THE EFFECT OF DIAZEPAM ON THE DEVELOPMENT OF GALLUS EMBRYOS

The aim of this study was to evaluate the teratogenic abnormalities re sulting from exposure of chick embryos in ovo to the anxiolytic drug d iazepam. Diazepam is known to be teratogenic in experimental animals, causing cleft palate in mice and inhibiting closure of the neural tube in four-somite chick embryo cultures. Eggs from an inbred White Legho rn population were divided into six groups. The airsac of five experim ental groups was injected, after 48 hours of embryonic development, wi th 50 mu l of respectively, 3.3 mu g, 5 mu g, 10 mu g and 20 mu g diaz epam or propylene glycol, the vehicle for diazepam. The embryos were a ll sacrificed on the eighth day of development and evaluated for morta lity gross abnormalities, body mass and total length. None of the cont rol group showed any gross abnormalities, whereas 35%, 43%, 73% and 10 0% of the embryos were affected, respectively from the lowest to the h ighest dosage groups. The abnormalities encountered were subcutaneous haemorrhage (20%), prominent blood vessels on the lateral body wall (1 5%), absence of the ventral body wall (11%) and anophthalmos (1%). In the propylene glycol group, 21% of the embryos were affected. The resu lts demonstrate increased toxicity in developing chick embryos with hi gher concentrations of diazepam. Exposure to toxic concentrations of d iazepam occurs commonly in humans and it is thus possible that materna l poisoning could cause embryonic abnormalities in man.