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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY OFF(CE OF RESEARCH AND DEVELOPMENT ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE CINCINNATI, OHIO 45268 Apri127, 1990 SUBJECT: Review of ETS Report FROM: Richard C. Hertzberg*44 Methods Evaluation and Development Staff TO: Christopher T. DeRosa, Acting Director The scope of this review has been narrowed due to the short time allowed and to other competing tasks. This review is restricted to the Executive Summary and the Appendices. In general, this document seems to have been written with exceptional care and particular attention to conceptual details. Executive Summary Page Comments 2 Last para. The report should also reference the EPA guidelines for risk assessment of chemical mixtures, since one of the key assumptions is that the tested complex mixtures (the spedfic ETS tested) can be surrogates for all of the untested ETS from other brands of cigarette. By citing the mixtures guidelines, the conclusions are strengthened for all ETS. The price is that this report must then include a section that concludes that ETS's from various cigarette brands are toxicologically similar. Note that section 3-3 discusses a related issue regarding the assumption of toxicological similarity between mainstream smoke and sidestream smoke. The mention of adjustments by Vutuc for tar content in the cigarettes (p. 3-16) raises the concern that the risk assessment may not be generally applicable. One suggestion is that the report state that the epi study populations reflect a large enough variety of cigarettes to be considered statistically representative of all cigarettes.

Pa e Comments 3 Para. 1 after the bullets. The statement that "50% equates to 125 million U.S. nonsmokers of age 18 and above" does not seem correct. I believe the entire population is around 250 million, many of whom are under age 18. The subpopulation reflected in the testing must then be much less than 250 million. Appendix A No comments. Appendix B B-4 Para. 2, line 3: "...a problem may specify the..." Problems do not specify; people do. This sentence needs to be revised for clarity. Also, in this sentence, both sets of parentheses are not balanced. B-4 Para. 2, next-to-last sentence ("For example, assuming ...") This example should be rephrased in a positive sense to show how the conversion makes the values more interpretable, e.g., add: "Using Table B-3, the desired proportion, V14, can be easily determined." B-4 Last para. , first sentence. State what "The procedure" is. Third sentence ("RRM is ..."): I believe the denominator, the unexposed NS, should be defined as "married to a non-smoker", instead of a never-smoker, since prior history of the spouse should have no bearing on current exposure. The last sentence should be moved to the beginning of the next paragraph. B-6 ~ Second para. Even if you have defined "excess risk" in the main text, you might consider defining it again in this appendix so the calculations can be easily understood using only the appendix. Appendix C I am not sure why this appendix is included. On pp. 3-14, 3-15, the appendix is described in terms of using the dose-response curve for active smoking to estimate cancer risk from passive smoking. The conclusion is that present information is inadequate to support such an extrapolation. If.that is indeed the sole purpose of Appendix C, then I recommend moving the first section (Introduction) of the appendix to p. 3-15 and deleting the remainder from this document. The remainder, in particular section C.2, should instead be compiled in a report on inhalation dosimetry, perhaps as a technical support document for the inhalation Reference Dose, and only cited in this ETS report.

The conclusions of this appendix need to be emphasized more and dearly stated. Other appendices were easier to follow since they had a special section for conclusions. In this draft, the conclusions of some sections are hard to locate (e.g., section C.3). The conclusions for each section should be dearly tied to the main conclusion concerning the applicability of dose-response data on active smoking to passive smoking. For example, Table C-2 illustrates that no single proportionality constant can be used to translate MS exposure into an estimate of SS exposure. The equations in this appendix should be renumbered to correspond to those in Appendix B, i.e., note them as (Cl), (C2), etc. Pagg Comments C-5 There is a key assumption for eq. (3) that must be stated: that the interval T is short enough that I(T) is linear in q(T) , i.e., that V is constant throughout the range of yrM . This can be effected by revising the phrase preceding eq. (3): "The lung intake for the ith chemical during a sufficiently short interval ..." C-20 I found the description of this table to be difficult to follow. As I understand it, in the last column is the ratio, for each compound, of the total mass emitted by the cigarette via MS or SS. In eq. (25), is MRsp equal to the sum of the items in column 2 (Average MS) for the particulate phase chemicals along with all the missing chemicals? If so, then the text should say so dearly, and be revised to note that the listed chemicals account for roughly 62% of the total: the sum of the non- nicotine amounts at 1µg or more =.985mg, and (14+.985)/24 = 0.62. I had trouble understanding eq. (25) and suggest consideration of rewriting it to show the SS mass ratio of chemical to RSP: Let (M; )(R;) = MSS; (average mass of chemical i in SS). The concentration of any other chemical in Table C-2 inhaled via SS can then be easily obtained: C; - 200 x MSS; ~MSSRSP In terms of values in Table C-2, this equation can be rewritten as: C; = 200 xf M'R' LMRSPRRSP C-22 This table is confusing. Should the ratio of the next-to-last column to the last column be the same as the last column in Table C-2? How is the last column determined? Is it total intake for the active smoker

Paze Comments (cont.) (MS+SS)? What does the subscript p denote in the last column of Table C-3? Appendix D As with Appendix C, it would have been easier to integrate all the information in this appendix had a conclusion section been included at the end. Page Comments D-4 First para. The table (D-1) is described as identifying information that could be useful for dose-response modeling, implying that none has been discredited. In the table, skin painting studies are highlighted, yet they have not been demonstrated, to my knowledge, to be predictive of dose-response relations, or even potency ranking, of another exposure route, such as oral or inhalation. ECAO-Cin investigated Albert's approach for oral potency estimation of PAHs several years ago (for revisions to Ambient Water Quality Criteria), and found skin painting to be unable to reproduce even the comparative ranking of the PAHs, much less the actual potency values. Since skin painting exposure seems extremely different from other routes regarding dose-response relationships, any documented justification for its use should be cited. D-4 Section D.1.2. This section includes an additionat assumption that is not noted. The use of "dose-additive" estimates is actually a toxicity equivalence factor method, that has its own problems in validation. This fact should be mentioned in the discussion of potential disadvantages. cc: L. Glass