Model systems and their predictive value in assessing teratogens.

Abstract

For ethical and regulatory reasons all newly developed drugs are evaluated for safety in a series of preclinical animal toxicity studies. Prior to the 1960's there were no standardized procedures or regulatory guidelines for specifically examining the teratogenic potential of a compound, although an evaluation of the overall effect on reproductive processes was recommended. Following the thalidomide saga, specific studies for evaluating teratogenicity were included in regulatory preclinical guidelines in most countries of the world. However, the level of confidence in the ability of these animal studies to be predictive for man remains far from high. Differences between model systems and man emphasize some of the reasons for the perceived low level of predictability of animal tests for man. Only when the mechanism of teratogenesis and the factors affecting species differences in teratogenic response are understood will we have confidence in the predictive accuracy of animal studies.