Experimental models for drug teratogenicity.
Teratogenicity a specific manifestation of embryotoxicity, is explored in the course of the preclinical phase of drug testing. The official routine rat-rabbit procedures employ an integral experimental model--the whole animal with its species-specific metabolism. Although it has been widely accepted that pharmaco-kinetics of drugs represents the most important source of interspecies differences in teratology, the official procedure is still considered satisfactory. The reason why a new thalidomide affair has not occurred can be explained by the extremely low expression of teratogenic potential at the human population level--a condition inherent in the principles of teratogenesis. On the other hand, many partial experimental models have been developed that use mainly suborganismic objects (i.e. isolated morphogenetic systems, explanted tissues and cell populations). These objects possess many limitations disgracing their use as candidates for replacing the whole-animal experiments. Nevertheless, some of the partial models can be used and must be used in deeper analysis of the teratogenic potential of drugs with the aim of improving the predictive power of embryotoxicity risk assessment. (Fig. 1, Ref. 7.)
Jelínek
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Institute of Experimental Medicine, Czechoslovak Academy of Sciences, Praha.
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D013723:Teratogens
D013723:Teratogens