smokes three c:Lgarettes per hour and takes ten minutes to smoke a cigarette. This means that with three smokers in a room, a cigarette will always be burning. (During growth, e. (3) becomes A= Ceq (1-exp-tN~) ; during decay, Ad ( t_T) = A exp-t v, where T is t~ie smoking duration. (Repace, 1987) A more d9etailed description of the derivation and validation of eq. 3 and the uses and limitations of these models is given by Repace, (IARC, 1987, chapter 3).) If the number of habitual smokers being modeled is only 2 or 1, steady-state conditions no longer apply, and other simple approximations have been suggested; (Repace (IARC, 1987) in lieu of using exact time-dependent growth and decay models. A one- smoker-approximation model proposed by Repace (IARC, 1987) agrees very well with the instantaneous predictions of an exact computer simulation performed by Rickert (1988), but significantly underestimates newly available field data, which represent time- averaged concentrations. On the other hand, by contrast, eq.(3) for less than 3 smokers represents an upper bound to the ETS concentration, and as is illustrated below, produces reasonable agreement with, and provides useful insights into, the analysis of field data. For example: As part of the the Harvard 6-City study of indoor and outdoor air quality, Spengler and colleagues (1981) collected RSP samples in 55 homes in 6 cities between May 1977 and April 1978. The number of smokers living in each home was recorded. The quantity of tobacco smoked was not reported, nor were the number of hours each smoker spent in the home or air exchange rates measured. The daily average "background," or mean indoor RSP level in the homes of nonsmokers was found to be about 24 ug/m3; using regression analysis, the authors estimated that the average impact of a single smoker (a composite averaged over both sexes) on 24-hr average RSP levels from ETS in a residence was about 20 ug/m3 above background. On average, two such habitual smokers would make about 40 ug/m3 above background (24-hr average), and so forth. Added to a background of 24 ug/m3, this yields a daily average RSP concentration for one smoker homes of 44 ug/m3, and for two-smoker 117 T1MN ®®3® 144

Draft - Do not cite or quote homes of 64 ug/m3. What does eq. 3 predict? Although'the air exchange rates were unknown, Fig. 2 shows a histogram of the frequency of occurrence of various air exhange rates (called infiltration rates) during the heating season for typical middle income housing (R. Grot, personal communication) for 266 homes in 14 cities around the US in 1978 (SG,1986). Occupants were asked to keep windows and doors closed during the tests. Under these conditions, the mean air exchange rate found was 1.1 ± 0.9 ach (Grot & Clark, 1979); this value is likely to be somewhat lower than a full seasonal average with no restrictions on door and window openings. The smoker density for a one-smoker home of volume 340 m3 has been given by Repace and Lowrey (1985) as Dh3 = 0.29 habitual smokers per 100 m'. Similarly, for a two-smoker home, Dha = 0.58. In•the absence of information on air exchange rates, let us assume, from Grot and Clark (1979), a rate, N,, = 1.1 ach. Then eq. 3 predicts a value of C~ = 217 x 0.29/1.1 = 57 ug/m3 during smoking, for a one smoker home, and 114 ug/m3 for a two-smoker home. From table Al for time budget studies in Repace and Lowrey (1985), averaged over employed men and women, and homemakers, the average amount of time spent awake in the home, (allowing for 8 hrs of sleep per day) is about 7.9 hours per day. Converting our calculations to a 24-hr average and adding a background of 24 ug/m3, yields an estimated 57 x 7.9/24 + 24 = 43 ug/m3 for a one- smoker home, and 114 x 7.9/24 + 24 = 62 ug/m3 for the two smoker home, in good agreement with the values of 44 ug/m3 and 64 ug/m3 from the 6-City study above. A comparison of the predictions of eq. 3 with 17 months of RSP data on 55 homes in 6 Cities (Spengler, et al., 1981) is given in fiq. 3. This example illustrates the utility of models in estimating nonsmokers' domestic exposures to ETS. As a second example, consider the measured aerosol mass concentration in a 700 m3 (25000 ft2 floor area) office with one smoker (smoking rate not reported), and a measured air exchange rate of 1 ach (see Fig. 4); the large impact on the office aerosol concentration caused by smoking is apparent by comparing the daytime and evening RSP concentrations.(IARC, 1987) The predictions of eq. 3 for Dhs = 1 smoker per 7 hundred cubic meters and N. 3 1• ach yields C = 31 ug/m3; with an 18 ug/m3 background added, the predicted RSP~level is 49 ug/m3, in good agreement with observations (fig 4). It is clear from fig. 4 and also from models, that ETS can be very persistent in indoor environments: at an air exchange rate of 1 ach, it takes 3 hrs for 95-% of the smoke from 1 cigarette to be removed (Repace, IARC, 1987) A third example, where more information is available on the smoking rates, home volumes and air exchange rates, is provided by the data obtained in the NYSERDA study of weekly average residential aerosol concentrations in 141 homes with 118 TIMN 0030145

Draft - Do not-cite or quote smokers.(Leaderer, et al., 1990) The measured weekly average RSP levels were 43 ug/m3 in the smoking homes, the background levels averaged 16 ug/m3 in the nonsmoking homes, the average air exchange rates were 0.54 ach, the average house volumes 353 m3, the average number of cigarettes smoked per week was 99.3, and the average number of hours of smoking per day is calculated at 7.1 hrs/day assuming 2 cig/smoker-hr (Repace and Lowrey, 1980). From this data, using eq. 3 as before, we calculate R= 217 x 0.28/0.54 x 7.1/24 + 16 = 49 ug/m3, in reasonable agreement with the observed average of 43 ug/m3, but higher, as expected. Thus, although eq. 3 for less than 3 smokers represents a simplified- upper-bound approximation, it has utility in producing estimates which are reasonably consistent with field data, and has the advantage that it is simple to use. However, since none of these studies were specifically designed for model validation, further comparisons with field data are important as new data sets become available. A sampling of whole-building air-exchange rates in 8 large federal office buildings in 7 states with different climates is shown in Fig. 5, and these generally approximate the ASHR.AE 62-81 ventilation standards for offices (20 cfm per occupant, equivalent t-o 0.84 ach, for smoking buildings), on average, although there are some buildings significantly lower. A recent EPA study of air exchange rates in 6 buildings (3 new, 3 old) did not show significant differences between the new (.5 ach) and old (.5 ach) buildings' airchange rates, although for a given building nighttime measurements tended to be lower. (Sheldon, et a1.,1987) Recent research has revealed several interesting factors in large office building air exhange. There are many pathways for floor-to-floor air communication, particularly return air shafts, where the existence of such pathways can cause a building's air exchange characteristics to closely approximate those of a single large open space; it does :not require unusual numbers or sizes of openings to create these conditions, (A. Persily, personal communication; Persily and Grot,1986) a condition for which eq. 3 was designed. This implies that ETS may diffuse throughout a large office building, exposing nonsmokers even in private offices. Nicotine measurements in office buildings support this observation. (Williams, et al., 1985; Vaughn and Hammond, 1989) .In summary, limited field tests of the general equilibrium model, in which some of the input parameters are measured and others are estimated from either chamber studies or building codes, have predicted RSP levels reasonably well over a wide range of values of input parameters. It is clear that both models and observations based on personal monitoring or area monitors in various microenvironments yield consistent results: RSP levels when smoking is allowed will result in substantial increases over RSP levels in nonsmoking occupancy.(NRC,1986) C. Tobacco Smoke and Ventilation 119 T1MN 0030146

Draft - Do not cite or quote Because of widespread public smoking, many buildings are contaminated with tobacco smoke combustion products. Many building owners and managers have assumed that ventilation is a viable control mechanism for the clouds of smoke that are generated by cigarettes, pipes, and cigars. In particular, the ventilation standards proposed by ASHRAE (the American Society of Heating, Refrigerating, and Air Conditioning Engineers) are often thought to afford adequate control of tobacco smoke. However, ASHRAE standards are not health-based standards designed to limit cancer risk or eye irritation to levels acceptable to nonsmokers. They are designed only to limit dissatisfaction with tobacco smoke odor to a maximum of 20% for "visitors" (a test panel consisting of 50% smokers and 50% nonsmokers) to a building where smoking occurs. Currently ASHRAE recommends 20 cubic feet per minute per occupant (cfm/occ) for this purpose. Providing ventilation adequate to control cancer risk has been estimated to require 5400 cfm/occ, an unrealistic ventilation rate.(Repace & Lowrey, 1985) Air cleaners have three fundamental problems. one, most air cleaners do not scrub gases from the air, and many of the harmful tars appear in the gases. (Pritchard, 1990) Two, air cleaners cannot remove smoke which encounters the nonsmoker before it reaches the air cleaner. Three, even air cleaners which are close to 100% effective in removing particles which reach them must process hundreds of room air volumes per hour to reduce cancer risk to an acceptable level.(Repace & Lowrey, 1985; Repace, 1989a) Separation of smokers from nonsmokers within a space will expose nonsmokers to smoke which diffuses from the smoking area. Separation on the same ventilation system will reduce peak concentrations to which nonsmokers are exposed, but will expose nonsmokers to smoke recirculated by the ventilation system. (Repace, 1989; Repace and Lowrey, 1987) The foregoing considerations demonstrate that source control, i.e., removing the smoking from the air volume containing nonsmokers, is the only viable control option. Source control adequate to protect nonsmokers takes two forms: separation of smokers from nonsmokers on separate ventilation systems, or restriction of smoking from the building. (USEPA, 1989) Separation of smokers in a designated smoking area exposes them to much higher levels of exposure to ETS, and may significantly increase an already considerable risk from active'smoking.(Repace, 1989b) D. Measured concentrations of ETS constituents: RSP: Both field studies (Table 1) as well as chamber studies have demonstrated that tobacco combustion has a major impact on the mass of suspended particulate matter in occupied spaces in the size range <2.5 um, defined here as RSP. RSP is a major component of ETS. Even under conditions of low smoking rates, easily measurable increases in RSP have been recorded above background levels. The term RSP, however, encompasses a broad 120 T'.IlV[N 0030147

Draft°- Do not cita or quote range of particulates of varying caemical composi-zlon and size emanating from a number of sources (outdoors, cooking indoors, kerosene heaters, etc.) (NRC, 1986) The apportionment of RSP indoors depend:; primarily on the presence of these other sources. However, in western society, there are few indoor sources generating concentations which approach in strength those due to ETS. There appears to be little variability between brands of cigarettes or tobaccos for RSP emissions, although cigars will produce greater emissions than cigarettes. Thus, it may be inferred from Table 1 that from a comparison of smoking and nonsmoking buildings, the bulk of the RSP found in buildings where there is smoking is due to ETS. For example, by comparison of the data of First (1984), Leaderer, et al (1986) and Repace and Lowrey (1980,1982) for a total of 42 smoking buildings and 21 nonsmoking buildings, the weighted average RSP level in the smoking buildings is 262 ug/m3, while in the nonsmoking buildings it is 36 ug/m', suggesting that about 85% of the indoor RSP levels in those buildings is due to ETS. Most of the buildings involved were public access buildings. Hammond et al. (1988) measured personal exposures to RSP in several hundred railroad workers. Mean calculated ETS-derived RSP exposures for railroad office workers averaged over 90 ug/m3; by comparison, all other sources of RSP _°or these diesel-exhaust exposed workers averaged 39 ug/m3. The U.S. Department of T'ransportation (1990) measured concentrations of RSP in the smoking section of a random sample of 69 smoking and 23 nonsmoking flights. Nonsmoking flight attendants must work in the smoking sections on aircraft. Levels of RSP on the smoking flights averaged 175 ug/m3, whereas measurements in the same section of the aircraft on no:nsmoking flights averaged 35 to 40 ug/m3. ~ Figure 6, (IARC, 1987) a plot of the data of Repace and Lowrey (1980, 1982) illustrates the large impact of smoking on RSP levels; smoking data points 'A' thru 'T' encompassed a wide variety building microenvironments,including 10 restaurants, 3 cockzail lounges, 3 bingo games, 2 dinner-dance halls, 1 bowling alley, 1 sports arena, 1 hospital waiting room, and a residence during a din`ner party. Studies of the dispersion of RSP from ETS in US homes showed at most a factor of 2 difference among various rooms in residences, averaged over 24 hrs. In a setting such as a work environment, where the average exposure is several hours, ETS would be expected to disseminate throughout the airspace where smoking is occuring.(SG, 1986) Although most people spend approximately 90 percent of their time in just two microenvironments (home and work), important exposures can also be encountered in other microenvironents, e.g., in transit, which accounts for 0.5 to 1.5 hrs per day for most people..(SG, 1986) Exposures on aircraft can also be considerable. (Repace and Lowrey, 1988; USDOT, 1989) BENZENE: Wallace (1989) in reporting the results of EPA's TEAM study with respect to the benzene exposure of the population, found that ETS was a significant source of population benzene exposure, accounting for about 5% of total nationwide exposure. Wallace 121 TjMN 0030148

Draft- Do not cite or quote reported that workplace exposures for nonsmokers not exposed to ETS at home, but who report being exposed to ETS more than 50% of the time at work showed significantly higher benzene concentrations than those who report exposure to ETS less than 50% of the time. Wallace estimates that ETS-benzene exposures are about equal at home and at work. NICOTINE: Leaderer and Hammond (in press) measured vapor phase nicotine and RSP concentrations in 96 residences. Vapor phase nicotine measurements were found to be closely related to number of'cigarettes smoked and highly predictive of RSP generated by tobacco combustion. The mean RSP background in the absence of measurable nicotine was found to be 15.2 ± 7 ug/m3. The mean RSP value in the presence of nicotine was 44.1 ± 30 ug/m3. Weekly mean nicotine concentrations in the residences was 1.1 ug/m3. Stillman et al. (in press) measured weekly average nicotine concentrations using the method of Leaderer and Hammond (above), in 9 (F. Stillman, pers. comm.) university offices. Concentrations averaged 2.1 ug/m3. After a smoking policy was implemented, the nicotine levels decreased by 9514. Vaughn and Hammond (1990) measured weekly average nicotine concentrations in offices in a modern office building using both active and passive samplers. Before the smoking control policy, nicotine vapor concentrations at nonsmokers' desks were about 2 ug/m3, and were reduced by 95% after a smoking policy was implemented, in good agreement with the findings of Stillman, above. Hammond et al. (1988) measured nicotine and RSP in two employee smoking lounges at the University of Massachusetts. RSP levels varied between 220 and 350 ug/m3 during smoking, with associated nicotine levels from 40 to 70 ug/m3. After charcoal-filter air cleaners were installed, nicotine levels were virtually unchanged, and RSP levels varied between 100 and 310 ug/m3. A study of personal exposures to airborne nicotine in 4 US office workers showed about a 0.1 mg mean exposure (mean personal nicotine concentration of 15 + 9 ug/m , daily workday average, times a 0.8 m3/hr inhalation rate times an 8-hr workday). The nonsmokers were exposed to the smoke of a co-worker who smoked 9 cigarettes per workshift, about half the rate of the average US smoker. (Hammond et a1.,1987) E. Exposure of nonsmoking populations to ETS in the general population (both sexes) aged >_ 17 years in 1980 (160,798,000 persons), a majority has smoked at some time: 32.6% were current smokers, and 21.3% were exsmokers, while 46.1% had never smoked (see Table 2). Among current 1980 smokers, 53% were male, and 47% were female, with some race- and gender-specific differences : white males, 35.9%, black males, 42.0%; white females, 29.3%, black females, 29.7%. (R. Wilson, NCHS, personal communication) In terms of the population at risk, both lifelong 122 TIMN 0030149

Draft - Do not cite or quote nonsmokers and former smokers, 66.7% of the adult population and the overwhelaning majority of children are potentially at risk from involuntary exposure to ETS (in 1970, Bonham and Wilson (1970) found in a national probability sample of children, that 62% of US homes with children contained 1 or more smokers). Exposure to various subpopulations or individuals, however, may vary considerably. For example, the prevalence of smoking among subgroups of the population who proscribe smoking on religious grounds (such as Mormons and Seventh-Day Adventists) is much lower: for example, in 1980, only 1.7% of Seventh Day Adventist men and 0.5% of Seventh Day Adventist women reported current smoking, although 35% of the total were exsmokers. The incidence of lung cancer -- a disease for which the majority of cases occur in smokers -- among SDAs is 21% of that in the general population. Thus, SDA homes would be, in general, expected to be ETS-free. .The microenvironments of importance for exposure to ETS will be those where the population spends the bulk of its time. As Table 3 (Ott, 1981) (based on 1972 data) shows, employed men spend an estimated 56% of their time at home, and 28% of their time at work, for a total of 84% of the time at home and at work; employed women spend 64% of their time at home, and 22% of the time at work, for total of 86% of the time at home and at work; while homemakers spend 85% of the time at home. When time spent in other peoples' homes and in non-work places of business are added in, the population averages about 88% of its time in homes and workplaces. These sites, therefore, must, on average, predominate as potential sites for exposure to ETS for the general nonsmoking population. A UK study of exposure to ETS in 20 nonsmoking men whose wives smoked showed that 78% of the men's reported hours exposure came from outside the home; by contrast, 90% of the ETS exposure of 101 nonsmoking men whose wives did not smoke was reported to come from non-domestic microenvironments. (Table 4). Since the second largest source of time spent by men is in the workplace (Table 3), this suggests the workplace may be the major source of exposure for nonsmoking men. Cummings et al (1990) studied the prevalance of exposure to ETS in 663 never- and ex-smokers who attended a cancer clinic in Buffalo, N.Y. in 1986, by questionairre and urinary cotinine level. 76% reported exposure to ETS in the 4 days preceding the interview, while 91% had detectable urinary cotinine levels. Reported exposure locations in order of frequency were workplace (28%), home (27%), restaurants (16%), private social gatherings (11%), in transit (10%), and in public buildings (8%), (total of 100%). 77% of subjects reported being exposed to tobacco smoke at work, while 22% of the subjects lived with a smoker. In a second study, Cummings et al. (1989) reported on 380 never smokers from the same study: A total of 87% reported exposure to tobacco smoke at work. 24.3% of the men reported spousal smoking, whereas 94.7% reported workplace exposure; significantly, when asked to rate the severity of exposure, on a scale where spousal smoking was normalized to 1, 123 TIMN 0030150

Draft - Do not cite or quota severity of workplace exposure was rated 5. 66% of women reported spousal smoking, whereas 83.5% reported being exposed to smoking in the workplace. The women studied rated the severity of spousal smoking at about 30% higher than workplace exposures. Coultas et al. (1990), in a pilot study of 15 nonsmokers in Albuquerque, N.M., exposure questionnaires and saliva, urine, and personal air samples were obtained pre- and post- workshift. Nicotine and cotinine levels were quantified, as were atmospheric nicotine and RSP samples. Statistically significant correlations were obtained between RSP and nicotine and total reported hours of exposure; between nicotine and total number of smokers, total hours of exposure, and postshift urinary cotinine; between urinary cotinine and total hours of exposure; and between salivary cotinine and total number of smokers. Objective evidence of exposure to ETS was obtained in various workplaces. Spengler et al. (1985) and Sexton et al. (1984) demonstrated by personal monitoring of RSP and the use of time-activity questionnaires that exposures to ETS both at home and at work are significant contributors to personal exposures. A survey of exposure to ETS in a California population subscribing to a health-maintainance plan indicated that 63% of nonsmokers surveyed reported exposures to tobacco smoke (Friedman, 1983) ; this occurred despite the fact that in the 1980's California has has been in the forefront of restrictions on smoking in public, with 44% of its population currently living in communities that have enacted workplace smoking restrictions. (SG, 1986) Garfinkel (1981), in a study of 176,000 nonsmoking US women (1960-1972), found 72% had smoking husbands. Kabat and Wynder (1986), in a recent study of 215 sixty-year-old US women nonsmokers, found that 65% were exposed at home and 67% reported exposure at work, averaged over adulthood. Studies of the concentration of nicotine and cotinine in the body fluids of nonsmokers report similar results (Table 4); Jarvis & Russell, (1984) showed that in a study of about 100 UK nonsmokers, only 12% of the subjects had undetectable cotinine levels. Moreover, in the latter study, surprisingly, nearly 50% reported no exposure, suggesting that ETS permeates indoor atmospheres to such an extent that many nonsmokers are unwittingly exposed. This is borne out by a study of 46 US infants, 40% of whom were reported by their mothers to be unexposed to ETS, but only 20% had undetectable urinary cotinine levels. (Greenberg, 1986) In a third UK study (Wald, 1986) of urinary cotinine in 221 nonsmokers, the 20% who reported no exposure had mean urinary cotinine levels which were 21% of the remainder of the group who reported exposure. The foregoing illustrates that exposure to ETS is very widespread in the population, even among those nonsmokers who believe themselves to be unexposed, however it tends to be greater in those who say they are exposed at home, possibly indicating a greater tolerance for ETS among men with nonsmoking spouses. 124 TIMN 0030151

Draft - Do not cite or quote Although there have been numerous measurements of ETS concentrations in various indoor settings, these data do not represent a comprehensive description of the actual distribution of ETS exposures in the US population. However, additional data on the distribution of smokers in the nonsmokers' environment- as well as the distribution of ETS levels in that environment, are needed in order to characterize the actual ETS exposure of the population. In the absence of such data, population exposures can be estimated by models or by extrapolation from biological markers from existing studies. (SG, 1986; IARC, 1987) In summary, exposures to ETS can be assessed by personal air contaminant monitoring, modeling of concentrations based upon air sampling, time-activity patterns, and questionnaires, or upon biological markers. The two best methods at present are based upon the biological markers, nicotine and its metabolite, cotinine, which are present in the saliva, plasma, and urine of active and passive smokers, and upon atmospheric markers such as nicotine in the vapor phase and RSP from the particulate phase of ETS, the latter of which has been used in many field studies because of the substantial emission of RSP from tobacco combustion. In US, ETS is generated by 50 million smokers, who smoke the equivalent (including pipes and cigars) of 610 billion cigarettes annually. Although the number of smokers has been declining, the percentage of heavy smokers has been increasing. There are models in use, based on the mass-balance equation, and validated both under laboratory and limited field conditions, which can predict the concentrations of RSP from ETS to a reasonable degree of accuracy.. Application of such models, together with field studies of RSP concentrations and sociological studies, has suggested that exposure to ETS is very widespread in the population. Environmental tobacco smoke is not readily controlled by either ventilation or air cleaning. Field studies of RSP in buildings where smoking occurs suggest that RSP from ETS contributes 80 to 90 percent of the particulate load during the period of smoking, and that it persists for long periods after smoking ends at typical building air exchange rates, thus prolonging nonsmokers' exposures. Available data suggest the workplace as a significant site of exposure to ETS. P. Integrated exposure analysis Exposure to ETS can be quantified either by atmospheric or biological markers. Of the latter, expired carbon monoxide, carboxyhemoglobin, plasma thiocyanate, plasma, urinary or salivary nicotine, and plasma, urinary, or salivary cotinine have been used to evaluate exposure to ETS. However, successful attempts to quantify the degree of exposure have been limited largely to measurements of nicotine and cotinine. Urinary nicotine is a sensitive indicator of recent ETS exposure, while cotinine appears to be the short-term marker of choice for epidemiologic studies. Nicotine and cotinine are the best markers currently available. 125 Z'IIMN 0030152

Draft°- Do not cite or quote Levels in body fluids may be elevated 10 or more times in the most heavily exposed groups compared with the least exposed groups. Mean levels of urinary nicotine and cotinine in body fluids increase with an increasing self-reported ETS exposure and with an increasing number of cigarettes smoked per day by active smokers. (SG, 1986) Coghlin, Hammond, and Gann (1989), in assessing current weekly ETS exposure in 53 nonsmoking volunteers by personal nicotine monitors, diaries, and questionnaires, found that the best predictor of total nicotine exposure was given by the formula hsp: the number of hours of exposure (h), times the number of smokers (s), times the proximity of those smokers (p), accounting for 83% of total exposure. A significant finding was that exposures derived from social situations (e.g. restaurants, bingo games, bars, and bowling alleys) (which are workplaces for some persons) may contribute significantly (34%) to total exposure. Nicotine is found in measurable concentrations in the saliva and urine of most urban nonsmokers, and is present in higher concentrations in those with some recent exposure. Estimating the magnitude of the passive smoking dose is difficult, and it is of doubtful validity to extrapolate from the uptake of one marker to another. Over a period when one cigarette equivalent of carbon monoxide is absorbed, the dose of nicotine appears to be only between 1/10 and 1/3 of a cigarette equivalent. Similarly, under extreme conditions of indoor pollution, it has been calculated that a nonsmoker would inhale volatile nitrosamines equivalent to 10 nonfilter cigarettes or 35 filter cigarettes.(Hoffmann. IARC, 1987) The average concentration of cotinine in the blood of habitual smokers is about 300 ng/ml, and is calculated to represent the consumption of about 36 mg of nicotine per day. On this basis, and on the assumption that formation of cotinine from nicotine and clearance from the body does not differ substantially from smokers to nonsmokers, present data suggest that average urban nonsmokers (in the UK) take in 0.2 mg of nicotine per day. (IARC, 1987) [.2 mg represents .6% of the smokers' dose] The highest plasma cotinine concentration observed in a nonsmoker corresponds to an approximate maximum dose of 2.5 mg of nicotine per day, 10 times higher, and 7% of the average smoker's dose. Recent studies of salivary cotinine in schoolchildren in the UK showed, in the case where both parents smoked, average concentrations just over 1% of the levels seen in heavy cigarette smokers.(IARC, 1987) Although the ratio of nicotine to other tobacco smoke constituents differs in MS and SS smoke, nicotine uptake may still be a valid marker for total ETS exposure. Nicotine uptake in nonsmokers has been estimated in terms of cigarette equivalents from various studies to vary between 1/6 to 1/3 of a cigarette per day. The NRC reports various estimates of cigarette equivalents based upon cotinine in nonsmokers ranging from 0.1 to 1 cigarette per day, and utilizes a ratio of urinary cotinine in ETS-exposed nonsmokers (25.2 ng/ml) to that in active smokers (1826 ng/ml) 126 7CIMN 0030153

Draft - Do not cite or quote yielding a 1.4% result.(NRC, 1986) [Assuming a usage of 32 cigarettes per day by habitual smokers based upon cigarette sales (Repace and Lowrey, 1980), this yields 57 ng/ml/cigarette, or 0.44 cigarette equivalents per day. Adjusting this by multiplying by the ratio of cotinine clearance in nonsmokers to that in smokers reported in one study, 49.7 hrs/18.5 hrs = 2.67, yields a higher value, 1.1 cigarette equivalents per day or 3.6% of the smokers' dose.] In summary, based upon the limited studies (none of which are a probability sample of US nonsmokers) of cotinine in body fluids of nonsmokers (see Table 5), nonsmokers appear to have of the order of 1% of the nicotine uptake of smokers. However, these estimates must be interpreted with caution; relative absorption of nicotine in smokers and nonsmokers may substantially underestimate exposure to other components of ETS. (SG,1986) Alternatively, human exposure to ETS can be estimated using approaches similar to those used for other airborne pollutants. Measures of exposure to individual atmospheric smoke constituents can be used as estimates of whole smoke exposure. The accuracy of this approach amy be limited by changes in the composition of ETS with time and conditions of exposure. Although lacking specificity Eor tobacco smoke, the prevalence and number of smokers correlates well with RSP levels in homes and other enclosed areas. In the Harvard study of indoor air pollution in 6 cities, Spengler et al. and Sexton et al. demonstrated by the personal monitoring of RSP and the use of time-activity questionnaires that exposures to ETS at home and at work are significant contributors to personal exposures. In general, measurements in a large number of locations using measures of smoke generation such as the number of people smoking or the number of cigarettes being smoked have shown a definite relationship of smoke generation to particulate levels. In US homes, there are few other sources of RSP, and therefore, the relationships of RSP measurements to ETS are quite accurate. (SG, 1986) Repace and Lowrey (1980) measured RSP concentration using a pie-Mobalance in several public and private locations, in both the presence and absence of smoking. They then developed an empirical model utilizing the mass balance equation (Eq.2). Using both measured and estimated parameters as input to the model, they validated the model for predicting an individual's exposure to ETS.(SG, 1986) Kuller et al (1986) in a review of estimates of the nonsmoking population's exposure to ETS, observed that cigarette smoking is probably the single most important source of indoor RSP; that a higher percentage of nonsmokers appear to be exposed out of the home, usually at work (Friedman, 1983); and that modeling of RSP has estimated that the average exposure of the nonsmoking adult population to tars from ETS was 1.43 mg/day, varying from 0 to 14 mg (Repace and Lowrey, 1985). Kuller et al. (1986) in reviewing the latter estimate, observed that the ratio of average exposure in passive smoking to that'in active smoking, was about 0.3%. This translates into 3% of the smoker' exposure for the most-exposed 127 TIMN 0030154

Draft - Do not cite or quota passive smokers, reasonably consistent with estimates based on doses from nicotine and cotinine, above. Table 6 gives estimates of the probability-weighted exposures to ETS for US nonsmoking adults at home and at work, the two most- frequented microevironments.(Repace and Lowrey, 1985) Table 6 is derived from RSP concentration modeling based upon Eq.'s 2-5, and from assessments of exposure probability based on a limited national survey of top management and health officials concerning prevalence of smoking in the workplace in 3000 US corporations, large, medium, and small (29t response), and a national probability sample of the prevalence of smoking in homes with children (used as a surrogate for all homes). Exposure probabilities were a weighted average taken over the number of workers in white-collar and blue-collar occupations, and including the different exposure probabilities for white and blue collar workers. Air exchange rates and building occupancies were taken from ASHRAE Standard ventilation rate tables for white-collar workplaces (which were used as surrogates for blue-collar workplaces). _ Table 6 estimates average the workplace ETS exposure probability at 63%, and the average estimated domestic ETS exposure probability at 62!k, where the focus was on estimation of ETS exposures in the 1950's to mid-1970's, since these exposures were held to be of primary significance for the studies of passive smoking and lung cancer, given the long latency for lung cancer. Comparison of these exposure probability estimates to adult life ETS exposure histories taken by Kabat and Wynder (1986) for 215 60-yr old female nonsmokers, 65-1 at home and 67% at work, shows good agreement. Table 6 estimates a 0.45 mg/day RSP exposure for nonsmokers at home, (weighted for male and female time-activity pattern differences, and for respiration rate) corresponding to a 19 ug/m3 24-hr average, in good agreement with results (19 ug/m3 per smoker) published in the 6-City study. (Repace and Lowrey, 1985) Table 6 also estimates a 1.82 mg/day RSP exposure for workers, (again weighted for male-female time-activity patterns and for respiration rate) corresponding to about a 230 ug/m3 workplace concentration, using ASHRAE Standard 62-73 for workplace occupancy and performing a weighted average workday for the different hours worked by men and women (Repace and Lowrey, 1985). This is in good agreement with the weighted average concentrations (262 ug/m3) reported for ETS in public access buildings. Riboli et al. (1990) in a 10-country collaborative study of exposure of nonsmoking women to ETS, examined the relationship between smoking by spouse and urinary cotinine levels as an indicator of exposure to ETS. Riboli et al. (1990) found that cotinine values were significantly higher for women exposed to ETS from the husband than from other sources; they also found that questionairres in epidemiological studies based upon self-reports of spousal smoking in fact identified a most-exposed population. A clear increase in urinary cotinine levels was found from the 128 TIMN 0030155

Draft - Do not cite or quote women who were exposed neither at work or at home, to women who were exposed both at work and at home, as suggested by the work of Repace and Lowrey, above. In summary, exposures to ETS can be assessed by personal air or area contaminant monitoring, modeling of exposures, or by biological markers of ETS contaminants in body fluids. Using either the biological markers such as cotinine or the atmospheric markers such as RSP produces a consistent assessment of ETS exposure, i.e., of the order of 1% of that in smokers. The most- exposed individuals appear to have levels about ten times higher. Based upon limited data, the typical nonsmoker appears to carry a daily body burden of about 0.2 milligrams (mg) of nicotine. The cotinine-based estimates have the advantage that they reflect actual dose of an ETS constituent. They have the disadvantage that they do not reflect a wide distribution of target populations, are based mostly on tJK ETS exposures, and may substantially underestimate exposures to other constituents of ETS. The RSP- based estimates have the advantage that they are model-based, can be used to esti.mate exposures in a variety of microenvironments, represent the great bulk of ETS carcinogens, and can be compared with atmospheric measurements of RSP. They have the disadvantage that they do not: represent whole smoke exposure, and do not reflect absorbed dose. The greatest source of uncertainty is that neither cotinine nor RSP measurements are based on a national probability sample, and on an absolute scale, represent a limited amount of data. Nevertheless, the NRC(1986), the SG(1986), and IARC(1987)• have found this data base acceptable for exposure assessment purposes. Estimates of the adult nonsmoking population's exposure to RSP from ETS suggest that the range of exposure is from 0 to 14 mg per day, with the population average put at 1.5 mg per day, where the peak-to-mean ratio is about a factor of 10, consistent with the biomarker-based findings. Summary 1. Nonsmokers' exposures may be assessed by mathematical modeling, as well as by biomarkers such as nicotine or cotinine in body fluids or atmospheric indicators such as nicotine or RSP. 2. Despite limitations of the data base, mathematical models, biological and atmospheric markers have produced: reasonably consistent assessments of nonsmokers' ETS exposure. 3. Exposure to environmental tobacco smoke is inadequately controlled by ventilation, air cleaning, spacial separation within a space, or on the same ventilation system. 4. Data indicate that ETS is a significant indoor pollutant of buildings, typically representing 80 to 90% of particulate indoor air pollution during smoking, and that nearly alll nonsmokers carry a significant burden of tobacco combustion products in their body 129 TIMN 0030156

Draft°~:- Dc not cite or quote fluids. 130 TIMN 0030157

Draft - Do not cite or quote References Bonham, G; Wilson, RW (1981). Children's health in families with cigarette smokers. Amer. J. Public Health 71: 290-293. Coghlin J, SK Hammond, PH Gann. "Development of epidemiologic tools for measuring e:nvironmental tobacco smoke exposure." Amer. J. Epidemiol. 130: 606-704 (1989). Coultas DB, JM Samet, JF McCarthy, JD Spengler. "A personal monitoring study to assess workplace exposure to environmental tobacco smoke." AJPH 80: 988-990 (1990). Cummings HIH, SJ Markello, MC Mahoney, JR Marshall. "Measurement of lifetime exposure to passive smoke." Am. J. Epidemiol. 130: 122- 132 (1989). Cummings KM, M Mahoney, AK Bhargava, PD McElroy, JR Marshall. "Measurement of current exposure to environmental tobacco smoke." Arch. Env. Health 45:74-79. First, MW (1984). Environmental tobacco smoke measurement: retrospect and prospect. Eur. J.Respir. Dis. 5(Suppl.):9-16. Garfinkel, L(1981). Time trends in lung cancer mortality and a note on passive smoking. J. Nati. Cancer Inst. 66:1061-1066 Greenburg, RA; Haley, NJ; Etzel, RA; Loda, FA. Measuring the exposure of infants to tobacco smoke: Nicotine and cotinine in urine and saliva. New England J. Med. 310: 1075-1078. Grot, RA, & Clark, RE (1986). 178-194. Measured air infiltration and ventilation rates in 8 large office buildings. ASTM Spec. Pub. 904, Ed. H. Trechsel & P. Lagus, ASTM, Philadelphia 151-183. Haley, NJ; Colosimo, SG; Axelrad, CN; Harris, R; Sepkovic, DW. Biochemical validation of self-reported exposure to environmental tobacco smoke. Environmental Research 49:127-135 (1989). Hammond, SK; Leaderer, BP; & Roche, A. (1987). Collection and analysis of nicotine as a marker for environmental tobacco smoke in personal samples.. Atmos. Env. Hammond SK, TJ Smith, SR Woskie, BP Leaderer, & N Bettinger. "Markers of exposure to diesel exhaust and cigarette smoke in railroad workers. Am. Ind. Hyg. Assoc. J. 49:516-522 (1988). Jarvis, MJ; Russell, MAH; Feyerabend, C; Eiser, JR; Morgan, M; et al (1985). Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of nonsmoking school children. Br. Med. J. 291: 927-929. 131 TIMN 0030158

Draft - Do not cite or quote Leaderer, BP; Cain, WS; Isseroff, G; Berglund, LG. (1984). Ventilation requirements in buildings. II Particulate matter and carbon monoxide from cigarette smoking. Atmos. Environ. 18: 99-106. Leaderer B, Koutrakis P, Briggs S, Rizzuto J. Impact of indoor sources on residential aerosol concentrations. Proc 5th Int Conf on Indoor Air Quality & Climate, V 2, 269-274. Toronto 29 July- 3 August 1990. Leaderer, BP (1990). Risk Analysis 10: 19-26 (1990). Leaderer, BP, and Hammond, SK. "An evaluation of vapor-phase nicotine and respirable suspended particle mass as markers for environmental tobacco smoke." Environmental Science & Technology, in press. Lofroth G, Burton.RM, Forehand L, Hammond SK, Sella RL, Zweidinger RB, and Lewtas J. Environ. Sci. Tech. 23: 610-614 (1989) . Matsukura S., et al. Effects of environmental tobacco smoke on urinary cotinine excretion in nonsmokers -- evidence for passive =oking. New England J. Med. 311: 828-832 (1984). Miesner EA, Rudnick SN, Preller L, Nelson W. Particulate and nicotine sampling in public facilities and offices. JAPCA 39: 1577-1582 (1989). National Research Council (1986). Environmental tobacco smoke -- measuring exposures and assessing health effects. National Academy Press, Washington, DC. Office on Smoking and Health (1988). Estimates of the mortality from smoking. Centers for Disease Control, Washington, DC. Ott, WR. Human activity patterns: A review of the literature for estimation of exposure to air pollution. U.S. Environmental Protection Agency, Washington, DC. Pritchard et al. (1990). Repace, JL (1989a) Smoking in the workplace: Ventilation. Smoking Policy Questions and Answers, #5, National Cancer Institute, Bethesda, MD. Repace, JL (1989b) Protecting workers from the threat of secondary smoke. Indoor Pollution Law Report, Cadwallader, Wickersham, & Taft, Leader Publications, Washington, DC. Repace, JL, and Lowrey, AH (1980). Indoor air pollution, tobacco smoke, and public health. Science 208: 464-472. Repace, JL, and Lowrey, AH (1982). Tobacco smoke, ventilation, and 132 TIMN 0030159

Draft - Do not cite or quote indoor air quality. ASHR.AE Trans. 88: 894-914. Repace, JL, and Lowrey, AH (1985). A quantitative estimate of nonsmokers' lung cancer risk from passive smoking. Environment International 11: 3-22. Repace, JL, and Lowrey, AH (1990). Rebuttal to Lee/Katzenztein commentary on passive smoking. Environment International, in press. Riboli E, Preston-Martin S, Saracci R, Haley NJ, Trichopoulos D, Becher H, Burc:h JD, Fontham ETH, Gao YT, Jindal SK, Koo LC, LeMarchand L, Segnan N, Shimizu H, Stanta G, Wu-Williams AH, and Zatonski W. Exposure of nonsmoking women to environmental tobacco smoke, a ten-country collaborative study. Cancer Causes and Control, 1: 243-252 (1990). Rickert, WS; Robinson, JC; Collishaw, NE (1987). A study of the growth and decay of cigarette smoke NOx in ambient air under controlled conditions. Environ. Internat. 13: 399-408. Rickert, WS; and Labstat, Inc. (1988). Some considerations when estimating exposure to ETS with particular reference to the home environment. Canadian J. Publ.Health 79:S33-S37. Sexton, K; Spengler, JD; Trietman, RD (1984). Personal exposure to respirable particulates: a case-study in Waterbury, Vermont. Atmos. Environ. 18: 1385-1398.- Surgeon General (1986). The Health Consequences of involuntary smoking. U.S. Dept. of Health & Human Services, WAshington, DC. Spengler, JD; Treitman, RD; Tosteson TD; Mage DT; and Soczek ML (1985). Personal exposures to respirable particulates and implications for air pollution epidemiology. Environ. Sci. & Teono l. 19 : 7 0 0-7 07 . Stillman FA, DM Becker, RT Swank, et al. "Ending smoking at the Johns Hopkins medical institutions: an evaluation of smoking prevalence and indoor air pollution. JAMA (1990), in press. Tobacco Institute (1987). Tobacco industry profile, 1987. Washington, DC. U.S. Department of Transportation. U.S.' Department of Transportation Study of Airliner Cabin Air Quality (1990). U.S. Environmental Protection Agency, Indoor Air Facts 1#5, Environmental Tobacco Smoke, Washington, DC, 1989. Vaughn WM & SK Hammond. "Impact of 'Designated Smoking Area' Policy on Nicotine vapor and particle concentrations in a modern office 133 TIMN 0030160

Draft - Do not cite or quote building. J.Air Waste Management Assoc. 40: 1012-1017 (1990) Wald, NJ; Nanchanai, K; Thompson, SG; Cuckle, HS (1986). British Med J. 293:1217-1222. Wallace LA. "Major sources of benzene exposure." Environ. Health Persp. 82: 165-169 (1989). Williams DC, Whitaker JR, Jennings WG. Measurement of nicotine in building air as an indicator of tobacco smoke levels. Environ Health Persp 60:405-410 (1985) TIMN 0030161 134

Draft - Do not cite or quote FIGiTRES AND TABLES FOR CHAPTER 6 135 TIMN 0030162

Draft - Do not cite or quote T.ABLT 1. Cantd.(NRC, 1986) Continued Type of Premise Volume. Occupancy m3 Ventilation Type/Rate Monitoring Type/Time Concentrations Mean (range). Kg/ m.t Comments Parker et al.. I residence 1 145 N/0.2-1.9 ach 0/24 h <10(-) TSP 1984 T=3 2 residences S = 1-2 N/0.2-0.7 ach 0/24 h. 10--t6 (-) TSP T=3-4 Repace and Outdooes - PJ2 min 42.9 (22-63) RSP, average of Lowrey. 1980. 1982 27 Public 0.13-3.54f - M/- P/2 min 278(86-1.140) 2-mtn samples RSP, average of s i l 2 Sexton et al.. buildings Outdoors - - G/24 h 17.0 = 1.b (6-23) e -m n samp RSP. repeat samples 1984 19 homes 24 residences NS`. N/- G/24 h 25.0 ~- 1.0 (13-d3) Used fireplaces Spengler Outdoors - G/24 h 21.1 ~ 11.9 (-) RSP. repeat measures et al.. 1981 35 residences NS N/- G/24 h 24.1 •} 11.6 (-) RSP. repeat measures 15 residences S = 1 N/- G/24 h 36.5 = 14.5 (-1 RSP, repeat measures 5 residences S = 2 N/- G/24 h '0.4 = 42.9 l-) RSP, repeat measures Spengler Outdoors - N/- G/24 h 18 ± 2.1 l-) RSP. repeat measures et al.. 1985 73 residences NS' G/24 h 28 ± 1.1 (-) RSP. repeat measures 28 residences S Gi24 h 74 ± 6.6 (-) RSP, repe•.t measures Strrling and I office S resir. Gl")/- 25.5 (15-36) TSP Sterling. 1983 22 ofTicrs S G(')/- 31.7 (-) TSP U.S. Department 8 domestic S - M/- G/1-1/4. Not given (-) TSP of Tnnspor- planes T = 27-110 2-1/2 h tation. 1971 20 military S - M/- G/6-7 h < 10-120 (-) TSP planes T = 165-219 WelxP and 44 offices S - P/2 min 133 ± 130 RSP, mmus Fischer. 1980 (30 ea) (962 peak) background level "Active smokers per 100 mi . ABBREVIATIONS: °Grams of tobacco consumed. ach = Air changes per hour `Somc smoking was reported during 9 of the 280 samples. G = Gravimetric "!titeasured during 24-h periods by the perfluorocarbon tracer tech• M = Mechanical ventilation nique. N = Natural ventilation °5ome?esidences had combinations of sources (kerosene heaters. !VS = No smokers wood stoves. etc.) and no cigarettes. O = Optical monitor /Active smokers density per 100 m3. P = Piezoelectric balance QCMI = Quality Crystal Microbalance Cosade Impactor RSP = Respirable suspended particles S • = Smokers T = Total occupants TSP = Total suspended particles restr. = building «ith, smoking restrictions TIMN 0030163

TaBLE 1 (NRC, 1986) Drafte - Do not cite or quota Particulate Levels Measured in Indoor Environments. Including Smoking and Nonsmoking Occupancy Study Type of Prernise Occupancy Volume. m3 Ventilation Type/Rate Monitoring Type/Time Concentrations Mean (range). tsg/m, Comments Btunekreef and 4 residencas NS N/- G/2 mo 55(20-90) TSP. repeat measures Boleij. 1982 0.2 mg 7 residenax S=1 N/- G/2 mo 125(60-250) TSP sensitivity 14 residences S=2 N/- G/2 mo 152(60-340) TSP sensitivity I tesidenctit S=3 N/- G/2 mo 335 (-) TSP sensitivity Outdoots - G/2 mo - (41-73) Cuddeback 2 taverns S = 5-40 - N.M/ 1-6 ach G/9 h 446(233-986) TSP ventilation et ai.. 1976 NS = 5-260 estimated T = 10-300 Elliot and 3 arenas NS - G/24 h 55 (42-92) TSP Rowe. 1975 3 arenas S - M/- G/0.3 h 350 (148-620) TSP T = 2.000- 14.277 First. 1984 1 school NS M/- P/- 20 (-) TSP 8 public buildings S P/- 260(40-660) TSP Hawtltorne et al.. 11 residences NS 150-674 M/0.18-0.96 QCMI/5-15 min (over 6 h) 9--i0 (-) RSP. winter/ summer- no sources 1984 8 residences NS 150-674 M/0.26-1.98 QCMI/5-15 min (over 6 h) 12-46 RSP, winter/summer- sources' 2 tesidences S 150-674 M/0.27-1.47 QCMI/5-15 min (over 6 h) 96-106 RSP. winter/summer- sources' + cig. Leaderer et al.. 3 public buildings NS 163-1.326 M/0.37-5.6d G/4-21 h 17.8 (9.1-32.2) TSP, repeat measures. all var. personal 7 public 1.7-4.576 1b8-600 M/0.77-7.53r G/2-24 h ,205.1(58-452) Measured communi- cation buildings T = 2-6 (160.0 peak) Moschandreas Outdoors - - G/24 h 17.0 (-) RSP. TSP atso et al.. 1981 measured 2 offices - - G/24 h 16.8-20.2 (53 peak) RSP. TSP also measured 5 residerces NS - N/0.5-1.3 ach G/24 h 19.4-4.01 RSP. TSP also T = 2-6 (118.9 peak) measured 5 residen:ces S - N/0.5-1.3 ach G/24 h 36.9-99.9 RSP. TSP also measured Nitschke Outdoors - - - G/168 h 11.3 ± 6.0 (1-28) RSP et a).. 1985 19 residences NS 315-1.021 N/- G/168 h 26.0 ± 22.6 (6-88) RSP. repeat measures. source mix, 11 residences S 290-800 N/- G/168 h 59.2 ; 38.8 (10-144) RSP. repcat measures. source mix' MN ~®3®164

Table 2. Number of persons 17 years and over, by cigarette smoking status, United States, 1980. (National Center for Health Comm.) race, sex, and age: Present Smokers Former Smokers Regular Regular Regul ar Regular All Total All and/or smoker and/or smoker Never occasional Race Sex and A e Po ulation Smoker occasional onl occasional 0 1 smoked smoked All races- Num bers in Thousands ~ Both Sexes 17 yrs. 160798 86611 52442 51770 33130 30731 74086 3486 17-24 years 32176 13286 10069 9827 3009 2632 18890 652 25-44 years 61042 35258 22916' 22656 11985 11167 28754 1269 45-64 years 43556 27170 15336 15236 11474 10541 16330 1144 65 years & over 24024 10896 4121 4050 6664 6341 13112 421 Male > 17 years 75970 49048 27751 27445 20672 19297 26906 1994 17-24 years 15699 6640 5018 4866 1504 1303 9039 405 25-44 years 23549 19696 12591 12503 6886 6393 9837 692 45-64 years 20830 16238 8402 8357 7612 7113 4593 645 65 year & over 9891 6473 1760' 1718 4670 4488 3413 253 Female> 17 years 84828 37563 24690 24325 12452 11434 47180 1492 17-24 years 16477 6646 5051 4961 1504 1379 9832 248 25-44 years 22725 15562 10345 10152 5099 4774 15917 577 45-64 years 31472 10933 6933 6880 3862 3423 11737 499 65 years & over 14133 4423 2361 2333 1993 1853 9694 168 White> 17yrs. 139036 76041 45090 44515 30197 27976 62910 3045 17-24 years 27095 11525 8582 ' 8400 2758 2463 15569 566 25-64 years 51889 30336 19723 19211 10728 9955 21471 1063 t7 45-64 years 38470 24160 13383 13284 10480 9622 14269 1036 M a 65 years & over 21635 10019 3676 3619 6231 5935 11600 380 rt Male 65941 43124 23654 23435 19025 17732 22802 1735 Female 73095 32917 21416 21079 11171 10244 40108 1310 ~ Black> 17yrs. 16767 8314 5903 5831 2209 2045 8439 350 C7 17-24 years 4094 1451 1264 1226 158 142 2643 * 56 0 25-44 years 6584 3656 2657 2624 874 829 2928 159 ~ 45-64 years 4071 2471 1636 1636 -785 711 1586 *108 rt 65 years & over 2018 736 346 346 391 369 1282 * 26 A Male 7465 4512 3136 3078 1258 1192 2953 184 N Female 9302 3802 2767 2753 950 853 5486 166 136 TIlV~ 0030165

Draft - Do not cite or quote. TABLE :3. (Repace and Lowrey, 1985) Time spent in various microenvitonments by persons in 44 L'.5. :itres. e.xpressed in average hours per day. (Ott, in press: NRC. 1981: Szalaa. 1972). yticroenvironmeat Employed Men, All Days Employed w'omen. All Days Mamed Housewtves. All Days Inside one's home 13.4 15.4 20.5 Ju.ct outside one's home 0.2 0.0 0.1 At one's woricpiacer 6.7 5.2 In transit 1.6 1..) 1.0 In other people's homes 0.5 0.7 0.8 In places of business 0.' 0.9 1.2 In restaurants and bars 0.4 0.2 0.1 In all other locations 0.5 0 3 0 3 . .o . ~ Tota1 24.0 24.0 24.0 TVqN 0030166

i Nit 15 YYSzu 39 dif °'A Mild AiE v v ~ iiiIjj ~ 1 1 1 1 1 1 1 E 1 i 1 dy Ie Uno go ~RE G- M &F Gt G~ uuud A A f. A A 111111111 ~~~•.~aLu f 6A a i W 4 "Y ilY f, 0 ~ M Y y J a H a O f I

Draft - Do not cite or quota. TABLE 4. CCTININ£ IN NONSMOKERS FROM DO9ESTIC AND NONDCKESTIC EXPOSURES.(NRC, 1986) 91% of the •s^,TS exposure of the ncnsmokina husbands of smoking wives came from non-domestic sources compared to 71% of the exposure of the nonsmoking husbands of smoking Wives.:... The nost probable non-domestic source of exposure is the workplace. -- ------I ----------------------------------------------------------- Urinary Cotinine Concentration and Number of Reported Hours of Exposure to Other Peflple's Tobacco Smoke Within the Past 7 Days in Nonsmoking Married Men According to Smoking Habits of Their W ives Urinary Cotinine ~~ i C Exposure to Other Peopie's Smoke in Preceding Week. h oncentrat on. Smoking No. f ng/ml Total Outside Home Category of Wife o Men Mean (SE) Median Mean (SE) Median Mean (SE) Median Nonsmoker Smoker 101 20 8.5(1.3)° 25.2(14.8) 5.0 9.0 11.0(1.2)b 23.2(4.1) 6.5 21.1 :,-! 0(1.2)` 6.0 Io.4(3.3) 10.7 NOTE: Differences (nonsmoking wife versus smoking wife): 0 p <0.05:bp <0.001: `p < 0.,06 (Wilcoxin rank sum test). SOU RCE: W ald and Ritctt ie (1984). TIMN 0030168

i e. ° ~ n o . . 1 1 1 t It It !a ..~ ~~ ti~ T~g, I t An 1 ~~...,.~...,a~ dr+r+d ~+:dod I 1/ I I 1 I 1 I I11111111 ( i. I I I 1 I I I 11111it11 1 I I I 1 t t I I J! ~ .8 MM~ ~.~...~...~..~,.~ A/~ A V V V4 4 4 ~

Draft- Do. not° cite -or quote TABLZ 6. Estimated average nonsmokers' exposures to RSP from ETS at hoie and at work.(Repace and Lowrey, 1985) The concentrations are calculated for model home and workplace micraae.nvironments and are weighted by average respiration rates and time budget-studies for percent of- time spent at home and at work by male and female nonsmokers. The typical nonsmoker is estimated to be exposed to from 0 to '14 mg of RSP from ETS per day, w3,th an average exposure of 1.5 mg/day. -------I -------------------------~-------------------------------- f Lifestyle: Exposure (mg) Daily Average FTobability of 8eing Ezposed Modeied Daily (Rounded Values) Daily Average Probabtlity-Weighteo At work and at home: P'e 63 x 62 - 39 2.27 0.89 .Neither at work nor at home: vo ' 37 x 38 =[a 0.00 0.00 At home but ;not at work: °'s 62 x 37 3 23 0.45 0.10 At work but not at home: v0 63 x 38 = 24 1.82 0.At Totil: 4% 100 1.43 The average nonexciusive probability of a nonsmoker being exposed to ETS at work is estimated as 63%; the probability of not being exposed at work is 37%; the nonexclusive probability of being exposed to ETS at home is estimated as 62%; the probability of not being exposed at home is 38%. ------------------------------------------------------------------ TIMN 0030170

Draft°- Do not cita or quote FIGiTRE '_ EPA's TF_AX Study demonstrates that smoking provides ttie dominant source of RSP in many buildings (Sheldon, et al, 1986) ----------------------------------------! -------------------------- 3t: r- ~- a 40 , 8: Ho $moters Dresent 'hrte SmOzE•S Nine $r;,xer5 S:OC Ph 5:30 6:00 6:30 ^.one-: ~ ~ .. 53 ` . TIMN 0030171

Draft.- Do-not cite or quote P'ZGZTR,E 2 Air exchange rates in homes.:are one determinant of nonsmokers' exposures to ETS. Low air exchange rates mean higher exQosures.. Shown is a histogram of infiltration values in a sample oiE 266 older US middle class homes around the country. Average heating season values are shown. The median of the distribution is 0.9 ach and the mean is 1.1 ± 0.9 ach. (Grot and Clark, 19'79) (NRC, 1986) _ ------------------------------------------=---------------------- ALL 14 CITiES 40 r 30 !' 20 10 \ \ ~ ~ \\\ , \\ \\\ X®. OF 4OUSES = 2s5 No. OF KtonKs = 10,*4 ~1 = 1.12 R!0 ~=o.1eHit-a \V~ 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 AIR €XC}{ANGF RATE (HR-' J Figure 3. Histogram of measured nitural air infiltration races for 14 vsach*rization sices TIMN 0030172

N V 0g >a 0 m V .,~ U V 0 120 r. O ~ 110 Q ~ 100 ~ ~ _ro 90 ~ b N In ~ n 80 70 $ ~ 60 ~ 50 ~ 40 m C" 30 . m 20 ¢ 10 0 Theory (eq. 3) = Indoor, t srnoker Indoor, = , > 1 smoker smokers smokers 2 smokers 1 smoker 0 smokers Nov. Dec. Jan. Feb Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec. Jan. Feb. Mar. Apr. 1976 1977 1978 FIGURE 3. -- Comparison of predictions of RSP model for smoking in single-family homes with field data (Spengler et al., 1981) for monthly mean RSP concentrations for 55 homes in 6 Cities. = Outdoor = Indoor, no smokers

FiGU'RE 4 The ef fect- of sackiaig on levelsr ih oae Minneapolis office building. The contrast betveen daytime RSP levels, 1rhen smoking occured, and night-time RSP levels, vhen it did not, is marked. ----------------------------------------------------------------- Aer:sol m3.ss concentratton !n a?00-mz office with one smoker (Nalsor, e1 al .1982', le smoking fnstrument and smoking rate were not specified. However, the air exchange rate ror the space may be calculated by means of equation 2. For the decay of ETS on Thursday, July 9, a non-linear regression analysis of the RSP levels, with an 18 µ9Im3 background level subtraction, yields Ca = 1.0 ach (r2 = 0.95). This value is close to the ASHRAE-{ecommende4 ventilation rate for office space. E• 2110 1 O 9O! +200 • Ac. MON 1200 IQ Julr Ffl1 0000 1208 ~I xa. SAT TIMN 0030174 0000 +200 WED I I 0000

Draft - Do not cite or quote FIGURE 5 Air exchange rates in commercial buildings are one determinant of nonsmokers' exposures to ETS in the workplace. Shovn are air exchange rates (infiltration plus ventilation) in eight. large federal office buildings in 8 US cities in 7 states. Air exchange rates in the tighter buridirags failed to meet a.SHRAE standards for occupied office space, (20 cfm/occ or 0.84 ach). The mean annual air exchange rate for all eight office buildings is 0.71 ± 0.25 air changes per hour, about one third less than :.n the sample of homes in fig. =.(Grot and Persily, 1986). ---------------------------- =i----------------------------------- F3G. 1-Locatron of the eight federal office buildings. BIIILaING DIKF-2ISIONS (100 mZ = 1000 ft2 ) Occupiable Floor Volume. Air exc.hange rate Location A rea. m2 tni ( ach ) Anchorage 45 500 174 000 0.32 ± .35 Ann Arbor 4 900 31 700 1.04 ± .69 Columbia 24 700 159 000 0.85 ± .23 Fayeneville 3 400 21 300 0.37 + .09 Huron 6 420 27 500 0.32 + .16 Norfolk 17 300 60300 0.79 + .19 Pittsfield 1 730 8 520 0.70 + .19 Springfield 13 500 57 700 0.79 + .18 TIMN 0030175

Draft - Do not cite or quote Fiqure 6. Indoor air pollution from ETS aerosol. Indoor levels of respirable particles in buildings where tobacco is smoked (data points (A-T)) greatly exceed those in which smoking is prohibited (unlabeled), and exceed. the levels for health-based U.S. ambient air quality standards. 1200 T I 1100 1000 NAAQS 24-H AV. SIGNIFICANT HARM LEVEL FOR TSP 900 E a00 NAAQS 24-H AV. AIR POLLUTION EMERGENCY LEVEL FOR TSP .  B ! SMOKER DENSiTY ESTIMATED 0 MEASURED DATA p CALCULATED EQUILIBRIUM LEVEL •C a am 0 500 400 A • 300 • G NAAQS 24-H PRIMARY LEVEL FOR TSP •F Ho •U 200 100 K NAAQS 24•H PRIMARY LEVEL FOR'(PM10) v~•M •N •-•L* So oa•4ip•0 NAAQS ANNUAL PRIMARY LEVEL FOR PM "--•- 33 DATA POINTS .5 1.0 1.5 2.0 2.5 3.0 3.5 Active smoker densitv (100 x bvirnino Moarettes oer m31

Draft - Do not cite or quote TIlVIN 0030177

Draft - Do not-cite or quote CHAPTER 8 DISCOMF'ORT ASSOCIATED WITH ENVIRONMENTA7L TOBACCO SMORE William 8. Cain PhD John Bi. Pierce Laboratory and Yale University New Haven, CT 06519 Introduction The atmosphere inside buildings contains many chemicals generated by the presence and activities of people. People's bodies give off small quantities of organic materials in the breath and from the skin and alimentary tract. Although a chemical analysis may reveal hundreds or even thousands of materials, we usually perceive them in the aggregate as what we call occupancy odor. We often notice it consciously when we enter a hot, muggy room. Nevertheless, occupancy odor exists in occupied spaces at essentially all other times, but remains at a low level because of ventilation with outside air (Yaglou, Riley,and Coggins, 1936). When engineers and public health specialists began to study ventilation requirements for buildings quantitatively, they started with the smell of occupancy (Cain, 1979). The fresh-air requirements so derived exceeded those based on metabolically-relevant gases (oxygen, carbon dioxide) several-fold. In general, occupancy odor poses a mild challenge to the HVAC engineer. (HVAC refers to heating, ventilating, and air-conditioning.) This odor constitutes the baseline case. Anything else that people do in the space will increase ventilation requirements. This would include cooking, painting, operating machines (e.g., photocopier), woodworking, smoking, and so on. Of these various activities, smoking has traditionally been the most common. In a questionnaire study of odor problems in such spaces, Leonardos and Kendail (1971) stated, "Tobacco smoke is by far the most important odor contributor in enclosed space as indicated by the consistent agreement of the panel [principally experts in HVAC], and by their rankings. Also, it is considered a problem in virtually all (11 of 14) of the enclosed spaces" (p. 101). Tobacco smoke has accordingly received considerable attention historically in studies of odor control via ventilation or filtration (e.g., Yaglou, 1955; Kerka and Humphreys, 1956; Weber, Jermini, and Grandj ean, 1976). As he has with occupancy odor, the HVAC engineer has confronted environmental tobacco smoke (ETS) via its sensory characteristics, i.e., its odor and irritation, rather than via its chemical or physical complexity. The chemical complexity of ETS likely exceeds that of emissions from bodies and chemical 137 TIMN 0030178

Draft - Do not cite or quote analysis of ETS-containing air has offered little of practical significance regarding specific chemicals responsible for its odor or irritation. Specification of the relevant chemicals might, however, assist in the mitigation of offending characteristics (National Research Council, 1986). In what follows, we shall review how human beings perceive ETS. We shall ask: How much ventilation air must be introduced into a space in order to satisfy visitors to that-space? Will the amount of air required by smokers differ from Z2hat required by nonsmokers? Does ETS-odor decay spontaneously after smoking ceases? Do occupants accustomed to the environment impose less stringent criteria for ventilation than visitors fresh from a nonsmoking space? Does the odor and irritation of ETS come from the smoke particles or from the vapors that accompany the particles? Does filtration offer opportunities for control? Ventilation Rectuirements Based on Responses of the 'Visitor' A customary setting to explore how indoor contaminants affect the senses is a climate-controlled -environmental chamber with relatively inert surfaces, e.g., aluminum or stainless steel, and variable ventilation. Such a model environment offers control over the physical and chemical characteristics at the expense of what we may call ecological realism, i.e., an everyday setting. For the study of occupancy odor, human beings occupy the chamber in order to generate the odor of interest. Judges may enter the chamber briefly or may place their faces into a box fed with the atmosphere of the chamber. (In so sampling the atmosphere, the judges essentially visit the space.) The odor judgment may comprise a mark on an annotated rating scale (e.g., 'no odor' to 'overpowering odor') or the choice of a matching odor intensity. The latter judgment generally entails the use of a device called an olfactometer that delivers the vapor of some standard odorant, such as n-butyl alcohol (1-butanol), at various concentrations. A matching odor has the advantage of reproducibility from lab to lab. Many modern investigations also obtain judgments of acceptability in order to 'calibrate' intensity judgments. Acceptability judgments address the question: How many people will object to any given level of odor (or irritation)? The answer will depend on individual differences in olfactory sensitivity and on esthetic criteria. Whereas we can expect average intensity judgments to remain constant through the decades for any fixed stimulus, we can expect acceptability judgments to shift somewhat with prevailing standards. Three or more decades ago, when approximately half the adult population smoked and when restrictions on smoking were relatively few, people seemed more tolerant of tobacco smoke odor than today (see Cain,1979). Figure 1 depicts how occupancy odor varied with 138 TIMN 0030179

Draft=-Do not cite or-: quote ventilation rate per occupant under nonsmoking occupancy in a study conducted in a 1200-ft3 climate chamber (Cain, Leaderer, Isseroff, Berglund, Huey, Lipsitt, and Perlman, 1983). Visitors made judgments of air circulated through an outside sampling-box and were therefore naive to the conditions of occupancy. The scale refers to the concentration of 1-butanol matched to the occupancy odor present afts:r one hour of occupancy. Just as odor level decreased with increases in ventilation rate, so also did dissatisfaction, i.e., judgments that the odor was unacceptable. The point of 20% dissatisfaction holds special interest. The ventilation standard of the American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) (1989) recommends a maximum of 20% dissatisfaction among visitors to a space. By this criterion, the data from the investigation imply the need for 17 cfm per occupant. The ASHRAE standard suggests 15 cfm or more per occupant for most spaces, e.g., 15 cfm for classrooms, aibraries, auditoriums, dormitories; 20 cfm for offices, conference rooms, dining rooms, lobbies; 25 cfm for discos, beauty shops; 30 cfm for bars, casinos; 60 cfm for smoking lounges (see Fig. 2). Hence, practice coincides with the experimental data, about as well as could be expected regarding the baseline case. When cigarettes were smoked in the climate chamber, odor level increased markedly. Figure 3 displays ETS odor for various conditions of smoking: intermittent (4 cig per hr) or Gontinuous (8 or 16 cig per hr). As Fig. 4 shows, the degree of dissatisfaction mirrored the higher odor level. Based on the rule of 20% maximum d.'lssatisfaction, the ventilation rate required per cigarette during active smoking exceeded 4,000 ft3. In order to convert ventilation per cigarette into ventilation rate per person for typical conditions of occupancy in a'smoking-permitted' space, it was assumed that 10% of occupants would be smoking at any given time (see Repace and Lowrey, 1980). The resulting ventilation rate equalled 53 cfm, three times that for nonsmoking occupancy. (The average smoking rate will of course vary and the estimate of 10% may be high for 1990. The assumption of a lower rate of smoking would entail a proportional change in rate of ventilation.) Does the higher ventilation rate for smoking imply that the judges in the investigation showed a special aversion to the odor of cigarettes? Apparently not. The judges, one-third of whom were smokers and two-thirds of whom were not, seemed to base their dissatisfaction strictly on odor intensity. Degree of dissatisfaction varied with odor intensity in the same way for both occupancy odor and tobacco smoke odor (Fig. 5). Stronger odors meant greater dissatisfaction irrespective of odor type. How well does the higher rate implied by the investigation compare with the ASHRAE standard? As indicated above, the standard recommended 60 cfm per occupant in a smoking 139 TIMN 0030180

Dratt° - Da ngt cite . quote lounge, where presumably most or all occupants wi e smox~~i5. If 1001 rather than 10% were smoking simultaneously, then the rate would need exceed an unachievable 500 cfm per occupant. if 50% were smoking, perhaps a more realistic expectation, then the rate would need to exceed a still unachievable 250 cfm per occupant. (The maximum achievable rate for typical design occupancy in a mechanically-ventilated space will usually equal about 60 cfm per occupant, though.as discussed below a generous allotment.of space per person can increase that value.) Fortunately, however, the smoker seems less concerned about the odor of ETS than the nonsmoker. As it turns out, smokers as a group seem satisfied with about one quarter the ventilation air of a mixed-group containing a typical proportion of smokers and nonsmokers. Hence, a rate of 60 cfm per occupant may actually almost meet the customary ASHRAE criterion of a maximum of 20% dissatisfaction. How about nonsmokers? Just as a group of smokers will hold a less stringent criterion than the mixed group, a group of nonsmokers will hold a more stringent criterion. The data from the investigation suggest that with 10g smoking at any given time, nonsmokers would need over 100 cfm per occupant to hold dissatisfaction at only 20% . At the present time, we do not know whether the difference between smokers and nonsmokers derives from =blfactory sensitivity to ETS or to esthetic criteria. Clausen (1986) confirmed differences in tolerance of ETS odor between smokers and nonsmokers. For any given level of odor (expressed as concentration of butanol), a group of nonsmokers expressed much more dissatisfaction than smokers (Fig. 6). Both groups exhibited a lawful relation between odor intensity and dissatisfaction, but the difference between the groups grew as odor level increased. At the point where 20% of smokers expressed dissatisfaction, almost half of nonsmokers did so. As ETS enters the atmosphere, its many chemical constituents react with each other and with surrounding materials both chemically and physically. Does this behavior change the nature of the contaminant over time? Yes and no. Irrespective of whatever chemical changes occur, the odor of ETS behaves in the short run like a stable contaminant. After the source has been removed, ETS odor decays in a manner entirely predictable from ventilation rate (Clausen, Fanger, Cain, and Leaderer, 1985). In this respect, it differs from occupancy odor which has a half-life of 55 min, presumably dictated by slow oxidation of its chemical constituents into less odorous products (Clausen, Fanger, Cain, and Leaderer, 1986). ETS odor offers no such easy benefit to the engineer. Indeed, when ventilation fails ;to eliminate the contaminant entirely, ETS carries a penalty derived from its physical interaction with surfaces. Because the ETS aerosol adsorbs strongly to walls, fabrics, and so on, it becomes a source of odor later. The background odor of the emitted products carries its own demands for ventilation, predictable in part from the 140 TIMN 0030181

Draft - Do not-cite-or quote typical amount of smoking in a space (Clausen, Moller, Fanger, Leaderer, and Dietz, 1986). In a laboratory situation where other sources of combustion can be eliminated, carbon monoxide can offer a gross index of level of ETS. Figure 6 shows that Clausen could relate dissatisfaction to concentration of carbon monoxide in ETS as well as to matched level of butanol. This occurred because of a strong correlation (r>0.90) between odor intensity and incremental carbon monoxide due to smoking. Such a relationship makes it possible, within limits imposed. by brand-to-brand variability in emitted carbon monoxide, to compare one study to another. We can ask, at what concentration of carbon monoxide will ETS reach a given level of dissatisfaction in one or another group? As Fig. 6 revealed, the concentration at which 20% of nonsmokers expressed dissatisfaction fell about eight times below that at which 20% of smokers expressed dissatisfaction. Resoonses of Occu•oants Up to this point, we have concerned ourselves only with the reactions of visitors. Standards for ventilation have focused on the re,actions of the visitor, rather than those of the occupant, because the visitor will have a more sensitive, and hence more critical, nose than the person adapted to the contaminant. On the other hand, a focus on the visitor sidesteps another important time-dependent sensory response of the occupant, irritation. Whereas air containing an irritant may seem only barely irritating at first, it may become intolerably so over time. Figure 7 illustrates the time-course of eye irritation experienced by occupants exposed to ETS at constant concentrations of 2 or 5 ppm carbon monoxide, used here as a tracer in the manner mentioned above (Cain, Tosun, See, and Leaderer, 1987). The lower concentration led to slight, though statistically sigflificant, irritation above pre-smoking baseline. The higher concentration led to irritation that increased over time in sensory magnitude and caused an increasing' degree of dissatisfaction. Whereas essentially none of the occupants found the irritation objectionable a1:t first, by the end of an hour about 30% found it so. In an extension, Clausen, Nielsen, Sahin, and Fanger (1987) found that an asymptotic level of 20% dissatisfaction would occur at a concentration of 3.8 ppm carbon monoxide. A comparison with the odor judgments of visitors in Fig. 6 reveals that only smokers would find such, a level tolerable by the '20% rule.' Clausen et al. estimated that the ventilation rate necessary to control irritation of occupants to a dissatisfaction of 20% would equal only one-tenth of that needed to control odor perceived by visitors to the same level of dissatisfaction. Although Clausen et al. did not argue in favor of 141 TIMN 0030182

Draft - Do not cite or quote lowering ventilation to meet only the dissatisfaction of occupants, there could exist some temptation to do so (see Winneke, Plischke, Roscovanu, and Schlipkoeter, 1984). Cain et al. (1987) cautioned against the temptation to see irritation and odor in the same light: Apart from the issue of whether visitors or occupants are more sensitive, there exists a question regarding whether the '20% rule' should govern dissatisfaction based on irritation just as it governs dissatisfaction based on odor alone. Whereas odor may be interpretable narrowly on grounds of comfort, irritation would seem interpretable on grounds of h e alt h. Some people may find themselves quite neutral with respect to one or another odor, but no one could plausibly argue neutrality with respect to burning eyes. It could be argued, therefore, that any consistent irritation above baseline should be deemed unacceptable. [p.352] Apolicability of Chamber Studies ' The data presented above may raise two issues of rconcern: 1) Should chamber studies influence ventilation policy in view of their remoteness from real-world circumstances? and 2) Would small errors in the results lead to large differences in recommended policies? The first issue has no simple answer. In the real world, people engage in such a wide variety of activities that any single field study, even assuming accurate execution, would itself have very limited generality. Only a set of field studies with a.variety of scenarios could even approach the generality desired. Such field studies have not been done. A group of subjects sitting in a chamber with no task other than to focus attention on odors might seem likely to behave very conservatively, i.e., to judge even weak odors unacceptable, which would in turn imply the need for high ventilation rates. We can neither confirm nor deny this tendency, though circumstantial evidence runs against it. As already noted, visitors in Cain et al.'s (1983) study found ETS odor no more objectionable than occupancy odor at the same perceived intensity. Could this just mean that subjects treat each odor equally conservatively? Unlikely, since the recommended ventilation rates for occupancy odor from that study converge with a great deal of other lab and field evidence regarding the need for about 15 to 20 cfm of ventilation per occupant. Even if the chamber experiment happened to encourage conservatism, persons who choose to participate in it and hence to expose themselves to potentially aversive environmental odors may represent a less reactive fraction of the population. Persons who find ETS odor aversive, for example, would seem unlikely to accept such work. Concern about these matters might, however, stimulate some productive research into the demographic factors 142 TIMN 0030183

Dratt-- Do not cite or quote that govern reactivity to indoor odors. Chamber experiments on ETS can be criticized because they have explored levels that largely exceed those of everyday life. The tendency to explore high levels derives in part from a desire to cover a wide range of conifk,:tions and in part from crude estimates of levels of smoking in the countries and during the eras when the experi:ments were performed. Even just ten years ago, smoking in the U.S.A. occurred more commonly and at higher levels than today. In countries such as Denmark, the location of some recent studies, smoking occurs with a higher frequency and with fewer restrictions than in the U.S.A. Some recent field surveys have found surprisingly low levels of ETS in common spaces, e.g., offices (Kirk, Hunter, Back, Lester, and Perry, 1988; Oldaker, 1989). In order to understand how to relate the chamber studies with such field data, we need to factor in the ventilation rates in the field (see Nystrom and Green, 1986, for a discussion of variables relevant to the evaluation of ETS). Although a building code may specify a ventilation rate of, say, 20 cfm per occupant, the actual per-occupant rate will depend on the number of occupants actually in the space. If a space typically contains only one-third the design number of occupants, the ventilation rate will equal 60 cfm per person. This situation occurs frequently since the design occupancy listed in a standard commonly comes from fire regulations regarding maximum density of occupancy. Accordingly, one cannot argue, as has been done, that a putative low frequency of complaints in field settings offers evidence against the recommendations; of chamber studies and in favor of lower ger-occupant rates. Field data, if collected in spaces occupied well below design levels and if reported without actual per-occupant ventilation rates, can give the illusion that rates of ventilation suitable for occupancy odor can lead to adequate control of ETS odor. When normalized to a per-cigarette ventilation rat:e and hence when seen without assumptions regarding occupancy, chamber studies have probably yielded quite valid data, irrespective of the levels of smoking explored. Regarding the second concern mentioned at the beginning of this section, small errors in the estimate of dissatisfaction could in fact lead-to large errors in recommended rate of ventilation since the relation between percent dissatisfaction and ventilation rate for ETS has a rather low slope (Fig. 4). Merely on general grounds, it would seem advisable to replicate this relation with new participants in order to check its stability and validity. Alternatives to Ventilation It might seem intuitively reasonable that the odor of ETS should come from its vapor phase and the irritation from 143 TMI1iT 0030184

Draft - Do not cite or quote its particulate phase. At one time this seemed likely, but recent investigations that have employed electrostatic air cleaning have shown clearly that the gas phase accounts for the majority of odor and irritation (cf. Hugod, 1984; Weber, 1984). Comparison of the right and left sides of Fig. 7 will reveal that elimination of the particulate phase had only a trivial effect on the eye irritation caused ETS at 2 and 5 ppm carbon monoxide (Cain, Tosun, See, and Leaderer, 1987). The same held true for judgments of odor and of nose and throat irritation. Clausen, Nielsen, Sahin, and Fanger (1987) confirmed these results. In finding that particles played essentially no role in odor, both investigations also confirmed Clausen et al.'s (1985) earlier experiments with visitors. Hence, particle filtration holds no promise for immediate elimination of the discomfort of ETS. The major advantage of such air cleaning will derive from reduction of haze and collection of 'tar' that would otherwise adsorb elsewhere in the space. Although both the odor and irritation of ETS come from the vapor phase, the chemical constituents that give rise to the one probably do not give rise to the other. Undoubtedly, the odor comes from a very large number of constituents. The sense of smell will respond to almost all airborne organic materials present :in sufficient concentration (Cain, 1988). For one substance, however, a 'sufficient concentration' may fall a millionfold below that of another. Furthermore, individual constituents will combine perceptually in mixtures in complicated, nonlinear ways. Although one or a few materials could in principle dominate the odor, it seems unlikely. Many fewer materials can cause irritation at the concentrations present in ETS and its irritation could realistically arise from a few or perhaps even one constituent. Little is known about how irritants combine with each other perceptually though it is known that odor and irritation interact (Cain and Murphy, 1980). Irritation can suppress the perception of odor and vice versa (Cain, See, and Tosun, 1986). In so far as irritation may have a less complex origin than odor, it may offer easier opportunities for control through filtration. As yet, however, experiments on the origin of ETS have told more about what fails to cause irritation than about what causes it (Weber, Jermini, and Grandjean, 1976; Weber-Tschopp, Fischer, and Grandjean, 1977;. Weber-Tschopp, Fischer, Gierer, and Grandjean, .1977; Hugod, Hawkins, and Astrup, 1978). The complexity of ETS more or less guarantees that almost any means of air cleaning will eliminate part of it, even though no simple procedure will eliminate all of it. Through the use of air washing that presumably eliminated some water-soluble constituents, Clausen, M(pller, and Fanger (1987) achieved some reduction in level of dissatisfaction though not in the perceived intensity of ETS. The air-washed ETS smelled fresher. The results offered little encouragement for the use air-washing alo4e, but 144 TIMN 0030185

Draft - Do not cite or quote showed that the odor.character of ETS`can play some.-role-in degree of acceptance. Undoubtedly, a combination of particulate air cleaning and vapor-phase cleaning via adsorption on activated carbon or via chemisorption on oxidant-impregnated alumina can control both the irritation and odor of ETS to some degree. Unfortunately, there exist no standards to assess the efficacy of vapor-phase filtration media. The installation of such media occurs more coatmonly in special environments, e.g., libraries and computer facilities, under expert guidance than in spaces designed for general occupancy. In the overwhelming majority of cases, attempts to control ETS rely on ventilation (dilution). As we have seen, however, ventilation has its limitations. SUMMARY 1. At an average smoking rate of 10% smoking at any one time, nonsmokers would need in excess of 100 cfm/occupant to hold dissatisfaction to the ASHRAE criterion of 20%. odor acceptibility. 2. Exposure to ETS generates odor and irritation in both nonsmokers and smokers. Nonsmokers as a group are less tolerant of ETS than smokers. 3. The irritation and odor from ETS appear to reside in the vapor- phase. The control of ETS irritation and odor by ventilation or air cleaning can provide only limited results. 145 TIMN 0030186

Draft - Do not cite or quote References American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) (1989). Ventilation for Acceptable Indoor Air Quality, ANSI/ASHRAE 62-1989. Atlanta: ASHRAE. Cain, W. S. (1979). Ventilation and odor control: prospects for energy savings. ASHRAE Transactions, 85 (1), 784-792. Cain, W. S. (1988). Olfaction. In R. C. Atkinson, R. J. Herrnstain, G. Lindzey, and R. D. Luce (Eds.), Stevens' Handbook of___Extperimental Psycholoay. Vol. 1: Perception and Motivation, rev. ed. New York: Wiley. Pp. 409-459. Cain, W. S. and Murphy, C. L. (1980). Interaction between chemoreceptive modalities of odour and irritation. Nature, 284, 255-257.. Cain, W. S., See, L.-C., and Tosun, T. (1986). Irritation and _9dor from formaldehyde: chamber studies. In IAQ '36: Manaaina Indoor Air for Health and Enerav Conservation. Atlanta: ASHRAE. Pp. 126-137. Cain, W. S., Tosun, T., See, L.-C., and Leaderer, B. (1987). Environmental tobacco smoke: sensory reactions of occupants. Atmospheric Envionment, 21, 347-353. Cain, W. S., Leaderer, B. P., Isseroff, R., Berglund, L. G., Huey, R. J., Lipsitt, E. D., and Perlman, D. (1983). Ventilation requirements in buildings - I. Control of occupancy odor and tobacco smoke odor. At:nosaheric Environment, 17, 1183-1197. Clausen, G. H. (1986). Tobaksrog - lugtgener og ventilationsbehov. Doctoral thesis, Technical University of Denmark. Clausen, G. H., Fanger, P. 0., Cain, W. S., and Leaderer, B. P. (1985). The influence of aging, particle filtration and humidity on tobacco smoke odor. In P. 0. Fanger (Ed.), Clima 2000, Volume 4: Indoor Climate. Copenhagen: VVS Kongres - VVS Messe. Pp. 345-349. Clausen, G. H., Fanger, P. 0., Cain, W. S., and Leaderer, B. P. (1986). Stability of body odor in enclosed spaces. Environment International, 12, 201-205. Clausen, G. H., Moller, S. B., Fanger, P. 0., Leaderer, B. P., and Dietz, R. (1986). Background odor caused by previous tobacco smoking. In IAO '86: Manaaina Indoor Air for Health and Energy Conservation. Atlanta: ASHRAE. Pp. 119-125. 146 TIMN 0030187

Draft-., -- Do not - cite or quote Clausen, G. H. ,Moller, S. B., and Fanger, P. 0. (1987). The impact of air washing on environmental tobacco smoke odor. In B. Seifert, H. Esdarn, M. Fischer, H. R den, and J. Wegner (Eds.), Indoor Air '87, Volume 2. Berlin: Institute for Water, Soil and Air Hygiene. Pp. 47-51. Clausen, G. H., Nielsen, K. S., Sahin, F., and Fanger, P. 0. (1987). Sensory irritation from exposure to environmental tobacco smoke. In B. Seifert, H. Esdorn, M. Fischer, H. R_den, and J. Wegner (Eds.), ;Cndoor Air '87. Volume 2. Berlin: Institute for Water, Soil and Air Hygiene. Pp. 52-56. Hugod, C. (1984). Indoor air pollution with smoke constituents - an experimental investigation. Preventive Medicine, 13, 582-588. Hugod, C., Hawkins, L. H., and _strup, P. (1978). Exposure of passive smokers to tobacco smoke constituents. international Archives of Occtroational and Environmental Health, 42, 21-29. Kerka, W. F. and Humphreys, C. M. (1956). Temperature and humidity effect on odor perception. Heatina, Piping.- and_ Air Conditioning, 28_, 128-136. Kirk, P. W. W., Hunter, M., Baek, S. 0., Lester, J. N., and Perry, R. (1988). Environmental tobacco smoke in indoor air. In R. Perry and P. W. W. Kirk (Eds.), Indoor and Ambient Air Ouality. London: Selper. Pp. 99-112. Leonardos, G. and Kendall, D. A. (1971). Questionnaire study on odor problems of enclosed space. ASHRAE Transactions, 77 (1),101-112. Leopold, C. S. (1945). Tobacco smoke control - A preliminary study. ASHVE Transactions, 51, 255-270. Nat~onal Research Council (1986). Environmental Tobacco Smoke - Measuring Exposures and Assessing Health Effects. Washington: National Academy Press. Nystrom, C. W. and Green, C. R. (1986). Assessing the impact of environmental tobacco smoke on indoor air quality. In IAQ '86: Manaain~c the Indoor Air for Health and Energy Conservation. Atlanta: American Society of Heating, Refrigerating, and Air-Conditioning Engineers. Pp. 213-233. Oldaker, G. B. (1989). Environmental tobacco smoke (ETS): How much is in the air? Presented at the International Tobacco Conference Minisymposium on Environmental Tobacco Smoke and Scientific Affairs, Winston-Salem, NC. Repace, J. L. and Lowry, A. H. (1980). Indoor air pollution, tobacco smoke, and public health. Science, 208, 464-472. 147 T-jMN 0030188

Draft - Do not cite or quote Weber, A. (1984). Annoyance and irritation by passive smoking. Preventive Medicine, 13, 618-625. Weber, A., Jermini, C., Grandjean, E. (1976). on man of air pollution due to cigarette smoke. Irritating effects American Journal of Public Health, 66, 672-676. Weber-Tschopp, A., Fischer; T., Grandjean , E. (1977). Reizwirkungen des Formaldehyds (HCHO) auf den Menschen. (Irritating effects of formaldehyde on men. ) International Archives of Occupational and Environmental Heal th,_ 39, 207-218. Weber-Tschopp, A., Fischer, T., Gierer, R., and Grandjean, E. (1977). Experimentelle Reizwirkungen von Akrolein auf den Menschen. (Experimentally induced irritating effects of acrolein on men.) Archives of Occuuational and Environmental Health, 40, 117-130. Winneke, G., Plischke, K., Roscovanu, A., and Schlipkoeter, H.-W. (1984). Patterns and determinants of reaction to tobacco smoke in .an experimental exposure setting. In B. Berglund, T. Lindvall, and J. Sundell (Eds.), Indoor Air, Vol. 2. Stockholm: Swedish Council for-Building Research. Pp. 351-356. Yagiou,•C. P. (1955). Ventilation requirements for cigarette smoke. ASHAE Transactions, 61, 25-32. Yaglou, C. P.,' Riley, E. C., and Coggins, E. I. (1936). Ventilation requirements. ASHAE Transactions, 42, 133-162. TIMN 0030189 148

Draft - Do not cite or quote Fic,Ture Captions Figure 1. Showing the relation between level of occupancy odor (indicated by concentration of 1-butanol matched to the odor) and ventilation rate per occupant when 4 to 12 persons occupied a climate chamber for an hour (filled squares). Judgments of odor were made by visitors who sampled the air of the chamber at a remote sampling box. Also shown (unfilled squares) is the frequency of dissatisfaction expressed by the visitors in response to the question, Is the air acceptable or unacceptable ? Dashed line shows ventilation rate that led to 20% dissatisfaction. Data from Cain et al. (1983). _. Figure 2. Frequency distribution of ventilation rates recommended for various types of spaces (e.g., offices, auditoriums, ticket booths, waiting rooms) by the ASHRAE standard on ventilation and indoor air quality. Figure 3. Showing the intensity of ETS odor perceived by visitors to the sampling box during and after intermittent (4 cig/hr) or continuous (8 and 16 cig/hr) smoking in the climate chamber. Results are expressed relative to level of butanol matched to odor during presmoking occupancy. The open squares in the left panel show a function for nonsmoking occupancy for comparison. Ventilation rate per occupant under smoking conditions refers to smokers, who were the only occupants in the chamber. From Cain et a1. (1983). Figure 4. Percent dissatisfaction among visitors vs ventilation during the last 15 min of smoking in the experiment shown in Fig. :3. Ventilation rate per cigarette based on 7<5-min smoking time per cigarette. Ventilation rate per occupant adjusted to conditions of smoking occupancy that assumed 10% of occupants will be smoking at any give time. Modified from Cain et al. (1983). Figure 5. Percent dissatisfaction vs odor intensity (graphic rating) for occupancy odor and for ETS odor. Data from Cain et al. (1983). Figure 6. Left: Percent dissatisfaction vs odor intensity (matched level of butanol) judged by smokers and nonsmokers. Right: Percent dissatisfaction vs increment in concentration of airborne carbon monoxide. Modified from Clausen (1986). Figure 7. Perceived magnitude of eye irritation and degree of dissatisfaction expressed by occupants exposed to ETS for an hour. Concentrations of carbon monoxide were held constant throughout the exposures and indicate severity of exposure. Filtration refers to elimination of particles via 149 TIMN 0030190

Draft - Do not cite or quota electrostatic precipitation. Filtration had little effect on irritation. From Cain et al. (1987). iso TIMN 0030191

Draft - Do not cite or quots TABLES AND FIGURES FOR CHAPTER 8 0030192

Draft°- Do not cite or quote ~ m 20 ~ ~ ~ ° 10 20 Ventilation Rate (cfm per occupant) Figure 1 TIMN 0030193

Draft ° Do not cite or quota ~ ; 40 I , Recommendations from ASHRAE Standard 15 20 25 30 35 40 45 50 55 60 Ventilation (cfm per occupant) Figure 2 TIMN 0030194

pisl,ro 3 1000 900 C L 500 ~ 400 300 200 100 4 Clyare/Ies/hr L•.1oco. I i I I i ~--smoking--~ 8 ClparaItes/hr 0 30 60 90 120 Time (min) 0 0 , 30 - 60 90 120 d 0 :3 0 rt 0 n

Draft-- Do not cite or quote Ventilation Rate per Occupant (c5~ ) 100 G 10 20 . 200 500 1000 2000 5000 Ventilation Rate per Cigarette (ft3) Figure 4 T IMN ®03 '196

Draft - Do not cite or quote 80 60 ~ y= 40 ~ a N N ° 20 4- 2 3 4 5 6 7 8 910 Odor Intensity (cm) Figure 5 TIMN 0030197

DI'aft>.. °° Do not cite or quote . ~ O N O 61 Smarer Non-smater m 40 1t .101 SO s0 70 to00M0 /t0 1 4 4 • 8 • 71 fI0 ]O •O SO 40 70 W00100 /t0 Butonol (ppm) Fig 6 Non-rmoRer . J: 1 7 a • S. 7 a .10 ®CO (ppm) TIMN 0030198

. u-~ NO PUTRATlON I F1lTRAT10N y Draft - Do not cite or quote • 2pPM • 5PPM 1.0 1 ..y'. 0.3 ... J.M..'.~ • l.. ~ . . . 1 NO f t.: rcAT10N 5o .o 30 . , l.• OrL+ • 0 13 30 A1 t0 TIME Fig. 7 ~~r...._. 0 tS (minutes) 30 L1 ~0 TIMN 0030199

Draft - Do not cite or quote CHAPTER 9 PASSIVE SMORiNG--BEILIEFS, ATTITUDES, AND EXPOSURES IN THE UNITED STATES Thomas E. Novotny, M.D. Oft`ice on Smoking and Health Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control Tntroduction The relationship among public attitudes, policies, and exposure to certain health hazards is complex. With the release of the 18th Surgeon General's report on smoking and health, The Health Consequences of Involuntary Smoking (PHS 1986), public attention on the issue of environmental tobacco smoke (ETS) was more strongly focused than ever before. For many years, however, pollsters, the tobacco industr'y,-'and the health promotion community have have been surveying the public concerning attitudes toward ETS and toward restrictions on smoking in public places. The Surgeon General's Report described data from several of those surveys as well as results from evaluations of worksite and local policy changes. Additional detailed data on public beliefs and attitudes toward smoking in general are found in the 1989 Surgeon General's Report: Reducincr the Health Consecruences of Smokina -- 25 years of Progress (PHS 1989). Recently, surveys have also included questions on beliefs about the harmfulness of ETS to the nonsmoker and on respondents' reported exposure to ETS. In addition to such measures of individual exposure to ETS, surveys of worksites and of personnel managers have provided information about restrictions on _;moking in the workplace. Because changes in public attitudes toward ETS usually precede laws or policies regarding ETS exposure (PHS 1986), examining trends in these data over time is useful. This chapter will summarize the most important findings from several different nationally based data sources. Some of this information was included in the 1989 Report of the Surgeon General (PHS 1989). Data Sources and Methodoloay Several surveys of public beliefs, attitudes, and reported exposures to ETS are available (Table 1). Although these surveys may report discrepant results, most discrepancies can be explained by the differences in methodology, especially in the ways questions are worded. To describe the effect of increasing numbers and strength of laws and policies against smoking in public places, 152 T1UN 0030200

Draft°- Do not cite or quote national surveys of worksites were also carried out in the 1980s (PHS 1986). These surveys indicate the degree to which workers may be protected from ETS exposure. The 1987 National Health Interview Survey of Cancer Epidemiology and Control also collected information about respondents' actions in response to ETS exposure. Tobacco Industrv Surveys 1. Roper Surveys: The Roper Organization conducted six biennial national ooinion surveys for The Tobacco Institute between 1966 and 1978. The 1974, 1976, and 1978 surveys focused on the passive smoking/nonsmoker's rights issue (Roper 1978); whereas all six surveys dealt with public attitudes toward the smoking and health issue in general, toward the tobacco industry itself, and toward government regulation of tobacco. The surveys were cross- sectional, population-based telephone interviews. The sample included over 2,000 adults, aged 17 years or older; other information about the exact methodology and response rates is unavailable. The 1974-1978 Roper surveys permit comparisons of data collected for the tobacco industry with similar data collected in the 1970s by the Office on Smoking and Health (OSH, formerly known as the National Clearinghouse for Smoking and Health). 2. Hamilton, Frederick, and Schneiders: In December 1988, the Tobacco Institute sponsored a telephone-based national adult survey of 1,500 adults (401 smokers and 1,099 nonsmokers) which was conducted by Hamilton, Frederick, and Schneiders (Hamilton,, Frederick and Schneiders, 1989). This survey asked about various public policy issues and was designed to measure levels of support for governmental'policy on smoking. The respondents were asked what they thought about restrictions on smoking in restaurants and worksites. Neither the response rates nor the results by smoking status of the respondents were reported. Other Public Oninion Survevs 1. Gallup Surveys: The Gallup Organization has published Gallup Poll results monthly since 1965. Surveys are either personal interviews or by telephone and have a population-based sample of at least 1000 adults, aged 18 years or older. The sampling error for overall responses is reported to be no more than +_3% (Gallup Report 1987). In addition, Gallup surveys may be commissioned by a variety of organizations. The surveys reported here were commissioned by the American Lung Association (1983, 1985, 1987, and 1989) and the American Cancer Society (1988) to describe both the prevalence of smoking and public opinions regarding smoking issues. An additional Gallup Survey was commissioned by the National Restaurant Association (1987) to obtain public opinion on smo'r.ir.g in restaurants. The 1989 Gallup Survey sponsored by the American Lung Association did not ask respondents about their smoking status. 153 TjMN 0030201

Draft.® Do not cita or quote 2. Harris Poll: Louis Harris and Associates have perfor.^ed eight national surveys covering smoking between 1974 and 1987 using probability samples of adults aged 18 years and older. These surveys were conducted on behalf of various organizations, including Prevention magazine and Pacific Mutual Life Insurance Co., to ascertain health practices of Americans. In 1987, 1,250 persons were also asked about regulating smoking in public places. Government Sponsored Survevs 1. Adult Use of Tobacco Surveys (AUTS): The Office on Smoking and Health commissioned surveys of adult smoking behavior, attitudes, and beliefs in 1964, 1966, 1970, 1975, and 1986. These surveys oversampled persons who had ever smoked, but final results were weighted to represent the United States resident population aged 21 years and older (1964, 1966, 1970, 1975). The 1986 AUTS oversampled ever smokers but collected data from persons aged 17 and older. The final data in this survey (overall response rate, 74.3%) were weighted to reflect the educational, regional, racial, and age distribution of the U.S. population on the basis of the 1986 Current Population Survey of the U.S. Bureau of the Census. The 1986 AUTS collected detailed information on attitudes, beliefs, and exposure regarding ETS. 2. National Health Interview Survey: The National Health Interview Survey of Cancer Epidemiology and Control (NHIS-CEC) collected data in-person from 22,000 adults aged 18 years and older in households throughout the United States. The data were weighted to reflect the adult U.S. population, and the overall response rate for NHIS-CEC was 82%. Respondents were asked about the harmfulness of ETS and about attitudes toward passive smoking. Questions included items on perceived annoyance and whether smoking should occur inside public places. Nonsmokers were asked how they would act in response to smokers' lighting up in their presence. Other Surveys 1. Bureau of National Affairs: The Bureau of National Affairs (BNA) and the American Society for Personnel Administration (ASPA) conducted a mail-in questionnaire survey of ASPA members, and 623 respondents reported on activities related to• smoking in the workplace. The response rate was 54%. A similar survey was carried out by the BNA in 1986 on 662 businesses. 2. Office of Disease Prevention and Health Promotion: In 1988, the Office of Disease Prevention and Health Promotion (ODPHP) of the United States Public Health Service reported on worksite health promotion activities, including smoking control. The survey, carried out in 1985 on a sample drawn from the Dun and Bradstreet 154 TIMN 0030202

Draft - Do not cite or quote list of businesses, used telephone interviewing. To develop a probability sample based on geographic region, size of firm, and industry type, 320 worksites with 50-90 employees and 1,338 worksites with 100 or more employees were surveyed. Questions about smoking restrictions were included. 3. American Board of Family Practice: In December 1984, the American Board of Family Practice (ABFP) sponsored a national telephone survey conducted by Research and Forecasts, Inc., of 1,007 adults aged :8 years and older and of 303 family phys+.cians. Questions were asked regarding beliefs about the harmfulness of ETS, the rights of smokers and nonsmokers, and whether smoking restrictions are effective in stopping or discouraging smoking. The final sample response rates were 41% for the general public and 37% for physicians. Data for the general public portion of this survey were weighted to reflect the estimated 1985 U.S. population. The physicians surveyed represented a random sample of U.S. family physicians. The results were published in a report entitled, Rights and Restionsi_bilities: Healthcare Opti,ons (ABFP 1985). *esults of Surveys 1. Perceived Harmfulness of Environmental Tobacco Smoke The Roper Surveys asked questions regarding harm and annoyance caused by ETS. All AUT surveys asked about annoyance caused by ETS, but only the 1986 AUTS asked if respondents believed that ETS is harmful to the nonsmoker. The 1983 and 1988 Gallup Surveys asked if respondents believed that smoking is hazardous to the health of nonsmokers. The 1978 Roper Survey, the 1986 AUTS, and the 1988 Gallup survey provide interesting information on the change over the last several years in public beliefs about the harmfulness of ETS to nonsmokers. The 1985 ABFP Survey asked both adults and physicians if they believed nonsmokers are harmed by breathing in the smoke of others in the same room. Questions regarding harm caused by ETS showed that between 1974 and 1986, the percentage of smokers who believed that ETS is harmful to the health of the nonsmoker more than doubled (Table 2). In 1974, most nonsmokers believed that ETS is harmful to •health in general,_and the percentage of those who held this belief increased substantially over time. In answering an additional question on the 1986 AUTS, 69% of nonsmokers felt that ETS is harmful to their own personal health. The results of the 1989 Gallup poll suggest that there is even stronger belief by respondents (smokers and nonsmokers) in the harm of ETS to pregnant women and children. These data show that there has been a major change in the perception of ETS as a health hazard over the last decade. TIMN 0030203 155

Draft`- Do not cite.or quote 2. Annoyance Caused by Environmental Tobacco Smoke The AUT surveys show an increasing trend in the percentage of respondents who are annoyed by ETS (Table 3a). Data regarding annoyance to ETS from Roper Surveys other than the 1978 survey are not available. However, the results of both the 1978 Roper Survey and the AUTS suggest that increasing numbers of Americans are annoyed by ETS exposure. The results of the 1987 NHIS-CEC also indicate increased annoyance from ETS. In this survey, a smaller percentage of current smokers reported annoyance than on the 1986 AUTS, but this difference may be due to different methodologies. The NHIS-CEC also collected information about what nonsmokers did in response to exposure to ETS (Table 3b)., About half of respondents moved away from the exposure source, 40% did nothing, 3% did something else, and only 4% asked the person not to smoke. Despite their high positive responses to perceived harm caused by ETS and annoyance from ETS, most nonsmokers remain rather passive in theirr behavior toward smokers (Davis et al., 1990). 3. Limi,tinQ or Bannina Smokinct in Public Places The majority of respondents to the 1978 Roper Survey felt that smokers should at least be segregated in all the public places cited (Table 4). After being asked about segregation of smokers and nonsmokers, respondents were then asked if smoking should be banned outright in selected public places. The majority of respondents favored smoking bans in retail stores, physicians' or dentists' waiting rooms, and elevators (Table 5a). The narrative description of the survey results pointed out that after recognizing the option to segregate smokers, respondents were probably less likely to be in favor of a total ban (Roper 1978). The two most important reasons given by Roper Survey respondents before 1978 as to why smoking should be restricted had to do with dangers to others, specifically, cigarette smoking as a fire hazard and ETS as a health hazard to nonsmokers. In 1978, the chief reason respondents gave in favor of public laws against smoking was that the "health of nonsmokers is harmed by other people smoking in their presence." In 1983, 1985, 1987, and 1989, the Gallup Organization conducted telephone surveys for the American Lung Association (ALA) that asked if smokers should refrain from smoking in the presence. of nonsmokers. Overall, the percentage of respondents to these surveys who agree that smokers should not smoke in the presence of nonsmokers has increased from 69% in 1983 to 82% in 1989 (Table 6a). This trend holds true for both smokers and nonsmokers. Unfortunately, the 1989 survey did not differentiate between smokers and nonsmokers. 156 - - TIMN 0Q3420 4

Draft - Do not cite or quote The ALA Gallup Surveys also included questions on where smoking should be restricted or banned. With regard to smoking in hotels, motels, and restaurants, the majority of respondents in 1983, 1987, and 1989 felt that certain areas should be set aside for smoking (Table 7). Complete bans were less favored, especially by persons who currently smoked. in addition, respondents to the ALA Gallup Surveys were asked in 1983, 1985, and 1987 if companies should have a policy on smoking at work. By 1985, almost 90% of all respondents, including 80% of smokers and 89% of nonsmokers, felt that smoking should be assigned to certain areas of the worksite or that it should be totally banned at work (Table 7). In 1987, the monthly Gallup Polls (not commissioned by the ALA) asked if respondents favored or opposed a complete ban on smoking in all public places. The results of these polls are much more strongly in favor of total bans on smoking in public places. These results contrast sharply with,the Roper results of almost a decade ago and are even more in favor of increased restrictions on smoking in public places than the ALA-sponsored surveys in the same year. Fn the Gallup Survey conducted for the National Restaurant Association in 1987, 61% of adults reported that they preferred no-smoking sections in restaurants. These included 20% of smokers, 65% of former smokers, and 83% of never smokers (Gallup 1987). These results are similar to those of the AUTS on preferences concerning no-smoking sections described later in this chapter. The 1987 NHIS-CEC.asked a slightly different question than either the Gallup Surveys or the AUTS. This question restricted the respondent to consider indoor public places. The percentage of all respondents, especially former smokers, agreeing that smoking should not be allowed inside public places, was higher on this survey than on the 1987 Gallup survey (Table 6b). The Gallup question applied to a general statement about refraining from smoking in the presence of nonsmokers. Interestingly, the Tobacco Institute-sponsored survey by Hamilton, Frederick, and Schneiders in 1988 showed even stronger preferences for restaurant and worksite restrictions than the ALA surveys mentioned previously (Table 5b). For each of these sites, the question referred to the "current policy" As a response choice; for restaurants, the "current policy" meant that customers must select smoking vs. nonsmoking sections; for worksites, employers and employees should decide on worksite restrictive policies. In this survey, 2t of respondents favored no restrictions on smoking in restaurants compared with.8% in the ALA survey, and 3% favored no restrictions on smoking in worksites compared with 10% in the ALA survey. Between 1964 and 1975, the percentage of respondents to the AUT 157 TIMN 0030205

Draft - Do not cite or quote :rveys who favored restrictions on smoking in public places :creased from 52% to 70% (strongly agree and mildly agree) (Table . However, the question asked in 1986 was quite different from :e questions asked in the earlier..surveys (Table 8). Between 1964 id 1975, AUTS respondents who favored more restrictions increased a 18 percentage points. About half of respondents in 1986 felt iat restrictions against smoking were adequate, perhaps because any more restrictions were in place by 1986. 1 1966 and 1975, respondents were also asked if employers have a ight to regulate smoking in their places of business. In 1966, 2% felt that the "employer has a right to tell a person when or ftere he can smoke while on the job," whereas in 1975, 78% felt hat "management should have the right to prohibit smoking in their laces of business." These are very different questions: the first oncerns management's right to regulate employees, and the second oncerns management's right to regulate customers, visitors, and mployees. :n 1987, respondentsa to the Harris Poll that was. performed for ?revention magazine were asked if laws should prohibit smoking in ?ublic places or require separate smoking and nonsmoking sections, ~r should smoking in public places not be regulated by law. Among ,1'21 respondents,-23% felt that laws should prohibit smoking in public places, 61% felt that laws should require separate smoking and nonsmoking sections, and only 131 felt that laws should not regulate smoking in public places at all (3% were unsure). Again, more than 80% of respondents, smokers and nonsmokers, favored restrictions against smoking in public places. 4. Public Opinion on Restrictions After Enactment of Laws Few evaluations of the acceptability of laws banning smoking in public places have been performed. New York City enacted a ban on smoking in most public places, including restaurants, in April 1985. Three months after the ban took effect, a telephone poll of 676 randomly sampled New Yorkers (New York Times/WCBS-TV poll) revealed that 73% of respondents approved of the law, including 84% of nonsmokers and 43% of smokers (New York Times, July 5, 1988). The 1986 AUTS asked respondents if they.would select nonsmoking sections in airplanes, restaurants, and other public places if given a choice. overall, 61% choose nonsmoking seating, including 82% of never smokers, 69% of former smokers, and even 14% of current smokers (CDC 1988). Finally, a clean-indoor-air ordinance that took effect in March 1987 in Cambridge, Massachusetts was evaluated by researchers at Harvard University after three months of implementation. This evaluation study revealed that 78% of Cambridge residents favored 158 T.IMN 0030206

Draft - Do not cite or quote the restriction, including 41% of smokers and 90% of nonsmokers (Rigotti 1988). 5. Exposure to ETS Many studies have demonstrated the biochemically measurable exposure of nonsmokers to ETS (PHS 1986). However, only the 1986 AUTS has asked a nationally representative sample of residents about exposure to ETS. a subsample of 8,600 working respondents from the AUTS was analyzed with respect to reported exposure at the worksite and reported policies restricting smoking at their worksites (Table 9). Fifty-three percent of respondents who worked in environments with restrictive smoking policies still reported exposure to ETS. Of these, 11% reported that their worksite is "very smoky." Even among the 2.5% of respondents reporting a total ban on smoking in the workplace, 21% reported still being at least somewhat exposed to ETS at work. These data help confir.a the notion that worksite restrictions decrease but do not eliminate reported exposure to ETS at the worksite. 6. The Increasing Number of Policies/Laws Restricting Smokina at the Works ite In 1987, 54% of respondents to the BNA/ASPA survey reported that their worksites had restrictive smoking policies, up from 36% in 1986 (BNA 1987). The 1986 figure was nearly the same as the percentage of individual workers reporting the presence of such policies in the 1986 AUTS. Among respondents to the 1985 ODPHP Worksite Survey, 35.6% of worksites reported offering smoking control activities, including classes, information, special events, or contests. Of those companies, 76.5% also had formal smoking policies (restriction or prohibition). In addition to frequently cited benefits--such as improved employee morale, improved employee health--respondents reported cleaner air and work environments, fewer smokers in the workforce, and fewer complaints from nonsmokers (PHS 1988). 7. Percei_v_ed Future-Effect Rest ctive Smokina Pol i.c_ies The National Survey of Healthcare Opinions sponsored by the ABFP and carried out by Research and Forecasts, Inc., in 1985 asked adults and family physicians if restrictions on smoking in medical facilities or on the job would be effective. in stopping or discouraging smoking. Among the nonphysicians, 57% felt that restrictions in medical facilities would be effective, and 40% felt that restrictions by employers against smoking on the job would be effective. Among physicians, 83% felt that such restrictions would be effective in health care facilities, and 67% felt that restrictions would be effective on the job. These responses should be differentiated from those in other surveys that ask about support for restrictive smoking policies. The ABFP survey tried 159 TIMN 0030207

Draft - Do not cite or quote to ascertain if respondents thought policies were an effective :.ntervention for smokers to refrain from using tobacco, whereas Sallup surveys tried to ascertain what people want in terms of protecting the nonsmoker from exposure to ETS. Few studies have actually been able to assess the effect of cestrictive smoking policies on smokers' behavior, but some studies from individual worksites show decreased numbers of cigarettes smoked per day without a change in the prevalence of smoking (Peterson at al., 1987, Rosenstock at al., 1986). Conclusions These data indicate an important shift in public beliefs and attitudes toward ETS over the last decade or more. The majority of U.S. citizens have recognized that cigarette smoking direc-tly harms the health of smokers (89% of men and 90.9% of women in 1975 CAUTS 1975] ; 92% of men and 91.8% of women in 1986 CAUTS 19861). Moreover, the percentage of survey respondents who believe that ETS also harms the health of nonsmokers has increased dramatically (46% overall in 1974 [Roper 1978) to 81% overall in 1986 CAUTS 1986, Gallup 1988]). Even more Americans agree that ETS harms vulnerable populations such as pregnant women and children. Many laws and local ordinances that were put into place during the last decade undoubtedly increased public awareness of ETS issues (PHS 1989). The National Academy 'of Sciences Report and the Surgeon General's Report on involuntary smoking were released in late 1986. However, not all of the change in belief about harmfulness to ETS can be attributed to the publication of these reports, even though they received enormous media attention; most of the 1986 AUTS had been completed by late 1986. Therefore, the increase in reported beliefs about the harmfulness of ETS likely reflects a growing and sustained awareness among U.S. residents rather than merely a public response to the highly visible Surgeon General's Report. This report may have convinced more persons about the harmful effects of ETS, as evidenced by the results of the 1989 Gallup Survey. The slightly discrepant results on attitudes toward laws regarding restricting smoking in public places found in the 1986 AUTS and the 1988 Harris Poll may be explained by the differences in the way the question was asked in this survey. Many laws were put into place by 1986, and respondents may have felt less concerned about increasing regulations than they did in earlier surveys, before these laws were in effect. These laws have been evaluated directly by researchers in some jurisdictions and indirectly by surveys, and they are apparently widely accepted by both smokers and nonsmokers. There appears to be a trend towards limiting smoking in workplaces. It is unclear whether laws and regulations restricting smoking in 160 --- 7CEVIN 0030208

Draft - Do not cite or quote public places (which became widespread in the late 1970s) were the stimuli for policies restricting smoking in the workplace (which are mostly a phenomenon of the 1980s) or whether simply the concern for the health of nonsmokers is the stimulus for this trend. The 1986 AUTS results, which show that even with a total ban on smoking in the workplace some workers are exposed to ETS, suggest that there is incomplete enforcement of restrictions. In worksites where smokers and nonsmokers are segregated, exposure to ETS may result from the inefficiency of separating smokers and nonsmokers within the same airspace. The 1986 Surgeon General's Report concluded that this level of restriction was inadequate to protect the nonsmoker from ETS (PHS 1986). The 1990 Health Objectives for the Nation, which were endorsed by the U.S. Public Health Service, recommend that all 50 states have laws by 1990 that both prohibit smoking in enclosed public places and require separate smoking areas in the workplace and in dining establishments (PHS 1980). The number and strength of these "clean indoor air" laws continues to increase at both the state and local level.(PHS, 1989) As of late 1988, 31 states had laws restricting smoking in public Worksites, 13 had laws restricting smoking in private worksites, and 26 had laws restricting smoking in restaurants (PHS 1989). Continuing to assess public knowledge and beliefs regarding tobacco use remains important as new information becomes available. These survey results assist public health providers in measuring the success of policies to control health hazards such as ETS. In addition, these data emphasize the change in the social milieu surrounding tobacco use. The shift in public attitudes away from the social acceptability of smoking may increase the pressure for smokers to quit and for potential smokers to avoid smoking. Policy-makers may also find it easier to address tobacco issues more directly if they understand the public opinions expressed through these surveys. SUNIlKARY 1. The majority (81%) of U.S. citizens have recognized that cigarette smoking harms the health of nonsmokers. 2. As of late 1988, 31 states had laws restricting smoking in public worksites, 13 had laws restricting smoking in private •worksites, and 26 had laws restricting smoking in restaurants. 3. There appears to be a trend towards limiting smoking in workplaces; however, there are indications, of incomplete enforcement of restrictions. TIMN 0030209 161

Draft ® Do not cite or quote References Bureau of National Affairs. Where there's smoke: problems and policies concerning smoking in the workplace. A BNA special report 2nd ed. Rockville, Maryland: Bureau of National Affairs, 1987. CDC. Cigarette smoking in the United States, 1986. MMWR 1987; 36 (35) :581-585. CDC. Passive smoking: Beliefs, attitudes, and exposures--United States, 1986. MMWR 1988;37(15):239-241. Davis RM, Boyd GX', Schoenborn CA. 'Common Couresty' and the- elimination of passive smoking. Results of the 1987 National Health Interview Survey. JAMA 1990; 263: 2208-2210. Gallup. Survey of attitudes toward smoking. Conducted for the American Lung Association. Princeton, New Jersey: Gallup Organization, July 1985. Gallup. Attitudes toward smoking in restaurants and fast food establishments. Conducted for the National Restaurant Association. Princeton, New Jersey: Gallup Organization, February 1987. Gallup. Majority backs ban on smoking in public places. Gallup Report No. 258. Princeton, New Jersy: Gallup Organization, March 1987. Gallup. On-the-go Americans prefer smoke-free air. Am J Pub Health 1988;78(5):563. Gallup. A telephone survey of 1549 adults conducted in 1988 for the American Cancer Society. The Gallup Report 1988, No. 268. Princeton, New Jersey: Gallup Organization, September 1988. Gallup. Survey of attitudes toward smoking. Conducted for the American Lung Association. Princeton, New Jersey: Gallup Organization, August 1989. Harris, Louis and. Associates. Prevention in America V: steps people take or fail to take for better health, 1987. Survey performed for Prevention Magazine. May 13, 1988. Appendix B:page 8. Hamilton, Frederick, and Schneiders. National Survey of American's Attitudes on Various Public Policies and Practices. Conducted for The Tobacco Institute, December 1988. National Center for Health Statistics. Smoking and other tobacco use: United States, 1987. Hyattsville, Maryland: National Center for Health Statisitics. DHHS Pub. No. 89-1597. NCHS Series 10, # 169. 162 TIli'IN 0030210

Draft - Do not cite or quote National Clearinghouse for Smoking and Health. Adult use of tobacco 1970. Rockville, Maryland: US Department of Health, Education, and Welfare. Public Health Service. June 1973. National Clearinghouse for Smoking and Health. Adult use of tobacco 1975. Rockville, Maryland: US Department of Health, Education, and Welfare. Public Health Service. Center for Disease Control, June 1977. National Clearinghouse for Smoking and Health. Use of tobacco: practices, attitudes, knowledge, and beliefs, United States--Fall 1964 and Spring 1966. Washington D.C.: U.S.Department of Health, Education, and Welfare. Public Health Service July 1969. Office of Health Promotion and Disease Prevention. National Survey of Worksite Health Promotion Activities. Washington, D.C.: U.S. Department of Health and Human Services. Public Health Service. Summer 1987. Peterson LR, Helgerson SD, Gibbons C.M, Calhoun CR, Ciacco KH, and Pitchford KC. Employees smoking behavior changes and attitudes 'following a restrictive policy on worksite smoking in a large company. Public Health Rep 1988;103(2):115-120. Public Health Service. Promoting health/preventing disease: objectives for the nation. Washington, D.C.: US Department of Health and Human Services, Public Health Service, 1980. Public Health Service. The health consequences of involuntary smoking: a report of the Surgeon General. Rockville, Maryland: US Department of Health and Human Services, Public Health Service, Centers for Disease Control, 1986; DHHS publication no. (CDC) 87-8398. Public Health Service. Reducing the Health Consequences of Smoking--25 Years of Progress. A Report of the Surgeon General. Rockville, Maryland: U.S. Department of Health and Human Servics, Public Health Service, Centers for Disease Control, 1989; DHHS publication no. (CDC) 89-8411. Public Health Service. Major local smoking ordinances in the United States. A detailed matrix of the provisions of workplace, restaurant, and public places smoking ordinances. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, 1989. DHHS Publ. T# (NIH) 90-479. Research and Forecasts, Inc. Rights and responsibilities -- a national survey of health care opinions sponsored by the American Board of Family Practice. Lexington, Kentucky: American Board of Family Practice, 1985. 163 TIIVIN 0030211

Draft - DognotYcita or quote Rigotti NA, Stoto MA, Kleiman M, Schelling TC. Implementation and impact of a Cambridge, Massachusetts, ordinance restricting smoking in public places and the workplace. In Aoki et al., eds. Smoking and Health 1987. Proceedings of the 6th World Conference on Smoking and Health, Tokyo, 9-12 November 1987. Amsterdam: Excerpta Medica, 1988. Roper Organization. A study of public attitudes toward cigarette smoking and the tobacco industry in 1978. New York: Roper Organization, May 1978. Rosenstock IM, Stergachis A, Heaney C. Evaluation of smoking prohibition policy in a health maintainance organization. Am J Public Health 198t5;76(8):1014-1015.. Anonymous. Support- for smoking ban. New York Times, July 5, 1988:B2. 164 TyM~T 0030212

Draft - Do not cita or quote FIGURES AND TABLES FOR CRAPTER 9 165 TIMN 0030213

Draft - Do not cite or.,quote Table 1. Surveys With Infornation on Beliefs, Attitudes, and Exposures to Environmental Tobacco Smoke . u e Ye&r Sponsor Adult Use of Tobacco '64,'66,'70,°?5,'86 Office on Smoking and Health Roper Organization '74,'76,'78 Gallup Survey '83,'85,'87,'89 Tobacco Institute American Lung Association Research & Forecasts '85 American Academy of Family Physicians Gallup Survey '87 National Restaurant Association Harris Poll '87 Prevention Magazine Gallup Survey '88 American Cancer Society Hamilton, Frederick '88 Tobacco Institute & Schneiders 166 - TVVdN 0030214

Draft - Do not cite or quote Table 2. Beliefs About Harmfulness of Environmental Tobacco Smoke to Nnonsmokers (% of Respondents) by Smoking Status Smokinq Status Survey Year Current Former Nonsmokers Never All Smokers Smokers Smokers Resmondent= Roper '74 30 57 46 Roper '76 38 61 52 Roper '78 40 69 58 Gallup '83 64 80 84 Research Forecasts'85 77 (Physicians=87) AUTS '86 69 82 85 87 81 NHIS-CEC '87 67 84 89 82 Gallup '88 64 86 89 81 Gallup '89 Harmful to adults 86 Harmful to pregnant women 88 Harmful to children 89 Source: Roper Organization 1978; Gallup Surveys 1983, 1988; Adult Use of Tobacco Survey 1986; Research and Forecasts 1985 167 Z'1MN 0030215

Draft - Do not cite or quote Table 3a. Annoyance Caused by Environmental Tobacco Smoke (~ of Respondents Reporting Annoyance) by Smoking Status =.nnoyed by ETS Smoking Status .urvev Current Former Nonsmokers Never Smokers Smokers Smokers Resoondents %UTS 1964 20 49 64 69 46 iUTS 1966 26 52 70 48 AUTS 1970 34 63 73 78 59 AUTS 1975 35 72 79 79 63 ROPER 1978 5 60 AUTS 1986 42 73 80 83 69 NHIS-CEC 198 7 34 75 88 69 Source: Adult Use of Tobacco Surveys 1964, 1966, 1970, 1975, 1986; Roper Organization 1978, NHIS-CEC 1987. 0030216

Draft - Do not cite or quote Table 3b. Reactions to Secondhand Smoke in Public Places, 1987* Former Never All Smokers Smokers Nonsmokers I I; i; Ask person not to smoke 4 5 4 Move away 52 46 52 Do nothing 40 47 40 Do something else 3 3 3 *Not asked of current smokers Source: 1987 NHIS-CEC (Davis et al.; 1990) TIMN 0030217 169

Draft - Do not cite or-quote Table 4. Public Opinion (% of Respondents Who Agree) on Separating Smokers and Nonsmokers in Selected Public Places, 1978 Smokina should be germitted: In separate sections Anywhere ;n trains, airplanes, and buses 91 7 - n theaters 83 11 :ri eating places 73 25 xt indoor sporting events 73 22 At public meetings 67 28 in train, plane, bus stations 62 34 In work places or•offices 61 34 In barber or beauty shops 53 42 Source: Roper Organization 1978 0 170 TIMN 0030218

Draft - Do not cite or quote Table 5a. Public Opinion (16 of Respondents Agreeing) on Banning Smoking in Selected Public Places, 1978 Should smokinc~be: Banned Not banned In elevators 86 12 In doctors' or dentists' waiting rooms 69 27 In retail stores 55 41 In theaters 44 47 At indoor sporting events 34 57 At.public meetings 32 58 In city, state, or federal buildings 32 63 In taxis 32 64 In trains, planes, buses 26 65 In eating places 23 68 In barber or beauty shops 21 70 In work places or offices 17 73 In train, plane, bus stations 16 75 .Source: Roper Organization 1978 TIMN 0030219 171

Draft - Do nct cita or quoe 'able 5b. Public Opinion (% of Respondents Agreeing) m Prohibiting Smoking or Retaining Current Policies in Selected Public Places, 1988 ttCurrsnt Policyi° Prohibit all Smokina No Restr4c`ion .rants 74 24 2 Ltes 7 6 2 0 3 3amilton, Frederick, and Schneiders 1988 172

Draft- Do not cite or quote Table 6a. Should Smokers Refrain from Smoking in the Presence of Nonsmokers? (% of Respondents) by Cigarette Smoking Status, 1983, 1985, 1987, and 2989 Aaree Disaaree Don't Know Survey Year: '83 '85 '87 '89 '83 '85 '87 '89 '83 '85 '87 '89 Smokinq Status Current Smokers Fo=er Smokers Nonsmokers All Respondents 55 70 82 69 62 78 85 75 64 76 86 77 2 39 22 14 25 37 22 15 24 31 19 10 19 5 6 8 4 6 1 0 * 1 5 5 4 4 2 *Less than 0.5% Source: Gallup Surveys 1983, 1985, 1987, 1989 173 TIMN 0030221

Draft - Do not cite or quote Table 6b. "If People Want to Smoke, They Should Not Do So Inside Public Places Where it Might Disturb Others" (% of Pespondents Agreeing) 1987 7rent smokers :mer smokers •,rer smokers i resrondents Agree Disagree No Ooinion 67 22 9 80 10 8 89 5 5 81 11 7 urce: NHIS-CEC 198;' (Davis et al., 1990) 174 TIMN 0030222

a) u e ~ o M N Table 7. Opinions Regarding Smoking in Selected Public Places O and Worksites, (% of Respondents With the Opinion) O a ~Ilotels and Hotel s by Smoking Status, 1983, 1985, 1987, 1989 O z V 0 Set Aside Totally Ban r. Certain Areas Smokin No Restrictions Don't Know 0 A '83 '87 '89 '83 '87 '89 '83 '87 '89 '83 '87 '89 I .~Current Smokers 49 61 7 6 42 30 2 1 ~ Former Smokers 54 72 13 9 27 16 6 3 N Nonsmokers 60 68 15 14 20 15 5 3 a All Respondents 54 67 63 12 10 12 30 20 18 4 3 6 Restaurants Set Aside Certain Areas Totally Ban Smoking No_ Restrictions Don't Know '83 '87 '89 '83 '87 '89 '83 '87 '89 '83 '87 '89 Current Smokers 74 79 12 7 13 13 1 1 Former Smokers 71 74 19 19 9 6 1 1 Nonsmokers 65 71 26 23 7 5 2 1 All Respondents 69 74 66 19 17 23 10 8 8 2 1 3 Worksites Set Aside Certain Areas Totally Ban • Smoking No Restrictions Don't Know '83 '85 '87 '89 '83 '85 '87 '89 '83 '85 '87 '89 '83 '85 '87 '89 Current Smokers 64 76 72 11 4 8 21 19 18 4 1 2 Former Smokers 68 80 73 14 12 16 14 6 8 4 2 3 Nonsmokers 63 80 67 24 9 23 9 10 8 4 1 2 All Respondents 64 79 70 65 17 8 17 21 15 12 11 10 4 1 2 4 Source: Gallup Surveys 1983, 1985 , 1987, 1989 ~, 175 !

Draft - Do not cite or quote Table 8. Restrictions on Smoking in Public Places (t of respondents favoring increase) by Smoking Status, Smoking Status 1964, 1964 1966, 1966 1970, 1970 1975, 1975 and 1986 1986* Current smokers •• 34 35 42 51 23 Former smokers ' 56 58 61 77 53 Never smokers 68 67 68 82 63 All Respondents 52 52 57 70 50 *The question for the first four surveys read "The smoking of ciga.rettes should 'be allowed in fewer places than it is now." Thee question in 1986 read "There are already enough restrictions on where people can smoke." Source: Adult Use of Tobacco Surveys 1964, 1966, 1970, 1975, and 1986. © 176 T~N 0030224

Draft° - Do not cite or quote Table 9. Reported Worksite Smoking Policies and Worksite Exposure to Environmental Tobacco Smoke (% of Respondents), 1986 Wor3csite Policy ~ Renorting Policy % Reporting Exposure to ETS Not Restricted 55.4 64.8 Restrictive 42.1 53.2 Total Ban 2.5 21.1 Source: Adult Use of Tobacco Survey 1986 177 TIMN 0030225

Draft-® Do not cite or quote BLANK PAGE 178 TIMN 0030226

Draft--- Do not cite or quote BLANK PAGE TIMN 0030227 179

Draft - Do not cite or quote CHAPTER 10 THE P.FFECTS OF PASSIVE SMOKING P.ND DAY CARE ON RESPIRATORY ILLNESSES Glen Bennett MPH Office of Prevention, Education, and Control. National Heart, Lung, and Blood institute Bethesda, MD 20892 1. INTRODUCTION Reports of the Surgeon General (43) and the National Research Council (27) concluded that children of parents who smoke have more lower respiratory diseases and otitis media. Other reviews (1, 17) showed that children in day care have more upper respiratory illnesses, especially otitis media. The overlap in these findings tiAises a new concern. Does passive smoking and day care attendance interact to increase the rate of respiratory diseases in infants and young children? This chapter examines the data to deter:nine if evidence exist to support this concern. The chapter begins with, a review of the day-care market to show its complexity. ignoring the diversity of day care might lead to faulty conclusions and recommendations. 2. DAY CARE IN THE U. S. 2.1. GENERAL CHARACTERISTICS In 1982, 6 million mothers (48.2's) with a child under the age of 5 were in the civilian work force. (28.) The most drastic change has been the return of parents to work while their children are infants. (26) These children get care in three basic types of day care delivery systems. They are in-home care, family day care, and group day care. Parents, relatives, or non-relatives provide in-home care in -the home of the child. They also give family day care (day care homes) in a private home other than the child's. (2, 50) Day care centers, including nurseries, provide care for 12 or more children in nonresidential buildings. (17, 49) This sector is almost always subject to government regulation and is the smallest of the 3 sectors. (17) However, centers are the fastest growing segment in the day care market. (1, 24, 28) 180 TMN 0030228

Draft - Do not_cite or quote Table 1 lists the percent distribution of the type of child day care used by the age of the child. Nine percent (9%) of working mothers were able to care for their children while working. Almost one-third (30.5%) arranged for in-home care of their children. However, day care homes were the predominate source of care,i.e., 40.2%. Table 2 describes the percent distribution of care-givers by the age of the child. Relatives provided child care to 29% and non-relatives provided 27.5% of all day care to children of working mothers. Data in Table 3 show that 22% of all children and almost 25% of infants and toddlers got care in the home of a non-relative. (28) 2.2. REGULATIONS The U.S. does not have a national policy on-child care and efforts to develop one have reached a stalemate. (35) Sponsors have withdrawn the 1980 Federal Interagency Day Care Requirements. However, they continue to serve as a guideline for minimum standards. (49) Each state regulates its own day care facilities. They have . written very tough requirements but enforcement is poor. (35) ,. All states have passed regulations which contain some provisions for health and safety. However, they are not consistent. (17) Licensing practices also vary from state to state. {24) Forty-four (44) states now regulate family day care homes. (49) However, children cared for in their own home are beyond the reach of federal and state policy (17). 2.3. PREVALENCE OF SMOKING In a 1980 survey, 28.9% of female child care workers smoked cigarettes. This is less than females in general. However, their rates are much higher than those for female elementary school teachers (19. 8%) and higher than secondary school teachers (2 Y. a~). (44) 3. RESPIRATORY INFECTIONS 3.1. MAGNITUDE OF THE PROBLEM Upper respiratory infections are the most common diseases affecting children under 5 years of age. They 'are important causes of childhood illness and their treatment consumes a large portion of health care resources. (8, 14, 17) Infants average 7-8 acute respiratory infections per year. Older children; i-5 years of age, , average one or two fewer infections than infants. (17) Acute otitis media (AOM) is the most common complication of upper respiratory diseases in infants and young children. (16, 1$, 31, 47) AOM is the largest single cause of morbidity with possible sequelae in children. (47) Recurrent episodes are also very common 181 TIMN 0030229

Draft - Do-not cite or quote in children during the first years of life. (23) AOM accour.t for one-third of pediatric office visits (31) and three-fourths of follow-up visits. (16) Nearly all children have at least one episode with effusion (OME) during their first 6 years of life. Some develop chronic OME or chronic otitis media with perforation and discharge. (45) Repeated episodes of OME in early life may lead to transient or permanent hearing loss and impeded speech. These conditions may then lead to developmental or educational delays. (17, 47) Bronchiolitis is the most common manifestation of lower respiratory infections in infants and small children. The true incidence is unknown. However, about 10 per 1,000 infant are hospitalized with bronchiolitis. The mean age for respiratory syncytial virus (RSV) bronchiolitis is 7.8 months and the peak age is 2 months. Half of children hospitalized for the condition are under 3 months of age. (42) 3.2. DAY-CISRE AND RESPIRATORY INFECTIONS Respiratory diseases are the most common ailments affecting (Shildren in day care. (1) Today, infants and pre-school age children get infections at earlier ages and are spending more ti:ne outside the home. A common factor in this changing pattern is the increasing popularity of day-care centers. (24) Day care centers with many children in the same place create favorable conditions for respiratory epidemics. (30) However, the total burden of respiratory diseases seems no greater for the day care child. They simply occur at younger ages. (1) The association of day care and respiratory diseases began in the 1920's. (17) In the 1970's, Scandinavian researchers (19, 23, 31, 32, 39, 41, 45) found an increased rate of otitis media among children in day care. Children in centers had the highest rate. Those in family day care held an intermediate position between centers and in-home care. Moreover, home-reared children with abnormal findings at first testing were significantly more likely to have normal results at subsequent testings. There are obvious difficulties in'transferring the results from studies conducted in Scandinavian countries. However, Haskins (17) concluded that the high quality of these studies make the findings •worthy of careful attention. They show that children in day care are at 2-3 times the risk of otitis media as those reared at home. Two American research teams (14, 42) confirmed the Scandinavian results. Visscher and colleagues (47) studied patients in a large pediatrics group practice in Minneapolis. They collected data on every child attending the clinic during a 2-week period in February, 1982. Cases were patient presenting with AOM on a study day. Controls had a diagnosis other than AOM and no prior history of otitis. Attending a day care facility was the second most 182 TIMN 0030230

DraftY- Do not cite or quote important risk factor. The risk increased with the number of czher children at the facility. Exposure to smokers was not a risk factor. Fleming and colleagues (14) also studied childhood infections in Atlanta. They found that children attending day care were significantly more likely to have an upper respiratory tract infections during a 2-week. Maternal smoking also increased the risk. The effects of attending day care and smoking mothers were independent. Age and living in crowded conditions were also risk factors. The researchers estimated that 311 of upper respiratory infections can be attributed to day care attendance. Most studies of bronchiolitis focused on children in hospitals. Comprehensive studies of this disease in ambulatory patients or day-care centers are lacking. (42) However, a Chapel Hill, NC study compared the rates of bronchiolitis in a day care center and a pediatric practice. The rate was much higher in the day care center for children 6 months of age or younger. However, the proportion of cases requiring medical treatment and hospitalization was less among day care children. (10) Reviewers (1, 17, 18, 19) have identified problems which limits uhe generalization of the findings from these studies. They are: 1. Control groups were less than satisfactory. Researchers observed children in day care more frequently than those in home care. 2. Some studies reported symptoms while others used diagnostic categories. 3. The ages of children studied and the manner of reporting illnesses by age category differed widely. 4. The reliability of case-controlled and cohort studies depends on the accurate quantification of disease occurrence. This raises the questions of whether day care' parents seek a physician for their children's illnesses more frequently. When a day care provider suggests taking a child to a physician this might have important effects on parents. 5. Most studies did not control for other factors that probably influence the incidence~ of respiratory illnesses. These factors include housing, humidity, ventilation, passive smoking, and other air pollution. Nonetheless, reviewers concluded that most studies have shown an increase in respiratory diseases among children in day care. There is stronger evidence for initial and recurrent otitis media. (17) The rate of otitis is greater in large group day care centers and 183 TIMN 0030231

Draft - Do.not cite or quote probably smaller day care homes. (2, 17, 18, 31) Studies also show reduced rates of both symptoms and acute illnesses with increasing age in all sites. However, there is very little evidence of an excessive rate of illness in day care children for the more serious respiratory diseases. (17) Asymptomatic children do not have higher levels of respiratory tract pathogens or even different pathogens than children reared at home. (1, 17, 40) However, The true incidence of infectious disease in family day care is unknown since most of it is unlicensed. (2) 3.3. PASSI4E SMOKING AND DISEASES IN INFANTS AND CHILDREN' A number of studies have demonstrated a positive association between passive smoking and lower respiratory symptoms (4, 5, 13, 36) and diseases. (11, 12, 22, 29, 48) The effect was stronger in infants. Maternal smoking, when measured, showed a high correlation. However, paternal smoking was rarely significant. Studies on the relationship of passive smoking to the development of bronchiolitis are less clear. Two studies (32, 38) showed a positive association with maternal smoking. However, another study (29) did not find a relationship. .Otitis media is the only upper respiratory disease reported in the literature as being associated with passive smoking. Five studies (3, 20, 21, 30, 34) showed an increased incidence of otitis media with maternal smoking. However, in five other studies (14, 39, 45, 46, 47) parental smoking was not significant. However, the study by Fleming and colleagues (14) included only 34 cases among the 575 children with upper respiratory illnesses. Pukander and colleagues (30) also suggested that day care attendance may mask the effect of parental smoking. Two comprehensive reviews (27, 43) concluded that lower respiratory diseases and otitis media occur more frequently in children with mothers who smoke. Two researchers (29, 48) offered explanations for the association with only maternal smoking. They argued that children are more likely to be with their mothers at the times smoking occur. Some mothers also remain at home with the child. This suggests that the duration of exposure to smoke rather than just the presence of a smoker is the more important factor. Both reports. (27, 43) emphasized the need for caution in the interpretation of these studies. Independent risk factors, such as age and sex, were not always taken into account. The use of questionnaires to collect information on symptoms are prone to recall bias. Most studies examined only the effects of exposure to parental smoking, excluding exposures outside the immediate family. Future studies must control for potential confounding variables. 184 TV'IN 0030232

Draft - Do not cite or quote 3.4. DAY CARE AS A CONFOtTNDING VARIABLE Passive smoking increases the risk of upper and lower respiratory diseases in infants. Day care attendance also increases the occurrence of upper respiratory infections and perhaps some lower respiratory illnesses in infants and toddlers. However, studies focusing primarily on the effects of passive smoking did not control for day care attendance. Many of the studies on day care infections did not consider parental smoking as a possible confounding variable. Moreover, none of the studies in either area considered the smoking habits of day care workers. Seven of the day care studies (14, 19, 30, 39, 45, 46, 47) did consider parental smoking. Two of these studies (14, 30) found an independent effect for both day care attendance and maternal smoking. The effect of day care was strongest in both cases. The remaining studies showed a statistical significance for day care attendance only. It is unfortunate that researchers have ignored the smoking habits Gf day care givers. Especially since the duration of exposure is 'important. (29,•4-8) Smoking by day care workers exposes the child to smoke. The Section on Allergy of the Canadian Pediatric Association (37) provided support for this premise. They reported that infants admitted to hospitals for chest problems had significantly more day care givers who smoke than did control infants. The smoking pract'ices of workers in day care homes deserve special attention. This sector includes more children and is especially popular with mothers of infants and toddlers. Day care providers who smoke probably spend as much time with these children as their mothers. Thus, the smoking habits of these workers potentially confound the results of studies of the effect of parental smoking. 4. ~ RECOMMENDATIONS 4.1. REGULATIONS Existing day care regulations clearly are deficient in mandating a safe and healthy day care environment. Federal regulation, while desirable, is not possible now. The prevailing attitude today is away from federal intervention and toward state and personal responsibility. (49) The regulation of day care homes, which contain the most children, is an especially: delicate issue. Increased regulation of homes might have the effect of actually decreasing the availability of this mode of child care. (2) Moreover, the sheer number of providers and the small size of these units would make effective oversight difficult. (17) 185 TIMN 0030233

Draft - Do.not cita-or quote The most import:ant interim steps are to give parents better information and improve state regulations that relate to health. (17) Requiring all facilities to have written policies on health and give copies to parents is a start. Parents should also be informed about the potential interaction between passive smoking and day care on the risk of early childhood infections. (14) 4.2. RESEAP.CH The smarse data available regarding family day care make it important to pay more attention to this mode. Since day care homes includes more children, particularly infants and toddlers, it is important to understand the disease experiences in these homes. (2) Surveys are needed to determine the smoking patterns of day care workers. Data from the National Health Interview Surveys, 1978-1980 put the prevalence of smoking among female child care workers at 28.9%. However, these data excluded private household child care workers. 4.3. EDUCATION ~resently, Parents must judge for themselves the quality of care given to their children. However, most parents do not know what to look for in a day care setting and there are no federal standards. (35, 50) There are, however, guidelines that the child- development community supports. (35) There is also a checklist that can differentiate between centers of high and low quality. The checklist includes one item on smoking: "Adults do not smoke in rooms where, children are." (7, 35) Education efforts to disseminate this information are needed. Low-cost materials must also be available to day care providers. (1) 5. CONCLUSION The children of working parents are receiving day care primarily in their own home, family day care homes, and day care centers. Family day care is the largest of the three sectors but day care centers represent the fastest growing segment. Studies, mostly in Scandinavian countries, have demonstrated that children attending day care have more respiratory infections. The effect was stronger among infants and toddlers. Another group of studies have linked parental smoking, primarily maternal smoking, with an increase in respiratory diseases among infants. However, most of these studies did* not control for attending day care. The few studies that controlled for parental smoking and day care showed a consistent and positive association for day care. Parental smoking was less clear. None of the studies, however, controlled for the exposure to smoke from day care workers. 186 0030234

Studies controlling for potential confounding lactoDos M d~~j'"Rnfl:y quote needed in this area. The smoking practices of day care workers, particularly day care homes, may have been a:,iajor uncontrolled factor in past studies. In the interim, parents must be educated. They must know about the harmful effects of parental smoking and the potential for added exposure from day care workers. Some 58% of one sample attended full-time day care, i.e., 40 hours or more per week. (14) Thus, children of nonsmoking parents are not without risk. Staying with day care smokers may increase their exposure to smoke simi_ar co that with smoking parents. Children of smoking parents may face as much as twice the exposure. This has special implications for day care homes. First, the children are younger. They also spend most of the time in a smaller environment with other children and the day care worker. If smoking occurs, the exposure should not be materially different from that found in the home. Day care providers must also know about the possible interaction of passive smoking and day care attendance. Those in day care homes, particularly, should not smoke in the presents of the children. Since strict regulations of this sector in not possible, the parents must insist upon this practice. Day care centers, while providing a different environment, should adhere to the same principle. They are similar to the school system where teachers can not smoke in the classroom. State regulatory agencies should also include this provision in the licensing of day care facilities. SUMMARY 1. Studies have linked both parental smoking and day care attendance with increased respiratory infections. Smoking by daycare workers may have been a major uncontrolled confounding factor in studies of infections caused by maternal passive smoking. 2. Parents and daycare providers should be educated to know about the harmful effects of parental smoking and the potential for added exposure from day care workers, which could double total ETS exposure. 3. State regulatory agencies should include prohibitions against smoking in daycare as they do in classrooms. TIMN 0030235 187

Draft. - Do-:r not=•cita. or quote 6. REFERBNCES 1. Aronson, SS; Osterholm, M. "Infectious Diseases in Child Care: Management and Prevention. Summary of the Symposium and Recommendations;" Review of Infectious Diseases; 1986, July-Aug; 8 (4) : 672-679 2. Bartlett, AV; Orton, P; Turner, M "Day Care Homes: The Silent Majority of Child Care;" Review of Infectious Diseases; 1986, July-August; 8(4): 663-671 3. Black, N. "The Aetiology of Glue Ear: A Case-Control Study," International Journal of Pediatric Otorhino].aryngology, 9(2): 121-133; July, 1985 4. Burchfiel, CM; Higgins, MW; Keller, JB; Butler, WJ; Howatt, WF; Higgins, ITT; "Passive Smoking in Childhood: Respiratory Conditions and Pulmonary Function in Tecumseh, _ Michigan," American Review of Respiratory Disease, 133(6): 966-973, June, 1986 5. Charlton, A. "Children's Coughs Related to Parental Smoking," British Medical Journal, 288(6431): 1647-1649;. June 2, 1984 6. Cherian, A and Feldman, W. Personal communications reported in: Section Allergy, Canadian Pediatric Association; "Secondhand Smoke Worsens Symptoms in Children With Asthma;" Canadian Medical Association Journal; 1986, August 2; 135(4): 321-323 7. Clarke-Stewart, A. Daycare, Cambridge, MA: Harvard University Press, 1982 8. Cypress, BK; "Pattern of Ambulatory Care in Pediatrics: The National Ambulatory Medical Care Survey: U.S., January 1980 - December 1981," in Vital Health Statistics, Series 13, No. 75; U.S. Department of Health and Human Services; Publication No. 94-1736; Government Printing Office, 1983 9. Denny, FW; "Childhood Acute Respiratory Tract Infections Deserve Our Attention;" American Journal of Public Health; 1988, January; 78(1): 16-17 10. Denny, FW; Collier, AM; Henderson, FW; Clyde, WA; "The Epidemiology of Bronchiolitis," Pediatric Research, 11: 234-236, 1977 11. Evans, D; Levison, M; Feldman, C; Clark, N; Wasilewiski, Y; Levin, B; Mellins, R. "The Impact of Passive Smoking on 188 TIMN 0030236

Emergency Room Visits of Urban CRE314tsetr DPi=t Alit=a;r quota American Review of Respiratory Diseases; 1987; 135: 567-572 12. Fergusson, DM; Horwood, LJ; Shannon, FT; Taylor, B. "Parental Smoking and Lower respiratory Illness in the First Three Years of Life," Journal of Epidemiology and Community Health, 35(3): 180-184; September, 1981 13. Ferris, BG; Ware, JH; Berkey, CS; Dockery, DW; Spiro III, A; Speizer, FE; "Effects of Passive Smoking on Health of Children," Environmental Health Perspectives, 62: 289-295; 1985 14. Fleming, DW; Cochi, SL; Hightower, AW; Broome, CV; "Childhood Upper Respiratory Tract Infections: To What Degree is Incidence Affected By Day Care Attendance;" Pediatrics; 1987, January; 79(1): 55-60 15. Fosburg, S; Family Day Care In The United States: Summary of Findings; Government Printing Office, 1981 16. Giebink, GS; "Epidemiology and Natural History of Otitis . Media;" in Lim, DJ; et al; Recent Advances in Otitis Media With Effusion; 1984; 5-8 17. Haskins, R; "Day Care and Illness: Evidence, Costs, and Public Policy;" Pediatrics; 1986; 77: 951-982 18. Henderson, FW; Giebink, GS; "Otitis Media Among Children in Day Care: . Epidemiology and Pathogenesis;" Review of Infectious Diseases; 1986, July-August; 8(4): 533-538 19. Ingvarsson, L; Lundgren, K; Olofsson, B; "Epidemiology of Acute Otitis Media in Children-A Cohort Study in an Urban Population;" in Lim, DJ; et al; Recent Advances in Otitis Media With Effusion; Philadelphia: B C Decker; 1984; 19-22 20. Iverson, M; Birch, L; Lundqvist, G; Elbrond, 0. "Middle Ear Effusion in Children and the Indoor Environment: An Epidemiological Study," Archives of Environmental Health 40(2): 74-79; March-April, 1985 21. Kraemer, MJ; "Risk Factor for Persistent Middle Ear Effusions;" Journal of American Medical Association; 1983, February 25; 249(8): 1022-1025 22. Leeder, SR; Corkhill, RT; Irwig, LM; Holland, WW. "Influence of Family Factors on the Incidence of Lower Respiratory Illness During the First Year of Life," British Journal of 189 TIMN 0030237

Draft - Do not cite or quote Preventive and Social Medicine, 30(4): 203-212, December, 1976 23. Lundgren, K; Ingvarsson, L; Olofsson, B; "Epidemiological Aspect in Children With Recurrent Acute Otitis Media;" in Lim, DJ; et al; Recent Advances in Otitis Media With Effusion; Philadelphia: B C Decker; 1984; 22-25 24. Marwick, C; Simmons, K; "Changing Childhood Disease Pattern Linked With Day-Care Bo om;" Journal of American Medical Association; 1984, March 9; 251(10): 1245-1247, 1250-1251 25. McConnochie, K; Hall, C; Barker, W; "Lower Respiratory Tract Illness in the First Two Years of Life: Epidemiologic Patterns and Costs in a Suburban Pediatric Practice;" American Journal of Public Health; 1988, January; 78(1): 34-39 26. Morgan, G; Stevenson, C; Fiene, R; Stephens, K; "Gaps and Excesses, in the Regulation of Child Care: Report of a Panel;" Review of Infectious Diseases ; 1986, July-August; 8 (4) : 634-643 27. National, Research Council; Environmental Tobacco Smoke - Measuring Exposure and Assessing Health Effects; Washington, DC: National Academy Press; 1986 28. O'Connell, M; Rogers, CC; "Child Care Arrangements of Working Mothers: June 198.2;" Current Population Reports (Bureau of Census); 1982; Special Studies P-23; No. 129 4 29. Pedreira, F; Guandolo, V; Feroli, E; Mella, G; Weiss, I; "Involuntary Smoking and Incidence of Respiratory Illness During the First Year of Live," Ped iatrics, 1985; 75: 594-597.. 30. Pukander, J; Luotonen, J; Timonen, M; Karma, P; "Risk Factors Affecting the Occurrence of Otitis Media Among 2-3 Year Old Urban Children;" Acta Otolaryngology [Stockholm]; 1985, September-October; 100(3-4): 260-265 31. Pukander, J; Sipira, M; Karma, P; "Occurrence of and Risk Factors in Acute Otitis Media;" iri Lim, DJ; et al; Recent Advances in Otitis Media With Effusion; Philadelphia: B C Decker; 1984; 9-13 32. Pullan, CR; Hey, EN. "Wheezing, Asthma, and Pulmonary Dysfunction 10 Years After Infection With Respiratory Syncytial Virus in Infancy," British Journal of Medicine, 284(6330): 1665-1669, June 5, 1982 190 TIMN 0030238 -

33. Draft - Do, qt cite Qr quote Ruopp, R; Travers, J; Glantz, F; Coelen, C. Chi~dren At tne Center: Summary Findings and their Implications; Cambridge, MA: Abt Books; 1979 34. Said, G; Zalokar, J; Lellouch, J; Patois, E; "Parental Smoking Related To Adenoidectomy and Tonsillectomy in Children," Journal of Epidemiology and Community Health, 32(2): 97-101; June, 1978 35. Scarr, S; Mother Care, Other Care; New York: Basic Books; 1984 36. Schenker, MB; Samet, JM; Speizer, FE "Risk Factors for Childhood Respiratory Disease: The Effect of Host Factors and Home Disease, Environmental Exposure," 128: 1038-1043; 1983 American Respiratory 37. Section Allergy, Canadian Pediatric Association; "Secondhand Smoke Worsens Symptoms in Children With Asthma;" Canadian Medical Association Journal; 1986, August 2; 135(4): 321-323 38. Sims, DG;. Downham, M; Gardner, PS; Webb, J; Weightman, D. - "Study oF 8-Year-Old Children With A History of Respiratory Syncytial Virus Bronchiolitis in Infancy," British Journal of Medicine, 1(6104): 11-14, January 7, 1978 39. Stahlberg, MR; "The Influence of Form Day Care on the Occurrence of Acute Respiratory Tract Infections Among _ Children;" Acta Paediatric Scandinavia [Supplement]; 1980; 282: 1-87 ' 40. Strangert, K; Caristrom, G; Jeansson, S; Nord, CE; "Infections in Preschool Children In Group Day Care," Acta Paediatric Scandinavia, 65: 455-463, 1976 417 Strangert, K; "Respiratory Illness in Preschool Children With Different Forms of Day Care," Pediatrics, 57(2): 191-196; February, 1976 42. Task Force on Epidemiology of Respiratory Diseases; Epidemiology of Respiratory Diseases; Division of Lung Diseases, National Heart, Lung & Blood Institute; November, 1981 43. Public Health Service, The Health Consequences of Involuntary Smoking: A Report of the Surgeon General, U.S. ~ Department of Health and Human Services, Rockville, MD: Government Printing Office, 1986 44. Public Health Service, The Health Consequences of Smoking: Cancer and Chronic Lung Disease in the Workplace, U.S. 191 Tm1v ®030239

Draft.- Do.not cita_..or quote Department of_ Health and Human Services, DHHS_ (PHS) 85-50207, 1985 45. Van Cauwenberge, PB; Kluyskens, PM; "Some Predisposing Factors in Otitis Media With Effusion;" in Lim, DJ; et al; Recent Advances in Otitis Media With Effusion; Philadelphia: B C Decker; 1984 ; 28-32 46. Vinther, B; Elbrond, CB; "A Population Study of Otitis Media in Childhood," Acta Otolaryngology, [Stockholm] Supplement 360: 135-137; 1979. 47. Visscher,, W; Mandel, JS; Batalden, PB; Russ, JN; Giebink; GS; "A Case-Control Study Exploring Possible Risk Factors for Childhood Otitis Media;" in Lim, DJ; et al; Recent Advances in Otitia Media With Effusion; Philadelphia: B C'Decker; 1984; 13-15 48. Ware, JI?(; Dockery, D; Spiro, A; Speizer, F; Ferris, B. "Passive Smoking, Gas Cooking and Respiratory Health of Children Living in 6 Cities;" American Review of Respiratory Diseases; 1984, March; 129(3): 366-374 Z9. Young, KT and Zigler, E; "Infant and Toddler Day Care: Regulations and Policy Implication," American Journal of Orthopsychiatry, 1986, January; 56(1): 43-55 50. Zigler, E; Muenchow, S; "Infectious Diseases in Day Care: Parallels Between Psychologically and Physically Healthy Care;" Review of Infectious Diseases; 1986, July-August; 8(4): 514-520 a 192 T1MN 0030240

Draft - Do not cite or quote 7. TABLES TYPE OF CHILD CARE BY AGE OF CHILD AGE < 1 Year Table 1 1-2 Years 3-4 Years TOTAL IN-HOME CARE 3 4. 3% 3 3. 3%. 2 4. 6% 30. 5% DAYCARE HOME 42.7% 43.0% 35.4% 40.2% GROUP CARE 5.3% 11.7% 25.8% 14.3% MOTHER 9.2% 8.6% 9.9% 9.1% TOTAL 91. 5% 9 6. 6% 9 5. 7•°s 94 . 6% Source: O'Connell and Rogers, 1982 (28) 193 T1MN 0030241

Draft ® Do®not cite.or quote CARE GIVER BY AGE OF CHILD Table 2 AGE < 1 Year 1-2 Years 3-4 Years TOTAL FATHER 13.9% 15.8% 11.0% 13.9% MOTHER 9.2% 8.6% 9.9% 9.1% GRANDPARENT 22.4% 16.8% 14. 6% 17.2% OTHER RELATIVE 11.3% 12.3% 12.8% 12.1% NONRELATIVE 29.4% 31.4% 21. 6 % 27.5% GROUP CARE 5.3% 11.7% 25.3% 14.8% TOTAL 91.5% 96.6% 95.7% 94.6% Source: O'Connell and Rogers, 1982 (28) TIMN 0030242 194

Draft - Do not cite or quote CAREGIVERS BY TYPE OF CaILD CARE AND AGE OF CHILD Table 3 AGE < 1 Year 1-2 Years 3-4 Years TOTAL IN-HOME CARE Father 13.9% 15.8% 11.0% 13.9% Grandparent 8.9-1 6.3% 3.6% 5.9% Other Relative 5.1% 5.0% 5.7% 5.2% Non-relative 6.4% 6.2% 4.3% 5.5% 'DAY CARE HOME Grandparent 13.5% 10.5% 11.0% 11.3% Other Relative 6.2% 7.3% 7.1% 6.9% Non-relative 23.0% 25.2% 17.3% 22.0% GROUP CARE Nursery 1.7% 3.2% 11.7% 5.6% Day Care Center 3.6% 8.5% 14.1% 9.2% MOTHER 9.2% 8.6-1 9.9% 9.1% TOTAL 91.5% 96.6% 95.7% 94.6% Source: O'Connell and Rogers, 1982 (28) 195 TIMN 0030243

Draft m Do rlot cite or quote FIGURE3 AND TABLE3 FOR CHAPTER 10 TIMN 0030244 196

Draft - Do not cite or quote CHAPTER 11 NO SMOKING POLICIES AT THE WORKSITE A Look at What Companies Are Doing Today Ruth Behrens* Washington Business Group on Health The movement of businesses to develop and implement-° smoking control policies appears to be strong, and may even by gaining momentum. A national survey released in 1987 by the Office of Disease Prevention and Health Promotion, U. S. Department of Health and Human Services, found that 27 percent of all U.S. companies with 50 or more employees had a formal smoking policy. Of these, 40 percent reported the policy was in place to protect nonsmokers; 40 percent reported the policy was designed to comply with regulations; 13:percent reported a need to protect equipment; and -~`percent advised that the policy was designed to protect employees at high risk for health problems.' A more recent study that looked only at large and medium-sized companies, the 42nd annual Northwestern University Lindquist- Endicott Report, found that 70 percent had restricted, or were prepared to limit, smoking in the workplace. The study was released in early' 1988 . 2 Another study of 916 large and mid-sized U.S. companies, conducted in 1989 by Hay/Huggins, a management consulting firm, found that 81 percent of surveyed firms with revenues of $1 billion or more res~trict smoking; the percent dropped to 65 percent for companies grossing less than $200 million per year.j A 1989 survey by the Gallup Organization commissioned by the American Lung Association found that 21 percent of individuals surveyed supported a total ban on smoking at the worksite, with an additional 65 percent in favor of smoking only in designated areas. ` The development and implementation of a no smoking policy within a business is a multi-faceted process. Experiences of the growing number of companies that have developed written statements spelling out how smoking will be limited or prohibited illustrates vividly that the process involves many individuals and groups, and that deliberations often are emotionally charged. 197 TIMN 0030245

Draft - Do not cite or quote This chapter, contains a series of- case -studies outlining how several companies have successfully approached this process. But before discussi:ng company-specific examples, there is merit- - in examining some of the key issues that must be looked at by any company considering developing a no smoking policy. Among zhe questions to be answered are: o What kind of specific smoking restrictions are best for the company? o What benefits can be realistically anticipated from the policy? o How should employees be involved? o How should unions be involved? o What kind of education should be offered and to whom? o What kind of incentives should be offered? o How should the policy be enforced? Further details about each of these steps are contained within che "Case Studies" section of this chapter. Options for Smoking Restrictions Restrictions on smoking in the worksite are not new. For years--even decades--businesses have had policies that banned smoking in specific areas such as elevators, hallways, auditoriums, sections of cafeterias, laboratories, rooms with delicate equipments, etc. In many instances, these restrictions were imposed because_of laws or ordinances requiring them or to protect property. Before the 1980s, they were seldom implemented. for health reasons. The assumption was, of course, the entire company is considered a Smoking Permitted area unless otherwise specified. Another type of policy began appearing with regularity in the mid and late 1980s. It banned smoking throughout the company except in designated areas. While many of these policies did not necessarily put greater limits on smoking--often allowing offices and work areas, special lounges, large parts of the cafeterias, etc, to be designated as Smoking Permitted areas, they did set the precedent that the company is Smoke Free except in specified areas. While the difference between these two types of policies may seem subtle at first glance, there is a strikingly different corporate 198 TV4N 00302 46

Draft - Do not cite or quote philosophy underlying the two approaches. And in the late 1980s, it was this latter approach--establishing a smoke free company, possibly with a few, carefully selected areas that permit smoking- -that appeared to be setting the pattern for worksite smcking policies. According to a spokesperson for Texas Instruments, Inc. (TI), determining what approach to take in limiting smoking was the most difficult aspect of developing and implementing its policy. As TI and many other companies have found, designating even a=_w smoking areas within a company can still pose serious health hazards for employees. Smoke from lounges, cafeterias, hallways, and enclosed offices, gets into the ventilation system and is circulated throughout the building, including into no smoking sections. (See "Case Studies: Pacific Northwest Bell.") As an interim step in a phased-in nonsmoking work environment, Pacific Mutual Life Insurance Company, Newport Beach, California, installed electronic filters in the temporary smoking area of its cafeteria. TI chose to avoid this problem by eliminating smoking from the worksite except for designated smoking areas which were, to the axtent possible, separately ventilated. Similarly, the headquarters complex of General Telephone of California prohibited smoking in all areas except a small portion of the cafeteria that has its own ventilation system. For others like American Family Insurance Group, Madison, Wisconsin, Pennsylvania Blue Shield, and UNUM Life Insurance Company, Portland, Maine, the choice to provide separate ventilation was either too expensive or physically impossible, so they chose to ban smoking completely at the worksite. On October 1, 1987, Ralston Purina's headquarters in St. Louis, Missouri, became the first Fortune 500 company to completely ban smoking in its facilities. Clearly, more and more companies are banning smoking or severely limiting it. Most require that all visitors abide by the company's regulations. Some will not allow smoking on company property, including grounds and parking lots. Groups like Michigan Bell, which has a large number of motor vehicles, are expanding their bans to all company-owned vehicles. However, others are voiding a ban in company cars and trucks because they believe enforcement will be virtually impossible. A few companies have gone even further, and may be bellwethers for a future tend. These companies recsire that all hew employees sign a statement that they are nonsa;.akers, even on their own time. Company policies prohibiting the hiring of smokers got nationwide publicity when Acoustical Products Company, a subsidiary of Chicago-based US Gypsum Corporation, announced that because of exposures to fibers that could have adverse health effects, all present workers were required to quit smoking or face termination, 199 TIMN 0030247

Draft- - Do not-cite-or quote and in the future, only nonsmokers would be hired. The Non-Smokers Inn in Dallas, Texas, provides only nonsmoking rooms and hires only individuals who do not smoke. At Cardinal Industries, Columbus, Ohio, new employees must state on the application form whether-or not they smoke, and only nonsmokers will be hired; but the company does not make any effort to validate applicants' statements. Louisiana Pacific Corporation, a Portland, Oregon-based national timber company with 15,000 employees, does not hire smokers in any of its plants or in corporate offices "because of the medical costs, absenteeism, environment of smoke in the workplace, the fire problems in the mills, and lung cancer. "2 The vast majority of companies still do not require -- that new employees be nonsmokers. But many companies with strict bans are seeing fewer smokers apply. "Why would a smoker want to work.for us," one company spokesman said, "when we deprive him of his habit for eight hours every workday?" Benefits of No Smoking Policies Developing and implementing a worksite no smoking policy may not be easy and may cause some discomfort for smokers and management alike. So why do companies do it? What benefits do they receive? In a recent national survey of all types of worksites with 50 or= more employees, the Office of Disease Prevention and Health Promotion, U. S. Department of Health and Human Services, asked those with smoking programs what benefits they perceived. 0 41 percent said smoking control policies and programs improved employees' health; 0 16 percent said they increased employees' productivity; 0 9 percent said they improved morale, and 0 8 percent said smoking control activities reduced costs.~ Some companies have conducted evaluations of the results from their smoking control efforts. Several of these studies, along with some anecdotal findings, are reported in this chapter's Appendix, "The Economic Justification for No Smoking Policies." To many companies, a reduction in the number or percent of employees who smoke is benefit enough from a policy. Smokers dropped from :Z1 percent of the workforce to 16 percent in two years at UNUM Life Insurance Company. In addition, 87 percent of the smokers reported they were smoking less after the policy was implemented.6 At Pacific Northwest Bell, smokers dropped from 28 percent at the time the ban was implemented to just 20 percent of employees two years later. 200 - TIMN 0030248

Draft - Do not cite or quote Employee Involvement Some companies, especially those wanting quick results that can be controlled, develop smoking policies at the top executive or management level and announce them to the employees. But a more frequently seen pattern today involves employees in the process of formulating and implementing a policy from the outset--but with varying degrees of direction from management. Companies have found that involvement of employees, including smokers, yacilit*ates compliance with the resulting policy. in some.companies, the involvement takes the form of responding to a charge. For example, an employee committee might be asked to examine the issues and problems related to smoking at the worksite and to present to management within three months recommendations for a policy and implementation plan to deal with them. In others, management may decide that smoking is a serious health hazard to its employees and that smoking is to be eliminated in 12 months. This organization's charge to employees might be to review how other companies have successfully moved to a smoke free workplace and to present recommendations for steps the company should tindertake during the next 12 months to make that transition both smooth and as painless for smokers as possible. Regardless of the approach, if employees are to be involved, it is important that their contributions have meaning and be listened to objectively by management. When tracing the history of smoking policies in organizations, it is not unusual to find that the initial push to limit or eliminate smoking came not from management, but from the employees, themselves. At UNUM Li'fe Insurance Company, employees' complaints, coupled wi.t h a Maine law requiring employers to reduce smoking, resulted in the company-wide ban. Pacific Northwest Bell emphasizes that no company officer or executive advocated its move to implement a smoking policy. Rather, the impetus came from employees. A grass roots group conducted a survey of workers and eventually recommended that PNW Bell ban smoking. The Employee Advisory Council at Cardinal Industries' Sanford, Florida, plant initiated the idea of a tough no smoking stand. (See "Case Studies--Cardinal Industries and Pacific Northwest Bell") At Holiday Corporation, Memphis, Tennessee, a task force of employees developed a Clean Air Policy covering its headquarters offices. The task force was originally set up as a Weilness Committee a full year before work began on the smoking policy. The employee group researched various aspects of the smoking problem by gathering data, talking to other companies that had already done 201 TIMN 0030249

Draft°- Do not cite_or quote :nd working with the :Local cancer-society and lung association. ;-rey was conducted of all employees to identify their - habits ittitudes related to smoking. The task force, itself, created phased-in process that resulted in Holiday Corporation cruarters and several of its subsidiary groups going smoke free anuary 1, 1987. the act of involving employees is not always as easy as it t seem, according to Charles Nielson of Texas Instruments. s important to involve employees in the process of developing 3licy as early as possible, and a survey of their habits and _tudes provides invaluable data to management, says Nielson. iuse TI has so many locations, however, timing of an employee rey was sometimes very difficult; in some locations, the policy already been set by corporate headquarters before the attitude Vey could be conducted. As a result, some employees felt they * being manipulated. "Data is vital to planning, but timing is o important so that: the company maintains its credibility," tions Nielson. .on Involvement any unionized organization, consideration must be given at the :set to how and when unions will be involved. Popular thinking st a few years ago was that unions would block most company- onsored weilness efforts, particularly those that interfered with dividual lifestyle choices, such as smoking. But through the rk of several pioneering unions such as the Amalgamated Clothing ad Textile Workers Union, the United Steelworkers Union, and the :ited Auto Workers, as well as the efforts of national groups icluding the Workplace Health Fund, more and more labor groups are -11ing to cooperate with management in reducing smoking if they =e approached properly--and early in the process.7 nions also recognize that their membership reflects closely the ational averages, therefore the vast majority of their members do ot smoke. As a result, many unions are receiving increased .ressure from their membership to help control smoking in the *orkplace. After having been involved in all aspects of policy ..evelopment, the Comnaunications Workers of America sent a memo to Lts 8,000 members at Pacific Northwest Bell acknowledging that the vompany was implementing a smoking ban, biit stating that CWA would .°aot oppose it because of the possibility that nonsmoking members aould sue the union--and probably win. (See "Case Studies: Pacific Northwest Bell.") In late 1985, the Workplace Health Fund, in cooperation with the Office of Disease Prevention and Health Promotion, (US DHHS), held a conference of union people to discuss the merits and value of health promotion. One of the outcomes of the meeting was a set of criteria for union involvement in worksite welZness efforts. 202 TIlMN 0030250

Draft - Do not-cite or quote Among the recommendations were two that placed heavy emphasis on the need to have a good working relationship between the union and management before attempting to implement any kind of wellness program. "Worksites in which labor and management are not cooperating to bring health and safety hazards under control should not be sites for health promotion activities." In addition, "where the worksite is not under control or the employer is uncooperative, and where the union has established the need for health ~nromotion, the programs should be conducted outside the worksite." But for any unionized company considering a smoking policy, the first step must be to 'look carefully at its union contracts, particularly for any wording that might guarantee members the right to smoke. If such agreements exist, the likelihood of the union supporting a no smoking policy is slim. Sue Pisha, area director of the northwest region of the Communication Workers of America, believes that with motivational information and education, there is the potential for unions to eventually become a proactive force for nonsmoking policies. "Policies seem to eliminate in-fighting," she says. "Without a ~olicy, the issue.is messy and polarizing."8 Education A companion element of virtually every successful workplace no smoking policy is an educational program designed to inform employees about the new rules•and to provide opportunities for smokers to kick the habit. While behavior modification programs are the most commonly presented, some companies have offered innovative approaches such as acupuncture, hypnosis, self-help materials, hot lines, incentives for nonsmoking employees to encourage and assist their co-workers to quit, and multi-day intensive programs for hard-core smokers. 0 Now that the nicotine in tobacco is widely recognized as an addictive substance, in much the same way that alcohol and drugs are considered addictive, other education techniques also have come into use. They include aversion techniques such as satiation and rapid smoking, relaxation training,9 coping skills training, stimulus control, and nicotine fading. In addition to on-site opportunities, businesses have gotten good results by encouraging participation in community-sponsored stop smoking classes merely by providing lists of sessions available through reputable groups such as cancer and lung associations, hospitals, Y's, and for-profit organizations. Because quitting can be very difficult and often is greatly enhanced by peer and family support, many companies make cessation 203 TIMN 0030251

Draft"' - Do not- cite _ orr°-quote ?portunities available to spouses and other.-immediate.family :mbers, as well. (See "Incentives.") ~tIM Life Insurance Company offers classes for a usually over- loked group, nonsmokers. The classes are designed to help those ao do not smoke understand the problems faced by smokers trying o quit and to urge them to encourage fellow workers to quit or to afrain from smoking. At Rainier Bank, Seattle, Washington, stress anagement classes were offered to help smokers adjust to the olicy as well as to asszst those who were trying to quit. hi1.e no national data: are available on worksite quit rates, strong orksite programs claim anywhere from 20 to 50 percent quit rates fter one year. However, most published studies..report six-month ,bstinence rates of 30 percent or less.1° As a result of an .ntensive smoking cessation campaign, Johnson & Johnson, New srunswick, New JersF.y, reports a two-year success rate of 23 zercent of all smokers in the company, not just 23 percent of those vho went through a program or completed it." incentives !Tany companies go a step beyond offering cessation classes by providing incentives for smokers to quit. Some also have devised rewards for non-smokers. The most widely used incentives for smokers are monetary, often tied to completing a cessation program and/or stopping smoking. Many companies offer cessation classes free to employees and their families, often during company time, or reimburse them for the cost of taking a community-based class. Others, like the Utah State Department of Health, reward smokers who actually quit. The "Healthy Utah" programs pays $25 to smokers who quit at the end of three smoke-free months, another $225 after six months, and $50 at the end of a year of not smoking. Nonmonetary incentives, too, can be appealing. Employees who participated in a 24-hour "Cold Turkey" stop smoking_day at 'ASI Insurance, Arden Hills, Minnesota, became eligible for a drawing for a frozen turkey. Those who quit for six months were eligible for a drawing for a free YMCA membership, and anyone who stayed off cigarettes for a full year was eligible for a weekend vacation.1 3 Some companies also have gotten creative in finding ways to re,4ard employees who are nonsmokers or who quit before a policy goes into effect. Employees; who take a health risk appraisal at Westlake Community Hospital, Melrose Park, Illinois, receive a $50 "bounty" for participating plus several "good health bonuses" including $25 for not smoking. Weekly paychecks at Speedcail Corporation, Hayward, California, include an extra $7.00 for those who do not smoke at work. Backsliders who light up one week and lose their reward are encouraged to get back quickly to not smoking; so the next week without smoking earns the $7.00 bonus again.t2 204 TIMN 0030252

Draft - Do not cite or quote Businesses also offer nonsmokers discounts on life and health insurance, a very visible and tangible incentive to stop smoking and improve health. Smoking Policy Enforcement Without'a doubt, one of the most difficult questions asked by companies considering a smoking policy is "How can a no smoking policy be enforced?" The response from most businesses that have moved to a ban is that the company must first demonstrate to employees that it is serious about eliminating smoking in all or parts of the building. Second, it must handle violations in the same way that infractions of all other personnel policies are dealt with. Cardinal Industries had a highly visible and dramatic way of demonstrating its commitment. Its president, Austin Gurlinger, a cigar smoker, stated to all employees that he would refrain from smoking at the workplace. Uaking certain that each employee receives a copy of the policy in advance of its implementation and posting signs clearly delineating where workers may and may not smoke are small steps that can help show a company's commitment to smoking controls and increase compliance, as well. Some companies are enforcing their no smoking policies by referring employees who are unable to quit because they are addicted to nicotine to an Employee Assistance Program. These companies may apply the same enforcement guidelines to addicted smokers as they do to users of alcohol or drugs, requiring that they overcome the habit in order to remain with the company. Most companies say that no employees have quit their jobs because of the new rules. However, most also point out that a few have "tested" the policy, with some pushing it all the way to probation. According to Dick Becker, employee services representative for American Family Insurance Group, "Some employees tested the waters, sneaking cigarettes in the rest rooms. Supervisors let it be known that smoking would be treated like any other'violation of policy, for example, inappropriate dress."6 Holiday Corporation follows its usual procedure for violation of any company rule--first a verbal warning, then a written warning, followed by a "final" warning, and if necessary, termination. But all agree, termination is not the objective. Everything possible should be done to encourage employees to comply, and most feel that peer pressure is the best policing mechanism. However, when an employee continues to break the rules, he or she must be 205 TIMN 0030253

Draft=- Do not cita or quote I L:.sciplined appropriately, or the entire policy will crumble. (See e following case studies illustrate how four widely different f l: t t~ l i a po .on o cy emen a mp ompanies approached the development and ,o reduce or eliminate smoking within their organizations. INDQSTRYES, INC. overall Policy: A total ban on smoking on any company pr 'ARDINAL 5 g rY exists; all new employees must attest to being nonszuokers ze innin Janua 1, 1987, the 8,650 employees of C ~.ndustries were assured of a totally smoke free work environment. )ne year prior to the ban, Cardinal, the nation's largest nanufacturer of modular homes, had taken an even more dramatic step by instituting a multi-faceted policy that included hiring only nonsmokers as new employees. ci,laate~d Benefits Anticipated Although carriers are saying it will take 12 to 18 months to see any decrease in insurance rates, Cardinal's management expects to significantly lower operating costs, increase productivity, reduce absenteeism, and eventually pay lower insurance premiums as a result of the new policy. Even more importantly, it expects to improve the health of its key asset-- its human resources. But employees at Cardinal's Sanford, Florida, location--one of four regional sites throughout the country--are convinced they would have gone smoke free even without the corporate edict. Why? Because employees wanted it, and because management recognized the negative impact of smoking on employees' health and productivity. The passage of Florida's Clean Indoor Air Act in October, 1985, focused attention on the plant's efforts and established it as one of the most progressive worksite no-smoking policies in the state, stimulating a letter of commendation from the governor. Employee Involvemelt Because of the nature of materials used at Cardinal, the second largest residential builder in the country, the company had a long- standing policy prohibiting smoking in its five manufacturing plants. But at the Sanford location, the real push for a tough operty . ardinal 206 TIMN 0030254

Draft - Do not cite or quote policy that extended beyond the manufacturing facilitJ came through its Employee Advisory Council in late 1985. Made up of employees elected by the workers within each department, the Council meets regularly with top management. Based on employees' suggestions, a three-phase policy was developed and implemented Jan. 1, 1986, that gradually eliminated smoking in meeting rooms, the cafeteria, and other common areas over the next 12 months. As part of the policy, which was designed to make Cardinal smoke-free by t.he end of the year, the company began hiring only non-smoking personnel. Current- employees' smoking privileges (in designated areas) were grandfathered for the remainder of the year. But before the policy was implemented, it required approval by top management, including the company's 33 year-old founder and president who was a cigar smoker--a situation that has stopped many other companies with good intentions. "We had been looking for ways to reduce our health care costs and at the same time improve efficiency and productivity," said a company spokesperson, "and the evidence about the health consequences of smoking were too powerful to ignore. When you add the fact that Cardinal pays for 7-00% of .employees' health insurance, the decision seemed inevitable." Enforcement in many ways,, the fact that' the chief executive at Sanford was a smoker aided in convincing employees that the plant was serious. The announcement that only nonsmokers would be hired and that there would be no exceptions to the rule--even the president--helped overcome one of company's biaaest obstacles to successful implementation...convincing employees that the company is serious about the ban. A second advantage Cardinal has in terms of enforcement is a highly desirable work environment. It pays top benefits and offers excellent working conditions. An employee must balance sacrificing his/her smoking habit for eight hours each day with sacrificing a job at Cardinal. So far, Cardinal has won every time. Not only has no one quit, but the ban has not even been tested. "They know we are serious, and if they test us, they must be willing'to live with the consequences." Management also believes that the long- standing positive environment among employees and management has contributed to the easy transition. Education During the 12 months between the announcement and the implementation, various company-paid educational programs and cessation classes were offered. In addition to regular stop 207 TVqN 0030255

Draft - Do not cite or_quote smoking seminars provided after business hours, employees and their families also were offered a hypnosis program, and for those who felt they were addicted to smoking, an intensive two-day, off-site treatment program was provided. FDA approved pharmaceuticals also were offered as quitting aides. During the period preceding the ban, smoking areas within the locations were gradually restricted until, on January 1, 1987, the entire company became smoke free. Blue Collar Rorkers° Although no survey has been taken to determine how many employeess have quit smoking, a survey taken before the ban was implemented revealed that more white collar employees than blue collar workers were smokers. At the Florida location, for example, some 40 to 45 percent of employees could be classified as "blue collar." But partly because the manufacturing plants were always nonsmoking, there has been no particular problem in implementation. off-Job Smokinc7 In a Position Paper discussing its policy, Cardinal Industries states, "The program only concerns itself with smoking in the workplace and not what employees do on their own personal time. Cardinal Industries never has, and never will try to regulate the activities of its employees on their own personal time." Thus, while Cardinal',s application form asks prospective employees whether or not they smoke, and while its policy prohibits the hiring of smokers, no attempt is made to test employees or to check on their off-work habits. 2EXAS INSTRL7MENTS Overall Policyi, Smoking is prohibited in all owned and leased- facilities except in specific locations in each facility that are designated as smoking areas and, to the extent possible, are separately ventilated. In late 1985 and, early 1986, several of the 37 major sites of Texas Instruments began implementing their own smoking policies as a result of employee complaints and local' Clean Air legislation. Rather than be faced with 37 different policies to implement, TI made a decision to implement a single corporate-wide policy. Employee Habits and Attitudes Before embarking on policy development, TI surveyed its employees to learn how many smoked and how they viewed worksite smoking restrictions. About half of the more than 50,000 workers surveyed 208 TIMN 0030256

Draft - Do not cite or quote took the time to respond, revealing that 77 percent of T~ employees were nonsmokers or exsmokers, and that just 23 percent were current smokers. Of those who smoked, over 40 percent said they wanted to quit. Corporate Obj ectives and Policy Before designing the Clean Air Policy, top corporate management agreed on three objectives that would form its underlying philosophy. There were to: o provide a healthful and safe working environment; o ensure high quality in all TI products; and o initiate the company's clean air approach rather than be forced to react to legislation (including the possibility of legislation from many different states-and municipalities). From these objectives grew TI's Clean Air Policy. •• "It is the goal of Texas Instruments to provide for its employees a healthful and safe working environment. In accord with this goal, Texas Instruments will prohibit smoking in all TI owned and leased facilities, except for specific locations in each facility which are designated as smoking areas." Education and Trainina To underscore the importance of the new policy, the eight-month, phased-in implementation process took a top-down track, with the President and CEO Jerry Junkins working directly with a key operating manager and the personnel director from each location th=ughout the organization. During the session, Mr. Junkins emphasized the organization's complete commitment to the new personnel policy and each individual manager's responsibility for its successful implementation. These teams then headed up similar training programs in their own locations. Training sessions were conducted for selected managers using a centrally prepared manual to ensure consistency among the.37 locations. Specially developed brief video tapes offered all employees an introduction to the policy (3 minutes), briefed managers and supervisors on issues related to• smoking (10 minutes), and assisted managers and supervisors in learning techniques for resolving smoking-related problems at the worksite (16 minutes). Making every effort to assist smoking employees to prepare for the new policy, TI provided company-paid smoking cessation programs on company time during the initial phase-in of the clean air program. Classes were scheduled to accommodate workers on all three shifts, 209 TIMN 0030257

Draft° - Do not cite or quote and "maintenance sessions" were offered to-:provide:roadditional support. More than 4,700 employees signed up for cessation classes, representing 40 percent of the company's smokers--almost exaczly the percent that said they wanted to quit in the employee survey. Of the group, 3,235 completed all the required classes (including maintenance classes), with 1887, or 58 percent, reporting they had quit by the end of the program. As a further aid, a Tip Sheet, "How to Make Life Easier Until the Next Cigarette Break" provided "some practical suggestions to help you when you need to change your regular smoking routine." A"Wrap Sheet: Daily Cigarette Count," designed to be wrapped around a pack of cigarettes, offered an easy place to keep track of how much was smoked, when and why, in the hope that the information would assist the smoker in altering his/her habits. However, all communication was not downward! Employees were given opportunities to ask questions and voice concerns during educational programs. Special attention was paid to employees concerns and complaints in in-house communication vehicles, as ,yell. Facilities Modification Because TI chose to designate a limited number of•areas in each building as smoking areas rather than to completely ban tobacco, it faced the problems of recirculating contaminated air. Thus, where necessary and possible, facilities were modified to provide separate ventilation. In addition, all cigarette machines were removed from TI facilities and a decision was made that no new ones would be installed. Enforcement TI made it clear from the beginning that a new personnel policy had been established that would be monitored and enforced in the same way as all other policies, such as attendance. Thus, anyone found smoking in non-designated areas would be given an oral warning. If there were no further problems, no further action would be taken. However, with subsequent smoking incidents, the employee would be given written guidance, followed by probation for additional infractions, with termination as a final step. But TI stressed to all supervisors that they should make every effort to educate smokers about the importance of the policy, rather than to be heavy-handed„ After nine months, "two or three cases" have gone to probation, but no one has been terminated because of smoking. Considering that 50,000 to 60,000 employees are covered by the 210 TIMN 0030258

Draft - Do not cite or quota policy, this is an excellent record, says Charles Nielson, Vice President and Manager of U.S. Employee Relations. Advice: Xeep Policy's Purpose in Persaective Nielson cautions other companies considering establishing a no smoking policy that one of the most difficult problems they face will be keeping the desire to eliminate the health hazards of smoking at the worksite in proper perspective. TI made a corporate decision to eliminate smoking at the worksite except in designated areas. The decision was a•business decision, not a moral or a value judgement. TI, which has 50 percent of its business in semiconductors, is facing intense competition, according to Nielson. Therefore, it must have productive employees. And that means it must have good relationships with all its employees. But smoking is an emotional issue for many people, both smokers and nonsmokers. "I'm not sure those of us in the ~ personnel field have yet learned, how to deal with this kind of highly charged issue and still maintain our productivity," states Nielson. "It takes a lot of hard work to achieve the desired atmosphere of teamwork, rather than an adversarial relationship." RAINIER BANE/RAINIER BANCORPORATION overall Policy: Following a one year phase in period, smoking is banned in 411 200 domestic facilities and in car pool vehicles. In September, 1985, the 5,800 employees of Rainier Bancorporation's U.S. facilities received a communication from their President, John D. Mangels stating that "We are committed to insuring a healthful and comfortable environment for all employees." As part of that commitment, he announced, the corporation would become smoke-free on October 1, 1986. As part of a transition plan, beginning October 15, 1985, smoking would be restricted to designated areas, and the company would sponsor and pay for smoking cessation classes to assist employees who choose to quit. Rainier Bancorporation is headquartered in Seattle, Washington, with 200 offices in Washington, plus Alaska, Oregon, California, Hawaii, Arizona, New York, and the Far East. Health Threats, Employee Complaints, Legal Concerns Prompt Policy According to Peter Broffman, personnel officer for Rainier Bank, the major subsidiary of Rainier Bancorporation, the policy resulted from three converging issues, the major one being a concern for 211 TIMN 0030259

Draft mDo not cite or quote employee health and wellness. Additional factors were an increasing number of employee complaints about smoke in the. workplace, and the changing legal and regulatory climate. In July, 1985, the state of Washington had adopted a Clean Indoor Air Act that prohibited smoking in public places, including public areas of banks, and there was reason to believe that unless employees acted on their own initiative, there might also be legislation regarding private workspace. That, coupled with an increasing number of court cases upholding the right of employees to have a smoke free workplace, added impetus to the development of a policy. Communications yital to Implementation once the decision was made to go forward with a phased-in ban, communications with employees became a key link to successful implementation. :Emphasis was placed on the fact that.Rainier was.:- prohibiting smoki.aq at the workplace, not smokers. Phase-In Period During the transition period, managers were given discretion to determine the most appropriate way to make the transition. The company policy stated that "The needs and 'comfort level' of both smokers and non-smokers should be considered during this period."' Guidelines for Phase I stated, in part: o All common areas, including lobbies, elevators, conference rooms, hallways, libraries, rest rooms and computer rooms will be smoke free. o In open-office work environments, managers should use discretion in deciding whether those areas should be smoke free. Individual employees.may, of.course, designate their assigned immediate work space as a no-smoking area. o Employees with enclosed offices may designate their area as a smoking or no-smoking area. However, the rights of non- smokers who must come into an enclosed office to conduct business should be respected. o Lunchroom and lounge areas will be divided into areas for smokers and non-smokers. Managers are given discretion to divide the rooms as appropriate for their locale. According to Broffman, there were relatively few difficulties in the initial phase of implementation. The few problems that did exist were due largely to differences in the ways various managers chose to implement and police their smoking restrictions. Occasionally disputes arose over what areas should be smoking and 212 TjMN 0030260

Draft°- Do not-cite or quote nonsmoking, especially in the smaller branch offices where there were few options for allocating space. For the most part, Broffman says, the problems were minor and easily resolved when the total prohibition was enforced. However, in retrospect Broffman believes that a shorter transition period might have been more desirable. "A three to six month phase-in period probably would have been adequate," he says. "Many smokers go through a adjustment period. A few indicated that putting off the inevitable ban for too long really isn't doing them a favor because it prolongs the period of anxiety and allows them to procrastinate in making the adjustment. Also, a shorter transition emphasizes the resolve of the company to become smoke free." In addition, any employees who want to defeat the policy will use the entire phase-in period to rally support. A shorter transition period would shorten the debate and lessen the possibility that the detractors will succeed. Enfo_rcinq the Ban Phase II, the total smoking ban, was introduced in a low-key, .matter-of-fact manner: a simple "reminder" that smoking would be prohibited in all work areas. With the exception of minor, final protests by a few "die-hards", employees accepted the new policy. Rainier has received no formal complaints, has had no problem with recruiting, and no one has resigned. The only complaint Broffman is aware of is that a few employees who still smoke do so immediately outside company building during breaks, and some employees are concerned about the impression this gives to customers entering the bank. Because of its stance that Rainier is eliminating smoke, not smokers, the organization makes no attempt to discriminate against hiring smokers. Bigdest obstacle to Policy: Fear Broffman acknowledges that when the policy was first proposed, there was concern on the part of a few senior manager of "What might happen." Although the majority and the leadership of senior management supported the policy, a few were initially concerned that there could be mass defections, that disagreements about smoking would cause major disruptions in work units, and that it could turn into an "employee rights" issue. However, these things did not happen at Rainier. "We had more complaints from nonsmokers before the policy was implemented than we got from smokers after it was enforced." Broffman says. His advice to other companies considering a smoking ban? "Do it! You can make it work!" 213 TIMN 0030261

;RTHWEST BELL ?olicy: Because of health concerns related to smoke, not allow smoking in any company facility. ar 15, 1985, Pacific Northwest Bell became the first large (15,000 employees in 750 buildings) to go completely smoke `s policy is simple; lth th ki t th h f PNB ill b l ea oyees, ere w e no smo ng ,ec e o emp zompany facility." for Smoking Restricl:ion3 - the establishment of the policy, PNB had allowed each work 3 decide, itself, whether or not it would be a smoking area. s arose, however, when adj acent work groups had dif fering aes. Smoke would drift around barriers, waft across no- desks, and generally infiltrate all areas of the building. assigned to no smoking areas would merely walk into work that permitted smoke, making the atmosphere even worse for :ers in the area. Difficulties occurred even within lua1 units that voted to eliminate smoking. If 60 percent to be a clean air area and 40 percent voted for smoking, the on arose as to whether the wishes of four-out-of-ten ees could really be ignored. 4 this kind of democratic approach had initially sounded like ;y way to avoid forcing a company-wide policy, it was seen as ,: and inequitable by most workers. No one was really fied and all the underlying problems still existed. ually both managers and employees began exerting pressure on o develop a company-wide policy. .3yee Znvolvement January, 1983, a Smoking Issues Steering Committee was bli.shed consisting of smokers, nonsmokers, and• a group often ;otten, former smokers. Employees representing their unions and i the legal, health services, safety, and many operating irtments were part of the task force. One of its first 'rtakings, an employee survey, brought an astonishing 74 percent Donse rate, attesting to the importance of the issue among ters. In addition to comments from those who were randomly ieyed, 151 people who were not part of the survey group made the Drt to get copies from their friends so they, too, could have Lr view heard. They included 135 nonsmokers and 16 smokers. 214 TIMN 0030262

DraftA- Do not cite or quote Results of the 1983 questionnaire showed that 28 percent of PNB employees smoked, but that the majority of employees were bothered at least occasionally by smoke at the workplace, and almost 80 percent said the company should be concerned about smoking at the worksite. Two-and-one-half years after its inception--following a great deal of research and discussion by the task force, as well. as involvement in the issue by numerous Quality of Work Life taams°and various ad hoc groups--the employee committee recommended to -he officers that smoking be eliminated at PNB. Union Involvement At PNB, unions were instrumental in all phases of policy development. Not only were they included in the employee committee making recommendations about a future policy, but-leaders of both unions were part of the June 1985 presentation to the company president of the committee's recommendation. "They were not there as advocates for a no smoking worksite," cautions Len Beil, =director of human resources planning and employee involvement. "They were present, rather, to state that they had been involved in the process and what their positions would be on a strong policy. While they did not endorse the complete elimination of smoking in all buildings, they stated that their unions would not formally fight its implementation, either." Bell adds that the union members on the committee were "extremely helpful" in all aspects of policy development, and that while they never fought against the policy, they negotiated successfully for several compromises that proved to be fair and beneficial for all employees. Initially, the company wanted to reimburse employees for smoking cessation classes after successful completion. The union position was that PNB's goal was to assist and encourage employees to live with the policy and comply with it--not necessary to get them to stop smoking. Therefore, they pressed, the company should reimburse totally for cessation classes, whether or not the employee completed the series. On the issue of smoking in company vehicles, union representatives stressed the difficulty of enforcement and potential problems if cigarette butts were found in a company car or truck ash tray. On both issues, PNB went with the unions' requests. All employees got full reimbursement for taking a cessation class and smoking in company vehicles is a matter of "common courtesy." The unions also urged that any policy be consistent throughout all company locations and for all employees. Education 215 TIMN 0030263

Draft-- Do not° cite or quote ie day the policy was announced, which.was 90 days before the 3licy was to go in effect, PNB provided two telephone hot lines o answer questions about the policy and provide information on .-ee cessation programs for employees and their dependents. "' A wide ange of quit opportunities were made available, many on company ime, with PNB paying all fees following completion. But PNB also arnered kudos from many employees by allowing them to take classes atside the company and still get reimbursement. The ability to noose their own quit method seemed to add to their commitment to ucceed and helped encourage a friendlier attitude toward the olicy. senefits 4ithin the first two years, 1,738 people had gone through cessation irograms--1,353 of them employees, 360 spouses, and 25 dependents- full ~eimbursement from the company for a cost of about -receivin , g $250,000. Is this investment worth it to PNB? "Yes," says Beil. "yIt is money well spent. This equals the cost of just•two or three cancers cases. And we would much rather pay for 1,738 to try to quit smoking than pay the results of their continued habit." Enforcement PNB reports that there have been "no real problems" with enforcement. On the first day, there were reports that one or two people were smoking behind closed doors in several locations. But "word got around" and by the second day they were abiding by the rules. Although several people threatened to contact lawyers and a few employees tried to organize a Smokers Rights day, nothing significant came from any of the attempts to block implementation. The bottom line: After two years, no one has quit because of the no smoking policy, there have been no grievances, and smokers at PNB have dropped from 28 percent to 20 percent in the two years since implementation. All in all, the company views its no smoking policy as an unqualified success. SUMMARY 1. The movement of businesses to develop and implement smoking control policies appears to be strong, and gaining momentum. 2. Employees and unions should be involved in the developement and implementation of workplace smoking policies. 3. Enforcement of smoke-free workplace policies has not proved to be a real problem for business. 216 TIMN 0030264

Draft - Do not cite or quote REPERENCZS 1. Office of Disease Prevention and Health Promotion, National Survey of Worksite Health Promotion Activities, U.S. Department of Health and Human Services, 1987, Washington, DC. 2. The Washington Post, "Around the nation: Many firms limit smoking," Washington, DC, February 23, 1988. 3. Hay/Huaains Benefits ReQort, November 17, 1989, Philadelphia. 4. American Lung Association, "Summary of results of the 1989 survey on public attitudes toward smoking," Nov. 1989, New York. 5. Tripp, J, "Tobacco smoke disappearing in workplace: Employers impose ban" The Orecronian, March 17, 1986. 6. Read, K. "Smoking bans: Corporate cold turkey," Corporate . Fitness: The Journal for Employee Health and Wellness Programs, Aug/Sept 1987. 7. Kaiser, J and'Behrens, R, Health Promotion and the Labor Union Movement, Washington Business Group on Health, July 1986. Washington, DC. 8. Smoking Policy Institute, "Smoking policies and the unions." 1986. Seattle, WA. 9. U.S. Department of Health and Human Services, The Health Consequences of Smoking: Nicotine Addiction--A Report of the Surgeon General, 1988, Office on Smoking and Health, Rockville, Md 10. U.S. Department of Health and Human Services, Office on Smoking and Health. The Health ConsecTuences of Smoking-- Cancer: A Re,port of the Suraeon General. U.. S. Government Printing Office, Washington, DC. Secondary Source: Office of Disease Prevention and Health Promotion, A Decision Maker''s Guide to Smoking at the Worksite, 1985. 11. Office of Disease Prevention and Health Promotion. A_ Decision Maker's Guide to Smoking at the Worksite. U.S. Department of Health and Human Services, 1985.. 12. Yenney, SL, Using Incentives to Promote EmAioyee Health, Washington Business Group on Health, 1985. Washington, DC. 13. Behrens, R. Reducing Smoking at the Workplace, Washington Business Group on Health, 1985. Washington, DC. 217 TIMN 0030265

Draft - Do not cite or•quote i4. Bureau of National Affairs, Where There's Smoke: Problems and Policies Concerninc SmokinQ in the Worktilace, Washington, DC. 218 TIMN 0030266

Draft - Do not cite or quote CHAPTER 11, APPENDIX IS THERE ECONOMIC JUSTIFICATION FOR NO SMOKING POLICIES AT THE WORRSITE? By Ruth Behrens* Washington Business Group on Health The health hazards of smoking--including smoking at the workplace- -have been well documented. Smoking greatly increases an individual's chances of contracting serious illnesses, such as cancer, chronic bronchitis, emphysema, and coronary heart disease, and of dying prematurely as a result of these diseases. There is little doubt that smoking also has a significant economic impact. It• is estimated that businesses pay over $100 billion per year in health care costs. A significant portion of this bill is.the result of smoking, and is paid out through insurance premiums for employees, dependents, and retirees who smoke or-breathe second- hand smoke, as well as for nonemployees who smoke or breathe others' smoke through programs supported by state and local taxes. rn other words, smoking is costing businesses a lot of money. How much does smoking cost U.S. businesses? No one knows exactly. But a growing list of researchers are tackling the difficult job of attempting to identify these costs. Costs of Smoking to the Nation At least three major studies have addressed the question of what smoking is costing the nation. In 1978, Luce and Schweitzer estimated the economic costs of smoking in the United States to be $47.6 billion. They further broke this down to $811 per adult smoker, or $1.56 per pack of cigarettes sold.~ In 1985, the Office of Technology Assessment, U.S. Congress (OTA), estimated that smoking costs the nation about $65 billion per year in lost productivity and health care costs alone. OTA estimates that smoking-caused illness results in $43 billion in lost productivity annually (or $1.45 for each pack of cigarettes sold), expenses borne largely by employers. Businesses also pay a significant portion of another $22 billion in smoking-related health care costs, since nearly t7ao-thirds of the costs are incurred by those under 65. According to the OTA, combined lost productivity and health costs related to smoking equal $2.17 per pack of cigarettes sold.2 219 TIMN 0030267

Draft -Do not- citas or~ quote Most recently in 1986, a group of researchers, which included the former director of the government's National Center for Health Statistics, concluded that smoking costs the United States at least $53.7 billion each year in direct medical costs and salary losses alone. These cost estimates were calculated by comparing the health costs and income losses from smokers in excess of the same amounts incurred by nonsmokers. The study concluded that smokers are sicker and require more medical care than nonsmokers.3 The coiaponents of the $53.7 price tag were broken out as follows. o Direct medical costs such as doctor bills, drugs, and hospital and nursing home expenses were $23.3 billion more for smokers than the average of nonsmokers. o A total of nearly $9.3 billion was lost in salaries due to smokers being sick with smoking-related diseases including lung cancer, heart attacks, stroke, emphysema, and other respiratory illnesses. o In 1984, lifetime earning losses from smoking related deaths were approximately $21.1 billion. The authors characterize their findings as "conservative" since they "did not take into account the adverse effects of passive smoking, risks of abortions, stillbirths, and neonatal deaths, or deaths under age 20 that might be associated with smoking.'+ In their paper published in The Milbank Quarterly, Rice et al translated all three of these studies to 1984 dollars. The result is three analyses of the economic impact of smoking on the nation that demonstrate enough similarity to underscore that smoking does, indeed cost our country a staggering amount:' o Luce & Schweitzer show a cost to the nation of $52.8 billion per year in 1984 dollars; o OTA, $62.2 billion in 1984 dollars; and o Rice et al, $53.7 billion in 1984 dollars.3 Differina Methodologies Make Pinpointinq Worksite Costs Hard A number of researchers also have attempted to assess the specific costs of smoking to businesses. But many problems arise when attempting to identify one, or even a "best" methodology for arriving at these costs. Among the difficulties in conducting any study of the costs of smoking is the fact that smokers differ from nonsmokers in several genetic, social, and economic characteristics that may contribute to disease. For example, the prevalence of smoking varies by race (more blacks smoke that whites), education (fewer college graduates 220 TIMN 0030268

Draft- Do not cite or quote smoke than persons with only some high school), income (males with lower income smoke more, while the opposite holds for women), and occupation (blue collar workers smoke more than professional or technical workers). If factors known to be related to health status and smoking habits are not controlled, the impact of smoking on health and the costs of smoking may be overstated.3 When examining smoking in the worksite, specifically, other methodologic issues must be resolved. Marvin M. Kristein and William Weis both published studies in the early 1980s identifying the cost to business of each smoking employee. Kristein estimated the cost in 1980 dollars to be between $336 and $601 per smoker annually,4 while Weis placed the figure nearer $4500.5 These findings are now outdated; in an article published in 1989, Kristein has stated that "...the typical smoking employee in 1988 cost the typical employer at least $1000 in excess costs" compared to a similar nonsmoker.6 However, a look at why their conclusions differed 10 fold dramatically illustrates two points: 1) the difficulty of pinpointing the cost of smoking to businesses, and 2) the wide range of business costs that can be affected by environmental tobacco smoke. Much of the rather staggering discrepancy between the two studies is attributable to their selection of different categories of costs to include in the equation, the weight given each category, and the salary assigned to the average smoker. According to Weis, business costs in at least ten areas are affected by smoking or smoking controls, including no smoking policies: health insurance; incremental absenteeism; life and disability insurance; fire, liability and industrial accident insurance; ventilation and energy consumption for heating and air conditioning; legal liability; property damage, depreciation and maintenance; time lost to the smoking ritual, employee morale, and corporate image.7 Kristein factors in health and life insurance, fir.2 losses, workers' compensation costs, absenteeism, productivity, and occupational health costs. (In a 1984 article, Kristein looked at only short-term costs and included fire, accidents, ventilation, cleaning, productivity, and occupational health risks.)a To help illustrate the differences between Kristein and Weis's total smoking-related costs, one can look at how each calculates the costs of absenteeism to employers due to smoking. Weis uses government data that shows a smoker is absent 2.2 days per year more than a nonsmoker. Using $30,000 per employee as the average annual wage and salary, including fringe and payroll taxes, the. company pays approximately $120 per working day for every employee on the payroll. Assuming a 25 percent return on payroll dollars, the direct cost to the employer is $150 per absence, excluding the cost of temporary replacements. According to this 221 TIMN 0030269

Draft - Do not° cita or quote formula, the total cost per smoker per year due to absenteeism is $310. A similar 7system is used by Weis in determining costs in other categories. Kristein, on the other hand, used 1979 data showing smokers are absent 33 to 45 percent more than nonsmokers, or 2.0 days more per year, and assigns a daily salary of just $40 per smoker due to smoking (versus $:L50 for Weis). Thus Kristein includes from $40 to $80 per smoker per yer attributable to absenteeism in his total (versus $310 for Weis) .2 While Kristein's estimates are based on what he called "real numbers" drawn from insurance companies, - U.S. government statistics, and detailed academic studies, he cautions, "We lack meaningful 'case controlled' company comparisons of experience with smoking employees versus nonsmoking employees....In general, the emphasis is on underestimatinct the costs to business."9 Economic Impact of Smokers on the Worksite ;.vidence also shows that, in addition to excess absences of two or more days per year, smokers exert other types of economic impacts on businesses over their nonsmoking counterparts. Studies have shown that: o smokers have twice as many job related accidents as nonsmokers.10 o Smokers are 50 percent more likely to be hospitalized than those who do not smoke. o Employers have been held legally responsible for at least part of the disability cost for smoking employees who contracted smoking related illnesses, in addition to claims from nonsmoking employees who were adversely affected by the smoke of others.11 o. Companies with certain occupational hazards can expect greatly increased costs related to smoking. For example, an asbestos worker who smokes is ten times more likely to die prematurely than his nonsmoking coworkers. A smoking uranium miner has six times the risk of contracting lung cancer as a nonsmoker in the same j ob . b In addition, many health consequences of smoking translate directly into increased health care,costs, since employers pay for a major portion of these costs for their employees, dependents, and retirees. 0 Heavy smokers (two or more packs a day) are 15 to 25 times more likely to die of lung cancer than nonsmokers, and 222 TIMN 0030270

Draft- Do not cite or quote, overall, smokers are ten times more likely to die of lung cancer than nonsmokers.' Z o Eighty to 90 percent of such long term severe lung diseases as emphysema and chronic bronchitis are related to smoking. o It is estimated that 30 percent of all cancers are caused by smoking. That means thatt338,000 Americans died of cancer in 1986 because of smoking. o Heavy smokers are three to four times more likely to die of cancer than nonsmokers and overall, the risk to smokers is two times greater than for those who don't smoke.12 o More than 550,000 Americans will die of coronary heart disease this year, and up to 30 percent of those deaths will be attributable to cigarette smoking. 14 o Heavy smokers have a 200 percent greater risk of dying from coronary heart disease than nonsmokers, and overall, the risk for all smokers regardless of the amount smoked, is 70 percent greater than for those who don't smoke.14 o Evidence demonstrates that smoking during pregnancy has a significant adverse effect upon the well being of the fetus and the health of the newborn, including causing lower birth weight infants and increasing the risk of spontaneous abortion and neonatal deaths.10 o Children of smoking parents have increased prevalence of respiratory symptoms and have an increased frequency of bronchitis and pneumonia early in life.t3 Two studies relate smoking directly with costly health-related events, stroke and automobile accidents. A study has concluded that smokers who quit can decrease their risk of having a stroke by more than half when compared to those who continue to smoke, thus cutting dramatically their potential health care costs.15 A two-year study in Worcester County, Massachusetts, comparing the motor vehicle driving records of smokers with nonsmokers found that smokers had 50 percent more accidents than nonsmokers and 46 percent more traffic violations. The study identified several reasons for the smokers' increased risk of being involved in costly accidents and violations, including o smokers' more frequent use of alcohol and drugs, o smokers' greater risk-taking behavior, and 223 TIMN 0030271

Draft- Do not-°cite or quote o smokers' diminished attention to ~driving due.. to the distractions associated with smoking. Individual Compaknies Document Costs, Consequences of Smoking While studies conducted by individual companies have varying degrees of validity, they do offer some further insights into the price businesses pay for their smoking employees. In a study of 40,000 employees at 27 locations of the.Control Data Corporation, CDC found that smokers cost the company substantially more in health related costs than nonsmokers. The study, using health data collected from 1981 to 1984, found: o' Smokers of one pack of cigarettes per day or more generate health claims 18 percent higher than nonsmokers. o Smokers of one cigarette to one pack per day accrue claims costs 10 percent:-higher than nonsmokers. o Heavy smokers have 25 percent more inpatient days than their counterparts who do not smoke. o Heavy smokers are 29 percent more likely to have health claims over $5,000 than those who do not smoke.17 One Los Angeles company estimates production losses alone at $675 per smoker per year. Adding longer term costs such as absenteeism, premature death, and illness would raise the cost to at least $1,000 per year for each smoker.t8 Provident indemnity Life Insurance Company charges its smoking employees the excess rate of their insurance coverage over that of nonsmokers, an amount in the-vicinity of $300 per year.t9 Smokinq and the: Bottom Line When viewed in the aggregate, these studies may appear to make a compelling case for the potential of smoking control programs and .policies to significantly cut long-term business costs. However, a number of researchers, including health promotion and smoking control advocates, point out that this conclusion may- not be justified. In some cases, the studies presented have significant methodological problems or their underlying assumptions may be flawed. Equally important, the total costs of developing and implementing smoking control programs and policies, coupled with the increased costs associated with longer life resulting from quitting smoking (pensions, retiree and dependent health care costs), may eliminate any financial gain for the company. 224 TIMN 0030272

1W Draft - Do not cite or quote Following are several examples and studies illustrating how these supposed cost savings may not be what they initially appear to be. As is pointed out in this appendix, many of the costs associated with smoking can be attributed to characteristics of smokers (risk- taking style, alcohol and drug use, low socioeconomic status). However, it is unlikely that these basic characteristics would change, even if the individual employee was induced to stop smoking. A portion of the supposed economic penalty associated with hiring smokers results from an increase in absenteeism seen in employees who smoke. Statistics indicate that people who smoke are eight times more likely than nonsmokers to have alcoholism. Thus, helping current employees stop smoking might not have the expected effect on absenteeism, since in some, alcoholism also is a root cause of the absenteeism.2° Some argue that smokers already are "paying their own way" through cigarette excise taxes. in examining the lifetime costs that smokers impose on others through collectively financed health insurance, pensions, disability insurance, group life insurance, fires, motor-vehicle accidents, and the criminal justice system, 'Willard G. Manning, et al, conclude that on balance, smokers probably pay for their own costs to society under the current level of excise tax on cigarettes.21 According to Kenneth E. Warner, Ph.D., a successful workplace smoking cessation program will reduce certain health care costs, life insurance copts, disability costs, and absenteeism, and it may increase productivity as well. "However, " he adds, "one thing that it is almost certain to do, by virtue of its success, is to extend the lives of a subset of employees well into retirement, implyin~ both pension and health care (and other) cost implications.... "` Warner concludes that when all costs are taken into account--such as, for example, the increased costs of pensions, health care, and disability for retired workers who live longer because they stopped smoking, versus the decreased costs for workers who continued to smoke, die prematurely, and are replaced by a younger, less expensive employee--businesses might very well conclude that, from a purely economic point of view it may be cheaper to allow employees to continue smoking.12 Louise Russell,~ Thomas Schelling,Z~ and others have come to similar conclusions based on cost savings alone. Individuals such as these, who debunk the idea that smoking control programs will result in cost savings for businesses, do not, however, conclude that it is in best the interest of businesses and society to advocate smoking or to shun smoking control policies. 225 TIMN 003®273

' Draft°® Do not cite or quote There are obvious short term benefits of a smoke free workplace, over and above the health-related savings Warner lists above. They include reduced building and equipment cleaning and maintenance costs, reduced costs from fire damage and insurance, reduced energy consumption cost because of reduced ventilation needs, and reduced turnover. In addition, there are the less tangible benefits of a working environment that is perceived as being better by the overwhelming majority of employees, as well as an improved company image. But for many, the potential of better health for employees, and of eliminating or delaying the onset of degenerative or fatal diseases is the most compelling reason to implement a company-wide smoking control policy. So the real bottom line for companies considering whether or not to implement a smoking control policy or a smoking ban may not be a simple dollars and cents formula. But rather, the bottom line may be as pragmatic as the need to comply with local legislation, or the desire to improve productivity, as paternalistic as the desire to have happy, loyal employees, or as altruistic the desire to "do the right thing" by providing the most healthful environment for its employees. If costs savings follow, these companies may, themselves, have received a bonus. SUMMARY 1. Smoking in the workplace increases business costs because the diseases of smoking increase absenteeism•and hospitalization, and may increase insurance, disability and legal dosts. However, these costs may be offset by the longer lifespan of employees who quit smoking as a result of workplace restrictions, increasing pension costs to employers. 2. The most compelling reason to restrict smoking in the workplace is the potential for better health for both nonsmoking and smoking employees, by eliminating or delaying the onset of degenerative or fatal diseases. 226 TIMN 0030274

Draft - Do-not cite or quote REFERENCES 1. Luce, BL and SO Schweitzer, "Smoking and Alcohol Abuse: A Comparison of their Economic Consequences," New Enaland Journal of Medicine 298, 569-571. 1978 2. Office of Technology Assessment, U.S. Congress. "Smoking- Related Deaths and Financial Costs." (OTA Staff Memorandum). 1985 Washington, DC. 3. Rice, DP , TA Hodgson, P Sinsheimer, W Browner and AN Kopstein. "The Economic Costs of the Health Effects of Smoking, 1984" The Milbank Quarterly. Vol. 64 , No. 4, 1986. Cambridge University Press. 4. Kristein, MM, "How Much Can Business Expect to Profit from Smoking Cessation?" Preventive Medicine, 12, 358-381, 1983. 5. Weis, WL. "No Ifs, ands or Buts: Why Workplace smoking should be banned" Management World, 339-44, Sept 198 1.. 6. Kristein,_* RM, "Economic issues related to smoking in the workplace." N.Y. State J Med. 89: 44-47 (1989). 7. Smoking Policy Institute, "The Costs of Smoking in the Workplace," 1986, Seattle, WA. 8. Kristein,MM "Wanted: Smoking Policies for the Work-Place," ` Business and Health, Washington Business Group on Health, Nov. 1984. Washington, DC. 9. Bureau of National Affairs, "Where There's Smoke: Problems & Policies Concerning Smoking in the Workplace," 1986, Washington, DC. 0 10. U.S. Department of Health, Education and Welfare, Office on Smoking and Health. Smoking and Health: A Report of the Suraeon General. U.S. Government Printing Office, 1979, Washington, DC. 11. American Lung Association, "Smoking at the Workplace: The Changing Legal Situation. More Facts & Features for Nonsmokers & Smokers. 1983. New York, New York. 12. U.S. Department of Health and Human Services, Office on Smoking and Health. The Health Consequences of Smoking-- Cancer: A Report of the Surgeon General. U.S. Government Printing Office. 1982. Washington, DC. 13. U.S. Department of Health and Human Services, Office on Smoking and Health. The Health Conseauences of Smoking-- 227 TIMN 0030275

Draft - Do not cite or quote Smokers," New EnQland Journal of Medicine, Sept. 18, 1986 315: 717--20. DiFranza, JR, et al, "The relationship of smoking to motor vehicle accidents and traffic violations," New York State Journal_of Medicine, Sept. 1986. Milliman & Robertson, Inc. Health Risk and Behavior: The Zmgact or~ Medical Costs. 19.87, Brookfield, WI. Rice, D]? and TA Hodgson, "Economic Costs of Smoking: An Analysis of Data for the U.S.," presented at the Allied Social Science Association annual meeting, San Francisco, CA Dec. 28, 1983. Behrens, RA. Reducing Smoking at_the Workplace. Washington Business Group on Health. Oct 1985 Washington, DC. 20. Warner, KE, Wickizer, TM, Wolfe, RA, Schildroth, JE, Samuelson, MH. "Economic implications of workplace health gromotion programs: review of the literature. J. Occ. Med. 30: 106-112 (1988). 21. Manning, WG, et al, "The Taxes of Sin: Do Smokers and Drinker:; Pay Their Way," Journal of the American Medical Associat:ion Vol. 261, No. 11, March 17, 1989. 22. Warner, KE, "Selling Health Promotion to Corporate America: Uses and Abuses of the Economic Argument," Health Education Quarter],y, Vol. 14, No. 1, Spring 1987. 23. Russell, LB, Is Prevention Better than Cure? Brookings Institute, 1986, Washington, DC. 24. Schelling, TC, "Economics and Cigarettes," Preventive Medicine:, Vol. 15, 1986. Chronic Obstructive Luna Disease: A Renort of the SurQeon General. U.S. Government Printing Office, 1984. Washington, DC. 14. U.S. Department of Health and Human Services, Office on Smoking and Health. The Health Consequences of Smokina-- Cardio_va.scular Disease: A Report of the Suraeon General. U. S. Gcvernment Printing Office, 1983. Washington, DC. 15. Abbott, RD, et a., "Risk of Stroke in Male Cigarette -------------------------------------------------------- * present address: 3026 East Marlette, Phoenix, AZ 85016 228 T1MrT 0030276 L