Commentary on Epa Review Draft 'health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children'

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Commentary on Epa Review Draft 'health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children'

Date: Sep 1990 (est.)
Length: 78 pages
87655327-87655404
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Author: Huber, G.L.
Alias: 87655327/87655404
Type: SCRT, SCIENTIFIC REPORT
Area: SPEARS,ALEXANDER/EXEC CONF ROOM STORAGE
Site: G65
Named Organization: Epa, Environmental Protection Agency; Ftc, Federal Trade Commission; Iarc; Medline; Natl Research Council
Named Person: Adams; Alligood; Anderson; Anselan; Bacal; Baker; Baldridge; Beem; Benner; Berglund; Berkey; Berwick; Binder; Blair; Bland; Bonham; Bouhuys; Brandt; Brunnemann; Burchfiel; Burrows; Caldwell; Camacho; Cameron; Carson; Chan; Chanock; Charlton; Chen; Colley; Conner; Corbo; Crouse; Dalhamn; Davies; Denny; Derrick; Dodge; Dube; Dutau; Eatough; Efor; Eisen; Ekwo; Erikson; Eudy; Evans; Fergusson; Ferris; First; Fleming; Fraser; Gardener; Gardner; Gelbard; Gellerbernstein; Glezen; Goren; Green; Guerin; Hammond; Harlap; Harrington; Harsten; Hasselblad; Hecht; Hey; Heyder; Hicks; Hiller; Hinds; Hinton; Hoffmann; Holberg; Holma; Hounam; Ingebrethsen; Kallail; Kaminski; Kapikian; Kasuga; Kauffmann; Keith; Kenny; Kerigan; Kerrebijn; Kim; Klus; Koo; Korppi; Kuhn; Lebowitz; Leeder; Li; Lippman; Love; Lutz; Magee; Mandi; Mantel; Marks; Martic; Martin; Martinez; Martonen; Masi; Matsunuma; Mcclelland; Mcconnochie; Mckenna; Meert; Melandre; Melia; Mills; Miolo; Montesano; Morrison; Mularoni; Murray; Nelson; Neuspiel; Nijssenjordan; Norman; Ogden; Ogston; Okada; Oldaker; Ostro; Park; Parrott; Pedreira; Persons; Phalen; Preussman; Proctor; Prodi; Pullen; Rantakallio; Reed; Reilly; Roghmann; Rooney; Ruuskanen; Rylander; Said; Schenker; Scherer; Schilling; Sears; Seinfeld; Shy; Sims; Somerville; Speizer; Stern; Strachan; Surgeon General; Tager; Tang; Tashkin; Teculescu; Thome; Tyrrell; Ware; Watkins; Weiss; Welliver; Willatt; Williams; Wilson; Witorsch; Wittekindt; Wynder <Wynder, E.>; Yu; Zweiman
Date Loaded: 12 Feb 1999
Master ID: 87653565/6821
Author (Organization): Univ of Tx Tyler
Litigation: Stmn/Produced
Characteristic: EXTR, EXTRA; MISS, MISSING PAGES
UCSF Legacy ID: xbe40e00

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COMMENTARY ON EPA REVIEW DRAFT "Health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children" Gary Louis Huber, M.D. Professor of Medicine University of Texas Health Center Tyler, Texas 75701

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COMMENTARY ON EPA DRAFT REVIEW Introduction My present and past qualifications as a commentator on the Environmental Protection Agency Review Draft on the "Health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children" are attached (Appendix A and Appendix B); a recent review article on environmental tobacco smoke (ETS) is also included (Appendix C), as is another recent review article on the physical, chemical, and biological properties of tobacco, cigarettes, and other tobacco products (Appendix D). For approximately the past year, I have spent almost all of my time reviewing the available literature on environmental tobacco smoke (ETS), as well as a considerable amount of additional relevant literature on several other aspects of tobacco and health. The comments that follow are based on this literature review. A number of cited, as well as uncited, bibliographical entries are included with my comments. Neither the comments included herein, nor the appended citations and bibliography, are intended in scope to be fully comprehensive; they are intended, however, to emphasize several crucial considerations that are not included in the EPA Review Draft. ~ N ~ Cj - 1 - iV m

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THE ETS LITERATURE DATA BASE I have studied carefully the EPA's Review Draft "Health Effects of Passive Smoking: Assessment of Lung Cancer in Adults and Respiratory Disorders in Children." This document appears to be based on a review of selected liteiature, to the exclusion of other very important publications. Why was important literature excluded from this review? By what criteria and with what justification were these numerous exclusions made? I have reviewed extensively and critically with computer-assisted analytical methodologies the scientific and medical literature related to these subjects, including several thousand more publications than are referenced in the EPA Review Draft on ETS, on tobacco, and especially on the confounding variables potentially affecting the interpretation of this literature. I will restrict my comments herein to the issues of (1) the selection processes involved in developing an ETS literature data base that is used for a review, and from which conclusions can be drawn; (2) the physical, chemical, and biological properties of ETS, especially as those properties might be important to the potential development of pulmonary diseases, including lung cancer; and (3) exposure to ETS and the development of childhood respiratory disease. My comments are based on a review of all of the literature that was cited in the EPA Review Draft, as well as substantial additional literature - 2 -

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that apparently was not included in this review effort by the EPA. THE ETS LITERATURE Any review of the literature on ETS is fraught with several serious difficulties. Overall, the scientific quality of the ETS literature is of a lesser standard than generally has been established for other topics or issues. The reasons for this are not clear, but it seems that the editorial review processes of several different journals have used less stringent scientific criteria in their evaluation and acceptance of ETS manuscripts than otherwise have been exercised for literature not related to tobacco. This may be due, in part, to the considerable difficulty in even defining precisely what environmental tobacco smoke is; therefore, some of the comments offered herein will address that point specifically. Any review process is left, then, with the complicated and difficult concern of evaluating many publications that are not very good and extremely few that are of excellent scientific quality. That problem aside, however, the scientific integrity of publications on ETS has been compromised in several other ways. A second major problem in any review of the ETS literature is the difficulty in identifying and incorporating negative results. All studies that do report "positive" results for ETS exposure--that is, results that demonstrate a positive - 3 -

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statistical correlation for adverse health effects of ETS--do so only at very low levels of significance. For instance, the risk ratios for the potential development of lung cancer in adults, as well as the risk ratios for adverse respiratory health effects in children, are at best weak, by criteria accepted widely in the disciplines of epidemiology and biostatistics (Mantel, 1987; Wynder, 1987). When risk ratios are weak--that is, when the risk for the development of disease is in the magnitude of 1.2 to 2.5, or so, compared to nonexposed or nondiseased controls--they must be interpreted with caution. This is especially true when known or established confounding variables appear to be related to the same disease associations. In fact, for each health issue of ETS that is of concern, not only are the health risk ratios weak, but the number of "positive" studies available in the published literature that addresses specifically the relationship of ETS to the development of disease generally equals, roughly more or less, the number of "negative" studies on the same issue. This is especially true for any consideration of adverse risk for lung cancer in adults and for any consideration of adverse respiratory health effects in children. This problem is confounded even further by the lack of publication of negative studies in general and by the difficulty in identifying literature that contains negative results for ETS exposure in publications that do not have considerations of ETS as their primary, or even secondary, ~ ~ CA - 4 - CV1 W CJ Mr

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focus. These specific considerations are addressed further in a broad sense as an addendum to this text (Appendix E). The third and most serious problem in any analysis of this literature is that of defining what is the "ETS universe," so to speak. - This is the most significant flaw in the EPA Review Draft, as well as in most previous reviews, including those from the Office of the Surgeon General in 1986 and from the National Research Council in 1986. All three of these reports have - reached comparable conclusions based on a selective analysis of a comparably selected finite body of literature. With the exception of some limited reservations, those generally would be the same conclusions that I, too, would reach, or any reasonable scientist would reach, if only that finite body of comparable literature were reviewed--that is, the literature cited in the 1986 Surgeon General's report on environmental tobacco smoke, the 1986 National Research Council report on ETS, and the recent EPA Review Draft on ETS. A very similar literature data base has been cited in other published reviews of ETS, and a comparable data base can be derived via MEDLINE or other related computer- assisted national data base retrieval systems key-worded to ETS. However, these literature data bases--that is, the literature data base cited in the 1986 Surgeon General's report, the literature data base cited in the 1986 National Research Council report, the literature data base cited in the EPA Review Draft--are limited and selective; they are not complete, and they - 5 -

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are not comprehensive. Because the literature data bases are limited and selective, the reviews derived from them are neither balanced nor even accurate. As a result, the conclusions that can be drawn, and indeed are drawn, from these reviews are less than scientifically valid, and cannot be accepted on reasonable scientific grounds when viewed in the context of a more comprehensive, expanded universe of available information in the published literature--an expanded literature universe that is excluded in the EPA Review Draft. The reasons for the limited and restricted selection of literature for these reviews are not clear. Surely such limitations and selections could not have been made by intent, for that would be irresponsible and would be paramount to scientific fraud; more likely, the restrictions exist because the issues surrounding ETS are very complex and impact with far more important variables and critical confounding influences than are related to tobacco smoke exposure alone. This is especially true for the potential effects of ETS on the development of lung cancer in adults, and to only a slightly lesser degree for any consideration of the potential health effects of ETS on infants and children. When evaluated in an expanded literature universe, the risk ratios between ETS and lung cancer in adults and between ETS and respiratory diseases in children--both of which at best are weak risk relationships to start with--lose much of their already very limited significance and must be viewed and - 6 -

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interpreted in a different context and with a significant degree of caution. Based on these qualifying considerations concerning the selection of literature for review, there are a number of serious problems with the EPA Review Draft. I will state in summary my concerns with two of these issues, and then provide a more detailed textual analysis. SUMMARY: OVERALL POSITIONS ON ETS LITERATURE REVIEW In my opinion, the conclusions of the EPA Review Draft that have been presented for the physical, chemical, and biological properties of ETS (especially as these properties relate to lung cancer in adults) and for childhood respiratory disease are not accurate and cannot adequately be supported by the scientific literature, if the full body of literature available for review is analyzed. The conclusions of the EPA Review Draft are not accurate because they are biased by selective exclusions of key literature that, if included, would alter their interpretation. SUMMARY: PHYSICAL, CHEMICAL, AND BIOLOGICAL PROPERTIES OF ETS Despite its initial "promise" not to do so, the EPA Review Draft builds its argument, in part, on extrapolation from mainstream and sidestream smoke to environmental tobacco smoke in developing risk assessments. No reliable or confirmed ~ Clt 7 - ~ W A

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assessments have been made on the basis of actual measurements of ETS itself, and for good reason: ETS is in itself almost a misnomer, is extremely difficult to define with precision, and is even more difficult to characterize reproducibly. It has always been assumed, and it is now thought to be "well-established" (if by nothing else, through the process of repetition) that for the- most part sidestream smoke is the same as environmental tobacco smoke. Such, of course, is not at all the case. Environmental tobacco smoke has never been well-characterized (and by that is meant that total ETS has not been measured, analyzed, or quantified under the real-life "smoke exposure" conditions where the risk allegedly rests), and those who work in this field are not even clear exactly what ETS really is. The EPA Review Draft notes "43 identified carcinogens in the smoke from a cigarette that are in sidestream smoke" without the clarification that these are not necessarily carcinogens related to the development of lung cancer in humans and that some of these proposed "carcinogens" have no relevance whatsoever in these considerations. It must be emphasized that in total only about 50 substances have been consistently identified under "real-life" conditions in ETS (as opposed by a factor of several fold to the much larger number in sidestream smoke) and that of these the alleged carcinogens have-not been found with consistency or certainty in doses that would reasonably be considered to pose a risk to humans. I 4M CA ~ - 8 - CJ CO! C!1

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Although the EPA Review Draft indicates some reservations about developing "cigarette-equivalent approaches to dose-response assessments," it then goes on to make similar - calculations using "new methods" to do essentially the same thing it stated it was not going to do! Because of the nature of ETS, it is absolutely impossible to make any cigarette-equivalent extrapolations from the active smoker to the passive smoker. Mainstream smoke and environmental tobacco smoke are very different substances--physically different, chemically different, and biologically different. The surrogate markers of ETS, particularly nicotine, exist essentially only in the gas phase of ETS. Therefore, nicotine and its metabolite, cotinine, cannot be used as an extrapolating marker of whole tobacco smoke, or for the particulate phase, in the active smoker. Although the document indicates that the cigarette-equivalent approach is not recommended, it nevertheless continues to take this approach in a variety of secondary or implied ways. SUMMARY: ETS AND CHILDHOOD RESPIRATORY DISEASE I have reviewed extensively all of the literature on ETS and children, a rather substantial portion of which was not cited in the EPA draft document; indeed, the crucial literature that has not been cited outweighs by a significant magnitude the selected literature referenced in the EPA Review Draft. Without exception, each of the cited studies in the EPA Review Draft - 9 -

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