ABSTRACT
The ability to predict the potential toxicity of an untested chemical based on structure-activity relationships (SAR) analysis is dependent on the knowledge of toxicological information on structurally or functionally related compounds and of the possible mechanism(s) of action that contribute to the specific toxicity endpoint of interest. Among all the toxicity endpoints, carcinogenicity is undoubtedly one of the most difficult endpoints to predict because of the complexity
of its mechanisms of action (see Sec. 2 below) and the difficulty of obtaining a robust, well-balanced database needed for effective SAR analysis. Beyond that, cancer data are often difficult to interpret or model because of variability associated with long-term studies, differences in the species=strains of testing animals used, the route of administration, and the specific testing protocol. Prospective validation and hypothesis testing are also difficult because of the high cost and the long duration of time needed for carcinogenesis bioassays.
