The effects of drugs on embryonic development.
A review of the literature demonstrated the difficulties in evaluating the teratogenic effect of drugs in man. Since epidemiologic studies provide suggestive rather than definitive data and results of the current drug testing in laboratory animals may not be applicable to man, the need to develop alternative methods of predicting teratogenicity was apparent. To develop such techniques by studying a possible mechanism of teratogenesis, experiments were performed using a teratogenic folic acid-deficiency and antagonism with 9-methyl pteroylglutamic acid in the pregnant rat. Embryos developing abnormally in response ot this regimen consumed oxygen at a significantly decreased rate. Similar significant reductions in oxygen consumption were found both in rat embryos malforming in response to maternal vitamin A acetate administration, and in mouse embryos in response to teratogenic doses of diphenylhydantoin. It was suggested that such measurements of oxidative metabolism or related techniques may have application in predicting drug teratogenicity and could aid present epidemiologic and empiric approaches to identification of human teratogens.
D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000139:chemically induced; D010672:Phenytoin / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000494:pharmacology*; D013997:Time Factors; D014801:Vitamin A / Q000494:pharmacology
D013723:Teratogens; D014801:Vitamin A; D010672:Phenytoin; D005492:Folic Acid