ABSTRACT
Comparison of drug disposition in animals and humans during the early stages of clinical investigation was recommended by the Food and Drug Administration (FDA) in 1968, so that the most comparable species or strains could be selected for the chronic toxicity studies. For risk-assessment purposes, the FDA currently requires a variety of studies in rodent and non-rodent species as prerequisites for the clinical investigation and eventual marketing of new drugs, and for marketing approval of new food additives. Benefit–risk decisions for drugs with neoplastic potential are particularly conservative because of an almost total lack of prevailing knowledge about the interpretation and extrapolation of carcinogenicity data in general, and the lack of known exclusion criteria for particularly susceptible individuals. Between 1938 and the mid-1960s the type and amount of toxicology testing for human drug development had expanded in a continuing effort to avert the unacceptable episodes of human toxicity that were experienced during this period.
