Investigation of the developmental toxicity of cocaine in in vitro cultured chick embryos: Correlation of effects with intra-embryonic drug levels.

The effects of cocaine and its primary metabolites, benzoylecgonine and ecgonine, on early embryogenesis were investigated in in vitro cultured chick embryos, and levels of cocaine and benzoylecgonine were measured in the embryo and in the culture medium. Neurulation was the only developmental process shown to be sensitive to cocaine. Closure of neural folds was inhibited within 4 hr of treatment of stage 6-8(-) embryos with 170-340 mug cocaine hydrochloride in 1 ml culture medium. Cocaine levels within embryos treated with 340 mug cocaine hydrochloride decreased from approximately 11 to 5 mug/embryo between 20 min and 4 hr of culture. Cocaine effects were more pronounced in continuously treated embryos.