ABSTRACT
The problem of extrapolation of animal teratogenicity data to human pre-natal toxicity risk was brought sharply into focus by the thalidomide tragedy. The failure to detect the teratogenic potential of this drug in the rat led to widespread use of the drug in humans during pregnancy with obvious disastrous outcomes. In a practical sense, experience with animal testing has often led to incorrect data with respect to human teratogenicity risk. Often, adverse effects on animal foetuses occur only at extremely high concentrations of drugs, far beyond normal human therapeutic exposures, and in the face of drug-induced illness in the maternal animal. Perhaps even more important in considering the role of animal testing in predicting human reproductive outcomes, however, is the very nature of the epidemiology of human drug-induced birth defects. Predisposition to a variety of idiosyncratic toxicities including hepatic damage, aplastic anaemia, and carcinogenesis may be generally determined.
