Consideration of Metabolism and Mechanistic Data in the Carcinogenicity Risk Assessment of 1,3-Butadiene. E. Anderson and J. Liccione, Sciences International, Inc., King Street Station, 1800 Diagonal Road, Suite 500, Alexandria, VA 22314
Cancer bioassay, genotoxicity, and mechanistic data demonstrate striking differences among species and strongly indicate that mice are particularly sensitive to 1.3-butadiene as a carcinogen and a genetic toxicant as compared to humans. The interspecies sensitivity to 1,3-butadiene may reflect species differences in the metabolism and pharmacokinetics of this chemical. The Environmental Protection Agency’s revised (draft) Cancer Risk Assessment Guidelines (1996) recommend that all available data pertaining to the mode of action of a chemical into the risk assessment models. This completeness allows for the dose-response analysis to be consistent with the chemical mode of action. It also allows for replacement of default assumptions thereby reducing the uncertainties associated with the cancer risk estimate. The incorporation of mechanistic data into the guidelines is a significant improvement over the 1986 guidelines. With regard to the EPA cancer assessment of 1,3-butadiene ("Health Risk Assessment of 1,3-Butadiene," 1998), a significant body of literature on mechanistic data were not utilized in the assessment. In this session, the important findings from in vitro metabolism studies, in vivo toxicokinetic studies, butadiene dosimetry modeling, and mutational spectra studies will be reviewed. The impact that these mechanistic data have on the cancer risk assessment for 1,3-butadiene will be discussed.
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