Symposium overview

The Life Sciences Research Office (LSRO) ofthe Federation of American Societies for Experimental Biology (FASEB), provides scientific assessments of topics in the biomedical sciences. Reports are based upon comprehensive literature reviews and the scientific opinions ofknowledgeable investigators engaged in specific areas of biology and medicine. The extrapolation of data on carcinogenic responses of animal models to estimations of risk of cancer in humans is a complex and controversial subject. The quantity of test substance responsible for the carcinogenic response is an inherent aspect of the process of risk assessment. There are two phases of evaluating dose response in the contemporary approach to risk assessment: dose-range extrapolation and dose scaling. Doserange extrapolation involves the estimation of low doses and their effects from high-dose exposures based on mathematical models of the dose-response function. Dose scaling is the process of interspecies conversion of dose-response data to equipotent doses for humans. Regulatory agencies have adopted several different strategies for interspecies dose scaling. As examples, the U.S. Environmental Protection Agency (EPA) computes the human equipotent dose in proportion to the 0.67 power of body mass, while the Food and Drug Administration (FDA) uses the first power ofbody mass for computations of permissible intakes of food additives and a constant fraction in the diet for permissible concentrations of residues in food. Numerous investigators, publications, and symposia have explored mathematical-statistical models from which dose-range extrapolations of carcinogenic risk are derived. In contrast, little has been published on the subject of dose scaling of carcinogenic potency. In addition, there have been few comprehensive reviews on the principles, applications, or limitations of dose scaling. The increasing use of alternative test systems in applied toxicology and findings from alternative ap-