Studies On Drug-Induced Congenital Malformations in Experimental Animals

Abstract

A study has been made of the relationship between chemical structure and salicylate-induced embryopathic effects. The subject of teratology is introduced from a historical viewpoint, and the more important pharmacological and therapeutic effects of salicylates are considered. Some emphasis is placed on the administration of these drugs during pregnancy, particularly when a teratogenic effect has been evoked. The distinctions between maternal toxicity and the different embryopathic effects are emphasised. The experimental section shows that AH A rats are sensitive to salicylate teratogenesis but that Dutch rabbits are not. The magnitude of the effect, in the case of aspirin, is related to its solubility. Investigations with a number of compounds with only minor structural differences from salicylate have yielded no malformation. The teratogenic effect is produced only in the presence of salicylic acid. The detailed examination of the rat foetuses has revealed a number of birth defects not previously associated with salicylates. Further, this report constitutes one of the first attempts to study the histopathology of many of these defects. In the General Discussion, these findings are related to the present knowledge of teratological principles. Finally, consideration is given to the variation in teratogenic response which is so evident in most studies of this nature. The only conclusion to be drawn from this discourse is that, in addition to the specific teratogenic agent, there are many other factors working simultaneously which are necessary to induce a malformation. This is encouraging because, in clinical terms, it is possible that the elimination of just one of these factors may prevent birth defects from occurring in a child.