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REVIc, W OF THE U.S. ENVIRONMENTAL PROTEC- TION AGENCY'S TOBACCO AND SMOKE STUDY HEARING BEFORE THE SUBCOiVMITTEE ON SPECIALTY CROPS AND NATURAL RESOURCES OF THE COMMITTEE ON AGRICULTURE HOUSE OF REPRESENTATNES ONE HUNDRED THIRD CONGRESS FIRST SESSION JULY 21, 1993 Serial No. 103-26 Printed for the use of the Committee on Agriculture U.S. GOVERNMENT PRINTING OFFICE 72-758 WASHINGTON : 1993 For sale by the U.S. Government Printing Office Superintendent of Documents, Congressional Sales Office, Washington, DC 20402 ISBN 0-16-041698-1

6 Mr. ROSE. Our first panel is Dr. William H. Farland, Director of the Office of Health and Environmental Assessment, Office of Re- search and Development, Environmental Protection Agency. He is accompanied by Dr. Steven Bayard, the Project Manager for ETS Risk Assessment, Office of Health and Environmental As- sessment, Office of Research and Development, Environmental Pro- tection Agency, Washington, DC; Dr. Hugh McKinnon, Director of the Human Health Assessment Group, Office of Health and Envi- ronmental Assessment, Office of Research and Development, Envi- ronmental Protection Agency, Washington DC. I want to thank you for being here. There were others from your Agency that we had hoped would be with us. Mr. Waxman changed the date of his hearing from to- morrow until today and was able to take several of our witnesses away from us. But we will do the best we can in no way diminishing your abili- ties and your statements. We thank you for being here. Dr. Farland. STATEMENT OF WILLIAM H. FARLAND, DIRECTOR, OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT, OFFICE OF RESEARCH AND DEVELOPMENT, U.S. ENVIRONMENTAL PRO- TECTION AGENCY, ACCOMPANIED BY STEVEN BAYARD, PROJECT MANAGER FOR ETS RISK ASSESSMENT, AND HUGH W. McKINNON, M.D., DIRECTOR, HUMAN HEALTH ASSESS- MENT GROUP Mr. FARLAND. Good morning, Mr. Chairman and members of the subcommittee. Thank you for the opportunity to appear before you today to discuss scientific and procedural issues regarding EPA's report on passive smoking. As you mentioned, I am accompanied today by Dr. Steven Bay- ard a biostatistician in our Human Health Assessment Group, who is the Project Manager, and one of the primary authors of the re- port. I also have with me Dr. Hugh McKinnon, a public health physi- cian who is Director of our Human Health Assessment Group. As you are aware, the U.S. Environmental Protection Agency published an assessment of the respiratory health risks of passive amoking in January of this year. The document has been prepared under the authority granted to the EPA Administrator, including title IV of the Superfund Amendments and Reauthorization Act of 1986-Radon Gas and Indoor Air Quality Research-which directs EPA to conduct research and disseminate information on all as- pects of indoor air quality. The report which was reviewed extensively by scientists from outside of the EPA concludes that exposure to environmental to- bacco smoke or ETS, commonly known as secondhand smoke, is re- sponsible for approximately 3,000 lung cancer deaths each year in nonsmoking adults in the United States and seriously affects the respiratory health of hundreds of thousands of children. My written testimony summarizes the development of the report, the scientific review process, the major findings, and the scientific approach. The 7 testimony concludes with some responses to several tobacco indus- try criticisms of the report. In recent years, comparative risk studies performed by EPA and its Science Advisory Board have consistently ranked indoor air pol- lution among the top five environmental risks to public health. As part of its efforts to address all types of indoor air pollution, EPA's Indoor Air Division in 1988 requested the EPA's Office of Research and Development to undertake an assessment of the respiratory health effects of passive smoking. Because of both resource and time limitations, the assessment was limited to respiratory health effects, both cancer and noncancer. The report was prepared by my office, the Office of Health and Environmental Assessment within the Office of Re- search and Development, and was written by both in-house staff and outside contracting assistance. Before being released in draft form for public review, the passive smoking report received many internal reviews, mostly from within the Office of Research and Development. Various parts of it were also reviewed by selected outside experts, both from other Federal agencies and from academic institutions. Revisions incorporated the reviewers' comments wherever possible. The first external draft of this assessment was released for pub- lic review and comment in June of 1990. In December 1990, EPA's Science Advisory Board, a committee of independent outside sci- entists, conducted a review of the draft report and submitted its comments to the EPA Administrator in April of 1991. In its comments, the SAB's Indoor Air Quality/Total Human Ex- posure Committee concurred with the primary findings of the re- port, but also made a number of recommendations for strengthen- ing it. Incorporating recommendations from both the public and the Science Advisory Board, a revised draft was transmitted to the board in May of 1992 for a second review. Following a July 1992 meeting, the SAB panel endorsed the report and its conclusions, in- cluding a unanimous endorsement of the classification of environ- mental tobacco smoke as a group A or known human carcinogen. EPA also received and reviewed ~public comments on the second draft and integrated all appropriate material into the final risk as- sessment. The final report was released in January of this year at a joint press conference held by former Administrator Reilly and former Department of Health and Human Services Secretary Sulli- van. Based on the weight of the available scientific evidence, EPA has concluded that widespread exposure to environmental tobacco smoke in the United States presents a serious and substantial pub- lic health risk. In adults, ETS is a human lung carcinogen, responsible for ap- proximately 3,000 lung cancer deaths annually in U.S: nonsmokers. ETS has been classified as a known human carcinogen under EPA's carcinogen assessment guidelines. This classification is re- served for those compounds or mixtures which have the strongest data to determine a cause-and-effect relationship, including data from human populations. Only 10 to 15 other agents, including as- bestos and radon, have been classified by EPA as group A carcino- YrT8MV09

8 gens, and ETS is the only one for which cancer has been observed at typ ical nonoccupational environmental levels. ETS has subtle but significant effects on the respiratory health of nonsmokers including coughing, phlegm production, chest dis- comfort, and reduced lung function. In children, ETS exposure increases the risk of lower respiratory tract infections such as bronchitis and pneumonia. Our estimates are that between 150,000 and 300,000 of these cases annually in infants and young children up to 18 months of age are attributable to exposure to ETS. Of these, between 7,500 and 15,000 are esti- mated to result in hospitalization. In addition, ETS exposure increases the prevalence of fluid in the middle ear, a sign of chronic middle ear disease. Fluid in the mid- dle ear is a major cause of hospitalization- of young children for an operation in the United States. ETS exposure in children irritates the upper respiratory tract and is associated with a small but significant reduction in lung function. In addition, ETS exposure increases the frequency of episodes and severity of symptoms in asthmatic children. The report esti- mates that 200 000 to 1 million asthmatic children have their con- dition worsenedby exposure to environmental tobacco smoke• and ETS exposure is a risk factor for new cases of asthma in chiidren who have not previously displayed symptoms. EPA reached its conclusions concerning the potential for ETS to act as a human carcinogen based on an analysis of all available data. Specifically, the finding that EPA should be classified as a group A carcinogen is based on the conclusive evidence of the dose- related lung carcinogenicity of mainstream smoke in active smok- ers, the chemical similarities of mainstream smoke and the side stream smoke given off the burning end of the cigarette and the known exposure and uptake of ETS at levels which could increase risk. The finding is bolstered by the statistically significant exposure- related increase in lung cancer in nonsmoking spouses of smokers which is observed in analysis of more than 30 epidemiology studies from eight different countries that examined the association be- tween secondhand smoke and lung cancer. The weight of the evi- dence analysis for the noncancer respiratory effects in children is based primarily on a review of more than 100 studies, including over 50 recent epidemiology studies of children whose parents smoke. EPA is not the only Federal agency that has evaluated environ- mental smoke. The EPA's conclusions on the respiratory effects of passive smokix~~g strengthen and confirm those of earlier assess- ments by the U.S. Surgeon General in 1986 and the National Re- search Council of the National Academy of Sciences in 1986. The World Health Organization has also concluded that ETS causes ex- cess risk of lung cancer in 1986 and other respiratory disorders in 1992. The National Institute of Occupational Safety and Health in 1991 concluded that occupational exposure to ETS causes increased risk of lung cancer and probable heart disease. The position of the National Cancer Institute in 1993 is that ETS is a proven cause of lung cancer in nonsmoking adults and is asso- 7VZM9v0g 9 ciated with an increased risk of coronary heart disease. Since the cutoff date for literature inclusion in the EPA report, several new studies have been published which provide additional evidence of respiratory effects from ETS exposure. Six of these are particularly relevant, one each on sudden infant death syndrome, SIDS, and asthma, and four on lung cancer. Three of the recent studies on ETS exposure and lung cancer in nonsmoking women add to the data base of the 30 studies analyzed in the EPA report. Two of these, Stockwell, et al. from the Journal of the National Cancer Institute and Brownson, et al. from the American Journal of Public Health are large U.S. case-control stud- ies which find significant increased risks among nonsmoking women in the highest category of ETS exposure based on the amount their husbands smoke. Similar results are reported in the very recent study of non- smoking Chinese women by Liu, et al., in the American Journal of Epidemiology; Liu also found a statistically significant increase in risk in the most exposed group, based on husband's smoking. In ad- dition, Stockwell, et al. found significantly increased risks for high levels of household exposure in children. I believe it is important that we put these risks associated with ETS in perspective. The EPA estimates that about 20 to 30 percent of all lung cancers caused by factors other than smoking are attrib- utable to environmental tobacco smoke. Another way of expressing this is that the increased risk of dying from lung cancer is about 1 in 1,000 from all ETS exposures out- side the home. For reference, a one-pack-a-day smoker experiences lung cancer risks approximately 100 times higher or a 1-in-10 risk. Exposure to ETS varies, but higher exposures are associated with higher risk. For example, people whose spouses smoke in the home face an average increased risk of 2 in 1,000. Estimated risks in this range are considered high. For comparison, EPA generally sets its stand- ards or regulations so that increased cancer risks are below 1 in 10,000 to 1 in 1 million. , In other words, the increased lung cancer risks associated with exposure to environmental tobacco smoke are at least an order of magnitude greater than the cancer risks for virtually any other chemical or agent that EPA regulates. The additional risks on childhood respiratory health make an even inore compelling case for the public health impact of ETS. In my written testimony I have also addressed many of the criticisms of EPA's approach to and findings of this analysis. We will now be pleased to answer questions from the subcommit- tee. [The prepared statement of Mr. Farland appears at the conclu- sion of the hearing.] Mr. RosE. Thank you very much, Dr. Farland. Could you describe to us EPA's guidelines for carcinogen risk as- sessment, and in particular, what those guidelines say with regard to the classification of a substance as a group A carcinogen? Mr. FARLArro. Yes, Mr. Chairman.

10 The Agency has a long history of documentation of its guidance on carcinogen assessment. It put out its first interim guidance in 1976 and followed with final guidance that we use today in 1986. That particular guidance is used by scientists within the Agency, and by those outside to understand how the information is going to be translated into risk assessments, and to help us with the work that we do in my office. We use a weight of evidence approach. This particular set of guidance stresses the importance of considering all the information, and it uses a classification scheme as one aspect of the guidance that breaks carcinogens down according to the understanding of the evidence available on them. They are categorized as A, known human carcinogens; B, probable human carcmogens; C, possibly human carcinogens; and then there is a D category, which is not classifiable; and an E category for those chemicals that have been sufficiently well tested and don't show a carcinogen response. The A carcinogen class is our highest class of evidence. It gen- erally will include human information, epidemiology studies, infor- mation on human metabolism, and other types of human data. It will have looked carefully at those epidemiology studies in order to attempt to rule out confounders that might cloud the analysis of those particular studies. This is a classification system that has been broken up into these five categories. Mr. ROSE. I understand that. You have been over the classifica- tion system. Is it not true that in your guidelines that you indicate that for a substance to be classified as a group A carcinogen there must be sufficient data in humans, that is, epidemiological data? Mr. Fnttr..ANn. The type of information that we are talking about is all of the human data. We are looking for a classification that would include sufficient human data. Mr. ROSE. You contend that you have sufficient human data? Mr. FARLAND. We do. That sufficient human data includes infor- mation on active smoking in humans, it includes information on the eXposure of humans to- Mr. ROSE. What are some other class A carcinogens? Mr. FAximn. The Ag ency has classified between 10 and 15, radon, benzidine, byschloromethyl ether, vinyl chloride, asbestos, nickel, arsenic-these are chemicals that have reached the cat- egorization of being known human carcinogens. Mr. ROSE. What are some class B carcinogens? Mr. FARLAND. Class B carcinogens have an adequate animal data base. Mr. ROSE. What are they? Mr. FARLAND. Formaldehyde- Mr. ROSE. So tobacco smoke is more carcinogenic than formalde- hyde? Mr. FARLMn. It is not a question of more carcinogenic; it is the data base that is available. Mr. ROSE. Environmental tobacco smoke is A and what was the classification for B? Mr. FARLAND. That is a probable human carcinogen. Formalde- hyde falls into that category and there is limited human e~idPncw on formaldehyde. IGUTMM9 11 Mr. ROSE. It might be poisonous if you drank it, but you are talk- ing about the vapor from it; is that correct? Mr. FnRLANn. Yes. There is limited human evidence that it causes upper respiratory tumors. Mr. ROSE. How was a determination as to formaldehyde arrived at? Was it done through a comparison of various studies that were done around the world or was there a particular test that you all conducted? Mr. FAxt.AND. The formaldehyde conclusion- Mr. ROSE. You were probably looking at studies that had been done in various places? Mr. FARLAND. That is right. Mr. RosE. Did you apply the 95 percent or the 90 percent con- fidence level in the case of formaldehyde? Mr. FARLAND. I would have to go back to look at that. The test for statistical significance in those cases would have been 95 per- cent. Mr. RosE. You applied 90 percent to environmental tobacco smoke which made it a class A carcinogen, but you haven't looked at formaldehyde or other substances at the 90 percent level? Mr. FARLArrD. No. The test for statistical significance is at the 95 percent level in both cases. Mr. ROSE. What did you change to 90 percent? I am not obvi- ously asking the right questions, Doctor. What did you change from 95 to 90 percent? Mr. FARLAND. The important issue is that the statistical significance- Mr. ROSE. What was the level that you changed from 95 to 90 percent in the case of environmental tobacco smoke? Mr. FARLAND. We used a 95 percent statistical significance test that is one-tailed and resulted in a 90 percent confidence interval. It is a standard statistical procedure. It is the confidence interval that comes from the 95 percent statistical test and is one-tailed. Mr. ROSE. So you did not use a 90 percent confidence downgrade in your conclusions as to environmental tobacco smoke? Mr. FARLAND. This is not a downgrade. A 90 percent confidence interval is not a downgrade. A 90 percent confidence interval is consistent with a 95 percent one-tailed test. And that is what we used, a 95 percent one-tailed test of significance to determine whether or not the observed relative risk was significant compared with controls. Mr. ROSE. All right. I better go back and learn new math. I thought 95 was higher than 90, but I am wrong. Mr. FARLAND. Mr. Chairman, you are correct that a 95 percent confidence interval is a more stringent statistical test and there are 95 percent statistical significance tests that use a 95 percent con- fidence interval. But in the case where one has evidence that the effect is likely to be adverse and not beneficial, the statistical use of a one-tailed test is appropriate. Mr ROSE. So you assumed it was bad and did a one-tailed test? %Ir FAHt.A*rD _ We assumed based on the evidence of lung cancer Nni mmAing thet the result would likely be an adverse effect and ...- %,..A a onN tailed test of significance.

12. Mr. ROSE. But based on your studies and the way you classified them, you are telling us that the fumes from tobacco smoke are more carcinogenic than the fumes from formaldehydes? Mr. FARLAND. This is a different- Mr. ROSE. There are people out there who obviously work for you who are shaking their heads. Mr. FARLAND. It is not a matter of quantification. It is not a mat- ter of it being more carcinogenic or less carcinogenic; it is the weight of the weight of the evidence that we have available on that substance. Mr. ROSE. You are really getting my attention. Mr. FARLAND. A known human carcinogen may not be as potent a carcinogen, as stronp a carcinogen, as one that we don't have human data op. There is a difference between hazard and potency. Mr. ROSE. What does the risk ratio of one mean? Mr. FARLAND. A risk ratio of one means that there is no increase in relative risk so that this is a ratio of Mr. ROSE. Increase? Mr. FARLAND. No increase in relative risk over a background or a control population. Mr. ROSE. So a risk ratio of less than one means what? Mr. FARLAND. A risk ratio of less than one depending on the con- fidence around the estimate, may mean that it is protective or it may mean that it is equivalent to one. Mr. ROSE. Above one, what does that mean? Mr. FARLAND. Again, it means in this case that there would be an increased relative risk or, depending on the confidence, it may be equivalent to one. Mr. ROSE. Looking at some studies that you have used, associa- tion between risk of lung cancer and childhood exposure to tobacco smoke among nonsmoking women, are the risk ratios above or below one? Mr. BAYARD. Are you talking about childhood exposure? Mr. ROSE. I just said that. Association between risk of lung can- cer and childhood exposure to tobacco smoke among nonsmoking women; the risks are all less than one. Mr. BAYARD. Did you look at Stockwell or Janerich? Mr. RosE. This is the Fontham study. Mr. BAYARD. That study showed no increase in risk in children. The Stockwell study has shown an increase in risk and the Janerich study showed an increase in risk. In the Fontham study, she discusses at the end that her study did not show an increase, and that conflicted with the Janerich study. Mr. ROSE. Then you could conclude that according to the Fontham study, you should expose children to tobacco smoke to re- duce their risk; is that right? Mr. BAYARD. Only if you are willing to conclude by the Fontham study that you should definitely not expose people to ETS at work because they showed a very large increase for people exposed at work. The relative risk for exposure as children was very close to one as I understand it; maybe 0.9-something. Mr. ROSE. So when you use a one-tailed approach as opposed to a two-tailed approach, you don't look at the upside and the down- side; you just assume that there is a danger here? 13 Mr. BAYARD. You assume that if there is any effect-this is for lung cancer-we did it different than for lung cancer than we did in noncancer respiratory effects. For lung cancer, we had evidence that high levels of tobacco smoke caused lung cancer and that is pretty good evidence, about 9 million people studied worldwide; and most people will admit that tobacco smoking causes lung cancer. So we believe that with the lower levels of tobacco smoke from environmental tobacco smoke there would not be a protective effect, but if there were any effect, it would be an adverse effect. So we only used a one-tailed test or 90 percent confidence intervals for the analysis of ETS epidemiology and lung cancer. But for the childhoad respiratory effects, we used 95 percent confidence inter- vals because we didn't have the evidence from smoking in children causing noncancer respiratory effects; so we did do it two ways in the same report. Mr. ROSE. I kind of broke a committee rule here. I should hear the whole panel. I have asked basically 1'rh questions. Are you the only one going tog~ve a statement, Dr. Farland? Mr. FARLAND. Yes, Mr. Chairman. Mr. ROSE. Then I am not wrong. Could you explain what criteria the Agency uses when evaluating epidemiolog~cal studies to deter- mine whether an association could be due to chance? Mr. FAWANn. The Agency uses an approach that was published by Bradford Hill. It is a traditional approach that goes through a number of criteria for causality, and it mcludes a number of things like consistency of the data, the number of studies, the strength of the response the biological plausibility and those sorts of issues. In addition to lat, we use statistical approaches as well as those gen- eral approaches for evaluating causality. Mr. RosE. Would you describe as sufficient any single epidemio- logic study or the combination of a series of such studies that re- ports a relative risk that is statistically not significant? Would you describe as sufficient any single epidemiologic study or the com- bination of a series of such studies that reports a relative risk that is statistically not significant? Mr. FARLAND. Mr. Chairman, the only example that I can think of where we have argued a strong case for known human carcino- genicity where the epidemiology data base may not be statistically significant is vinyl chloride where there is a very limited number of cases, but there are very specific types of cancers so the cause and effect relationship based on the biological arguments is very strong. Mr. RosE. Dr. Farland, at the Science Advisory Board review of ETS risk assessment in July 1992, you stated that ETS risk assess- ment has been an innovative approach and that it bears some merit in terms of future approaches for risk assessment. Does that mean that in the future EPA will place undue emphasis on the much criticized statistical technique of meta-analysis? Does the Agency have guidelines on the use of meta-analysis? And moreover, if the ETS risk assessment is to be a template for future directions, does it mean that the Agency intends to override existing carcinogen risk assessment guidelines in favor of a less strict weight of evidence approach that would leave the Agency much more freedom to interpret data as it might wish? F XVT8MV0Z

14 Mr. FARLAND. I am not sure that I got all those questions. Mr. ROSE. At the Science Advisory Board's review of the risk as- sessment on July 1992, you stated that ETS assessment has been an innovative approach, that it bears some merit in terms of future ap roaches for risk assessment. Sne, does that mean that in the future you will place em hasis on the much-criticized statistical technique of meta-analysis? Two, does the Agency have guidelines on the use of meta-analysis; and three, if environmental tobacco smoke risk assessment is to be a template for future directions, does it mean that the Agency in- tends to override existing carcinogen risk assessment guidelines in favor of a less strict weight of the evidence approach that would leave the Agency much more freedom to interpret data as it might wish? Mr. FAR[.Arrn. Thank you for repeatinP. I made a statement about the innovative approaches that we use. I think this is a unique data base where one has 30 lung cancer studies and over 100 studies in children. Fortunately, we don't have many cases where we have that much human data on an en- vironmental contaminant. With regard to your question on the emphasis on meta-analysis, the use of meta-analysis depends on the quantity and quality of the studies that you have available, whether they can be combined, and there will be few cases where we will have enough information, sufficient data, sufficient numbers of studies of similar design and so on to be able to use meta-analysis. We are committed to use this particular approach which is gaining favor within the epidemiologic and statistical community in future cases where it would fit. In terms of guidelines for meta-analysis, the Agency has none, but it does very carefully lay out the process it used for meta-anal- ysis and subjects it to external peer review as part of its peer re- view process. In addition, we are working with industry and aca- demic groups to hold a workshop on meta-analysis in this upcom- ing year to look at some of the princip:es that would be included in a general guidance document on meta-analysis. In terms of the cancer guidelines, we are in the process of revis- ing our cancergu idelines to move along with the evolution of the scientific data. We will focus on weight of the evidence approaches and will continue to focus on a strong scientific judgment compo- nent within ourgu idance. Mr. RosE. Is there any substance for which EPA has used a set of epidemiologic studies pertaining to a substance other than the one under study, even though perhaps similar in some respects, in order to determine a group A classification? Is there any substance that you have used a set of studies per- taining to a substance other than ETS, even though perhaps simi- lar in some respects, in order to determine a group A classification? The answer is no, isn't it, Doctor? Mr. FARLAND. I think the best example that we have of that is the case of our evaluation of benzidine containing dyes. In that par- ticular case, benzidine is known to be a human carcinogen. Dyes that contain benzidine that are likely to be metabolized, and have been in some cases shown to be metabolized by humans so that benzidine appears in the urine, are considered as known human 15 carcinogens where there is no direct epidemiologic data on those dyes. In that case, we use the surrogate data from benzidine and the epidemiology studies there to make conclusions on these other dyes. Mr. ROSE. The EPA risk assessment on environmental tobacco smoke determined that ETS could be classified as a group A car- cinogen solely on the basis of comparisons with the epidemiology of active smoking. This is at odds_ with the recommendations of EPA's Science Advisory Board. Could you explain why in this instance EPA decided to reject the advice of the Science Advisory Board? Mr. FAxt.ArID. Let me comment and perhaps Dr. Bayard would like to add an additional comment. My understanding was that the Science Advisory Board suggested to us that although we had spent a lot of time evaluating the epidemiology studies, that it was pos- sible to make a conclusion simply on the similarities between active and passive smoking. They didn't suggest that we should do that instead of evaluating the epidemiology studies; they just said that the strongest case would be based on both of those and that we should go back and improve the arguments on the correlation with active smoking in addition to our analysis of epidemiology studies. Mr. BAYARD. The statement you are referring to I think was made by Dr. Lippman at the second Science Advisory Board meet- ing July 22, 1992. That statement, as a lot of statements made at that meeting, did not get into the Science Advisory Board report to us on November 20, 1992, so that oral statement did not represent the Science Advisory Board's consensus. Our conclusion was that we could label environmental tobacco smoke a known human carcinogen based on the similarity of envi- ronmental tobacco smoke to mainstream smoke, with both contain- ing the same carcinogen, and the known lung cancer response from mainstream smoke down to very low doses with no evidence of a threshold. This conclusion was in the draft which we sent to the SAB for review, and to which that report of November 20 referred. So our conclusions were in the second draft which went to the Science Advisory Board for review. They agreed with the conclu- sions in their November 20 report to us, and it remained in our final report which was published in December. Mr. ROSE. I have a lot more questions for Dr. Farland, and for Dr. Bayard, but in fairness to the members of the panel, I am going to yield to Mr. Lewis for questions and then to my colleagues on my right and then Mr. Lewis, whoever he will wish to recognize. Mr. Lewis. Mr. LEwis. Thank you, Mr. Chairman. Dr. Farland, Dr. Shapiro of the Sloan Epidemiological Unit stat- ed in a paper that the use of meta-analysis and observational re- search should be abandoned and the guidelines also go on to state that negative results from a well-designed and well-conducted study that contains usable exposure data can be used to define the uppEr limits of risk. What implications does this have for a series of studies where several of the larger studies report no increase in risk? UT8~VMZ

16 Mr. FARLAND. As I mentioned there is controversy with regard to the use of meta-analysis, but it is growing in favor in terms of trying to combine studies to increase their power to evaluate ef- fects. There are individuals in the scientific community who are not comfortable with the use of meta-analysis and feel that perhaps it should not be used. There are others who have used it extensively to evaluate car- cinogens. A report by Sir Richard Doll, for instance, used meta- analysis extensively and suggests that it is the best way to evalu- ate a particular class of compounds that he is looking at. The impli- cations of the meta-analysis approach is that one can combine stud- ies showing an effect, that have an increased relative risk, with those that could not show an effect and get some sort of a sense as to the contribution of that no effect finding on the overall esti- mates of relative risk. There is a rationale for doing that sort of thing, and there is a basis for, rather than focusing only on the positive studies, using the positive and nonpositive studies, the no relative risk increase studies, in trying to reach your conclusions. That is what meta- analysis helps us to do. Mr. LEWIS. One of the largest studies by Brownson reports no in- crease in risk. This should have a significant implication for the risk assessment, is that true? Mr. BAYARD. The Brownson study is 1 of 33 studies on lung can- cer and environmental tobacco smoke among never-smoking women. The Brownson study found a significant risk among the women most heavily exposed. If you take all the women, the women who were ever exposed versus those never exposed to their husband's smoke, the Brownson study found no overall increase in risk. You have to understand that these epidemiology studies done at true environmental levels are not the easiest studies to detect any kind of an effect. In fact when EPA calls something a known human carcinogen, most often the studies are based on high occu- pational levels, anywhere from 100 to 1,000 times what a typical environmental level will be. ETS is the only agent which EPA has ever found to be, ever declared, a known human carcinogen, which has actually been found to be carcinogenic at true environmental levels. Getting back to the Brownson study, Brownson concluded that ours and other recent studies suggest a small but consistent in- creased risk of lung cancer from passive smoking. Two other stud- ies which have also appeared since our cutoff date for literature re- view have also found statistically significant increases at the high- est level and one found a significant dose response trend. The question is would Brownson have changed our results? The answer is no. That would have been 1 of 33 epidemiology studies on ETS and lung cancer, but there are tons of other studies that also went into our weight of evidence, hundreds and hundreds of other studies. The answer is no. Mr. LEwIS. Is there any other substance for which EPA has used a set of epidemiology studies pertaining to the substance other than the one under study even though perhaps similar in order to determine a group A classification? M8Mfn i 17 Mr. BAYARD. Nickel causes lung cancer and nasal cancer in pyrometalurgical refinery workers. Those people are exposed to high doses of nickel which also probably contains sulfuric acid, so we have found that, yes, some of these nickel salts are carcmo- genic. But do we know if it is ever going to cause lung cancer at typical environmental levels? We don't know that. We have never seen- with the exception of environmental smoke-cancers from our group A carcinogens at typical environmental levels that we know about. Asbestos, we have never seen cancer from background levels in schools. We know we spend a lot of money to clean them up, but we have really never seen cancer at these levels in schools. We hypothesize that that is going to be the case based on model- ing but that is not true for environmental tobacco smoke. So nickel is one. Coke ovens is one. Coke oven workers who have high expo- sure to coke oven emissions come down with lung cancers. By the time these emissions have dissipated and get into the ambient en- vironment we don't particularly know if they are actually going to cause lung cancer. Does that answer your question? Mr. LEwIs. I think it does because I really don't know what you used. It was my understanding you only used environmental to- bacco smoke. Apparently you are telling the subcommittee that you did use others for companson. Mr. BAYARD. The question you asked was whether there were any other chemicals for which we used like studies, I thou ght that meant, in which the studies that we used were actually different from what was available in the environment. My response was that, yes, with both nickel and coke ovens we had occu~ pational exposures which are probably going to be some- what different from what the environmental exposures would be; not only in dose, but in physical chemical characteristics. Mr. FARLAND. Mr. Lewis, I also mentioned to the chairman the idea that in the case of some of the benzidine containing dyes, we had used epidemiology studies from benzidine in order to classify those specific dyes. That would be another case where we have used surrogate data. Mr. LEwis. After EPA's adjustment to the 90 percent confidence interval, how many of the studies reported statistically significant increase in risk? Mr. FARLAND. Could I use the chart that we had up here? That would be helpful. Mr. LEwis. Fine. Mr. FARLAND. This chart basically just shows the weight of evi- dence approach that we used. There were 30 epidemiologic studies of ETS and lung cancer. If you compared the 30 studies for ever versus never exposed which is the lowest level of evaluation, of the 30 studies, 24 showA an increased relative risk 9 were statistically significant. That is a finding that would not likely be due to chance. The probability of getting 9 statistically significant studies among 30 by chance is a 1 in 10,000 probability. When we broke that group of 30 down into the 17 studies which characterized ex- posure and used that exposure level and looked at the increased

18 risk in the highest exposure level, 17 out of 17 studies showed an increased relative risk, 9 were statistically significant in that group and that is a probable finding of 1 in 10 million. We wanted to see which studies showed a positive dose trend. Of the 14 Studies that showed the characteristics to evaluate dose re- sponse, 10 were statistically significant. By chance, about 1 in 1 billion that you would get 10 out of 14 coming up as a probability of occurrence by chance. Mr. LEwIS. Could I stop you there for a moment and ask you, in the first instance you said nine were statistically significant? Mr. FARLAND. Correct. Mr. LEwts. In the second, 9; and in the third, 10. That was 9 out of 24 or 30, and 9 out of 17 Studies and 10 out of 14. How about the rest? - Mr. FARLAND. The others were studies of lesser power, smaller studies. They showed a nonstatistically significant increase or no increase at all. That could be due to the nature of the study. It could be a true evaluation of that particular test, or it could be due to chance that those results showed no increase. Mr. LEWIS. Wouldn't those studies be significant to bias these nine in some way? Mr. FAIU.AtvD. They continued to raise uncertainty within the overall assessment because not all studies have shown a positive response, but not all studies are equal. They are not designed the same way, looking at the same populatione Mr. LEWIS. You can design a study to be the way you want it. Mr. FARLAND. I would agree that that could be done. I would hope that it would not be done. Mr. LEWIS. At the 95 percent confidence level, Doctor, how many of the United States' ETS epidemiological Studies of spousal emoke exposure to lung cancer report significant results as employed in this risk assessment? You did mention this in your opening statement, but at the 95 percent confidence level, how many? Mr. BAYARD. May I answer that? For the ever versus never e osed, I think there was only one or two, Fontham or Fontham an~ Chorea. Only 1 or 2 out of the 11 showed overall atatistical significance. When you start looking- you would have only expected out of 20, if there is no effect, re- member we talked about the 5 percent significance level. When you deal with a 5 percent significance level, if there is no effect, it would be significant 1 time of 20. If no effect, we would have expected 0.5 of the 11 studies or less than one study to be sta- tistically significant. Of the ever versus never exposed, there were one or two U.S. studies which were statistically significant. When you start looking at trends, two or three were statistically significant and in the highest exposure groups, three were, but a lot of Studies just didn't have the information available to test at the highest exposure groups. So based on the 11 studies, we didn't see a tremendous ef- fect in the United States and we explained that by looking at all different countries and our analysis separated the results by the different countries. 19 Mr. LEWIS. Didn't you find that those studies at the 95 nercent confidence level did not meet the criteria that you are telling me until it was dropped down to 90? Mr. BAYARD. No. That isn't the way I remember it. You are talk- ing about only the 11 U.S. studies? Mr. LEWIS. Yes. Mr. BAYARD. It doesn't matter whether there were two studies, if there were two significant studies at the 95 percent level or one or two with the one-tail test. I don't think there was much of a dif- ference because even at the 95 percent level, there wasn't that much significance; if you did the ever versus never, which is a crude measure. A better measure to take is the highest exposure ou Don't forget, everyone is exposed to ETS. If you take ever versus never, even the people you say are never exposed will be exposed, so you are comparing risks of those with a little bit more exposure to those with a little less exposure. It is hard to define a result from any one study. That is why we tried to take all possible stud- ies, the positive and the negative studies, and tried to see what the story was. Mr. LEWIS. I understand as scientists you have to defend your studies. Mr. BAYARD. They are not my studies. We just did the analysis. Mr. LEWIS. I have a problem as the chairman did, going from 95 to 90, it seems like it was establishing a atatistical modality in order to meet a study requirement. I am not accusing you of that, but it is confusing to me. Mr. BAYAxD. We did it two different ways in the same report. For the childhood respiratory effects, we used a two-tailed test, for the lung cancer analysis we used a one-tailed test based on the prior evidence that active smoking causes lung cancer. So we did it two different ways. Mr. LEWIS. Mr. Chairman, I have one last question for Dr. Bay- ard. You stated at an open meeting in EPA on January 7, 1993, chaired by Mr. Bretthauer, that the use of 90 percent confidence intervals was justified because you had a prior feeling that ETS would cause cancer and so it was appropriate to use a so-called one-tailed test and look only at increased risk. How often has EPA adjusted its statistical standards on the basis of a prior feeling? Mr. BAYARD. We do use 90 percent confidence intervals when we extrapolate from high animal to low human exposure, so in that sense yes, we do use 90 percent confidence intervals. The question of whether we adjusted these intervals to get the desired results, it is just the way we did it. We looked-before we even looked at the data, we said what is our prior belief on environmental tobacco smoke; is it going to be beneficial or adverse? Do we have enough evidence to say it is not going to be beneficial? If you don't know which kind of effect you are going to have, you use a two-tailed test. If you have a strong enough belief that any effect you have is going to be adverse, you use a one-tailed test and that is exactly what we did. My belief is that any effect of environmental tobacco smoke would be an adverse one for lung cancer. 4,VT8~VMZ

20 That is not true for childhood respiratory effects. We didn't have that prior belief. This is standard statistical procedure. It was something we raised to our Science Advisory Board. We did not change the methodology. We used a one-tailed test in the first draft, we used a one-tailed test in the second draft, we used a one- tailed test in the final, for lung cancer. We used a two-tailed test in the first draft for respiratory effects, we used two tailed in the second draft for respiratory effects and we used two tailed in the final. We did not change it. We brought it before the SAB and they examined it and said it is fine. It is standard statistical procedure. You learn it in your first course in statistics. Mr. LEWIS. Mr. Chairman, I didn't want to confuse anything. Mr. ROSE. Mr. Baesler. Mr. BAESLER. From your last statement, Doctor, you did start this study with the feeling that you felt there was a problem? Mr. BAYARD. No. Mr. BAESLER. You just said that. Mr. BAYARD. When I started in 1988 I didn't know anything about- Mr. BAESLER. The previous answer to his question you said that you did a one-tailed test because you had the prior feeling that, first of all, there wasn't anything positive out of tobacco smoke, it was going to be negative, and therefore you did the one-tailed test and you had a prior feeling that there was going to be a problem. Mr. BAYARD. With respect to lung cancer? Mr. BAESLER. Yes. Mr. BAYARD. We felt if there was an effect- Mr. BAESLER. You said you had a prior feeling that the effect would be negative. You didn't say if there was an effect. Mr. BAYARD. If there were an effect of environmental tobacco smoke we did not expect it to be protective- Mr. BAESLER. You are backing up. Nowhere did you put if there was effect. The answer to his question was you had a prior feeling there was going to be a negative effect. That is the way you just answered the question. I think that is a big difference to suggest that if there was an effect. The critics will say that you never went into this, EPA never went into this study with the question if there is an effect. The crit- ics will say you went into the study, there will be an effect, how do we substantiate it? Is that true or not true? When you started the study, yo~u had a prior feeling there would be a negative effect; therefore. Therefore you wanted to use a one-tailed effect-mumbo jumbo, nobody understands, thou gh you have said a great deal, and I don't. Representing the largest burley industry in the country, it concerns me that assumptions that you make so cavalierly you make that can so negatively affect such a large industry, which this feeling that you had when you started this bothers me. You said we had this feeling that there was going to be a nega- tive effect; therefore, we did this one-tailed study, which for what- ever scienctic reason, we went from 90 percent to 95 and nobody understands it, unless it is another scientist. We did that, nothing wrong with that. You answered the question about in 1992 some person ques- tioned on the panel about well, are we doing it right or not and you 21 cavalierly threw that off, that wasn't the consensus of the panel, that was one fellow and we didn't use it until the next two times. We have cavalierly thrown off every dissenting view and that bothers me. I have no idea what you are talking about, haven't un- derstood a thing you said all day other than the fact you are trying to defend a study that basically attacks a large industry and you started with the presumption that it would be negative. That both- ers me, because you are supposed to represent all of us, not just one side. The second concern is you said a minute ago in answer to a ques- tion, something about animals. Am I wrong or right? I have no idea, but do you often in these type of studies, class A, use animal- type testing? You do, don't you? Mr. BAYARD. We look at all the evidence. Mr. BAESLER. Did you in this one? Mr. BAYARD. Yes. We looked at animal evidence. Mr. BAESLER. With respect to smoke? Mr. BAYARD. Yes. Mr. BAESLER. So you did that the same as you do the others; cor- rect? Mr. BAYARD. We looked at animal evidence; yes. Mr. BAESLER. How did it affect the animals? Mr. B4YARD. It is more mutagenic than mainstream smoke when applied to the mouse skin and in cell colony tests. Mr. BAESLER. Maybe it is not possible, but can you just-I think basically maybe I am dumb, but I don't understand a thing you are saying. Maybe that is intentional. Tell us in common terms that somebody will understand what we are talking about. We are not scientists. Mr. ROSE. What does mutagenic mean? Mr. BAYARD. Causes gene changes in the DNA which is thought to be a mechanism related to the start-up of cancer. Mr. BAESLER. We talked about 11 studies that you had used in your approach to this analysis. The meta-analysis, you used 11 studies. Mr. BAYARD. No. We used 30 epidemiology studies in the meta- analysis. Mr. BAESLER. Did you combine 11 studies into one big study, or is that wrong? Mr. BAYARD. That is correct. We used 30 studies and when you use a meta-analysis you decide whether or not the studies are dif- ferent between countries-the results are different between coun- tries. We found that we had eight countries which broke into six country groupings. There were 11 United States studies and 5 from Japan and 4 from China, Greece, the United Kingdom, and Sweden. We found that the results differed between countries. Mr. BAESLER. The 11 U.S. studies, that is where the term 11 comes from? Mr. BAYARD. That is correct. Mr. BAESLER. How many of those studies had concluded there wasn't a problem, of the 11? Mr. BAYARD. Out of the 11, probably none, but let me tell you how. Out of those 11, 8 showed increased risk. Between one and SVTSMVOz

r 22 three was statistically significant, depending on how you count them. One showed a slightly decreased risk. That was Janerich, which found a highly significant increased risk for childhood exposure. I am trying to remember the two that actually showed decreased risk, and I don't remember offhand. Mr. BAESLER. Eight of the studies showed increased risk and you said according to how you view it, it could be a problem? Mr. BAYARD. I am sorry, I missed the question. I don't under- stand you. Mr. BAESLER. Not necessarily one to three. I thought you had a statement about according to how you view it could have been a problem. Mr. BAYARD. Eight showed increased risks for the ever versus never exposed. One of those was statistically significant for the ever versus never exposed. Mr. BAESLER. One of the eight? Mr. BAYARD. That is correct. Another two were statistically sig- nificant if you looked at dose response trends or the high exposure groups. Mr. BAESLER. Let me ask a simple question. You individually, did you think there was aproblem when you started? Mr. BAYARD. No. I didn t think that at all. I started in 1988. I didn't know what an RSP was. Mr. BAESLER. You said you started in 1988- Mr. BAYARD. I first was introduced to this problem in 1988. All I do is risk assessment for a living. That is my job. This is just an- other pretty face. I do these things. I don't belong to any program office. We are a group that does this for a living. That is my train- ing. So my answer was no, when I first started I didn't believe it at all. It was only when I saw the evidence on dose response trends and the epidemiology studies that I couldn't explain any other way. Mr. BAESLER. Thank you. Mr. ROSE. Mr. Goodlatte from Virginia. Mr. GOODLA'rrE. I am concerned about how this environmental tobacco smoke policy guide was developed. Can you-Dr. Farland, can you enlighten me on that? Mr. FARLAND. Mr. Goodlatte, the policy guide is a product of the Office of Air and Radiation, not of our Office of Research and De- velopment. We had no involvement in the policy guide other than to make sure that they didn't somehow change the science that was being provided to them through our report. Mr. GooDLATrE. So you don't know how they contracted for the development of that guide? Mr. FARLAND. That was not within our purview. Mr. GoODL.A'rrE. Is there anybody here with you today that- Mr. FARLAND. They are in the other hearing. Mr. GoODLATTE. Maybe I need to go to the other hearing. Mr. BAYARD. You could have invited them over. Mr. GOODLATTE. Let me go back to this 95 percent confidence level versus 90 percent confidence level, Dr. Bayard, do you under- stand the implications of this study? I 23 Tell me what you understand are the public implications of the study that you put out here? Mr. BAYARD. Of the EPA study? Mr. GOODLATTE. Yes. Mr. BAYARD. It hasn't been helpful to me. Mr. GoODLArrE. I am talking about the enormity of this; not just talking about the effect on a major industry , but the implications and considerations every person has to take into account based upon this report that you presented. This is an enormous consider- ation, what your association is with others in the workplace, your homes, your children, and so on. Mr. BAYARD. Much more than I ever thought it would be. Mr. GoODLnTTE. Under those circumstances, do you think it is appropriate to use a lower standard to measure the tests than you use ordinarily in epidemiological studies? Mr. BAYARD. Let me turn that around and say if I am testing at true environmental levels where everyone is exposed, do I want to be 95 percent certain that something causes cancer or am I happy to be 90 percent certain? Mr. GoODLA'rTE. I don't think that is the measure here. The measure here is the number of tests that you can throw out at the 95 percent level as compared to the 90 percent level. Mr. BAYARD. If the question is what is the difference in signifi- cance tests as between the one-tailed and the two-tailed- Mr. GoODLATTE. Here we have what could be one of the most im- portant studies that you have ever participated in, and one of the most important considerations that this panel will consider regard- ing the danger of something to society, and you step down to a lower level of confidence, and I don't understand why you do that. The Washington Post on June 23, quoted EPA as saying that the unquestionable link between smoking and lung cancer makes it de- fensible to accept a lower standard of proof in the case of ETS. Now, we don't accept that kind of lower standard in other meas- ures of determining culpability in our society. We don't say that if somebody is guilty of one murder and it is proved beyond a reasonable doubt that we can accept a lower standard, that we can accept a lower standard of significantly like- ly because they have already been convicted of one murder if the other murder is unrelated to that-we don't accept that in terms of scientific possibility, sayin~ the first poll showed that x was like- ly to be the opinion, so we will accept a lower standard now. Since we are doing it again, and the first one turned out that way we expect the second will turn out that way. Mr. BAYARD. Do you willingly expose yourself to asbestos because it happens to cause cancer in workers exposed somewhere around 100 times what you might get from a little dose? Mr. GOODLATTE. The studies conducted should be accepted. When there are other studies out there that countervail that, why would you apply a lower standard? Mr. BAYARD. There were 30 studies out there and we tried to in- clude them all. I think that is something that wc did that hasn't been done as much in the past. In the past EPA reports have fo- cused more on the positive studies. We tried to focus more on the negative studies. GV M{'.7N09

24 Mr. RosE. Mr. Bishop. Mr. BISHOP. Thank you very much, Mr. Chairman. The release of this risk assessment of environmental tobacco smoke has really been harshly criticized by a number of independ- ent scientists. I have a serious concern with reports that the Agen- cy staff may have ignored the universally accepted standards of sci- entific evidence in order to justify its position. So I really want to focus on the scientific review process to make sure that we have a scientific determination here rather than just a policy review to rubber stamp a preconceived idea. I would like to ask a few questions and maybe get some re- sponses. There have been some allegations that the Science Advi- sory Board panel that reviewed the risk assessment was comprised of a number of individuals that had conflicts of interest and that they had obvious biases against smoking. There are also allegations that some of them had actually been involved in preparing the document that they were asked to re- view. Also there were allegations that a number of well-funded re- cipients of EPA grants were included in the Science Advisory Board panel that conducted the review. Also, there are allegations that the EPA staff had engaged in be- hind-the-scenes maneuvering in order to stack the panel in favor of the Agency's position. I don't know whether that is true or not, but if those kinds of Agency allegations are out there, I think it is incumbent, particularly with the tremendous ramifications of these findings, or these alleged findings, on the environment throughout our country, and not to say what the ramifications will be on the tobacco industry, which is a very important economic contributor, I just think that we need to look at the science of it. Let me just ask you a couple of specific questions. One, did members of the EPA Science Advisory Board assist in the development of your findings in the risk assessment report, yes or no? Mr. BAYARD. Mainly based on their comments at public reviews, with one exception that I can think of. On my first draft in 1990, before we released it for public review, we asked one fellow who subsequently became a member of the Science Advisory Board for his comments, David Burns from the University of California, San Diego, and he provided comments. David Burns had been the sen- ior editor in many of the Surgeon General's reports, including the 1986 report. So I asked for his comments. He gave me a lot of com- ments and subsequently became a member of the SAB. I actually recommended that he was suitable to review our re- port. Dr. BISHOP. Do you see a conflict of interest on having an advi- sory board of scientists reviewing a report which they contributed to the findings of? Mr. BAYARD. He was 1 of 18 members of the SAB. I rec- ommended Nathan Mantel a consultant to the Tobacco Institute, Dr. Gross-no not Gross-Joseph Fleiss, who is a well-known biostatistician. All these people had been recommended to me by the Tobacco Institute. 25 Dr. Kabot, I recommended, who had been recommended by the Tobacco Institute and Dr. Kabot and Dr. Burns were chosen. Those were the only two people that I recommended who were chosen. Mr. BISHOP. It is my understanding that there was a policy or an understanding established that if the data and the EPA's sci- entific guidelines did not show that ETS was a carcinogen, then the Science Adviso Board felt that the guidelines should be revised. Is that accurat~ Mr. FARLAND. Mr. Bishop, maybe I can address that point. The chairman of the Science Advisory Board took a question at the end of one of the public meetings about the sufficiency of the data for environmental tobacco smoke and the question was whether or not according to EPA's guidelines this could be classified as a class A carcinogen. His response was with this amount of information, if it could not be classified as a class A carcinogen, then the guidelines would have to be changed. That is, if the guidelines were getting in the way of the classification of this as a class A carcinogen be- cause they were somehow restrictive to certain types of data, and wouldn't allow you to use all the information available, then there would need to be a change. That was not a SAB finding. It was a comment of the chairman to a question of him. It specifically points to the fact that the guide- lines where not restrictive, that they are meant to be used with sci- entific ,~'udgment and to weigh all of the evidence available. Mr. BISHOP. The draft report of April of 1991, page 29, "If the guidelines for carcinogenic risk assessment can be used to cast doubt on a finding and inhalation of tobacco smoke by humans causes an increased risk of lung cancer, the situation suggests a need to revise the guidelines." Now, I really am not in a position to determine whether there is a risk of harm that is created or not. My concern is with the ef- fect of what you are doing here and the effect of this EPA study on our country that we ought to really be looking at a scientific process and that we ought to be acting on and be driven by science and not by a policy and trym g to come on the back end and justify a policy that has been predetermined. Tlus is just a lack of objectivity. It suggests a subjective approach here, to change the rules to fit what you expect-what you want the outcome to be. That concerns me because of the effect that what you are doing could have on my district. Mr. FARLAND. Mr. Bishop, I would like to try and convince you that this study was extensively reviewed by our scientific peers. We took a lot of comment and responded to those comments in terms of the development of this report. The Science Advisory Board se- lection of members was done in an open process, as is always done. I can't comment personally on the selection of those individuals since that is outside of my jurisdiction, but as Dr. Bayard men- tioned we did submit a series of names that were scientists who were well-qualified and had represented a number of sides of this particular issue. The question about the guidance that is put out there is clearly one that is an argument for the use of scientific judgment and not for allowing a strict framework in which one eliminates information so as not to consider it when you reach your conclusions. This is not looking at an issue of trying to change the

GU approach in order to fit the end. This is a strong endorsement of using good science, using good scientific judgment, and this is something that both we and our Science Advisory Board are com- mitted to. Mr. BISHOP. I appreciate the statement you are making, but it does not seem consistent with what has been brought out today and what I have seen. It seems to me that there is more of a cloud here than there is clarity. Based upon the process, it seems to me the integrity of the story of the study has certainly come into ques- tion. Based upon the objectivity of the contributors or the lack of objectivity, it seems there is more of a cloud than clarity. Mr. BAYARD. Did you know we are criticized more by the antismoking folks for the makeup of the Science Advisory Board? Did you know Dr. Lippman was attacked because he was chairman of the committee for indoor air research [CIAR.J, which is heavily funded by the Tobacco Institute. Did you know Dr. Woods was in the process of negotiating a $1.2 million grant with the Tobacco Institute at that time? In fact, 6 of the 17 members had financial ties to the Tobacco Institute. We were heavily criticized by the antitobacco folks. Mr. BisHop. It seems like what you are saying is you are agree- ing more of a fog has been created? I don't think what you need is to have- Mr. FAR[.ANn. I think what we are seeing is these are individuals with strong scientific credentials, and that is not an issue with re- gard to where their funding is coming from in terms of their ability to reach conclusions on this particular report. We were criticized from both sides because of the makeup of this report. It was a bal- anced report and very strongly scientifically staffed. Mr. BISHOP. I appreciate your comments. I am not certain that I have any more clarity now that I did before you started answer- ing. Thanks a lot. Mr. RosE. I told Mr. Lewis I was going to call on Mr. Barlow next, then our colleague here and then over here. Mr. Barlow. Mr. BARLOW. Doctors, thank you very much for being here. I have not had a chance to go through all your studies. I assume they will be in the record. I wonder if you might help me. You all obviously saw these and prayed over them for a long time. Mr. FARLAND. Once or twice. Mr. BARLOW. Give me help here, basic down-to-earth help and guidance, if you can. How many of these studies would you esti- mate deal with physical dimensions of the areas in which environ- mental tobacco smoke arises? In other words, to give you an exam- ple: Environmental tobacco smoke in a room the size of this may not be as omnipresent as the same amount of tobacco smoke in a closet might be. Can you give me an estimate on the numbers of studies that cover that? Mr. FARLAND. The 30 epidemiology studies we looked at were based on exposure of nonsmoking women, spouses of smokers in their home; so that the exposure to tobacco smoke in the home was Te ;~T8MV0Z 27 considered to be the exposure under test in these epidemiology studies. Mr. BARLOW. Now somebody smoking over in the far corner of that room, of this room here-which is a very large room, for the record-may not have an~ yimpact on me sitting up here on the op- posite side of the room. Would you agree? Mr. FAx[.ANn. The smoke will be diluted as it goes up into the room; that is correct. Mr. BARLOW. May not even reach this side of the room, depend- ing upon the drafts and so forth? Mr. FARt.ArID. It is possible; that is right. Mr. BARLOw. Are variations such as that taken into account? Mr. FAR[.Arm. Again the way this was done was to look specifi- cally at spouses of smo6rs; and in that particular case, as Dr. Bay- ard mentioned, these are very difficult epidemiology studies be- cause we all have some exposure to environmental tobacco smoke, so we were looking for groups of people, or the investigators were looking for groups of people, who had a higher than normal expo- sure to environmental tobacco smoke-still environmental levels but a higher than normal average exposure-so that they could de- termine whether an effect was produced. That is what all 30 of these studies tried to look at, smoking in the home. Mr. BARLOW. It is difficult to construct a case when you have an extreme variation in physical surroundings; you would agree, ri ght? Frequency of smoke, it is very difficult again to make a statis- tical-one statistical finding based on many variations and fre- quency of smoke. If someone were to smoke a cigar in the back of this very large room, it might not have any impact upon me; espe- cially if I am only coming in once a week, twice a week, and that person may be only smoking a cigar once or twice a week. Mr. BAYARD. Not only that, but for lung cancer you have to fig- ure out what the exposure has been over the past 30 years. Mr. BARLOW. You have a very difficult job coming up with a sta- tistical sample. Mr. BAYARD. It is hard to believe any of these studies a priori would show an effect. Mr. FAFU.A1vn. I think that is an important point with regard to the chart we showed. The first aeproach I showed analyzmg the 30 studies, was a question of "ever versus "never." ~t wasJ ust sim- ply whether or not you lived in a home with a smoker. There are vast differences in those types of studies. Mr. BARLOW. Wouldn't you say it might be unfair to tobacco farmers and the tobacco industry to make a one-phrase condemna- tion which-environmental tobacco smoke is kind of becoming a pejorative phrase, a negative phrase-when you have many vari- ations and conditions over many years? Wouldn't you say that might be unfair? Mr. FAR.ANn. Again, I think the point we are making is that from a scientific and a public health perspective, we can talk about the hazards, about the risks; but people have to make their own judgments and risk managers in local situations, in States, in res- taurants, fiave to reach conclusions with regard to how that risk is going to be managed.

r 28 This is not a general condemnation in the sense that a small amount of environmental tobacco smoke will cause all of these ef- fects we are talking about. This is a discussion about real people who have experienced effects. That has been measured in scientific studies both in lung cancer and in childhood respiratory effects. Peopie have to take that information and make informed risk management judgments, whether personal judgments or whether or not they are some sort of regulatory judgments at the State, local, or Federal level. Mr. BARLOW. You are making a judgment applying one short phrase, environmental tobacco smoke, which, as I say and many people feel, has gotten to have a negative implication connotation on the worse case situations. You are classifying the heavy smoke in a very confined space like a closet, equating that with very infre- quent smoke in a room as large as this? Mr. Fn[u.AND. In terms of a hazard call, it is equivalent to talk- ing about asbestos as a carcinogen based upon occupational expo- sures. It is based upon talking about other types of occupational ex- posures to chromium, or other types of inetals or benzidine dyes or any of those in terms of a hazard. There is a hazard to exposure to environmental tobacco smoke. Now, the risks depend upon the exposure. If you can avoid envi- ronmental exposure, or if you can lessen your exposure to environ- mental tobacco smoke, you are going to lessen your risk. Mr. BARLOW. Some of those hazards may be very minimal, right? Mr. FARLANn. Under certain conditions, absolutely. Mr. BARLOW. I can recall in my lifetime my father would smoke an occasional pipe or cigar. I enjoyed as a young child smelling the smoke as it wafted across the room; and any hazard I mi ght have incurred in that process might have more than been made up for the love of being with my father and enjoying his enjoyment of his pastime, true? Mr. FARLANn. Mr. Barlow, that is a personal choice. I think it is absolutely true. I think you ought to be informed about the po- tential hazards and then make that judgment. Mr. BARLOW. Thank you, Mr. Chairman. Mr. ROSE. Thank you. But the data would suggest that what you just described would be good for you. Mr. BARLOW. Yes. Mr. ROSE. Mr. Lewis. Mr. LEWIS. Mr. Kingston of Georgia. Mr. KINGSTON. Thank you, Mr. Chairman and Mr. Lewis. I want- ed to ask you about the integrity of the study, which I know you are getting pounded on a lot. I hate to be redundant; but my father was a college professor. He told me years ago when, unfortunately, Federal dollars got involved on university campuses, all the studies suddenly became politically correct, with the conclusion meaning that more money had to be spent on that particular item that they were studying. In other words, it was predestined, whatever their conclusion was going to be. Knowing the pressures you folks are under, do you feel in your heart of hearts that this study was objective and just-I am not trying to belabor. Just a simple yes. Z~l 8MV0Z I 29 Then, since you are shaking your heads yes, all three of you agree with that-another thing that we studied-I studied chem- istry in college. Whenever you do a study, you have to look at the prejudice of the scientist. With that in mind, do you folks smoke? Do any of the people in the study smoke? Or was it-maybe a little bit, as Mr. Bishop suggested, maybe there was some antismoking sentiment in the scientists, that was there. Is that the case? Do you think-did you have a mixture? That is very important to know what the prejudice of the scientist is. Mr. BAYARD. I think probably it is better I answer that. If you want Dr. Farland to- Mr. KINGSTON. No. I know you are the point man. Mr. BAYARD. I am the project manager for this. I had something to do with choosing the contracting support. In terms of money, my paycheck just doesn't change. It hasn't changed for 14 years other than cost-of-living allowances. I have never been offered money from the antitobacco folks or the tobacco folks. I don't know what that means. In terms of smoking, I smoke an occasional cigar or occasionally smoke a cigar-good ones, actually. In terms of the objective, a couple of my-I have five children. Four are adult children. Two smoke, two don't. My exwife smokes, but I don't blame smoking for her. In terms of objectives, this is what I do for a living. In terms of getting people, now, what I tried to do was get people-the most unbiased people, people who knew nothing about tobacco smoke be- cause it had been- Mr. KINGSTON. The reason I am concerned about that, as a new Member of Congress, I find almost whatever you are trying to find out about, if it comes from one party, it goes this way; if it comes from another party, it goes that way. It is not tobacco studies but budget, anything you ask. In fact, I don't know if you have seen the arGicle-I will be happy to share it with you-a book called Galileo's Revision: Junk Science in the Courtroom. In it, Peter Huber of the Manhattan Institute for Policy Research talked about how lawyers get scientists in a court- room, that come up with conclusions that basically back up their argument. I just see a real corruption in the pure aA of science these days. It really depends on who is writing the check for the grant, the study. I say that because the National Cancer Institute had done a very comprehensive study which they released in November that said there was no significant link; and, I don't know if this is-if we are getting politics in the lab. That worries me. Mr. BAYARD. I can tell you I am not antismoker. I don't get paid any more for what I say. No matter what I say today, I will get paid the same tomorrow. I get paid every other Tuesday. You are going to get some other contractors coming up here. You ask them if they will get paid tomorrow depending upon what they say.

30 I stand by my own personal objectivity. I am sure if I had had any links, they would have been discovered by now; you would have known about them. Mr. FARLAND. To follow up on that, I think it is important we understand the process used for this report. We had numerous sci- entists involved in reviewing the drafts, as it was developed. Cer- tainly, within our own Office of Research and Development, there was a lot of internal peer review, scientific peers who had no par- ticular biases or no particular connection with this report as they made their views known. The external scientists that we go to routinely-we go to a wide range of scientists. As Dr. Bayard mentioned earlier, there were some 18 scientists on the Science Advisory Board panel. I men- tioned in my opening remarks, in my testimony, that these were follow-up reports to the U.S. Surgeon General's report in 1986, the National Research Council, Academy of Sciences in 1986; the World Health Organization in 1986 and 1992; National Institute of Envi- ronmental Health Sciences in 1991; and the National Cancer Insti- tute in 1993. To suggest that all of those individuals would somehow be biased in a way that would argue wrongly that there is a public health impact of environmental tobacco smoke, I just don't believe it is possible. Mr. KINGSTON. I am glad to hear that. Let me ask one other question that gets to Congressman Barlow's question. In terms of the size of a room or whatever, when somebody is smoking and the smoke becomes diffused, I suppose the smoke chemically reacts with some other chemical in the air, that the smoke intermingles with oxygen or whatever is out there. In your study, did you study the effect of a household in the inner city, for example, or maybe one that never uses air-condi- tioning, compare those two, versus one that is outside with a good breeze? Did you weigh out differences like that? Mr. FARLAND. Again, these studies are from eight countries around the world. Some of them were actually looking at the use of smoky coal from a heating source. In fact, there appeared to be lung cancer associated with the use of that smoky coal as an indoor air pollutant. Mr. KINGSTON. Would that skew the study? Mr. FARLAND. In that particular case, it quite likely wiped out any small effect associated with environmental tobacco smoke. Mr. KINGSTON. You would eliminate that household from the study? Mr. FARLANn. In that particular study, the study was actually of a group of individuals who lived under those kinds of conditions. It looked at a number of different ways of evaluating lung cancer; and in that particular study, there was no indication of environ- mental tobacco smoke or tobacco use causing an increased risk. There was an association with the smoky coal. Mr. KINGSTON. Would you do the same or did those studies do the same thing if there was radon in the air or somebody living un- derneath an el train and somebody-in an inner city versus some- body living in suburbia. 31 Mr. FARLAND. This is why it is difficult using one study to reach conclusions. This is why we had to use all the information available to us. I think what it shows is some studies were much more pow- erful than others. That some showed no increase may very well have been because both the exposed and the control individuals were showing some lung cancer risk from some other source; and because it pushed both of them up, it washed out the effect of the smoking. We just do not know. That is the nature of these studies. Again, this is a fairly unique data base because these are results that are being looked at at environmental levels as opposed to very high levels in the workplace, or what have you. Mr. KINGSTON. In the 90 versus 95 percent, would that tie into that at all? Mr. FARLAND. Again, I really believe that the issue of 90 versus 95 percent is a red herring. It is a statistical test of significance that is a 95 percent test. It has a confidence interval of 90 percent; and that 90 percent, as we have agreed to here, is less than 95 per- cent. But if the results that one finds are significant at 90 percent, and not significant at 95 percent, in light of all of the biological infor- mation, in light of all of the other studies that have been done on animals and other groups like that, you are not going to be con- vinced by that simple statistic. You. are going to make a decision on the basis of biological plausibility, on the basis of consistency of results, of findings from other studies and so on. That is very important. Mr. KINGSTON. Thank you, Mr. Chairman. Mr. ROSE. Thank you very much. Any further questions? Mr. Inslee. Mr. INSLEE. Thank you, Mr. Chairman. As far as ETS, I am trying to get a grasp of what you are saying. It has been very educational. But is this a situation where you as- sume that ETS has carcinogenic properties, so the real question be- comes, is there enough exposure in real life to produce carcinogenic effects? Do you see what I am driving at? In other words, is that the real heart of this study? Mr. FARLAND. Mr. Inslee, you asked the right question: First of all, is there a hazard, a carcinogenic hazard, associated with ETS? The answer to that was brought up in the first discussion. We categorize it as a category A known human carcinogen. We are quite confident. The question of risk has to do with how much exposure we get. Now, it is-for chemical carcinogens where there is a substantial data base on mechanisms of action, we can generally assume that there is a linear response from high doses to low doses, so that the probability of a cancer response will decrease as the exposure de- creases. At some point, we are going to reach a level where that prob- ability of cancer risk is no longer significant. It may still be there. There may still be a very small cancer risk associated with it; but given our lifestyle, everything else we do, it will not be significant. ~I~IRMVn71

Ir 32 That is what we really have to take into account as we make risk management decisions. Are we dealing with a situation that is high enough to be of concern to us, or are we dealing with occasional ex- posures that are not necessarily going to be a risk? What we are telling you in this particular case is that in individ- uals who lived with smokers we were able to measure-our inves- tigators were able to measure an increased cancer risk using a very crude tool which is an epidemiology study. So it is quite likely that the significance of that cancer risk is sufficient to be a public health concern. Mr. INSLEE. The report, at least my brief scan of it, indicated there were not workplace studies, that we do not have good epide- miological studies on workplace environments. Is that accurate? Mr. FARLANn. We did not focus on the workplace environments. I will let Dr. Bayard explain why. We actually talked about that in our report, so it was clear why we used these other studies. Mr. INSLEE. I think I can assume the reason why. You had lesser levels of exposure, not as much stability in the exposure, those rea- sons. But does that indicate that in our public policy we should not use this study for workplace policym aking questions? Mr. BAYARD. That would be for my response. The fact that a workplace is a much tougher place to look at exposure of environ- mental tobacco smoke doesn't mean that-I am sorry. To me, if en- vironmental tobacco smoke is carcinogenic in the home, because you are exposed in the home and because you can measure it better in the home means you should be careful in the workplace, too. In fact, in the numbers in our report we look at both home and nonhome exposures and calculate a total number of potential can- cer cases from home and nonhome exposures. Mr. INSLEE. That is included in the number, then? Mr. FARLmD. That is right. Mr. INSLEE. As far as peer review, has this study undergone or should it undergo a peer review process that, customarily, the study would be exposed to? Mr. FAFUANn. This study has undergone as much or more than studies that we have been doing over the past 8 to 10 years. Mr. INSLEE. As far as this was just an academic study that, as I understand the process, will commonly go through peer review process, has this gone through a similar process? In other words, do you have a study coming out in a journal? Mr. BAYARD. We do a few articles for journals. There are usually two or three reviewers. This one had 18, plus all the public review. Mr. FARLAND. This one was extensively peer reviewed. Mr. INSLEE. Thank you. Mr. ROSE. We have been 2 hours on this. We have had our first witness. So we will be here until midnight. Dr. Farland, in March of 1990, you sent an internal review draft of the ETS risk assessment to various groups within EPA, includ- ing the Environmental Criteria and Assessment Office in Cin- cinnati. What is the role of this office and what type of expertise does it have? May I suggest an answer for you, and you tell me if I am riRht or wrong. If you want to add to it, tell me, and you can. VMMM 33 Is it not true the Cincinnati ECAO group is a team of scientists with complementary expertise that involves itself in health risk as- sessments? The group includes experts in epidemiology and toxi- cology ? Mr. FARLnND. Yes, Mr. Chairman. Mr. ROSE. Would you add to that? Mr. FARLAND. I would say, yes. That is part of my group. That is my Cincinnati office. Mr. ROSE. I have seen from the documents that you provided to us that in a letter to you from Dr. Sonic from-which one is that; all right-dated April 27, 1990, signed by Acting Director, Dr. DeRosa, the Cincinnati group questioned the use of meta-analysis to support the classification as a group A carcinogen and suggested that the epidemiologic studies more appropriately reflect limited evidence of human carcinogenity. They also stated that there are substantial differences between mainstream smoke and sidestream smoke, or ETS, and con- sequently it is difficult to generalize about the properties of one study from the other. Thegr oup also commented that, finally, there are tremendous scientific regulatory and political ramifications of categorizing a substance as a group A carcinogen. With all due respect to the epi- demiologists who produced the report, given the inherent limita- tions of the data and the comparative novelty of the approach used to interpret the data, I would recommend that this approach not be used as the basis of a group A classification. Now, none of the documents that you provided to us contained-~ ~ any response to these comments either by you or by Dr. Bayard. What response did you give le Cincinnati group? Here is the document, technical manuscript review form, recommendations, ac- ~eeptable after major revision. OK? Mr. FARLeNn.es, Mr. Chairman. That was the first draft. As I said, it went through extensive internal review. This is our group. My response to that was to have a conference call to follow up with the scientists who were involved in the Cincinnati review and with our own scientists here to discuss the data, to discuss the is- sues they had laid out in that memo; and we took to heart their perspectives on that. They are certainly not the only oneQ that have provided that type of a perspective. - -: , :-.. ^ . 1. . . And we indicated that we would further strengthen the docu- ment as we went through the draft, taking other comments into ac- count; and we would supply it to the Science Advisory Board to help us finalize it. So, again, I think it points out that there is a diversity of views on these particular issues, those within our own group. But we did very strongly address many of the issues that were raised simply because that is the purpose of peer review, trying to understand where the misconceptions or the changes might be. Mr. RosE. All right. On March 9, 1992, you sent a memorandum to several EPA grousm asking for a second internal review of a revised draft, I ~,r.a that would be the second draft of the risk assessment. How I.~n~ wr. the dr.ft document at this time and can you tell us how m.nr Mre ke were allowed for this review of your second draft?

r 34 My indication is that the document was between 300 to 600 pages long, and you gave them about 13 to 14 days to review it. Mr. FARLAND. That is not unusual, Mr. Chairman, when we are dealing with the second draft of a document. About 2 weeks is what I would have said, although I do not really know that for sure. Mr. RosE. Let me move on to my real question here. I gather the Environmental Criteria Assessment Group in Cin- cinnati was critical of the time allowed for the review. It so indi- cates? Mr. FARLAND. That is also not unusual. Mr. ROSE. I understand. Dr. Harvey, Director of the ECAO in Cincinnati at that time, wrote on March 24, 1992 in this document that "No one liked the 11-day time allotted for review." He contin- ued "I suggest that the document manager consider more time for ev2uation to balance the seriousness of this document as applied to the public health and the intrinsic value of doing it right on this key health topic." What was your response to this criticism? Do you think it appro- priate to allow 11 days for the thorough review of a 600-page-you already said that is typical. What was your response to Dr. Harvey's- Mr. FARr.AND. Again, Dr. Harvey is my director out there at ECAO; we did talk about that. This is certainly not the only docu- ment we worked on. We work on lots of different things. We put time pressures on our scientific staff to review these. This document was 4 years in the making. It went through a tre- mendous amount of peer review. While we may not have gotten the extensive commentary from Dr. Harvey's group, we feel it was ade- quately peer revie edw Mr. ROSE. Now, you told us affter this April 27, 1990, first draft, you had a conference telephone call, and you took things that they said into consideration; so here comes the-their review of the sec- ond draft which, as you observed, they had 11 days to look at and gave it-sent it out on March 24, 1992, almost 2 years later. The ECAO group.in Cincinnati seemed hi ghly critical of this re- draft of the risk assessment, as it existed in March 1992. While Dr. Murphy appealed for more time, she did in her limited review find plenty to criticize about the risk assessment. She wrote, "Was there any attempt made to include nonpublished studies which are likely to have nonpositive findings in the review?" She concluded later, "I, feel that the importance of the trend test and its associated prob- ability value is overstated. Misclassification and measurement error can mask a dose response trend, but can also sometimes cre- ate one." Moreover, she wrote, concerning the lack of consistency of the histologic-type of lung cancer that, "I feel that it distracts from the presumed causal relationship of lung cancer and ETS." Here again, we have no copies of your response to that. What was your response to these concerns? Mr. FARLANn.Ag am, these comments, along with the other com- ments from the other groups, were passed on to Dr. Bayard as the manager. He had the opportunity to address those comments. I can let Dr. Bayard speak to that directly. a~~~~~9~(17 35 Mr. ROSE. Make a note, Dr. Bayard. We will come back to you. Let me just get one more thing out here. Then I am about through. Dr. Harvey also wrote in his March 24 letter to Linda Bailey- Becht, "I suggest a full discussion of carcinogen category A versus B based on the absence of definitive data of passive ETS in hu- mans. Like it or not, EPA should live within its own categorization framework or clearly explain why we chose not to do so." Dr. Harvey also wrote that "ECAO-CIN will be most happy to spend further time improving the quality of this document." What was your response to these criticisms that the Agency's guidelines were not being followed? Did you have discussions on these matters with either Dr. Harvey or his staff? How was this matter resolved? Mr. FAxl,Alvn. I did have discussions with Dr. Harvey on that particular issue because Dr. Harvey had been with us for a little over a year at that time. He had not been involved in the develop- ment of the guidelines, and the discussion about how EPA's classi- fication system was dealing with various types of chemical cases was not particularly well known to him. We talked about the category A classification. We talked about efforts that were going on to revise our guidelines and to use a nar- rative-type of approach rather than an alphanumeric classification, a box. Mr. ROSE. Could you provide for the record any correspondence or notes you had on this subject, please? Mr. FARLAND. Mr. Chairman, I will look. I don't believe I have any notes on that. I think they would have been sent up before if they were available. Mr. ROSE. Take another look. We haven't had a chance to ask you all the questions that we have, but we would like to supply them for the record. [The information follows:] A copy of EPA's Carcinogen Riek Assessment Guidelines and a list of documents on compounds that have been evaluated for carcinogenicity were provided to you in your onginal reque®t. We ~~ill be happy to provide further discussion of such docu- ments if you with. Mr. ROSE. If you will shepherd that effort to get us that informa- tion, we would appreciate it. Mr. FA13.LANn. We will be pleased to deal with those questions. Mr. ROSE. Dr. Bayard, did you have anything to do with the se- lection of the companies that were contracted with by EPA to do your study, your evaluation? In other words, you were the Project Manager. Actually, how many contractors out there were working under you? Mr. BAYARD. Let me try to get to that the best I can. Mr. ROSE. That is what I want you to do, but quickly. Five, six, 10? 1±4r. BAYARD. ICF was a contractor; Battelle was a contractor. Those two, but most of those had subcontractors. Mr. ROSE. All right. And who made the choice about those two? Mr. BAYARD. I did not choose- Mr. RosE. Beg your pardon? You made the decision?

36 Mr. BAYARD. To choose ICF? I guess I did, but it was chosen mainly as an umbrella contractor. Mr. ROSE. Yes. Mr. BAYARD. I am not the Project Officer on any of those. Mr. ROSE. You were the Project Manager. Mr. BAYARD. I am the Project Manager, but not the Project Offi- cer on contracts. Mr. ROSE. Did they work for you? Mr. BAYARD. I am a Work Assignment Manager on contracts. I submit the work assignment I want done. Mr. ROSE. To ICF, is it ICI? Mr. BAYARD. ICF was one. Battelle was another. Mr. ROSE. They subcontracted the contract to the Institute for Smoking Policy? Mr. BAYARD. No. I had nothing to do with that. Mr. ROSE. That was my question. I didn't ask, did you have any- thing to do with it. I said the contractor that you picked. ICF, they assigned it? Mr. BAYARD. The Institute for Smoking Policy had nothing to do with the risk assessment. They had to do with the workplace policy guide. I am here to discuss the risk assessment. I also used con- tractors from ICF. If you want, I will be glad to talk about that. Mr. ROSE. No. You had experience with these people before, had you not? Mr. BAYARD. ICF? Mr. ROSE. Yes. Mr. BAYARD. A very good atatistician worked at ICF, we used for the first draft. Mr. ROSE. We have to go vote. We will be back within a few min- utes. I think Mr. Baesler has a few more questions. We will try to be back within 10 minutes. [Recess taken.] Mr. ROSE. The subcommittee will come to order. I will restate for the record that we have a lot of questions that have not been an- swered, that we would appreciate the Agency responding to us in the usual timely fashion. Mr. Baesler. Mr. BAESLER. We have talked about several studies during the day. I would like to talk about one particularly. I notice that the Fontham study-we note in this regard that the revised drafts of the risk assessment dates from fall of 1992, not long after the Fontham study appeared, take the study results fully into the ac- count. You did take the Fontham study results fully into account; is that correct? Mr. BAYARD. Yes. Mr. BAESLER. We see amonp the documents provided a memo stating that even more emphasis needed to be put on the Fontham because it was NCI funded and it was the largest study. Brownson was also NCI funded and even larger than Fontham. Finally and perhaps most disturbing we have seen a document in which Kenneth Brown promises Dr. 'Fontham to hold up the cir- culation of the revised risk assessment draft until her study ap- 37 pears in the scientific literature. On October 12, 1991, we see that Kenneth Brown wrote to Dr. Fontham and said of the inclusion, "The time element is of concern to EPA, but I will not violate your request for propriety. Without permission from you I will hold a re- vised version that includes your study until it appears in print and is thus publicly available." It is my concern and the committee's concern that you seem to spare no effort to take into account the studies that help your case, but you didn't give the same consideration to studies that didn't help your case. How do you respond to that? Mr. FARLANn. The report published in December of 1992 listed a number of studies that came out shortly after the Science Advi- sory Board had looked at our report and had essentially given us a final sign-off. They included Stockwell and Brownson. As you are probably aware, scientists who are involved in this particular field get preprints of the materials before they are fi- nally published. We had preprints of the Fontham study, preprints of the Brownson study as they were being developed, but there is a reason that one cannot cite certain studies until they have ap- peared in the published scientific literature. I will let Dr. Bayard speak specifically to the issue of how we dealt with the Fontham study. We have taken into account the two other studies that were men- tioned, particularly Stockwell and Brownson. Both are consistent with our results. They are not at odds with our results, and I think you will see that in our report there is a statement to that effect. So we have not ignored those studies at all. Mr. BAESLER. Another question on the Fontham study. The risk assessment classifies the Fontham study as tier 1, these being studies that are of greatest utility for investigating a potential as- sociation between ETS and lung cancer. You say use of dietary, oc- cupational, and other exposure data in that analysis, along with an additional 2 years of subject accrual, will make the completed study for this, which constitutes an interim report, even more valu- able. From this I understand that you realize that the Fontham study published in 1991 did not attempt to analyze the effect of confound- ing factors. Since your guidelines for carcinogen risk assessments require you to rule out the possibility that confounding factors might account for an observed increase in risk, I assume that you asked Fontham to undertake analysis of the effects of compounding factors such as diet and previous lung disease, yet I see no commu- nication between EPA and Dr. Fontham in these documents that you supplied to me that discusses this matter. Did you commu- nicate with Dr. Fontham on this matter? Mr. BAYARD. On the matter of confounding? Mr. BAESLER. Yes, sir. Mr. BAYARD. I communicated with Dr. Fontham a lot-not that much-and we talked about confounding. The way the study was designed made it really helpful because there were very few con- founders left. Mr. BAESLER. I will read from the study. Mr. ROSE. Do you have an answer, sir? 9~TSMfi0Z

38 Mr. BAYARD. Yes. We talked to her about workplace, about child- hood exposures, about the exposure measurements, about whether or not we should pick population controls or the colon cancer con- trols. We talked about-there was one more-I am sorry I forget. Mr. BAESLER. Fontham did appear before the SAB in July 1992 where she stated, the approximate 30 percent risk of lung cancer associated with s ousal ETS exposure persisted after adjustments for vegetable consumption which was the most significant food or nutrient factor, family history of lung cancer and employment in hi gh risk occupations or industries. Whether or not this is correct, these findings have not been pub- lished in the peer review literature; have they? Mr. BAYARD. I think that is correct. Mr. BAESLER. Moreover, there is no evidence that EPA even thought this analysis to be important, though clearly some of us would think it was. Also Dr. Wu Williams, a coauthor of the Fontham study, cur- rently has a grant with NCI to undertake the analysis that Fontham said were complete to the SAB; is that correct? Mr. BAYARD. I don't know. Mr. BAESLER. Dr. Wu Williams is a coauthor of the Fontham study. He applied to the National Institutes of Health in October 1991 for a grant to analyze the Fontham study data. D,r. Wu Wil- liams' project description includes a proposal to evaluate "the inde- pendent effect associated with each of the above factors, indoor air pollution, diet and instances of previous lung disease and its poten- tial confounding effect on the passive smoking lung cancer associa- tion." A summary statement of a special review committee that re- viewed the grant proposal of the National Institutes of Health stat- ed that, "given the relatively small risk found for passive smoking, it is critical that ETS possible confounding factors be investigated to determine whether the passive smoke effect is merely the result of confounding or of other variables." This grant was awarded with an initial project period from June 1992 to May 1993. Were you aware of this? Mr. BAYARD. No. Mr. BAESLER. Do you agree with the comments of the NIH Spe- cial Review Committee that it is critical that other possible con- founding factors be investigated to determine whether the passive smoke effect is merely the result of compounding smoke or other variables? Do you agree with that? Mr. BAYARD. In the Fontham study or all studies? Mr. BAESLER. How about the Fontham study and all-include ev- erything. About the Fontham study first. Mr. BAYARD. My answer is no. Mr. BAESLER. On both cases, right? Mr. BAYARD. No. The question was is it critical with respect to our finding whether or not the Fontham study might have had more confounders and the answer is no because the Fontham study would have been one of 33 studies on epidemiology Mr. BAESLER. What steps did you take to insure that the relettvr risks reported in the Fontham study were not merely the reMult 4 V.1~ I 8~V ~V 09 39 confounding of other variables? Did you take any steps in your study on that? Mr. BAYARD. We examined every one of the studies where con- founders were addressed. We couldn't identify any one confounder that could have possibly been responsible for dose response rela- tionships that we saw or the fact that we saw these increases in all different countries. For instance, diet changes in every country, and yet we saw the effect of passive smoking in all the countries we looked at, with the exception of China, where the studies were mainly to examine the effects of smoke and other indoor air pollutants. Mr. BAESLER. It seems to me that there are many doubts sur- rounding the Fontham study in terms of there being an incom lp ete report that did analyze for potential confounding factors. I tlunk' everybody agrees that there wasn't analyzing for confounding fac- tors. That the study should not have been mcluded in the meta- analysis of the U.S. studies. I gather that a meta-analysis of the U.S. studies, including the two new studies, but excluding Fontham, gives us a statistical nonsignificant summary risk of 1.04. This suggests to me a considerable instability in the data. How can you claim such confidence in your analysis when slight changes of studies considered have such effects? In other words, if we take out the Fontham study, it seems it changes the whole thing. Mr. BAYARD. Why would you take out the best study we have available? Mr. BAESLER. Maybe because they didn't take into account the confounding factors. Mr. BAYARD. It was a published study in a well-respected journal supported by the National Cancer Institute the same way the Brownson study and Stockwell study were. Why should we take that out? It seems to me you are just being critical of the studies that were positive. Mr. BAESLER. Do you think it is relevant that now we have a grant Oven to study this study and how confounding factors might affect it. The National Cancer Institute has given a grant to study the effect of confounding factors as pointed out by the Fontham study, which you indicate is the best study you had to make your ar ment and the results of the ETS problem. ur. BAYARD. It was the only tier 1 U.S. study, if I am not mis- taken. There were several tier 1 studies in other countries. Mr. BAESLER. Maybe I just don't know enough, but you admit that we didn't do an analysis on what the other confounding effects might have had on Fontham's results? Mr. BAYARD. If I had had the information on diet, if I had known it existed, I would have done the analysis on confounding. Mr. BAESLER. You wouldn't do it, but the National Cancer Insti- tute thinks it is relevant enough that they will give, a grant to a Qroup of people to do a study that you said wasn't relevant. ktr F kHt.A~.n Mr Baesler, I think it is very important that you un=1, r%tand that we would have follow-up studies on the majority „/ t he r{~iArmi~~lolry studies that are published in the literature t,-1~~ TIwow studies find information, they develop additional

40 hypotheses and they suggest additional studies that need to be done. That is the way that the epidemiology work is done. I think this was a well-designed study that took into account a number of these issues with regard to confoundinP that many oth- ers did not. While there was not a specific analysis of confounding published with that study, I wouldn't argue that the answer was in and that we shouldn't do any additional research. The authors of the study came into the National Cancer Institute to get an additional study. They may find when they collect more information that the relative risks may go up, they may go down, or are not clear. Mr. ROSE. One question. Did you do a one-tailed analysis of the Fontham study? Mr. BAYARD. Yes. Mr. RosE. And the issues around confounded hadn't been re- solved; is that correct? Mr. BAYARD. That is correct. Mr. ROSE. And if you had done a two-tailed study on Fontham, your-what is the- Mr. BAYARD. Significance level Mr. RosE. Your confidence level would have been 95 percent; right? Mr. BAYARD. That is correct. It is close enough. Mr. ROSE. But you did a one-tailed study and essentially your confidence level is 90 with the one-tailed study? Mr. BAYARD. Yes. Mr. ROSE. That is all I was trying to get at earlier, Dr. Farland. Why did you have so much trouble answering my question? Mr. FAItLArID. This is a very difficult statistical issue. Mr. ROSE. I know. Now, if the statistical confidence level of a one-tailed study produces a 1.04, could that number have gone down with a two-tailed study? ' Mr. BAYARD. The two-tailed test on the ever versus never, I think, was 0.99, with the 95 percent confidence interval-the lower 90 rcent interval was 1.04. Jr. ROSE. If you had done the two-tailed study, you could have had a confidence level of 95, but your statistical significance could have been below one?' Mr. BAYARD. I know what you mean. Mr. ROSE. Do you see why we are a little suspicious about this game? Mr. BAYARD. That is true for the ever versus never. Mr. ROSE. That is the only American study with any statistical sigm ficance and you do a one-tailed study with a 90 percent con- fidence level. If you had done a two-tailed study, it probably would have been below one. You haven't figured in the confounding fac- tors that we just talked about and yet you issued this report in a hurry between changes in administrations and drive policy in this country from every courthouse, every workplace, every building in America. I have nothing to argue about the fact that direct smoking can cause serious results in human beings, but when you are in such a hurry to reach a result like this on this kind of weakness, I think we have a right to ask some tough questions. 41 Dr. Farland, why didn't you go for a separate study, an American Congress funded, whatever, an EPA request for one massive study of this issue in America, do it right, do it long enough, get this issue cleared up once and for all? Why didn't you do that, sir? Mr. FARLAND. Mr. Chairman, again, these issues have been under discussion in the scientific community for many years. This was not done in a hurry. The evaluation of these 30 studies is a umque data base. We have very few situations where we have this many studies to work with. I would not argue at all with the need to get addi- tional data on this issue. As a scientist, I agree with you. Mr. ROSE. How many other countries in the world consider envi- ronmental tobacco smoke under their system equivalent to a class A carcinogen? How many other countries in the world? Mr. FARI,AND. I think it is probably most important that the World Health Organization has taken the position that environ- mental tobacco smoke causes lung cancer. Mr. ROSE. When did they take that position? Mr. FAxt.AND. They took that in 1986, and on the issue of other respiratory disorders in 1992. Mr. ROSE. How was that conclusion reached? Mr. FARLAND. The same way that the Surgeon General's conclu- sion and the National Academy of Sciences conclusion was reached. Mr. ROSE. Was that on environmental tobacco smoke? Mr. FAIU.A1vD. Yes, it was, with 14 epidemiology studies at that time, not 30, and not nearly of the power of Fontham and Brownson. This is an issue that has been dealt with in the sci- entific community for a long time. I am certainly willing to answer technical questions about the way that we went through this, but not that we hurried. Mr. RosE. I would appreciate it if you would wow me with some data, if you can provide for the record whatever you have on the way in which the World Health Organization reached its conclusion and why you think it was based on sound science. I am sure that is around EPA somewhere since this has been studied so long and so carefully. Mr. FAItLAND. We will provide you with a copy of the report. [The information follows:] Copies of the WHO documents are enclosed for your use. All of the WHO docu- ments receive .rorldwidepeer review before publication. The International Agency for Research on Cancer (IARC) document on Tobacco Smoking ham been used in nu- meroue countries in establishing policies on smoking.