Potentiative interactions between caffeine and various teratogenic agents [Pregnant rats, embryotoxicity]

Acetazolamide and inhibitors of DNA synthesis (hydroxyurea, 5‐fluoro‐2′‐deoxyuridine), RNA synthesis (actinomycin D), and protein synthesis (cycloheximide, emetine) were each administered to pregnant rats together with caffeine at doses where each agent alone caused minimal embryotoxicity. Caffeine co‐administered with any of the other agents induced a powerful potentiative response. It is not clear from the present experiments whether much lower caffeine dosage, as normally encountered in humans, would potentiate embryotoxicity due to other agents.