Reports that Matter

United States v. Philip Morris USA Inc.: Amended Final Opinion

The Consensus of the Public Health Community Is that ETS Causes

Section 78 of 129

The Consensus of the Public Health Community Is that ETS Causes

Disease in Nonsmokers 3306. Secondhand smoke, also called passive smoke or environmental tobacco smoke

("ETS"), is a mixture of mostly sidestream smoke given off by the smoldering cigarette and some mainstream smoke exhaled by smokers. Samet WD, 171:2-14; 186:10-13.

  1. Evidence of the health risks of passive smoking is derived from many sources. It comes from knowledge of the health risks of active smoking, the carcinogenicity and toxicity of the components in mainstream and sidestream smoke, the evidence that nonsmokers absorb the disease-causing components of tobacco smoke, and epidemiological studies that have assessed the association of passive exposure to tobacco smoke with disease outcomes. Samet WD, 185:21- 186:23; see also TLT0240387-0537 at 0470-0480, 0485-0517 (US 60597) (1972 SGR); 03763710- 3956 3804-3833 (US 34340) (1975 SGR); VXA1604926-6020 at 5418-5457 (US 64071) (1979 SGR); TLT0242222-2551 at 2468-2484 (US 60598) (1982 SGR); VXA1601456-1742 at 1649-1675 (US 64059) (1984 SGR); VXA2110670-1053 at 0806-0865 (US 63709) (1986 SGR); VXA2111054- 1229 at 1072-1092 (US 63708) (1986 NRC Report); VXA1600406-0824 at 0483-0598 (US 64066)
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(1986 IARC); DXA0390094-0699 at 0142-0194 (US 88654) (1992 EPA Risk Assessment); JDM1870820-1333 at 0864-0867 (US 76125) (1997 California EPA Report); 2065192422-2615 at 2438-2448 (US 22092) (1997 Australia Report); VXA1600843-0981 at 0872-0879 (US 64063) (1998 UK SCOTH Report); VXA1600982-1000 (US 64062) (1999 WHO); VXA1240568-1258 at 0928-0957 (US 64315) (2001 SGR); TLT0970001-1455 at 1191-1230 (US 86746) (2002 IARC).

  1. Conclusions about the causal relationship between secondhand smoke exposure and adverse health effects are based on the extensive evidence derived from both epidemiological and toxicological investigation of active smoking. Additionally, studies using biomarkers of exposure and dose, such as the nicotine-specific metabolite cotinine, document the absorption of known disease-causing components of secondhand smoke by exposed nonsmokers, confirming the observed associations of secondhand smoke with adverse health effects. Samet WD, 172:17-173:18; VXA2110670-1053 at 0866-0914 (US 63709) (1986 SGR); VXA2111054-1229 at 1127-1140 (US 63708) (1986 NRC Report); VXA1600406-0824 at 0563-0570 (US 64066) (1986 IARC); DXA0390094-0699 at 0181-0189 (US 88654) (1992 EPA Risk Assessment); JDM1870820-1333 at 0875-0884 (US 76125) (1997 California EPA); 2065192422-2615 at 2444-2446 (US 22092) (1997 Australia Report); TLT0970001-1455 at 1207 (US 86746) (2002 IARC).

  2. In his 1964 Report, the Surgeon General set forth the five criteria which, according to the consensus of the scientific community, describe a causal relationship:

a. Consistency of the Association. Nearly all the retrospective and prospective studies produced comparable results, despite the fact that different methods were employed for collecting data. b. Strength of the Association: the ratio of lung cancer rates for smokers versus non-smokers. The Committee assessed the

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significance of the dose effect phenomenon, finding that risk increased with amount smoked. According to the Report:

[A]verage smokers of cigarettes have a 9- to 10-fold risk of developing lung cancer, and heavy smokers, at least a 20-fold risk. Thus it would appear that the strength of the association between cigarette smoking and lung cancer must be judged to be high.

c. Specificity of Association. This criteria, according to the Report:

implies the precision with which one component of an associated pair can be utilized to predict the occurrence of the other, i.e., how frequently the presence of one variable (e.g., lung cancer) will predict, in the same individual, the presence of another (e.g., cigarette smoking). In a discussion of the specificity of the relationship between any factor possibly causal in character and a disease it may produce, it must be recognized that rarely, if ever, in our biologic universe, does the presence of an agent invariably predict the occurrence of a disease. Second, but not less important, is our growing recognition that a given disease may have multiple cause.

d. Temporal Relationship of Associated Variables:

Exposure to an agent presumed to be causal must precede, temporally, the onset of a disease which it is purported to produce. . . .

e. Coherence of the Association:

A final criterion for the appraisal of causal significance of an association is its coherence with known facts in the natural history and biology of the disease.

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VSA1601844-2232, at 2033-36 (US 64057) (1964 Surgeon General Report); Brandt WD, 105:6- 111:7. No one criteria is determinative or dispositive. Public health authorities view the totality of all data under consideration. Id.

  1. Individual studies of the relationship between exposure and disease result in a determination of a relative risk, i.e., the increase or decrease in exposed people. For example, if a study of ETS exposure found a 1.44 relative risk, that would mean that individuals exposed to ETS in the study had a 44% increased risk of disease than those not exposed. Scientists determine a "confidence interval" around the relative risk figure which describes the range of the risk which they believe the study has demonstrated. Scientists commonly use a 95% confidence interval, i.e., the range of risk that they believe, with 95% certainty, the study demonstrates. Hypothetically, scientists might determine the 95% confidence interval in the example cited to range between 1.36 and 1.50. While there is no specific criteria for statistical significance (i.e., the likelihood the results of the study are not simply the product of change, but actually demonstrate a real relationship), Dr. Samet noted that often, if the lower end of the confidence interval is below one, then the results of the study may not be statistically significant. The experts in this case did not, however, state a bright-line test for statistical significance. Moreover, even if the results of a study are not statistically significant, the inquiry does not end there. Again, to determine a causal association, all of the five criteria above, together with the entire collection of data about the relationship, must be considered. See Samet TT, 9/29/04, 1077:6-22. In short, there is no one "magic evidentiary bullet" that has produced the consensus in the public health community that ETS causes diseases in non-smokers. Rather, over time, many different types of studies have, block by block, built that scientific consensus.
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a. The Development of the Consensus 3311. Several years after the 1964 Surgeon General's Report concluded that active smoking

caused lung cancer and other diseases in smokers, the issue of the harms of exposure to secondhand smoke began to receive public attention.

  1. In January 1971, Surgeon General Jesse Steinfeld spoke before the National Interagency Council on Smoking and Health, where he advocated adoption of indoor smoking regulations to protect nonsmokers. Steinfeld stated that: "Finally, evidence is accumulating that the nonsmoker may have untoward effects from the pollution his smoking neighbor is forcing upon him," and that "it is high time to ban smoking from all confined places such as restaurants, theaters, airplanes, trains, and buses." Dr. Steinfeld's speech generated press coverage across the country. TIMN0121541-1558 (US 65632). As a result, in 1971, the Interstate Commerce Commission mandated separate smoking sections in the rear of all interstate buses. VXA2110670-1053 at 0973 (US 63709); see 37 F.R. 5700 (Mar. 18, 1972) (ICC order issued on November 8, 1971 and effective April 17, 1972).

  2. In February 1972, Surgeon General Steinfeld issued a new report to Congress that collected and reviewed the mounting body of scientific evidence concerning the risks of passive smoking. The Surgeon General described studies showing that "'tar' and nicotine levels in sidestream smoke may be significantly higher than mainstream smoke and may be harmful to the nonsmoker." TLT0240387-0537 at 0505 (US 60597) (1972 SGR); Samet TT, 09/29/04, 1044:25- 1045:13.

  3. In his 1972 Report, the Surgeon General also summarized the scientific evidence on the adverse effect of ETS on nonsmoker allergies:

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Tobacco smoke can contribute to the discomfort of many individuals. It exerts complex pharmacologic, irritative, and allergic effects, the clinical manifestations of which may be indistinguishable from one another. . . . Exposure to tobacco smoke may produce exacerbation of allergic symptoms in nonsmokers who are suffering from allergies of diverse causes.

TLT0240387-0537 at 0495 (US 60597).

  1. Chapter 8 of the 1972 Report, titled "Public Exposure to Air Pollution from Tobacco

Smoke," catalogued the existing scientific findings concerning carbon monoxide and other constituents of tobacco smoke that can exacerbate existing heart disease and other conditions:

The level of carbon monoxide attained in experiments using rooms filled with tobacco smoke has been shown to equal, and at times exceed, the legal limits for maximum air pollution permitted for ambient air quality in several localities and can also exceed the occupational Threshold Limit Values for a normal work period presently in effect in the United States as a whole. The presence of such levels indicates that the effect of exposure to carbon monoxide may on occasion, depending upon the length of exposure, be sufficient to be harmful to the health of an exposed person. This would be particularly significant for people who are already suffering from chronic bronchopulmonary disease and coronary heart disease. . . .

Other components of tobacco smoke, such as particulate matter and the oxides of nitrogen, have been shown in various concentrations to adversely affect animal pulmonary and cardiac structure and function. The extent of the contributions of these substances to illnesses in humans exposed to the concentrations present in an atmosphere contaminated with tobacco smoke is not presently known.

TLT0240387-0537 at 0513 (US 60597).

  1. In 1973, the Federal Aviation Authority adopted new federal regulations making nonsmoking sections in airplanes mandatory. VXA2110670-1053 at 0973 (US 63709). See 38 Fed.

Reg. 12207 at 12211.

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  1. Several of the earlier studies from the 1960s had focused on measuring allergic and toxic substances in sidestream smoke -- notably particulates in the form of soot and ash, but also carbon monoxide, nitrogen oxides, and other noxious/poisonous gases. A 1967 study by Czech researcher Milan Srch, for example, examined the impact of riding in a closed car with smokers and found that levels of carbon monoxide in the blood of the nonsmokers increased by 250%. TLT0240387-0537 at 0507 (US 60597) (1972 SGR).

  2. A different methodology was used in a 1973 experiment by the U.S. Department of Transportation, which measured ambient carbon monoxide in a bus where twenty-three cigarettes were smoked, compared to a situation where three cigarettes were smoked. At the driver's seat, carbon monoxide levels rose to 33 parts per million (ppm) when twenty-three cigarettes were smoked, compared to 18 ppm when three cigarettes were smoked. 03763710-3956 at 3812 (Table 2, ref. 44) (US 34340) (1975 SGR). Both situations exceeded the Surgeon General's "maximum acceptable ambient level of 9 ppm." 03763710-3956 at 3748-3749 (ref. 4) (US 34340) (1975 SGR).

  3. More generally, scientific studies documenting the health hazards of secondhand smoke increased in both quality and quantity in the 1970s. In 1970 and 1971, German researcher Hans-Peter Harke studied nonsmokers in smoky environments where there was ventilation and found a 50% increase in carbon monoxide in the blood. 03763710-3956 at 3816 (ref. 23) (US 34340).

  4. Other studies further analyzed the chemical composition of secondhand smoke. Ulrich Hoegg, in 1972, conducted one of a number of studies at this time exploring the concentration of carbon monoxide in closed, smoke-filled environments. He found that the sidestream smoke contained a concentration of carbon monoxide nearly five times as great as that derived from mainstream smoke. 03763710-3956 at 3809-3810 (ref. 32) (US 34340).

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  1. The 1975 Surgeon General's Report conducted another review of the increasing scientific evidence demonstrating that secondhand smoke causes adverse health effects, particularly in children. In Chapter 4, the Surgeon General reviewed the causation of disease in newborns: "Children of parents who smoke are more likely to have bronchitis and pneumonia during the first year of life, and this is probably at least partly due to their being exposed to cigarette smoke in the atmosphere." 03763710-3956 at 3829 (US 34340).

  2. Carbon monoxide in secondhand smoke continued to pose a health risk. When discussing research on carbon monoxide levels, the Surgeon General also stated in his 1975 Report: "[E]ven in cases where the ventilation was adequate, the measured CO levels did exceed the maximum acceptable ambient level of 9 ppm". 03763710-3956 at 3811 (US 34340) (1975 SGR). The 1975 Report also warned of effects on patients with heart disease: "Levels of carbon monoxide commonly found in cigarette smoke-filled environments have been shown to decrease the exercise tolerance of patients with angina pectoris." 03763710-3956 at 3829 (US 34340).

  3. In the late 1970s and continuing thereafter, more studies focused on hazardous components in secondhand smoke, as well as links to lung cancer, heart disease, and health effects on children. There was increasing attention given to nitrosamines, a family of carcinogens already coming under scrutiny for their presence in smoked and nitrate-cured meats. Studies by Klaus Brunneman and his colleagues in the late 1970s, for example, showed the presence of n-nitrosamines (which derive from nicotine), carbon monoxide, and other substances in sidestream smoke in even far greater concentrations than in mainstream smoke. The concentrations of these substances are five to ten times higher in sidestream smoke. VXA1604926-6020 at 5422, 5633 (US 64071) (1979

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SGR). In addition, scientists had reached the important conclusion that n-nitrosamines (NNN, NNK, etc.) were carcinogenic. VXA1604926-6020 at 5631-5633, 5648-5649 (US 64071) (1979 SGR).

  1. Based on these studies and others, the Surgeon General stated in his 1979 Report: "Many of the substances, including nicotine, carbon monoxide, and ammonia, are found in much higher concentrations in sidestream smoke than in mainstream smoke. Thus, the total smoke exposure of nonsmokers is quantitatively smaller than the exposure of smokers, but the smoke nonsmokers inhale may be qualitatively richer in certain compounds than mainstream smoke. This qualitative difference in smoking exposure makes the quantification of the involuntary smoking exposure in terms of 'cigarette equivalents' confusing and inaccurate." VXA1604926-6020 at 5422- 5431 (US 64071).

  2. The 1979 Report, as the 1972 and 1975 Reports before it, addressed possible health effects of passive smoking. After reviewing the scientific evidence and earlier warnings about the adverse effects of secondhand smoke, and emphasizing the effects of carbon monoxide on nonsmokers and the effects of tobacco smoke on exposed children, the Surgeon General warned:

Tobacco smoke can be a significant source of atmospheric pollution in enclosed areas. Occasionally, under conditions of heavy smoking and poor ventilation, the maximum limit for an 8-hour work exposure to carbon monoxide (50 ppm) may be exceeded. The upper limit for CO in ambient air (9 ppm) may be exceeded even in cases where ventilation is adequate. . . . Children of parents who smoke are more likely to have bronchitis and pneumonia during the first year of life, and this may be due to their being exposed to cigarette smoke in the atmosphere. Levels of carbon monoxide which can be reached in cigarette smoke-filled environments have been shown to decrease the exercise duration required to induce angina pectoris in patients with coronary

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artery disease . . . [and to] reduce the exercise time until onset of dyspnea in patients with hypoxic chronic lung disease."

VXA1604926-6020 at 5449-5450 (US 64071); see Samet TT, 9/29/04, 1045:15-24.

  1. In 1980, following the lead of earlier researchers, James Repace of the United States Environmental Protection Agency and Alfred Lowrey of the United States Naval Research Laboratory conducted measurements of respirable particulates (hazardous particles less than 4 microns in size in the air) in cocktail lounges, restaurants, and public halls in both the presence and absence of smoking. Repace and Lowery found that short-term measurements in rooms with smokers yielded high respirable particulate concentrations, varying from 100 to 1000 micrograms per cubic meter. VXA2110670-1053 at 0826, 0852 (US 63709) (1986 SGR).

  2. James White and Herman Froeb, Scientists at the University of California Department of Physical Education, published an article in the New England Journal of Medicine that same year finding that nonsmokers working in smoky environments tend to have pulmonary functions similar to light smokers. White and Froeb calculated that in terms of long-term lung (small-airway) dysfunction, nonsmokers working in a smoky environment had about the same risk of impairment as smokers who smoked between one and ten cigarettes per day. VXA2110670-1053 at 0744 (US 63709) (1986 SGR).

  3. In 1981, the results of three major epidemiological investigations were published. First, Takeshi Hirayama, Chief of Epidemiology at Tokyo's National Cancer Centre Research Institute, published a study titled "Non-Smoking Wives of Heavy Smokers Have a Higher Risk of Lung-Cancer: A Study From Japan" in the British Medical Journal. Hirayama's study showed a significant correlation between lung cancer and ETS based on his epidemiological studies of 91,540 nonsmoking Japanese women over nearly fifteen years. Hirayama's evidence demonstrated that wives of heavy smokers had "a higher risk of developing lung cancer" than wives of light smokers and nonsmokers, and that "the effect of passive smoking was most striking in younger couples and in agricultural families (ruling out the complication of urban air pollution), relative risk reaching 460% increase, probably because of the lesser extent of the exposure to passive smoking outside the family in the case of rural residents." 2046342378-2380 (US 22963); Samet WD, 176:15-177:4; US 17172 (summary chart of Hirayama study).

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  1. Second, Dimitrios Trichopoulos, working with colleagues from the University of Athens School of Medicine and the Harvard School of Public Health, published a case-control study of 51 Greek women suffering from lung cancer in the International Journal of Cancer, finding that the non-smoking wives of heavy smokers had elevated lung cancer risks. 504437867-7870 (US 50615); see also Samet WD, 177:5-23; (no bates) (US 17201) (summary chart of Trichopoulos study). Trichopoulos, like Hirayama, found that lung cancer was about twice as common among nonsmoking women whose husbands smoked as among nonsmoking women whose husbands did not smoke. 504437867-7870 (US 50615).

  2. Later in 1981, the results of a third study were also reported in the Journal of the National Cancer Institute by Lawrence Garfinkel, an epidemiologist with the American Cancer Society, in a paper titled "Time trends in lung cancer mortality among nonsmokers and a note on passive smoking." Garfinkel observed risks of lung cancer of 1.27 for women married to men who smoked less than 20 cigarettes per day, and 1.10 for women married to smokers of more than 20 cigarettes per day. However, in contrast to the observed risks found by Hirayama and Trichopoulos, the elevated risks in the Garfinkel study were not statistically significant. TLT0242222-2551 at

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  1. All three major epidemiologic studies published in 1981 showed an increased risk of lung cancer with passive smoke exposure. For the first time, the Surgeon General in his 1982

While the nature of this [lung cancer] association is unresolved, it does raise the concern that involuntary smoking may pose a carcinogenic risk to the nonsmoker. Any health risk resulting from involuntary smoke exposure is a serious public health concern because of the large numbers of nonsmokers in the population who are potentially exposed. Therefore, for the purpose of preventive medicine, prudence dictates that nonsmokers avoid exposure to second-hand tobacco smoke to the extent possible.

TLT0242222-2551 at 2228 (US 60598).

  1. The 1982 Report reviewed the three 1981 epidemiological studies, along with evidence of carcinogens in both mainstream and sidestream smoke, and concluded that:
  1. Mainstream and sidestream cigarette smoke contain similar chemical constituents. . . These constituents include known carcinogens, some of which are present in higher concentrations in sidestream smoke than they are in mainstream smoke. . . .
  1. In two epidemiological studies, an increased risk of lung cancer in nonsmoking wives of smoking husbands was found. In these studies, the nonsmoking wife's risk of lung cancer increased in relation to the extent of the husband's smoking. In a third study, the risk of lung cancer among nonsmoking wives of smoking husbands was also increased, but the difference was not statistically significant.
  1. Although the currently available evidence is not sufficient to conclude that passive or involuntary smoking causes lung cancer in nonsmokers, the evidence does raise a concern about a possible serious public health problem.
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  1. The 1984 Surgeon General's Report continued to review the passive smoking evidence, looking specifically at the evidence of biomarkers showing exposure to and absorption of secondhand smoke components. The Surgeon General concluded, "Cigarette smoke can make a significant, measurable contribution to the level of indoor air pollution at levels of smoking and ventilation that are common in the indoor environment." The Report added that: "Nonsmokers who report exposure to environmental tobacco smoke have higher levels of urinary cotinine, a metabolite of nicotine, than those who do not report such exposure." The Report also reviewed the scientific evidence on adverse health effects on children and reiterated the conclusion from the 1982 Report: "The children of smoking parents appear to have an increased prevalence of reported respiratory symptoms, and have an increased frequency of bronchitis and pneumonia early in life." VXA1601475-11742 at 1475 (US 64059).

  2. Studies confirming the original Hirayama/Trichopoulos findings continued to accumulate in the 1980s. See, e.g., VXA2110670-1053 at 0755-0775 (US 63709). In addition, Hirayama published follow-up studies in 1983 and 1984 finding essentially identical results to those reported in his 1981 paper. VXA2110670-1053 at 0755, 0759 (US 63709) (Reported relative risks were 1.42, 1.58, and 1.91 for nonsmokers married to smokers of 1-14 cigarettes/day, 15-19 cigarettes/day, and 20+ cigarettes/day, respectively.). Trichopoulos also published a report in 1984 updating his findings. VXA2110670-1053 at 0763 (US 63709) (Reported relative risks were 1.9 and 2.5 for women married to smokers of 1-20 cigarettes/day and 21+ cigarettes/day, respectively.)

  3. Based on the mounting evidence, the Surgeon General reached the following conclusions in his 1986 Report:

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  1. Involuntary smoking is a cause of disease, including lung cancer, in healthy nonsmokers; 2. The children of parents who smoke, compared with the children of nonsmoking parents have an increased frequency of a respiratory infections, increased respiratory symptoms, and slightly smaller rates of increase in lung function as the lung matures; and 3. Simple separation of smokers and nonsmokers within the same air space may reduce, but does not eliminate, the exposure of nonsmokers to secondhand smoke.

VXA2110670-1053 at 0673 (US 63709).

  1. That same year, 1986, two separate, independent reviews also concluded that exposure to secondhand smoke was a health hazard. First, the National Research Council (NRC) of the National Academy of Sciences issued "Environmental Tobacco Smoke, Measuring Exposures and Assessing Health Effects." The 1986 NRC Report found that known toxic and carcinogenic chemicals in mainstream smoke are also found in ETS, and that respiratory effects, such as wheezing and coughing, are increased in children of smoking parents. With respect to lung cancer, the NRC Report concluded:

Considering the evidence as a whole, exposure to ETS increases the incidence of lung cancer in nonsmokers. . . . Since carcinogenic agents contained in ETS are inhaled by nonsmokers, in the absence of a threshold for carcinogenic effects, an increased risk of lung cancer due to ETS exposure is biologically plausible.

VXA2111054-1229 at 1066 (US 63708).

  1. Second, the International Agency for Research on Cancer (IARC) of the World Health Organization, titled "Tobacco Smoking," the latest in a series of IARC "Monographs on the
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Evaluation of the Carcinogenic Risk of Chemicals to Humans," which concluded that secondhand smoke was a health hazard and a carcinogen:

Tobacco smoke affects not only people who smoke but also people who are exposed to the combustion products of other people's tobacco. The effects produced are not necessarily the same, as the constituents of smoke may vary according to its source. Three main sources exist: (I) mainstream smoke, (ii) sidestream smoke, and (iii) smoke exhaled to the general atmosphere by smokers. . . . Examination of smoke from the different sources shows that all three types contain chemicals that are both carcinogenic and mutagenic. The amounts absorbed by passive smokers are, however, small, and effects are unlikely to be detectable unless exposure is substantial and very large numbers of people are observed. The observations on nonsmokers that have been made so far are compatible with either an increased risk from "passive" smoking or an absence of risk. Knowledge of the nature of sidestream smoke 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 cancer.

The Report concluded:

There is sufficient evidence that tobacco smoke is carcinogenic to humans.

VXA1600406-0824 at 0714 (US 64066).

  1. In April 1987, the General Services Administration restricted smoking in Federal buildings. 41 C.F.R. §101-20.105-3, 52 Fed. Reg. 11263 at 11269 (April 8, 1987).

  2. In 1988, the Federal Aviation Administration imposed a smoking ban on all domestic commercial flights of two hours or less. See 14 C.F.R. §121.317, 52 F.R. 12358 (April 13, 1988)

(effective April 23, 1988). Subsequently in 1990, the FAA's smoking ban was extended to domestic flights of six hours or less. See 55 C.F.R. 8364 (March 7, 1990).

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  1. On June 25, 1990, the EPA released for public comment its draft Risk Assessment of ETS-related lung cancer in adults. The Agency's draft risk assessment classified ETS as a Group A carcinogen and attributed approximately 3800 nonsmoker lung cancer deaths per year to ETS. 2046522986-3260 at 3002-3010 (JD 004716). The draft Risk Assessment followed the Agency's release of a draft "Compendium" of passive smoking data and information in November 1989. After a period of public review and comment, EPA issued its second draft of the ETS Risk Assessment or Review Draft in May 1992, titled "Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. 2504201767-2298W (JD 004717).

  2. The final ETS Risk Assessment was published in December 1992. The EPA concluded: "ETS is a human lung carcinogen, responsible for approximately 3,000 lung cancer deaths annually in U.S. nonsmokers." The Risk Assessment included a meta-analysis of 31 epidemiological studies that showed a relative risk of 1.19 (for lung cancer with exposure to ETS) that was statistically significant using a 90% confidence interval.29 TLT0780160-0684 at 0175, 0180 (US 78711).

  3. The EPA Risk Assessment recited the scientific standard and the types of evidence that EPA considered in concluding that secondhand smoke was a Group A carcinogen. Except for examining six more years of scientific endeavor, the types of evidence that were evaluated by the EPA were the same as those considered by the Surgeon General, the NRC, and IARC in 1986.

The weight-of-evidence analysis for lung cancer hazard identification is developed in accordance with U.S. EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a) and established principles for evaluating epidemiological studies. The analysis

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considers animal bioassays and genotoxicity studies, as well as biological measurements of human uptake of tobacco smoke components and epidemiologic data on active and passive smoking. The availability of abundant and consistent human data at actual environmental levels of exposure to the specific agent (mixture) of concern, allows a hazard identification to be made with a high degree of certainty. The conclusive evidence of the dose-related lung carcinogenicity of MS in active smokers (Chapter 4), coupled with information on the chemical similarities of MS and ETS and evidence of ETS uptake in smokers (Chapter 3), is sufficient by itself to establish ETS as a known human lung carcinogen, or "Group A" carcinogen under U.S. EPA's carcinogen classification system. In addition, the document concludes that the overall results of 30 epidemiological studies on lung cancer and passive smoking (Chapter 5), using spousal smoking as a surrogate of ETS exposure for female never smokers, similarly justify a Group A classification.

DXA0390094-0699 at 0116-0117 (US 88654).

  1. Defendants focused their extensive public criticism of the Risk Assessment's conclusion on only one of the many types of evidence considered by EPA, namely, the epidemiological data. Bradley TT, 3/14/05, 15456:7-10, 15457:17-15459:23. EPA itself acknowledged the difficulties of making a pinpoint quantification of the disease risk from the epidemiological studies:

For lung cancer estimates among U.S. nonsmokers, the substantial epidemiology database of ETS and lung cancer among U.S. female never-smokers was considered to provide the most appropriate information. From these U.S. epidemiological studies, a pooled relative risk estimate was calculated and used in the derivation of the population risk estimates. The large number of studies available, the generally consistent results, and the condition of actual environmental levels of exposure increase the confidence in these estimates. Even under these circumstances, however, uncertainties remain . . . . Still, given the strength of the evidence for the lung carcinogenicity of tobacco smoke and the extensive human database from actual environmental exposure levels, fewer assumptions are necessary than is usual in EPA quantitative risk assessments, and confidence in these estimates is rated medium to high.

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DXA0390094-0699 at 0117-0118 (US 88654); see also DXA0390094-0699 at 0120-0122 (US

  1. (executive summary of epidemiological studies); Chapters 5 and 6 (detailed analysis of epidemiological studies). EPA's evaluation of the weight of the evidence resulted in a primary finding that "Passive smoking is causally associated with lung cancer in adults, and ETS, by the total weight of evidence, belongs in the category of compounds classified by EPA as Group A (known human) carcinogens." DXA0390094-0699 at 0120-0122 (US 88654).
  1. Defendants criticized EPA's meta-analysis of U.S. epidemiological studies, particularly its use of an "unconventional 90 percent confidence interval." Bradley TT, 3/14/05,

15456:7-10. However, Dr. Burns, who participated in the EPA Risk Assessment, testified that the

EPA used a one-tailed 95% confidence interval, not a two-tailed 90% confidence interval. He also explained in detail why a one-tailed test was proper:

The EPA did not use a 90% confidence interval. They used a traditional 95% confidence interval, but they tested for that interval only in one direction. That is, rather than testing for both the possibility that exposure to ETS increased risk and the possibility that it decreased risk, the EPA only tested for the possibility that it increased the risk. It tested for that possibility using the traditional 5% chance or a P value of 0.05. It did not test for the possibility that ETS protected those exposed from developing lung cancer at the direction of the advisory panel which made that decision based on its prior decision that the evidence established that ETS was a carcinogen. What was being tested was whether the exposure was sufficient to increase lung cancer risk, not whether the agent itself, that is cigarette smoke, had the capacity to cause lung cancer with sufficient exposure. The statement that a 90% confidence interval was used comes from the observation that if you test for a 5% probability in one direction the boundary is the same as testing for a 10% probability in two directions.

Burns WD, 67:5-15. In fact, the EPA Risk Assessment stated, "Throughout this chapter, one-tailed tests of significance (p = 0.05) are used . . . " DXA0390094-0699 at 0223 (US 88654).

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  1. In 1997, California's EPA reviewed the evidence on passive smoking and concluded that exposure to secondhand smoke causes lung cancer, heart disease, and other adverse health effects. This report was also issued as NCI Monograph 10 and stated: "Using the most up-to-date evidence available, Cal/EPA concluded that ETS causes not only lung cancer in adults and respiratory problems in children, but also low birth weight, sudden infant death syndrome, middle ear infections, nasal sinus cancer, and heart disease morbidity and mortality." JDM1870820-1333 at 0834-0836 (US 76125); DXA0581235-1694 at 1236 (US 78716).

  2. In August 1997, President William Clinton phased in the elimination of smoking in federal facilities over a one-year period. Exec. Order 13058, 62 F.R. 43451 (August 9, 1997).

  3. In June 2002, IARC released "IARC Monograph (Vol. 83), Tobacco Smoke and Involuntary Smoking." The 2002 IARC Monograph was the product of a scientific working group of 29 experts from 12 countries who "reviewed all significant published evidence related to tobacco smoking and cancer, both active and involuntary." The Monograph concluded, "There is sufficient evidence that involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke ) causes lung cancer in humans. . . . Involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) is carcinogenic to humans (Group 1)." TLT0970001-1455 at 1413 (US 86746).

  4. Since the 1986 Surgeon General's Report, every major scientific review and assessment of the science on passive smoking and its health effects has independently and consistently concluded that passive smoking causes disease and other adverse health effects in adults and children. See, e.g., DXA0390094-0699 (US 88654) (1992 EPA Risk Assessment); 2065192422- 2615 (US 22092) (1997 Australia Report); JDM1870820-1333 (US 76125) (1997 California EPA); VXA1600843-0981 (US 64063) (1998 UK SCOTH); VXA1600982-1000 (US 64062) (1999 WHO);

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VXA1240568-1258 (US 64315) (2001 SGR) (); TLT0970001-1455 (US 86746) (2002 IARC); see also Samet WD, 198:7-8 (1992 American Heart Association).

b. The Consensus 3349. Using the five criteria adopted by the Surgeon General as a framework for evaluating

causality (see ¶3309, herein), scientists in the public health community view the accumulation of data to determine if a causal relationship exists. In this case, the overwhelming accumulation of data demonstrates that ETS causes disease.

  1. Passive exposure of infants and children to tobacco smoke has adverse effects on their respiratory health, including increased risk for severe lower respiratory infections, middle ear disease (otitis media), chronic respiratory symptoms, and asthma. Passive exposure also causes a reduction in the rate of lung function growth during childhood, and is linked to Sudden Infant Death Syndrome (SIDS). Samet WD, 132:10-14 (SIDS), 209:11-15 (acute respiratory infections), 220:1-6 (middle ear disease); 211:11-16 (chronic respiratory infections), 217:1-218:2 (asthma); 213:9-15 (reduced rate of lung growth), 220:11-13 (summary statement); (no bates) (US 17304); see also 03763710- 3956 at 3829 (US 34340) (1975 SGR); VXA1601456-1742 at 1665-1670 (US 64059) (1984 SGR); VXA2110670-1053 at 0720-0744 (US 63709) (1986 SGR); DXA0390094-0699 at 0320-0387 (US 88654) (1992 EPA Risk Assessment); JDM1870820-1333 at 0940-1153 (US 76125) (1997 California EPA); 2065192422-2615 at 2164-2193 (US 22092) (1997 Australia Report); VXA1600843-0981 at 0876-0877 (US 64063) (1998 UK SCOTH Report); VXA1600982-1000 (US 64062) (1999 WHO).

  2. In adults, exposure to secondhand smoke causes lung cancer. Passive exposure causes two to three percent of all lung cancer cases in the United States. Compare DXA03900940699 at 0118, 0309 (US 88654) (1992 EPA Risk Assessment) (over 3,000 deaths annually) with Samet WD, 63:15-64:5 (155,000 lung cancer deaths from all causes in 2000) and DXA0390094- 0699 at 218 (US 88654) (98,451 lung cancer deaths in 1979); see also (no bates) (US 17140).

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  1. Exposure to secondhand smoke can also cause coronary heart disease in adults. Samet WD, 198:1-21 (coronary heart disease); (no bates) (US 17304) (summary chart of authoritative scientific conclusions); JDM1870820-1333 (US 76125) (1997 California EPA Report at Table ES.1); VXA1600843-0981 (US 64063) (1998 Report of the UK Scientific Committee on Smoking and Health); VXA1240568-1258 at 0957 (US 64315) (2001 SGR at 372).

  2. Secondhand smoke is also linked to the exacerbation of asthma, reduced lung function, and respiratory symptoms in children. Samet WD, 132:10-14 (SIDS), 209:11-15 (acute respiratory infections), 220:1-6 (middle ear disease); 211:11-16 (chronic respiratory infections), 217:19-218:2 (asthma); 213:9-15 (reduced rate of lung growth), 220:11-13 (summary statement). See generally (no bates) (US 17304) (summary of authoritative conclusions).

  3. Dr. David M. Burns testified as a Government expert witness on the science of tobacco and health, disease causation, the adverse health effects of secondhand smoke, and the effects of nicotine on smokers. Dr. Burns is a professor of medicine at the University of California San Diego's School of Medicine and a licensed physician who is board certified in pulmonary and internal medicine. He is a recipient of the Surgeon General's Medallion and has participated as an author, editor, or reviewer on 18 Surgeon General's Reports. Dr. Burns was the Senior Scientific Editor and author of the 1986 Surgeon General's Report "The Health Consequences of Involuntary Smoking." Dr. Burns has been the editor of ten National Cancer Institute monographs in its series on smoking and health. He remains an active researcher and has published over 30 peer-reviewed articles on issues involving smoking and health. He is a member of the EPA's Indoor Air Quality Board and NCI's Advisory Committee for the COMMIT trial, which researched innovative treatment for cardiopulmonary disease. Based on his superb academic credentials, his extensive experience working on Surgeon General Reports and NCI monographs, his ongoing clinical research, as well as his demeanor and responsiveness to cross-examination, the Court fully credits his testimony. VXB3740061-0081 (US 78526).

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  1. Dr. Burns testified that since the 1986 Surgeon General's Report, reviews and assessments of the science on ETS conducted by other public health authorities have reviewed available evidence and consistently concluded that ETS causes lung cancer in adults. Burns WD, 12:8-14:19, 68:12-69:2. Indeed, each Surgeon General's Report is intended to represent and, as a result of an extensive peer-review process, does represent the scientific consensus on smoking and health topics. Burns WD, 13:7-15; 14:10-19; 16:12-17. Dr. Burns' expert opinion is that:

Multiple reviews conducted by medical and governmental organizations over the years leave no doubt that environmental tobacco causes disease in nonsmokers and is particularly dangerous for children.

Burns WD, 68:12-69:2.

  1. As noted in Section V(A), supra, Dr. Jonathan M. Samet testified as a Government expert witness on the science of smoking and health, including epidemiology, pulmonary medicine, and internal medicine. Samet TT, 9/29/04, 1026:10-18. Dr. Samet is professor and chair of the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. He is also a licensed physician who is board certified in pulmonary and internal medicine. Dr. Samet is a member of the National Academy of Sciences' Institute of Medicine, the Board of Scientific
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Counselors of the National Cancer Institute, and EPA's Clean Air Scientific Advisory Committee. He is a recipient of the Surgeon General's Medallion and has participated as an author and/or editor of nine Surgeon General's Reports, including as Consulting Scientific Editor and author for the 1986 Report. He has participated in four NCI monographs in its series on smoking and health. He chaired the 2002 review of active and passive smoking and health for the International Agency for Research on Cancer of the World Health Organization. Dr. Samet remains an active researcher and has published over 80 peer-reviewed articles on topics related to smoking and health. As with Dr. Burns, after considering Dr. Samet's superb academic credentials, his vast experience working on Surgeon General Reports and NCI monographs, his continuing practice of medicine, as well as his demeanor and responsiveness to cross-examination, the Court fully credits his testimony. VXB3740316-0364 (US 78540).

  1. Defendants have recognized Dr. Samet's expertise and conservatism regarding opinions on the causal relation between adverse health effects and passive smoking in an internal litigation document that was written in approximately August 1994:

Dr. Samet is highly respected by his professional constituency. His scientific/medical capabilities appear to be quite sophisticated and are recognized as such by the professional societies with which he is affiliated. . . . This is probably due at least in part to his scientific conservatism regarding inference and interpretations from limited information; in most instances, Dr. Samet carefully assesses the available information prior to drawing general conclusions. . . . He seems to be a believer in the 'weight-of-the-evidence' approach and, usually, does not form conclusive opinions until the available data are sufficiently consistent and of high enough quality to warrant such opinions.

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  1. The Court accepts and credits Dr. Samet's conclusions, based on his expertise, as well as the other factual findings herein, that exposure to secondhand smoke causes lung cancer and coronary heart disease in adults and a number of respiratory diseases in children. The Court also accepts and credits his conclusions, based on his expertise, as well as other factual findings herein, that the knowledge gained from active smoking, the knowledge of the components of sidestream smoke, and the absence of a "safe" level of exposure to the carcinogens and toxins found in tobacco smoke, were sufficient evidence on which to conclude that the health risk posed by exposure to secondhand smoke is significant.

[C]igarette smoke contains carcinogens and inhaling smoke causes cancer. We have no scientific evidence to postulate that there is a level of smoke exposure that does not increase lung cancer risk. On this basis alone, including our knowledge of the nature of the carcinogens in secondhand smoke and the evidence from active smokers, I conclude that exposure to secondhand smoke poses a significant health risk to nonsmokers. The association of involuntary smoking with lung cancer derives biological plausibility from the presence of carcinogens both in secondhand smoke and in sidestream smoke, its main source, and from the lack of a documented threshold dose for respiratory carcinogens in active smokers. In my opinion, therefore, the question is not whether secondhand smoke poses a risk; rather, the question is how much of a risk does secondhand smoke pose. That question has been studied by epidemiologists and public health officials over the past three decades, and they have quite consistently shown and concluded that secondhand smoke causes disease, including lung cancer, in nonsmokers. Those findings would be expected, as secondhand smoke contains the same irritants, toxicants, and carcinogens that are found in sidestream and mainstream smoke, and biomarkers of tobacco smoke, such as cotinine and the carcinogen NNAL, show that secondhand smoke is absorbed by non-smokers.

Samet WD, 186:5-21.30 secondhand smoke is a health risk to both adults and children, Defendants called only one expert witness, a statistician, Edwin Bradley. Dr. Bradley's opinion was that "the existing epidemiologic evidence does not demonstrate a valid association between ETS exposure and either lung cancer or heart disease." Bradley WD, 1:17-19. The Court rejects that opinion and finds it not credible for all the following reasons.

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Dr. Bradley is not a medical doctor, epidemiologist, biologist, or toxicologist. Bradley TT, 3/15/05, 15553:2-23. Dr. Bradley is not aware of the components of tobacco smoke or what components might be carcinogens. Id. at 15538:5-15539:19. Dr. Bradley has never published on passive smoking; in fact, he has never published on smoking and health generally. He has never been the principal investigator on any grant of any kind. (no bates) (JD 025137); Bradley TT, 03/15/05, 15564:19-15566:15, 15568:3-16. None of his analyses has ever been subjected to peer review or published. Id. at 15564:19-24. He retired from his position at the University of Alabama at Birmingham in 1997 to become a full-time professional witness and litigation consultant, predominately for the Defendants. Bradley WD, 10:4-5, 11:15-19; Bradley TT, 03/15/05, 15554:12- 15555:24. He has earned over $800,000 from the tobacco industry. Bradley WD, 18:14-16.

In active smoking cases, Dr. Bradley continues to dispute the overwhelming scientific consensus that smoking causes disease, conceding only that smoking "may" cause lung cancer, heart disease and emphysema. Bradley TT, 3/15/05, 15559:3-24.

Dr. Bradley's "methodology" depended on his evaluation of statistical significance. His position was that any epidemiological study whose result is not statistically significant must be discarded and cannot be relied upon to determine whether an association exists. Dr. Bradley stated: "If a purported association is not statistically significant, your inquiry can end there." Bradley WD, 25:8-14, 99:1-3; Bradley TT, 03/14/05, 15426:6-9.

No scientific or medical authority shares Dr. Bradley's view. Statistical significance is not one of the Surgeon General's criteria for causality. As described below, it is a statistician's term of art, a tool to evaluate the possibility of chance in a particular study. Dr. Bradley's testimony confirms that even he recognizes this. Bradley WD, 21:19-22:15.

Moreover, Dr. Bradley admits that he stands alone in adopting and applying his test. When confronted with the conclusions of Sir Richard Peto, Sir Richard Doll, the Surgeon General, the EPA, WHO, IARC, National Research Council, and the American Heart Association, Dr. Bradley responded:

I didn't say they were wrong. I said that my opinion is that [causation of lung cancer and CHD] has not been established. Now they have other judgments and methodologies they used to come to that

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conclusion. Using my methodology, I cannot establish an association.

Bradley TT, 03/15/05, 15563:3-15564:4. Dr. Bradley did not testify that he consulted with any scientific or medical authority in establishing his causal criteria or reaching his conclusions.

The foundation of Dr. Bradley's opinion was his reliance on statistical significance. As already noted, his views are not shared by any scientific or medical authority. As a term of art, statistical significance is determined by whether the given confidence interval contains the value 1.0. If the interval contains 1.0, there is the possibility that the observed association is due entirely to chance. This value for 1.0 is also called the "null hypothesis." Bradley TT, 3/14/05, 15427:16- 15429:6. In determining statistical significance, no other causal evidence is evaluated.

Rothman & Greenland's MODERN EPIDEMIOLOGY, identified by Dr. Bradley himself as a leading epidemiological text, specifically rejects his position that statistical significance is a bright line test by which to accept or reject results of epidemiological studies. Bradley TT, 03/14/05, 15465:8-23. Instead Rothman & Greenland state:

Although a single confidence interval can be . . . informative, it is subject to the misinterpretation that values inside the interval are all equally compatible with the data, and all values outside it are equally incompatible. The specific level of confidence used in constru,cting a confidence interval is arbitrary, however; values of 95% or, less often, 90% are those most frequently used. A given confidence interval is but one of an infinite number of ranges nested within one another. Points nearer the center of these ranges are more compatible with the data than points further away from the center.

(no bates at 191) (JD 003150).

Indeed, as Rothman & Greenland emphasize, the point estimate found in a study is always the best answer to what the effect is, even if the confidence interval includes 1. Or, stated another way, "results that are not significant may be compatible with substantial effects. Lack of [statistical] significance alone provides no evidence against such effects." (no bates at 192) (JD 003150).

Rothman & Greenland specifically use active smoking and coronary disease (CHD) and secondhand smoke and lung cancer as examples of weak associations that are recognized to be causal: "Cigarette smoking is not seriously doubted as a cause of cardiovascular disease. Another example would be passive smoking and lung cancer, a weak association that few consider to be noncausal." (no bates at 24) (JD 003150).

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  1. One of Defendants' primary criticisms of the overwhelming data demonstrating that ETS causes disease is that each study fails to account for the possibility that bias or confounding (risk factors which are not taken into account but which may be causing the documented association between exposure and disease) is responsible for the demonstrated increased risk. For example, many of the seminal epidemiological studies on ETS used a proxy to measure exposure to ETS, e.g. being married to a smoker, rather than measure actual exposure, which would be much more complicated and invasive. As to those studies, Defendants claim the demonstrated increased risk of disease may be due to something other than exposure to ETS. It was Dr. Samet's conclusion, which the Court credits, that bias and confounding did not account for the magnitude of the excess risk of passive smoking shown in the epidemiological studies. Samet WD, 176:16-177:4, 177:9-23, 180:11-19, 187:9-188:3 ("The extent to which this bias explains the numerous reports of association between spouse smoking and lung cancer has been considered and found to be an insufficient basis for explaining the association of spouse smoking with lung cancer."); Samet WD, 188:4-189:7 ("Thus, confounding cannot explain the consistent findings by researchers over the past 25 years that secondhand smoke is associated with lung cancer."); see also Samet TT, 9/30/04, 1244:7-1245:17.

(...continued) Under questioning, Dr. Bradley admitted that his methodology was in "fundamental

disagreement" with Rothman & Greenland about "how much weight . . . should be given to the factor of statistical significance." Bradley also admitted that under the recognized methodology of Rothman & Greenland, secondhand smoke studies whose confidence intervals include 1, and are therefore not statistically significant as a technical matter, are nonetheless more compatible with a positive association. Bradley TT, 3/15/05, 15548:22-15549:8, 15546:9-15.

Dr. Bradley chose to limit his analysis to epidemiological studies from the United States. In so doing, he arbitrarily eliminated all foreign studies, whether statistically significant or not, including the Hirayama and Trichopoulos studies. Bradley WD, 55:4-60:6.

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  1. Moreover, the scientific community has routinely addressed the issues of bias and confounding in evaluating studies of the association between lung cancer and passive smoking. All of the major reviews of the evidence on the lung cancer and heart disease risks of ETS discuss both bias and confounding at length and take both factors into consideration. See, e.g., VXA2110670- 1053 at 0787 (US 63709) ("Speculation that the positive results reported in Japan and Greece were due to cultural bias against admission of smoking by women in these more traditional societies may be discounted because positive significant findings have now been observed in the United States . . . where no comparable social stigma exists."); DXA0390094-0699 at 0243-0246, 0267-0279 (US 88654) (1992 EPA Risk Assessment) ("In summary, an examination of six non-ETS factors that may affect lung cancer risk finds none that explains the association between lung cancer and ETS exposure as observed by independent investigators across several countries that vary in social and cultural behavior, diet, and other characteristics."); TLT0970001-1455 at 1264-1266, 1269, 1409 (US 86746) (2002 IARC) ("The excess risk is of the order of 20% for women and 30% for men and remains after controlling for potential sources of bias and confounding.").

  2. Scientific authorities have recognized that studies are also subject to biases and confounding that would tend to reduce reported risks. For example, the 2002 IARC Monograph stated, "Studies of the risk for lung cancer exposure to secondhand smoke have defined the reference [or control] group as never-smoking women with husbands who are nonsmokers. However, these women although not exposed at home, may be exposed to secondhand smoke outside the home. This bias will tend to underestimate the true relative risk." TLT0970001-1455 at 1264 (US 86746) (2002 IARC).

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