Embryotoxicity of acrylonitrile in whole-embryo culture

Abstract

Day 10 rat embryos were cultured in rat serum for 26 hr in the presence of acrylonitrile at concentrations ranging from 76 to 760 μ m. Survival was not affected at any concentration tested. Normal development was observed at 76 μ m. Acrylonitrile induced concentration-related decreases in growth parameters (yolk-sac diameter, crown-rump length, head length, number of somite pairs), which were statistically significant at concentrations of 304 μ m or above. An acrylonitrile concentration of 152 μ m induced a significant increase in the incidence of malformations, which rose by 100% at 304 μ m. Malformations mainly consisted of a reduction of the brain and a shortened caudal extremity. The presence of 0.1–2.2 m m-reduced glutathione in the culture medium moderated the embryotoxic effects of 304 μ m-acrylonitrile in a concentration-related manner. Growth retardation and severity of malformations induced by 304 μ m-acrylonitrile were significantly increased by the addition of a hepatic microsomal preparation (S-9, microsomes) and cofactors for cytochrome P-450-dependent biotransformation (NADPH, glucose-6-phosphate) to the culture medium. Our results show that embryotoxicity of acrylonitrile does not require extra-embryonic biotransformation. However, the enhancement by exogenous cytochrome P-450-dependent monooxygenase systems supports a role for oxidative biotransformation in acrylonitrile embryotoxicity.