Species, sex, and tissue specificity in toxicologic and proliferative responses

Responsible regulatory decisions regarding the fate of new chemicals require careful evaluation of a host of health, economic, and social factors, in addition to a thorough evaluation of potential risks. In risk assessment, laboratory animals are used as human surrogates in testing for potential chemical effects since mammals are anatomically, physiologically, and biochemically similar and, in most cases, have similar responses to exogenous chemical, biologic, and physical agents (with differences in response usually quantitative rather than qualitative). Unfortunately for the sake of proper extrapolation to humans, qualitative differences do occur, resulting in species, sex, and/or tissue specificity in toxicologic/proliferative responses. Since the toxicologic pathologist is trained in comparative medicine he/she must play a primary role in recognizing and demonstrating specificities in tissue alteration of laboratory animals by new chemicals of potential importance to society. A model exemplifying the recognition and demonstration of species, sex, and tissue specificity of test substance response will be described. In this model a presumably unique alteration of male rat kidney occurred in response to a specific class of test substances. The decision tree in establishing specificity, as well as the nature of the test substances, will be described.