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A n AN ESTIMATE OF NONSMOKERS" LUNG CANCER RISK FROM PASSIVE SMOKING A quantitative assessment is made of nonsmokers' lung cancer risk from breathiing ambient tobacco smoke. This assessment 'is based on an exposure model incorporating average concentrations of tobacco smoke expected to be encountered in the two microenvironments, at home and at work, in which the average adult appears to spend about 900. of the time, weighted by the estimated probabillities of co-occupation by smokers and nonsmokers, ar by typical' respiration rates. It is al'.so based on a response estimated from epidemioli studies of lung cancer in nonsmokers with certain lifestyle characteristics. James L. Repace, MS., and Alfred H. Lowrey, PhD.t KEY WORDS: Risk Assessment; Indoor Air Pollution; Tobacco Smoke; Lung Cancer Approx. 5000 words in text 1500 words in appendices 6 tables ACKNOWLEDGEMENTS: The authors are grateful to RL Phillips for unpublished data from his published studies of mortality in members of the Seventh Day Adventist Church. We also thank B Fischoff, J Horowitz, D Patrick, G Sugiyama, W Ott, and J Wells for useful discussions. tJames L. Repace is a physicist and policy analyst in the Office of Air and Radiation, U'.S. Environmentali Protection Agency, Washington, DC 20460. Aifred~H. Lowrey is a researc- chemist inithe Laboratory for the Structure of Matter, Navall Research Laboratory, Washing. DC 20375, The views presented in this article are those of the authors, and do not necess reflect the policies of the agencies named. • t

, , 0 a ABSTRACT We have performed'a quantitative assessment of nonsmokers' risk-of lung cancer fr- passive smoking. Our estimates should be viewed as preliminary and subject to chan5e as improved research becomes available. We estimate that nonsmokers are exposed to from 0 to 14 mil.lilgrams of tobacco tar per day, and that the typical passive smoker is exposed'to 1.5 milligrams per day. We derive a phenomenological exposure-response relationship yielding 5 lung cancer deaths per year per 100,000 persons exposed, per milligram daily tar exposure. Aggregate exposure to ambient tobacco smoke is estimated to produce about 5000 lung cancer deaths per year (range 3000 to 14000) in U nonsmokers aged > 35 years, with an average loss of life expectancy of 17 + 9 years pe fatality. The modeled loss of life expectancy for the most-exposed passive smokers app to be about 2/3 of that reported for pipe smokers and 1/2 of that for cigar smokers. Mortality from passive smoking is estimatedto be from one to three orders of magnituc higher than that estimated~for carcinogens currently regulated~as hazardous air pollutants under the federal Clean Air Act. 4r_

I INtROOUCT~ION' Exposure of nonsmokers to indoor air poLlutton from tobacco smoke (also known, as involuntary or passive smoking) has recently become a public health concernl for several reasons: o Such exposure is widespreadZ+3 a Studies of the effects of tobacco smoke on smokers worldwide have implicated'it as the most_important cause of lung cancerl,4 o Existence of a threshold for carcinogenesis is doubtfu11,5- o There is suggestive new evidence of lung cancerl' (and other serious health effects) in nonsmokers exposed to ambient concentrations of tobacco smoke.2,9.10 In the 1982 report on cancer and smoking,1 the Surgeon General asserted that despite the incompleteness of the evidence, nonsmokers should avoid exposure to second-hand smoke to the extent possible, a judgement supported by the World Wealth Organization and the National Academy of Sciences1'1. Nonsmokers are commonly exposed~to tobacco combustioniproducts in diluted side- stream and~exhaled'mainstream tobacco smoke from cigarettes, cigars, and pipes.2 Tobacco smoke contains 60 known or suspect carcinogens, i~ncluding 51 in the particula: phase; the carcinogenic activity of tobacco smoke appears to require this phase.1 Biloassays indicate that sidestream tobacco tar is more carcinogenic per unit weight than mainstream tar.1 This raises the question of whether the quantity of tobacco tar to which the average nonsmoker is exposed creates a significant risk of lung,caneer. In order to answer this question, we first justify, and thenperform, a quantitative risk assessment (QRA). QR2, deals with the question of how much morbid'ity and mortality an agent is likely to produce given specified lievel!s of exposure; typicalily utilized' in the regulation of carci'nogens, it is important because control efforts cannot proceed without assurance that the health gains are worth the costs.14 QRA involves knowing: the health effects from exposure, the distribution of exposure to the polTutant, the population, at risk, the dose response function, and exposure to and effects of confounding, substances.5,6>7,14 On the basis of such assessnients,

t . -2- infbrmed risk management judgements can be made; in this manner, five carcinogens have been regulated as hazardous air pollutants.14' In this work, we draw upon the epidemiology of lung cancer1,8,15,16 and on indoor air pollUution physics2+11'',1'7 to produce a risk analysis5,6,14,18,19 in whi'ch we correlate nonsmokers' lifestyles, exposure to airborne tobacco tar, and incidence of lung cancer. In our analysis, we first review estimates of the average exposure of the general population to ambient tobacco smoke. Second, we elucidate studies linking tobacco-related disease in nonsmokers to exposure-related variations in lifestyle. Third, we couple these two factors to develop a phenomenological estimate for the aggregate lung cancer risk to the U.S. nonsmoking population, and to develop an exposure-response relationship for the estimation of the risk to the most-exposed. Fourth, to check the reasonableness of our estimate, we compare our estimated level of lung cancer mortality and resul~tant loss of life expectancy from passive smoking to those from cigarette, pipe, and cigar smoking, employ an alternative method of calculating an aggregate risk based on the lung cancer risks of active smoking, and make a crude estimate of the range of risk. Finally, we compare our estimated risk from ambient tobacco smoke to that from various ai'rborne carcinogens currently being regulated as hazardous air pollutants, to determine the significance of the estimated risk. 0 YARIATION'0F EXPOSURE WITH LIFESTYLE In earl!ier work2,9,20L27 we studtied factors affecting non-mokers" exposures to tobacco smoke, and conducted! fi'eld~ surveys of the levels of respi'rable particles indoors and out, in both smoke-free and smoky environments. This work established that ambient tobacco smoke imposed significant air potlution burdens on nonsmokers, and', using controlled experiments, we devel'oped a model' to estimate those exposures. This model predicts that the exposure of U.S. nonsmokers ranges from 0 to 14 milligra:-.. of cigarette tar per day ('mg/day), depending upon the nonsmcker''s lifestyle,2 and that the average population exposure for'adults of working age is about 1.5 mg/day.25 A W dh-m

3. 0 . Table 1, derived from the model,26 estimates probabilrity-weighted exposure to the particulate phase of ambient tobacco smoke for a typical M. adult nonsmoker. We omit exposures received'in other21 Indoor microenvironments, outdoors, and'lin transit,, which account for the remaini'ng 121. of people's time. The table is derived from considerations that ambient concentrations of ambient tobacco tar have been found to be directly proportional to the smoker density and~inversely proportional to the effec tive ventilation rate.2 The ventillatton rate tables given by ASHRAE29 can be used to estimate both the range in effective ventilation rate (from the design mechanical rates) and smoker density (from the design occupancies), and thus upper and lower bounds and average concentrations for model workplace and home microenvi'lronments can be estimated.2,20,26 Table 1 suggests that individuals receiving exposure both, at home and at work constitute a high exposure group, with the workplace appearing four times as strong a source of exposure as the home; the reason for thi'ls differentia is the generally higher occupancy (i.e., smoker density),encountered'in the workplace. This estimate of exposures represents a mod'eled'weighted average taken over the entir=_ populati~on, including those who are not exposed. A limited comparison of these estimates can be made with the results of a study of the prevalence of perceived passive smokiing in metropolitan San Francisco. Friedman et al.3'questiloned nearly 38,000 adult nonsmokers and ex-smokers who receive_ mulittphasic healthicheckups in 1979 and 1980. In general, sex and race were found to __--be correl'ated to passive smoking only to a small degree, and self-reported exposure of at least one hour per week during the working years ranged frcm a high of 78;. during ages 20 to 29, to a low of 600. during ages 50 to 59. Friledman et al.3 conclude that passi!ve smoking is a hiighly prevalent phencmenon, in qual'itative agreement witti = findings.2,26 Quantitati'.vely, Table 1 suggests that employed persons receive exposure_ with an 85: probability, greater than that reported by Friiedman, et ali. for their sub_ Our estimates are for the general U.S. popullation. Friedman et a13 caution tha_ tne "health~conscious" subpopulation may be 'atypical. Also, differences between our es-.i-

exposure probabilities an&those reported by Friedman, et al.'s3 subjects might be due to such poorly understood'factors as differences between people's perceptions and actual exposures,21 given the persistence of tobacco smoke ilm indoor spaces long after smoking has ceased.2,20,27 E.g., Jarvts and Russell* in a study of _ urinary cotinine in a sample of 121 self-reported nonsmokers, state that only 12: of subjects had undetectable cotinine levels, despite nearly 50% reporting no passive smoke exposure. VARIATION OF RISK WITH LIFESTYLE White and Froeb3U evaluated the effect of various degrees of long-term j>20 yrs workplace exposure to tobacco smoke on 2100 healthy middle-aged workers. Of the workers, 83: held~professional, managerial, or technical positions, whi'1e the remaini: 17» were blue collar workers. Passive smokers of both sexes suffered stati'stically significant decl!ines in mid- and end-expiratory flow rates which averaged about 113,5 percent and 22 percent respectively, and did not differ significantly from the values measured in noninhaling or light smokers of cigarettes, pipes, and cigars. They concluded that chronic exposure to tobacco smoke inithe work environmen- is deleterilous to the nonsmoker and significantly reduces small airways function to the same extent as smoking 1 to 10 cilgarettes per day. Kauffmann et al.,31 compared pulmonary functioniin about 3800 people in France: 849 male "true" nonsmokers (defined as those not exposed at home)' 165 male passive smokers (defined as those exposed at home), 826 female "true" nonsmokers, and 1941 female passive smokers./ The authors restricted the analysis to~subjects aged 40 years or more (i.e., to~those who had been exposed for 15 or more years to:smoking by their spouses) and who were 1!iving in households with no persons over the age of 118 years except their spouses. They found that nonsmoking subjlects of either sex whose spouses were current smokers of at least 10!grams of tobacco a day had~mi'd'-expiratory flow rates averaging 11.500 lower than those married to nonsmokers. For women in soc;: classes withithu highest percentage of paid work, the effect of workplace smoking 'J'arvis MJ1, r7ussei'1 MAM, measure:nent ana estlmat7on or smoxe cosage to nonsmoKers f c- environmental tobacco smoke Brit. Med. J!, iln, press. w.1 Ci+7 -r

n o. apQeared to confound'the effect of passi've smoki'ng at home. However, in the large subgroup of women without paid work (i.e., not exposed to workplace smoki'ng)i, a clear dose-response relationship to amount of husbands' smoking was observed. They concluded that women living with heavy smokers appeared to have the same _ reductions in mid-expiratory flow rates as light smokers, and that after 15 years exposure in the home environment, passive smoking Is deleterious to pulmonary function. A third study by Kasuga* of urinary hydroxyproliine levels as a function of passive smoking status showed that urinary hydroxyproline levels in nonsmoking wives and chilidren varied in a dose-response relationship with husbands and parental smoking habits, when adjusted for pre-existing respiratory disease. Elevated urinary hydroxyproline levels have been correlated with degradationlof lung,tissue.* These three epidemiologic studies provid'e evidence that variations in the exposur of adult nonsmokers to ambient tobacco smoke at home and'at work camproduce obser- vable vable pulmonary effects. Like effects have been observed in ~hildren exposed at home.= LIFESTYLES WITH INCREASED LUNG CANCER RISK Nine epidemiologic studies have examined the lung cancer risk incurred by the nonsmoking spouses of cigarette smokers. In each study, the only exposure variable was the strength,of the spouse's smoking habit. The studies were conducted in Greece33, Japan34, the U.S,35,59,70,71, Germany60, Scotland72, and' Hong Kongt,73, In the Greek study, Trichopoulos et. al.33 used the case-controli technique: - involuntary exposure to cigarette smoke as measured by the husbands' daily consumptic7 was foun6to increase the average risk of lung cancer by a factor of 2.4 (p<.01) when lung cancer patients were compared to 225 controls,64 and a dose-response relationsn- was observed. Divorce, remarriage, husband's death, or change in smoking habits t Chan WC, Fung SC, Lung Cancer in Non-Smoker In Hong Kong, Unpublished. *Kasuga H, Hydroxyproline and Passive Smoking, presented at 'New Etioliogies in Lung Cancer, Honr_ Hawaii, March 21-23, 1983.)

0 6. wer,e considered. Although the sample was small'., Trichopoulos et. al.33 suggest that the conservative social setting,rendered the study less susceptible to bias due to smoke exposures outside the home. In the Japanese study (1966-1981) of lung cancer in 91,540 nonsmoking women, Hirayama34 used the prospective technique: relative to those women not exposed at hoMe (controls), involuntary exposure of wives of smokers was found to increase the average risk of lung cancer by a factor of 1.8 (p<.0U1), where the exposure was also estimatec from husbands' daily consumption. The annual LCD rate in the controls was 8.7 per 100,000. Hirayama34 found that the exposed wives experienced an average annual increase in lung cancer mortality rate of 6.8 per 100,000, with a range of from 5.3 to 9.4 per 100,000, in a dose-response relationship depending upon the degree of the husband's smoking. Hirayama34 found further that the risk of lung cancer death in nonsmoking women increased both with the time of exposure and number of cigarettes smoked daily by the husband. Hirayama34 also reported a factor of 2.9 (+ .3, at the 95~~ conf. Level!), for increased risk of lung cancer in 1010 nonsmoking husbands with smoking wives. More recently, Hi'irayama extend'ed his earlier work to suggest74 increased risk of nasal sinus cancer, emphysema, chronic bronchitis, and ischemic heart disease in passive smokers, and evidence of decreased risk ilninonsmoking wives _ exsmokers. In one U.S. study, Garfinkeli35 reported results from an analysis of data collected from the American Cancer Soci'ety"s (ACS) prospective study of lung cancer risk in 176,- nonsmoking womeni(1960 to 1972), as a function of involuntary exposure as indicated by their husbands' cigarette consumption. 72: of the nonsmoking women were married' to smokers. Three smoking categories were identified: none, less than a pack per day, or greater than a pack per day. The U'.S, study reported~nonsienificant risk ratios of 1.001, 1.27, and 1.10 respectivel!y for the three categories (averace risk ratio Is 1.1~9 for wives whose husbands smoke). .. m . ~ ~ . U± L ~

b A great deali of correspondence, pro and con, on the relative merits of these three studies was generated, and is summarized in the Surgeon General's Report.l Hirayama34 suggests that the disparity between the findings of hiis study and that of Garfinkel'35 may be due to the smaliler room size in Japanese houses and the closer proximity between Japanese spouses compared with American spouses. In attempting to explain the different results between the ACS and the Greek and Japanese studi!es, Garfinkel35 and Hammond and Selikoff37 have suggested that husbands' smoking habits are not good surrogates for the total tobacco smoke exposure of nonsmoking wives. Friedman et ali.3 have suggested that although traditional Greek and Japanese wives' passive smoking may have depended almost entirely on theiir husbands' smoking habits, contemporary (1981)A.S. spouses' smoking habits appear to be an inaccurate index of passive smoking. In 1965, 3810 of U.S. women were in the civilian labor force, up only 3 percentage points from 1955.38 8ased'on Table 1, we estimate that a person exposed on the job but not at home, would receiive an averae_ exposure 4 times as high as one exposed only'at home. Presumably then, 38: of the ACS"control"group ha&unaccounted-for workplace exposures whichimay have been four times higher than 62: of his "exposed" group. This may explain,the different results of the Hirayama34 and Garfinkel35 studies.75 In the second U.S. study, Correa, et al!.59, studied &male and 22 female non- snoki'ng lung cancer cases and 180 male and 131female controls as part of a larger study including smokers, with 13381ung cancer cases and 1393 controls, in Louisiana, andreported that nonsmokers married to heavy smokers had an increased risk of lung c_ cer, as did smokers whose mothers smoked. Men with smoking wives had a nonsigniifiicanc risR ratio of 2.0 compared to~their counterparts with nonsmoking wives, and women with smoking husbands had an average rtsk ratio of 2.07 (,p<.05) compared~to women wi•- nonsmoking husbands. A dose-response rellationshi!p was observed, with the peak rilsk reaching 3.52 (p<.05)1. The combined data for men and women passive smokers was signtficant (p<.05) for the heavier smoking category (141 pack-years).

~ Preliminary -u- /' dataffrom a third U.S. study, by Kabat and Wynder70, a case-control study of passive smoking in nonsmokers in 25 male cases and controls, and 53 female cases and controls, where the majori'ty, of the patients were from New York City. The controls consi~sted of patients hospitalized for non smoking-related diseases, roughly two-thirds being cancer patients. No differences on exposure to passive smoking at home or at work were found in the women. However, the male passive smokers displayed a statistically significant (p=0.05) dtfference in lung cancer (odds ratio 1.6)) relative to the non-exposed group. Interestingly, when the data are further broken down and~the male cases and controls are reclassified into exposure categories based upon home and workplace, the odd5 ratios are: 1.00 (neither at work nor at home); 2.4 (at home only); 3.4 (at work only); 9.6 (both at work and at home), although the number of cases is extremely smal!l and the confidence intervals very wide, and the breakdown ratios do not attain statistical significance.* A fourth U.S. study by Miiller71 of mortality from all forns of, cancer in 123 nonsmoking women (only 5 lung cancer cases) as a function of husband's smoking_histor; reported!a non-significant odds ratio of 1.4 for all women (p=.15) for wCmen whose husbands smoked relative to those who did not, and when empl!oyed women were excluded the odds ratio increased to 1.94 and was statistically significant (p<.02). Knoth et al.60'reported on a stud'y of 39 nonsmoking German females with lung can-- 61.5Z were found to have smoking spouses. The authors state that this was threefol'd that expected on the basis of smoking habits of German malles. Chan and Fung* studied lung cancer cases in 397 persons iiniHong Kong, 2 nonsimoke- out of 208 male cases, and 84 nonsmokers out of 189 female cases. Among nonsmoking women, the proportion of cases reporting passive smoking was 40.5: compared to 47'.51. amongithe controls (a risk ratio of 0.35) and it is stated that more non-smoking patients had nonsmoking,spouses; however, the proportion of married women among the cases is not given. Wynder and Goodman61 in reviewing this manuscript, stated that the nature of the survey question'~egarding,exposure was unclear. *Kabat G, private communication. ~ .