Experimental animal studies sometimes provide a means of identifying agents with teratogenic potential before humans have been harmed. Unfortunately, it is usually impossible to extrapolate findings in animals to a clinical situation involving an individual pregnant woman. Species differences in placentation, pharmacodynamics, embryonic development, and innate predisposition to various fetal anomalies are well recognized. Moreover, teratology experiments in animals often employ agent dosages which are many times greater than those likely to occur in humans, and maternal toxic effects may confound interpretation of fetal outcome. It is even more difficult to assess the relevance of in vitro teratology assays to pregnant women.
Reproducibility is judged by whether similar findings have been obtained in independent studies.
Concordance is considered to be particularly important if the studies are of different design and if the types of anomalies observed in various studies are consistent. Effects seen in animal investigations are weighed more heavily if the exposure is similar in dosage and route to that encountered clinically and if the species tested are closely related to humans phylogenetically. Of critical importance is that observed associations make biological sense. Exposures which produce malformations in the embryo or fetus should do so only during organogenesis or histogenesis, and affected structures should only be susceptible to the teratogenic action of an agent at specific gestational times. Systemic absorption of the agent by the mother and its presence at susceptible sites in the embryo or placenta should be demonstrable.