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I I I I I I i I I I I I I I I I I I CRS-7 discussed some of these criticisms in an economic analysis of proposed increases in tobacco taxes.9 In testimony before a Senate subcommittee, CRS concluded that "the statistical evidence does not appear to support a conclusion that there are substantial health effects of passive smoking."to The controversy over the ETS studies stimulated subsequent requests of the Congressional Research Service to review the issue in more depth. This report is in response to those requests. The report concentrates on the possible relationship between ETS and lung cancer in non-smokers. The study was carried out by a review and analysis of the major published literature, the preponderance of which is on ETS and lung cancer risk. The analysis was supplemented with a one-day meeting held in June 1995 of independent experts and representatives of the different agency and institutional views on possible health effects of ETS. One finding of the meeting was that detailed analysis of other potential health effects - heart disease and childhood respiratory illness - would require substantial additional efforts by CRS. Such efforts are beyond the resources of CRS. As a result, this report only briefly reviews current knowledge about those other topics. This report is divided into four chapters. The first chapter summarizes the physical and chemical composition of ETS, and the evidence for ETS exposure and uptake among non-smokers. The second chapter examines the results of the various epidemiologic studies, with some emphasis on the implications of the 1st Session, July 21, 1993; (ii) U.S. Congress, House Committee on Agriculture, Subcommittee on Specialty Crops and Natural Resources, Review of the U.S. Environmental Protection Agency's Tobacco and Smoke Study, 103d Congress, 1st Session, July 21, 1993. Three recent reviews in support of EPA's analysis are (i) Trichopoulos, D., Principles and Practice of Oncology: PPO Updates Volume 8, August 1994, pp. 1-8; (ii) Consumer Reports, January 1995; and (iii) Jinot, J. and S. Bayard, Risk Analysis, Vol. 15, No. 1, 1995, pp. 91-96. For a summary of the tobacco industry's criticism of the EPA report, see The Tobacco Institute, EPA Report Scientifically Deficient. Additional articles critical of EPA's analysis include: (i) The Alexis de Tocqueville Institution, Science, Economics, and Environmental Policy: A Critical Examination, August 1994, pp. 1-13; and (ii) Smith, C.J. et al., Toxicologic Pathology, Vol. 20, No. 2, pp. 289-303. For a critical review of the ETS-lung cancer risk that is written for the layman, see Huber, G.L. et al., Consumers' Research, July 1991, pp. 10-15, 33-34. Finally, see Choices in Risk Assessment: The Role of Science Policy in the Environmental Risk Management Process, Chapter 10, Workplace Indoor Air Quality, Regulatory Impact Analysis Project Inc., Washington, D.C. 1994, for a criticism of OSHA's proposed indoor air quality regulation. 9 In their report, Cigarette Taxes to Fund Health Care Reform: An Economic Analysis (CRS Report 94-214 E, March 8, 1994), J.G. Gravelle and D. Zimmerman reviewed estimates of the economic costs that smokers impose on nonsmokers. The report reviewed the evidence of a passive smoking health risk because this is a potential component of the cost calculation. It concluded that (i) the evidence that passive smoking causes disease is far less certain than for active smoking, and (ii) the health costs of these potential passive smoking effects, if any, are likely to be quite small. 10 Testimony of Drs. J.G. Gravelle and D. Zimmerman on May 11, 1994, before the Senate Committee on Environment and Public Works, Subcommittee on Clean Air and Nuclear Regulation. I

CRS-8 dose-response trends for estimating the lung cancer risk among non-smokers. A discussion of confounding, smoker misclassification, and recall bias - the principal sources of uncertainty in the epi studies - is presented, including implications for the dose-response observations. The third chapter discusses the potential lung cancer death risk of ETS including the consequences of an upward dose-response trend. This chapter also puts the potential risk of ETS in the context of other risks faced by the general population. The fourth chapter reviews the Occupational Safety and Health Administration's (OSHA) assessment of occupational ETS lung cancer risk, part of its proposed indoor air quality rule.tl The report also includes two appendices. Appendix A presents a brief overview of the evidence linking passive smoking with heart disease and childhood respiratory illnesses. Appendix B lists the principal ETS studies reviewed for this report. 11 U.S. Dept. of Labor, Occupational Safety and Health Administration. Indoor Air Quality. Notice of proposed rulemaking; notice of informal public hearing. Federal Register, v. 59, no. 65, April 5, 1994. p. 15968. I I ~ I I I I I i I I I I I I I I

a I I I I I I I I I I I I I I I I CRS-9 ENVIRONMENTAL TOBACCO SMOKE This section of the report briefly describes the chemical and physical characteristics of mainstream and sidestream smoke (the two major components of ETS) and discusses studies which have measured indoor ETS levels, and estimated ETS exposure and uptake among nonsmokers. Researchers have concluded that ETS contains most, if not all, of the carcinogenic and toxic compounds that are present in mainstream smoke. The studies also indicate that*there is widespread exposure to ETS, and some measurable uptake of ETS by nonsmokers. MAINSTREAM AND SIDESTREAM SMOKE12 Environmental tobacco smoke is a combination of mainstream smoke (MS) exhaled by smokers and sidestream smoke (SS) released directly from the burning tip of cigarettes. It is typically highly diluted. Mainstream smoke is comprised of small particles averaging 0.35-0.4 µm in diameterlg (particle phase) and a mixture of gases (vapor phase). The particle phase includes several metals (e.g., cadmium and zinc) and a variety of non-volatile organic compounds of high molecular weight. The vapor phase includes numerous highly volatile compounds such as carbon monoxide and hydrogen cyanide. Nicotine and many other semi-volatile constituents of tobacco smoke occur both in the particle phase and the vapor phase depending on their volatility and the prevailing conditions. These compounds tend to be present in the particle phase of highly concentrated inhaled MS, but evaporate into the vapor phase as exhaled MS rapidly dilutes during the formation of ETS. Sidestream smoke is the primary contributor to ETS, providing most of the vapor phase and over half of the particles. It is produced by the same fundamental processes as MS and consists of the same chemical compounds including many known or suspected human carcinogens. However, SS is generated at lower temperatures and at a higher pH than MS, and as a result it has a different relative chemical composition. Table 1 lists the concentrations of various compounds in both phases of MS delivered by unfiltered cigarettes, as measured by a standard smoking machine. The table also compares the amount of each compound delivered in MS and in SS by computing a SS/MS ratio.!'' These ratios indicate that, with the 12 For a more comprehensive discussion of the physical and chemical characteristics of mainstream and sidestream smoke, see M.R Guerin et aL The Chanistry of Enoironmental Tobacco Smoke: Composition and Measurement, 1992, Lewis Publishers, Inc., Chelsea, Michigan. lg One micron ( m) = 1/1000 millimeter (mm). 14 There is no standard method for collecting and analyzing SS, unlike MS. Researchers have used a variety of small chambers in which to confine the burning cigarette and collect the SS. These devices produce a somewhat artificial smoking environment compared to that associated with human smoking, and, of course, do not take into account the dilution that occurs during the I

CRS-10 exception of hydrogen cyanide and organic acids, the majority of compounds are TABLE 1. Comparison of Mainstream and Sidestream Smoke Deliveries for Selected Compounds Mainstream per Constituent Cigarette• SS/MS Ratio Mainstream vapor phase Carbon monoxide 10-23 mg 2.5-4.7 Carbon dioxide 20-40 mg 8-11 Benzeneb 12-48 g 5-10 Acetone 100-250 g 2-5 Hydrogen cyanide 400-500 g 0.1-0.25 Ammonia 50-130 g 40-170 Pyridine 16-40 g 6.5-20 Nitrogen oxides 100-600 g 4-10 N-Nitrosodimethylamine` 10-40 ng 20-100 Mainstream particle phase Nicotine 1-2.5 mg 2.6-3.3 Phenol 60-140 g 1.6-3.0 2-Naphthylamine6 1.7 ng 30 4-Aminobiphenylb 4.6 ng 31 Cadmiumc 100 ng 7.2 Nickelb 20-80 ng 13-30 Lactic acid 63-174 g 0.5-0.7 Succinic acid 110-140 g 0.43-0.62 ` The units are in milligrams (1 mg = 1/1000 g), micrograms (1 g= 1I1000 mg), and nanograms (1 ng = 1/1000 g). b Known human carcinogen, according to EPA or IARC. 0 Probable human carcinogen, according to EPA or IARC. Source: National Research Council, 1986. Table 2-2. released in greater quantities in SS than in MS. In its analysis of MS and SS emissions data, EPA found that all of the five known human carcinogens, nine probable human carcinogens, and three animal carcinogens are emitted at higher levels in SS than in MS, often by a factor of ten or more. formation of ETS. I I I I I I I I I I I I I I I I I

I I I I I I I I I I I I I I I I I CRS-11 ETS COMPOSITION AND MF.ASUREMENT`b There is limited information on the chemical composition of ETS. Exhaled MS, which can contribute between 15 percent and 43 percent of the particulate matter in ETS, has yet to be characterized. There is also little data on the impact of dilution on SS emissions. During ETS formation, both SS and exhaled MS are diluted by many orders of magnitude and subsequently undergo physical transformation and alterations in chemical composition. Numerous studies of the impact of smoking occupancy on indoor air quality have measured several ETS-related compounds of human health concern, including known and suspected carcinogens, in a variety of settings (e.g., residential, office, transportation, etc.). Researchers have concluded (1) that many of the potentially harmful compounds in SS are also present in ETS, and (2) that these ETS contaminants are found above background levels in a wide range of indoor environments in which smoking occurs. These studies indicate that the composition of ETS can be highly variable depending on the smoking rates, the amount and type of ventilation, contact with indoor surfaces, and a host of other environmental conditions. Given that ETS is a complex mixture of thousands of compounds, many of whir'.i change chemically and physically over time, it is necessary to identify a chemical marker to represent the frequency, duration, and magnitude of ETS exposure. An ideal marker would be a compound that is specific to tobacco smoke, easy to measure, and that behaves similarly to ETS as a whole. Several markers have been identified, though none meets all these criteria. However, vapor phase nicotine and respirable suspended particles (RSP) is are both suitable indicators of exposure to ETS. A variety of methods have been used to measure indoor nicotine and RSP levels in order to assess ETS exposure. Air sampling devices may be placed a specific indoor locations for varying periods of time (stationary sampling) or worn by individuals (personal monitoring). Researchers have also measured chemicals (biomarkers) in the blood and urine of ETS-exposed nonsmokers. Tobacco combustion produces significant emissions of respirable suspended particles (RSP). There are a number of accepted methods that permit accurate measurement of RSP concentrations in indoor environments for sampling times ranging from seconds to several days. Studies have shown that RSP levels in smoking environments are usually higher than in non-smoking environments. Leaderer and Hammond conducted a large chamber study using smokers and 16 For more information on the chemistry of ETS and on chemical markers for ETS, see EPA Report, chapter 3; and Guerin et al., 1992. le Respu.able suspended particles (RSP) refers to particles that are small enough to reach the deepest recesses of the lungs during inhalation. There is some disagreement among researchers as to the upper size limit for RSP. Some investigators use a conservative value of 3 m, others use values of 10 or 15 m. However, if one is using RSP as a marker for ETS, choosing among these values is largely irrelevant, because most ETS particles are less than 1 m. I

CRS-12 reported an average RSP emission rate per cigarette of 17.1 mg." RSP emission rates among different brands of cigarettes were similar. Respirable suspended particles are also generated by other types of combustion. At low smoking and high ventilation rates, it might be difficult to distinguish ETS-associated RSP from a background of RSP from other indoor sources (e.g., kerosene heaters) or even outdoor sources. However, studies by Repace indicate that the fraction of indoor RSP attributable to smoking is typically 80 to 90 percent of the total RSP.'a Vapor phase nicotine is the most common ETS marker. Nicotine is unique to tobacco and can be reliably measured using a variety of methods. Average indoor air concentrations typically range from 1-to -10 micrograms per cubic meter (Ag/ms). Several studies have shown that weekly nicotine concentrations are highly correlated with the number of cigarettes smoked. One of these studies also reported a strong correlation between weekly nicotine concentrations and RSP levels in smoking households.19 The RSP-to-nicotine ratio in this study was approximately 10:1, which is similar to the ratio seen in chamber studies and other field studies, including a recent California State report.20 Nico:i ze is not an ideal ETS marker because it is readily adsorbed onto surfaces, thus reducing its concentration relative to other E T S components as ETS ages. Some studies have demonstrated that vapor phase nicotine is depleted from a smoking environment more rapidly than the particulate portion of ETS. This could lead to an underestimation of ETS exposures. Nicotine also evaporates from surfaces onto which it has been adsorbed, which results in measurable concentrations even in the absence of active smoking. The affinity of nicotine for surfaces may limit its use as an ETS marker in environments where ETS concentrations are very low. However, under normally encountered smoking rates, the uncertainties associated with nicotine's high adsorption rate are likely to be small. ETS INDOOR AIR CONCENTR.ATIONS AND EXPOSURE Numerous studies have measured concentrations of nicotine and RSP in a variety of indoor environments. These studies employed a range of sampling devices, sampled over varying timeframes (from minutes to days), and included highly variable information on various factors affecting the measured 17 Leaderer, B.P. and S.K Hammond. Environ. Sci. Technol., Vol. 25, 1991, p. 770-777. 18 See, for example: Repace, J.L. Tobacco Smoke Pollution. In Nicotine Addiction, Principles and Management. Orleans, T. and A.H. Lowrey, eds. Oxford University Press, New York, 1993. 19 Leaderer, B.P. and S.K Hammond, 1991. 20 The California Air Resources Board report, Toxic Volatile Organic Compounds in ETS: Emissions Factors for Modeling Exposures of Californain Populations, was prepared by the Lawrence Berkeley Laboratory and concluded that nicotine and ETS-RSP behave similarly. I I I I I I I I I I I I I I t+3 ~ cs 4A an ~ 0 ~ ~ I I

I I I I I ~ I I I I I I I i I I I CRS-13 concentrations, such as number of cigaretts smoked and ventilation rates. EPA summarized much of this information in its report, to which the reader is referred for more detailed information.21 Stationary Air Samplers Most of the studies used stationary air samplers. Although the results were highly variable, nicotine and RSP concentrations in smoking environments were consistently higher than in non-smoking environments. Table 2 shows the range of average values obtained in these studies. The minimum and maximum values are also presented in parentheses. Only studies reporting sampling times over four hours were included in the data on residential and office settings so as to more closely approximate occupancy time. Since --occupancy time in restaurants is likely to be shorter than four hours, data from studies using shorter sampling times were included in the table. TABLE 2. Indoor Nicotine and RSP Concentrations with Smoking Occupancy: Range of Average Values Reported (Min - Max Values) Location Nicotine ( g/ms) RgP ( g/m3)a Residential 2-11 18-95 ( < 1-14) (5-560) Office 1-13 <5-62 (< 1-35) (<5-90) Restaurant 6-18 35-986 (< 1-70) (10-1370) ` RSP levels associated with smoking occupany were calculated by subtracting background RSP levels associated with non-smoking occupancy. Source: Figures 3-7 and 3-8, EPA, 1992. The summary nicotine data in the table indicate that average concentrations in residences with smoking occupancy range from 2pg/ms to 11 Ng/mg, with high values up to 14 µg/m3 and low values down below 1Wjmg. Offices with smoking occupancy have average nicotine concentrations that are similar to those in residences, but with significantly higher maximum values. The data from restaurants show even higher maximum values. With regard to RSP concentrations, there is also broad overlap in the average values obtained from residential and office environments. However, the data from restaurants show a much wider range of values. In a recently published study, Hammond and coworkers measured average weekly nicotine concentrations at 25 diverse worksites including fire stations, newspaper publishers, textile dyeing plants, and a variety of manufacturing 21 EPA Report, chapter 3. I

CRS-14 companies.' Between 15 and 25 samplers were placed in each worksite. Worksite smoking policy had a significant effect on the nicotine concentration. The median' nicotine level in open-plan offices that allowed smoking was 8.6 µg/mg, but only 1.3 ug/m9 in worksites that restricted smoking to designated areas. In worksites that banned smoking, the median nicotine level was 0.3 Azg/mg. Guerin and Jenkins measured the concentrations of ETS constituents, including nicotine and RSP, in "typically encountered" residential and occupational indoor settings and found that low-level concentrations were much more common than higher-level concentrations.u These results reflect the fact that the researchers included a significant number of non-smoking and smoking- restricted sites. Very high concentrations were generally found in enclosed areas designated for smoking, and in poorly ventilated areas where smoking intensity was high. Personal Monitors Measurement of indoor air concentrations of ETS components indicates the potential for exposure, but actual exposure also depends on the amount of time spent in a particular environment. The amount of exposure will depend on the individual's circumstances. A woman who lives with a nonsmoker but works in an oiiice with smokers will receive most of her ETS exposure at work, whereas someone who lives and works with smokers may receive the majority of her exposure in the home where more time is spent. Personal monitoring allows researchers to estimate individual exposure. Study participants wear a monitor that continuously samples and records the concentration of air contaminants to which individuals are exposed in the course of their daily activities. If subjects use different monitors in different indoor environments (e.g. home vs. workplace) and record the amount of time spent in each setting, then researchers can calculate the contribution of each environment to total exposure. To date, few studies have measured ETS exposure to nicotine and RSP using personal monitors. Limited published data on nicotine show a wide range of ETS exposures in indoor environments with smoking occupancy, with average concentrations ranging from less than 5 Fcg/mg up to 40 ug/ms. Other personal I I I I I I I I I I I I I I 22 Hammond, S.K et al. J. American Medical Association, v. 274, no. 12, 1995. p. 956-960. 23 The median value is the mid-point of a range of measurements. Half of the values are less than the median, half are greater than the median. 24 For more information, see Guerin et al., 1992; Guerin, M.R. and R.A. Jenkins. Recent Advances in Tobacco Science, Vol. 18, 1992, p.95-114; and Guerin, M.R. Environmental Tobacco Smoke Exposure Assessment. Paper presented at Japan Indoor Air Research Society, April 1993. Sponsored by U.S. Dept. of Energy. NTIS/DE93015521. I I tia Co I

I I I I I I I I I I I I I 1 I I I CRS-15 monitor studies found that ETS exposure increased RSP levels between 18 µg/m3 and 64 mg/m3.26 It is difficult to assess the ETS contribution to nicotine and RSP levels for each indoor environment using these data. In many cases, study participants wore the same monitor for 24 hours, and the reported nicotine and RSP levels represent 24-hour average values. These values may underestimate the contribution of some non-residential indoor environments as they include home sleeping hours when presumably there was little if any ETS exposure. Unpublished data from a recent multi-city study using personal monitors suggest that typical exposures are low relative to estimates obtained using stationary air samplers. This- large study, conducted jointly by Oak Ridge National Laboratory and R.J. Reynolds Tobacco Company, recruited approximately 100 nonsmokers in each of 16 cities nationwide. Study participants were provided with two monitors - one to wear at work and the other for the remainder of the 24-hour period - and required to keep a detailed written record of their activities. In addition to nicotine and RSP, the monitors measured five other ETS constituents. The average nicotine concentration in 415 smoker-occupied homes was 2.16 gg/m3, with a median level of 0.68 Mg/m9, indicating that most participants received relatively little ETS exposure. The average and median nicotine levels in workplaces without smoking restrictions were 2.77 wJms and 0.58 µg/m3, respectively. Researchers calculated total daily exposure to nicotine in each indoor environment by multiplying the average nicotine concentration by duration of exposure and breathing rate. Total daily nicotine exposure in smoker-occupied homes was 6.8 µg per day (µg/day), compared to a value of 5.8 µg/day for workplaces without smoking restrictions. The study's authors suggested two explanations for the fact that average nicotine concentrations recorded in this study lie at the bottom end of the ranges reported in earlier studies. First, fewer smokers are lighting up in the presence of nonsmokers, a response to changing societal attitudes toward smoking. Second, nonsmokers are spending less time in obviously smoky environments. Nonsmokers who come in contact with smokers may receive relatively little exposure depending on their proximity to the smoker and the length of time spent in that indoor envirohment. Noting the tobacco industry's involvement in the study, critics claim that it underrepresented the amount of ETS exposure among nonsmokers. The study sampled a disproportionately low number of smoker-occupied workplaces. Out of 1,356 workplaces sampled, only 168 (12.4 percent) allowed smoking without restriction. National estimates of workplace smoking prevalence suggest that a significantly higher percentage of workplaces allow smoking (see later section on occupational ETS exposure). However, it is not possible to determine whether the recruitment procedures used in the study led to the u' EPA Report, tables 3-5 and 3-6. I

CxS-1s selection of participants whose ETS exposure in smoker-occupied indoor environments was significantly below average exposure levels for nonsmokers nationwide. Biomarkers The presence of a biomarker in the blood or urine provides direct evidence of ETS exposure and uptake. The relationship between the biomarker and exposure is complex due to many environmental and physiological factors. The most commonly used and widely accepted ETS biomarker is cotinine, the major metabolite of nicotine inside the body. Nicotine has a half-life of about 2 hours in the blood and is metabolized to cotinine and excreted in the urine. Cotinine has a half-life of approximately 20 hours in smokers, somewhat longer in ETS- exposed nonsmokers, which makes it a good indicator of ETS exposure and uptake over the previous two days. Studies show that blood and urine cotinine levels in ETS-exposed nonsmokers are generally higher that those in nonsmokers reporting no ETS exposure, but far lower than the levels of cotinine in smokers. Comparisons of cotinine levels in smokers and nonsmokers indicate that ETS-exposed nonsmokers receive approximately 0.7 percent of the nicotine dose of an average smoker.' Cotinine levels in nonsmokers have also been found to increase with self-reported ETS exposure. There is considerable variation in cotinine levels among smokers and ETS-exposed nonsmokers because of individual differences in the uptake, metabolism, and elimination of nicotine. ETS CANCER RISK The EPA classified ETS as a carcinogen based on the chemical similarities between inhaled MS and ETS, and evidence of ETS exposure and uptake by nonsmokers. Studies indicate that tobacco smoke is a lung carcinogen even at the smallest exposures to active smoking, and the risk increases with exposure, as measured either by number of cigarettes smoked per day, or years of cigarette smoking. According to the EPA, exposure to ETS, which is qualitatively similar to MS, therefore, should also increase the risk of lung cancer, and the evidence of widespread exposure to, and uptake of, ETS components in the general population is sufficient to conclude that ETS is a lung-cancer hazard.27 A few researchers have challenged the classification of ETS as a known human carcinogen based on its relationship to MS. They point to the fact that MS contains chemicals at concentrations of up to one million times those found in ETS, and that more of the chemicals are in the particle (tar) phase of MS. Differences between passive smoking (normal inhalation) and active smoking 26 Jarvis, M.J. Mutation Research, Vol. 222, 1989. p. 101-110. ' 27 See, for example, testimony presented by Dr. Douglas Dockery, Harvard School of Public Health, on July 21, 1993, before the House Committee on Agriculture, Subcommittee on Specialty Crops and Natural Resources. I t I I I I I I I I I I I I I t I