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THE USE OF NON-TUMOR DATA IN CANCER RISK ASSESSMENT: REFLECTIONS ON BENZENE, BUTADIENE AND VINYL CHLORIDE
Citation:
Albertini, R., H. Clewell, M. Himmelstein, R. Irons, S. S. Olin, R J. Preston, L. G. Scarano, M. Smith, J. Swenberg, R. Tice, AND C. Travis. THE USE OF NON-TUMOR DATA IN CANCER RISK ASSESSMENT: REFLECTIONS ON BENZENE, BUTADIENE AND VINYL CHLORIDE. REGULATORY PHARMACOLOGY AND TOXICOLOGY 37(1):105-132, (2002).
Description:
1.0 Introduction. Quantitative estimation of human cancer risk from exposure to chemicals has traditionally been almost exclusively based on tumor incidence in experimental animals. While improvements in carcinogenicity testing in experimental animals (1,2) and structure-activity correlations have provided new insights for the prediction of carcinogenic potential, the induction of tumors remains the central focus of efforts to identify and regulate chemical carcinogens (3-5). It is widely recognized that reliance on animal tumor incidence, with its inherent need to extrapolate to humans, introduces considerable uncertainty into the risk assessment process and that the risk characterization process needs to be expanded to include other types of data that may reduce uncertainty.
There is a growing recognition that non-tumor data can play an important part in cancer risk assessment. (4,6). Such data include information on metabolism, formation of DNA adducts, various types of genetic damage, pharmacokinetic models, information on mode of action, etc. However, exactly how these data can be used to improve risk estimates is less apparent and, in fact, may be case-dependent. To examine this question, the ILSI Risk Science Institute convened a working group to characterize the types of non-tumor data available for the three chemicals 1,3-butadiene, vinyl chloride and benzene, and to suggest how these data might be used in cancer risk assessment. This paper summarizes the observations and conclusions of this working group. We begin with a discussion of possible uses of non-tumor data, followed by an overview of non-tumor data for each of the three example chemicals. We conclude with a statement of general principles for the appropriate use of non-tumor data in cancer risk assessment.