Action on Smoking and Health A National Legal-Action Antismoking Organization Entirely Supported by Tax-Deductible Contributions    Search  | Info About  | ash.org| To Join |  Email Page

10th Report on Carcinogens
Environmental Health Perspectives (NIEHS), 2002-12-11
U.S. Department of Health and Human Services Public Health Service

Tobacco Related Exposures

Introduction

Tobacco Smoking, Smokeless Tobacco and Environmental Tobacco Smoke were all listed in the Ninth Edition of the Report on Carcinogens (RoC) in 2000. The profiles for tobacco smoking, smokeless tobacco, and environmental tobacco smoke follow this introduction. The listings for tobacco smoking, smokeless tobacco, and environmental tobacco smoke in the Tenth Edition of the RoC are as follows:

Tobacco smoking is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans which indicate a causal relationship between tobacco smoking and human cancer (IARC 1986).

The oral use of smokeless tobacco is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans which indicate a causal relationship between exposure to smokeless tobacco and human cancer (IARC 1985, 1987, Gross et al. 1995).

Environmental tobacco smoke (ETS) is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans that indicate a causal relationship between passive exposure to tobacco smoke and human lung cancer (IARC 1986, EPA 1992, CEPA 1997). Studies also support an association of ETS with cancers of the nasal sinus (CEPA 1997).

KNOWN TO BE A HUMAN CARCINOGEN TENTH REPORT ON CARCINOGENS
ENVIRONMENTAL TOBACCO SMOKE*
* No separate CAS registry number is assigned to environmental tobacco smoke. First listed in the Ninth Report on Carcinogens

CARCINOGENECITY
Environmental tobacco smoke (ETS) is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans that indicate a causal relationship between passive exposure to tobacco smoke and human lung cancer (IARC 1986, EPA 1992, CEPA 1997). Studies also support an association of ETS with cancers of the nasal sinus (CEPA 1997).
Evidence for an increased cancer risk from ETS stems from studies examining nonsmokingspouses living with individuals who smoke cigarettes, exposures of nonsmokers to ETS in occupational settings, and exposure to parents’ smoking during childhood. Many studies, including recent large population-based case control studies, have demonstrated increased risks
of approximately 20% for developing lung cancer following prolonged exposure to ETS, with some studies suggesting higher risks with higher exposures. Exposure to ETS from spousal smoking or exposure in an occupational setting appears most strongly related to increased risk.

ADDITIONAL INFORMATION RELEVANT TO CARCINOGENESIS OR POSSIBLE MECHANISMS OF CARCINOGENESIS

ETS is a complex mixture of gases and particles comprising smoke from the burning cigarette, cigar, or pipe tip (sidestream smoke), smoke which is drawn through the tobacco column and exists through the mouthpiece during puffing (mainstream smoke), and exhaled smoke.

Sidestream smoke and mainstream smoke contain many of the same chemical constituents, including at least 250 chemicals known to be toxic or carcinogenic. There is evidence from animal studies that the condensate of sidestream smoke is more carcinogenic to the skin of mice than equivalent weight amounts of mainstream smoke. Exposure to primarily mainstream smoke
through active tobacco smoking has been determined to cause cancer of the lung, urinary bladder and renal pelvis, oral cavity, pharynx, larynx, esophagus, lip, and pancreas in humans. Between 80 to 90% of all human lung cancers are attributed to tobacco smoking.

Exposure of nonsmokers to ETS has been demonstrated by detecting nicotine, respirable smoke particulates, tobacco specific nitrosamines, and other smoke constituents in the breathing zone, and by measurements of a nicotine metabolite (cotinine) in the urine. However, there is no good biomarker of cumulative past exposure to tobacco smoke, and all of the information collected in epidemiology studies determining past exposure to ETS relies on estimates which may vary in their accuracy (recall bias). Other suggestions of systematic bias have been made concerning the epidemiological information published on the association of ETS with cancer. These include misclassification of smokers as nonsmokers, factors related to lifestyle, diet, and other exposures that may be common to couples living together and that may influence lung cancer incidence, misdiagnosis of metastatic cancers from other organs in the lung, and the possibility that epidemiology studies examining small populations and showing no effects of ETS would not be published (publication bias).

Three population-based (Stockwell et al. 1992, Brownson et al. 1992, Fontham et al. 1994) and one hospital-based (Kabat et al. 1995) case control studies have addressed potential systematic biases. The three population-based studies each showed an increased risk from prolonged ETS exposure of a magnitude consistent with prior estimates. The hospital-based study gave similarly increased risk estimates, but the results were not statistically significant. The potential for publication bias has been examined and dismissed (CEPA 1997), and the reported absence of increased risk for lung cancer for nonsmokers exposed only in occupational settings has been found not to be the case when the analysis is restricted to higher quality studies (Wells 1998). Thus, factors related to chance, bias, and/or confounding have been adequately excluded, and exposure to ETS is established as causally related to human lung cancer.

PROPERTIES
Environmental tobacco smoke (ETS) is a complex mixture of thousands of chemicals that are emitted from burning tobacco. Tobacco smoking produces both mainstream smoke, which is drawn through the tobacco column and exists through the mouthpiece during puffing, and sidestream smoke, which is emitted from the smoldering tobacco between puffs. Approximately
4,000 chemicals have been identified in mainstream tobacco smoke and some have estimated that the actual number of compounds may be more than 100,000; however, the current identified compounds make up more than 95% of the total mass. ETS is the sum of sidestream smoke, mainstream smoke, compounds that diffuse through the wrapper, and exhaled mainstream
smoke. Sidestream smoke contributes at least half of the smoke generated. The composition of tobacco smoke is affected by many factors including the tobacco product, properties of the, tobacco blend, chemical additives, smoking pattern, pH, type of paper and filter, and ventilation (IARC 1986, NRC 1986, EPA 1992, Vineis and Caporaso 1995, CEPA 1997).
Although many of the same compounds are present in both mainstream and sidestream smoke, important differences exist. The ratios of compounds in sidestream and mainstream smoke are highly variable; however, there is less variability in emissions from sidestream smoke compared to mainstream smoke because smoking patterns and cigarette design have more of an impact on
mainstream smoke (CEPA 1997). Sidestream smoke is generated at lower temperatures than mainstream smoke (600
C versus 900
C), in an oxygen-deficient environment, and is rapidly diluted and cooled after leaving the burning tobacco. Mainstream smoke is generated at higher temperatures in the presence of oxygen and is drawn through the tobacco column. These conditions favor formation of smaller particulates in sidestream smoke (0.01 to 0.1 µm) compared to mainstream smoke (0.1 to 1 µm). Sidestream smoke also typically contains higher concentrations of ammonia (40 to 170 fold), nitrogen oxides (4 to 10 fold), and chemical carcinogens (e.g., benzene, 10 fold; N-nitrosoamines, 6 to 100 fold; and aniline, 30 fold) than
mainsteam smoke (IARC 1986).

Tobacco pyrolysis products are formed both during smoke inhalation and during the interval between inhalations (NRC 1986). A number of chemicals present in ETS are known or suspected toxicants/irritants with various acute health effects. Prominent among them are the respiratory irritants, ammonia, formaldehyde, and sulfur dioxide. Acrolein, hydrogen cyanide, and formaldehyde affect mucociliary function and at higher concentrations can inhibit smoke clearance from lungs (Battista 1976). Nicotine is addictive and has several pharmacological and toxicological actions. Nitrogen oxides and phenol are additional toxicants present in ETS. Over 50 compounds in ETS have been identified as known or reasonably anticipated human
carcinogens, including some naturally occurring radionuclides. Most of these compounds are present in the particulate phase (IARC 1986, CEPA 1997).

USE
ETS is a by-product of smoking and has no industrial or commercial uses. ETS is used in scientific research to study its composition and health effects. See the profile on “Tobacco Smoking” for a brief description of the history and uses of tobacco products.

PRODUCTION
Burning tobacco products generate ETS. Tobacco has been an important economic agricultural crop since the 1600s. The total tobacco harvest in the U.S. ranged from approximately 1.19 to 1.79 billion lb/yr between 1987 and 1997. The tobacco harvest in 1997 was the highest for this reporting period (USDA 1993, 1998). In 2000, the U.S. imported more than 11 billion cigarettes and exported more than 148 billion cigarettes (ITA 2001).

EXPOSURE
Smoking prevalence in the U.S. has declined by approximately 40% since reaching a peak in the mid 1960s. In recent years, public policies have restricted smoking in buildings and other indoor public places. Nevertheless, ETS remains as an important source of exposure to indoor air contaminants. Based on data from the Third National Health and Nutrition Examination Survey
(NHANES III) conducted from 1988 to 1991, approximately 43% of U.S. children aged 2 months to 11 years lived in a home with at least one smoker. In addition, 37% of non-smoking adults reported exposure to ETS at home or at work (Pirkle et al. 1996). It is estimated that more than half of U.S. youth are still exposed to ETS (CDC 2001) and approximately 9 to 12 million
children, aged six and younger, are exposed to ETS in their homes (EPA 2002).

Because ETS is a complex mixture, measuring ETS exposure is difficult. Various monitoring methods typically focus on nicotine levels or respirable suspended particulates in indoor air, or conitine levels (the primary metabolite of nicotine) in blood, saliva, or urine.

Mean nicotine levels in a variety of indoor environments ranged from 0.3 to 30 µg/m 3 . Typical average concentrations in homes with at least one smoker ranged from 2 to 14 µg/m 3 . Nicotine concentrations measured at work from the mid 1970s to 1991 were similar to those measured in homes; however, maximum values were much higher at work (CEPA 1997). Levels of ETS in restaurants were found to be approximately 1.6 to 2.0 times higher than other office workplaces and 1.5 times higher than residences of at least one smoker. Isolating smokers to a specific section of restaurants was found to afford some protection for nonsmokers, but the best protection resulted from seating arrangements that segregated smokers by a wall or partition.

Nonsmokers are still exposed to nicotine and respirable particles. Food-servers, who spend more time in restaurants, are exposed even more to ETS, though they may work in nonsmoking sections (Lambert et al. 1993).

Levels of ETS in bars were found to be approximately 3.9 to 6.1 times higher than in office workplaces and 4.4 to 4.5 times higher than in residences (Siegel 1993). Nicotine levels as high as 50 to 75 µg/m 3 were measured in bars and on airplanes (before smoking was banned). The highest measured nicotine concentration (1,010 µg/m 3 ) was measured in a car with the
ventilation system shut off (CEPA 1997).

ETS exposure levels have been estimated by measuring respirable suspended particles (RSP) (particles <2.5 µm in diameter) in many studies. The average RSP values reported in these studies generally ranged from 5 to 500 µg/m 3 . RSP values in homes with one or more smokers had concentrations that were 20 to 100 µg/m 3 higher than in comparable homes with no smokers
(CEPA 1997).

The NHANES III survey indicated that approximately 90% of the U.S. population aged 4 years and older had detectable levels of conitine (Pirkle et al. 1996). The median serum conitine level among nonsmokers was 0.20 nanograms per milliliter (ng/mL) in 1991, but decreased by more than 75% to 0.05 ng/mL by 1999 (CDC 2001). An independent, nonfederal Task Force on
Community Preventive Services, in collaboration with the U.S. Department of Health and Human Services and various public and private partners, recommended various strategies for reducing cigarette smoking and exposure to ETS. The baseline levels for cigarette smoking (1997), nonsmokers exposed to ETS (1994), and children exposed to ETS (1994) were 24%, 65%, and 27%, respectively. The objective is to reduce cigarette smoking to 12% and ETS exposure to 45% and 10%, in nonsmoking adults and children, respectively, by 2010 (CDC 2000).

REGULATIONS
EPA regulates environmental tobacco smoke under the Clean Air Act (CAA).
NIOSH reccomends that the exposure to environmental smoke be the lowest feasible
concentration. Regulations are summarized in Volume II, Table 176.

REFERENCES
Battista, S. P. Ciliatoxic components of cigarette smoke. Smoking and Health. I. Measurement In the Analysis and Treatment of Smoking Behavior. NIDA Research Monographs. In: Wynder,

E.L., Hoffmann, D., and Gori, G.B. DHEW Publ. No. (NIH) 76-1221. U.S. Government Printing Office U.S, Department of Health Education and Welfare, Washington, D.C. 48, 517-534. 1976.

Brownson, R.C., M.C. Alavanja, E.T. Hock, and T.S. Loy. Passive smoking and lung cancer in nonsmoking women. Am J Public Health. Vol. 82, 1992, pp. 1525-1530.

CDC. Centers for Disease Control. Strategies for reducing exposure to environmental tobacco smoke, increasing tobacco-use cessation, and reducing initiation in communities and health-care systems. A report on recommendations of the Task Force on Community Preventive Services. MMWR Weekly Report Vol. 49, No. RR-12,
http://cdc.gov/tobacco/researchdata/environmental/MMWR_rr4912_press.htm, 2000.

CDC. Centers for Disease Control. National Report on Human Exposure to Environmental Chemicals. Reduced Exposure of the U.S. Population to Environmental Tobacco Smoke.
http://cdc.gov/nceh/dls/report/highlights.htm#ReducedExposure, 2001.

CEPA. California Environmental Protection Agency. Health Effects of Exposure toEnvironmental Tobacco Smoke. Office of Environmental Health Hazard Assessment. 1997.

EPA. U.S. Environmental Protection Agency. Respiratory Health Effects of Passive Smoking: Lung Cancer and other Disorders. EPA Office of Research and Development, Washington, D.C.

EPA/600/6-90/006F. 1992.

EPA. U.S. Environmental Protection Agency. Indoor Air – Secondhand Smoke. Secondhand Smoke/Smoke-Free Homes. http://www.epa.gov/iaq/ets. Last updated March 21, 2002.

Fontham, E.T., P. Correa, P. Reynolds, A. Wu-Williams, P.A. Buffler, R.S. Greenberg, V.W.
Chen, T. Alterman, P. Boyd, and D.F. Austin. Environmental Tobacco Smoke and Lung Cancer
in Nonsmoking Women. A Multicenter Study [published erratum appears in JAMA 1994 Nov 23- 30;272(20):1578]. JAMA Vol. 271, 1994, pp. 1752-1759.

IARC. International Agency for Research on Cancer. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Tobacco Smoking. Vol. 38. 421 pp. Lyon, France: IARC, 1986.

ITA. International Trade Administration. U.S. Department of Commerce. Subheading 240220: Cigarettes Containing Tobacco. http://www.ita.doc.gov/td/industry/otea/Trade-Detail, 2001.

Kabat, G.C., S.D. Stellman, and E.L. Wynder. Relation between exposure to environmental tobacco smoke and lung cancer in lifetime nonsmokers [published erratum appears in Am J Epidemiol 1996 Mar 1;143(5):527]. Am. J. Epidemiol. Vol. 142, 1995, pp.141-148.

Lambert, W.E., J.M. Samet, and J.D. Spengler. Environmental Tobacco Smoke Concentrations in No-smoking and Smoking Sections of Restaurants. Am. J. Public Health. Vol. 83, 1993, pp. 1339-1341.

NRC. National Research Council. Environmental Tobacco Smoke. Measuring Exposures and assessing health effects. Board on Environmental Studies and Toxicology, Committee on Passive Smoking. Washington, D.C. National Academy Press. 1986.

Pirkle, J.L., K.M. Flegal, J.T. Bernert, D.J. Brody, R.A. Etzel, and K.R. Maurer. Exposure of the US population to environmental tobacco smoke: the Third National health and Nutrition
Examination Survey, 1988 to 1991. JAMA. Vol. 275, 1996, pp. 1233-1240.

Siegel, M. Involuntary smoking in the restaurant workplace. A review of employee exposure and
health effects. JAMA. Vol. 270, 1993, pp. 490-493.

Stockwell, H.G., A.L. Goldman, G.H. Lyman, C.I. Noss, A.W. Armstrong, P.A. Pinkham, E.C. Candelora, and M.R. Brusa. Environmental tobacco smoke and lung cancer risk in nonsmoking women. J. Natl. Cancer Inst. Vol. 84, 1992, pp. 1417-1422.

USDA. U.S. Department of Agriculture. Field Crops. Final Estimates 1987–1992. National Agricultural Statistics Service, Statistical Bulletin No. 896. http://usda.mannlib.cornell.edu/data-sets/crops/94896/sb896.txt, 1993.

USDA. U.S. Department of Agriculture. Field Crops. Final Estimates 1992–1997. National Agricultural Statistics Service, Statistical Bulletin No. 947. (Field Crops). http://www.usda.gov/nass/pubs/histdata.htm, December 1998.

Vineis, P., and N. Caporaso. Tobacco and Cancer: Epidemiology and the Laboratory. Environ. Health Perspect. Vol. 103, 1995, pp.156-160.

Wells, A.J. Lung Cancer From Passive Smoking at Work. Am. J. Public Health. Vol. 88, 1998,
pp. 1025-1029.