Tobacco Documents Online

The above document which is now open for public comment attempts to associate the appearance of lung cancer in a non- smoking population with exposure to environmental tobacco smoke (ETS). I should like to comment on this document for the benefit of the Science Advisory Board, which will assess this document, because I disagree with the conclusion. For your information, my professional background can be noted from my Curriculum Vitae, which I have appended to this statement. At various times I have been a consultant to government agencies, including the U.S. EPA. Some time ago, I chaired meetings between the AWWA (American Water Works Association) and the EPA. I was a member of the "Drinking Water Health Effects Task Force" for the U.S. EPA Safe Drinking Water Act Amendments of 1986 (Report published in 1989 by Lewis Publishers); I was the toxicologist consultant for the CDC on some aspects of the Agent Orange problem. On August 1990, OSHA asked me for a copy of my CV as a potential toxicology consultant to the Department of.-Labor. It is in light of these activities that I would like to make my comments. In drawing the conclusion that there is a causal association between exposure to ETS and lung cancer, the document incorrectly applies the criteria for determining human carcinogenicity. The epidemiology is not well established; the animal data, all showing an opposite effect, are not considered. Over a period of 2

years, there has been a set of criteria to determine whether or not a substance can be deemed a human carcinogen. I have been concerned with the need for such criteria for many years. I believe I published the first set of criteria, at least for metal carcinogenesis; this was in 1969 (Progress in Experimental Tumor Research, vol. 12, S. Karger Pub.). Later, at a Toxicology Forum in Washington D.C., I asked the toxicologists of the different government agencies to help us with a relatively uniform set of guidelines; following this the Interagency Committee was organized. The determination of what is a human carcinogen is not simple, and cannot be established from the conclusion(s) of a single discipline--certainly not by epidemiology alone. The "Guidelines for Carcinogenic Risk Assessment," as promulgated by the U.S. EPA, are clearly and unambiguously stated in the Federal Register (Vol. 51, No. 185, Wed. September 24, 1986, 33992- 34003.) The antecedent to these guidelines was the recognition that the various government agencies had different "definitions" of a carcinogen. Subsequently, an Interagency Committee was selected to obtain a consensus of which factors must be considered before an agent was to be designated as a human carcinogen. That Interagency Committee, composed of scientists from the EPA, [as well as from FDA, CPSC, NCI, NIEHS, DOA, and NIOSH], published their recommendations in the Federal Register (49 FR 46294, November 9, 1984, 21593-21661) and later expanded 3

their views in a comprehensive report ("Chemical Carcinogenesis: A Review of the Science and Associated Principles," Environ. Health Perspect., 67: 201-282 (1986)). Following public comments, and after the review by their Science Advisory Board, the Executive Committee presented its report to the Administrator of the U.S. EPA. The U.S. EPA then published the revised "Guidelines for Carcinogenic Risk Assessment" in the Federal Register cited above. In essence, the determination of what constitutes a human carcinogen depends on the agreement of conclusions from several disciplines, not only one. This was discussed in the EPA, September 1986 Guidelines, on page 33916, C. Weight of Evidence. In the case of ETS, these Guidelines require the inclusion of epidemiology studies, results from two animal experiments, and some corroborating genotoxic tests. In 1984, a distinguished committee chaired by Professor P. Shubik (of Oxford University) published similar conclusions in SCIENCE (Title: "Criteria for evidence of chemical carcinogenicity"; vol. 225, pp. 682-687, (1984)]; and in addition to the criteria set by the U.S. EPA, this committee suggested that the mode of metabolism of the suspected carcinogen (metabolic pathways) be investigated in the determination of the carcinogenicity of an agent. More recently, Furst [Title: "Yes, but is it a human carcinogen"; J. Am. Coll. Toxicol. vol. 9, pp. 1-18 (1990)] expanded on these themes, and made strong 4

suggestions that only adequate epidemiology and VALID animal bioassays form the basis for such decisions. Nowhere did any of these publications conclude that cause could be determined by epidemiology alone (See EPA document of September 1986, pg. 3400.) The EPA Review Draft on ETS does not follow the U. S. EPA guidelines on the weight of evidence. As an experimental toxicologist, I am surprised that the document does not deal with the animal experiments on ETS. Nowhere is there a recognition that every animal inhalation experiment conducted with ETS failed to induce lung cancer. In fact the Review Draft does not reference the early publication by Wynder who exposed mice to ETS without inducing cancer. (Wynder, E. et al., Proc. Am. Assoc. Cancer Res., pg. 77 (1966). Studies from the American Health Foundation reported on the exposure of rodents to side stream smoke (SS) with no tumors observed. The EPA Review Draft references two publications by Dontenwill on exposure of hamsters to main stream (MS) smoke, but does not list Dontenwill's publication on the exposure of hamsters to ETS which resulted in no induction of lung cancer. (Dontenwill, W. et al. Arzneim. Forsch. 21: 142-143 (1971)). In yet another publication, Haley (in: Indoor Air '87, 2: 68-71) exposed hamsters to SS for 18 months with no report of cancer. 5

Mainstream smoke (MS) of cigarettes is perhaps the most studied of all substances in inhalation experiments. After exposing animals to nose only or whole body exposures, for the life time, no laboratory has been able to induce human-type lung cancer. Since animals do not develop lung cancer after being exposed to (MS) smoke, it is not surprising that those exposed to ETS smoke would also not develop lung cancer. Reports which ask if an individual was exposed to passive smoke, and which do not provide any indication of the air concentration of ETS, cannot be considered adequate for making final conclusions as to the cause of lung cancer. Risk assessments should only be made on the basis of quantitative measurements. It is axiomatic in toxicology that the agent under investigation must be characterized. In the case of ETS there is much confusion as to what precisely is under investigation. Some publications discuss SS alone, while others consider a combination of SS and exhaled smoke as ETS. It is not logical to equate the concentration of a substance near the end of a burning cigarette to the final extremely diluted mixture in the interior of a room. In addition, other exposures, e.g., particulate matter and gases, have to be considered; would not exhaust fumes from internal combustion engines, both gasoline and especially diesel, be important confounding factors? 6

In conclusion, the animal inhalation experiments with ETS are all negative with regard to the induction of lung cancer. The epidemiology is based on qualitative information without adequate quantitative values of exposure. None of the studies on epidemiology of spouse's lung cancer and exposure to ETS contain actual measurements of exposure; many have no estimated dose-response information. There is no question that, from the information which is obtained from the two disciplines--epidemiology and experimental animal studies--there is no basis to quantify the number of lung cancers induced by ETS; and above all there is no scientific reason to classify ETS as a group A carcinogen. 7