Effect of diazepam on the embryonic development of the palate in the rat

The results of previous studies on the effect of diazepam on palate formation in animals have been inconclusive. Teratogen-induced cleft palate is usually caused by a delay in palatal shelf elevation. The present study investigated the effect of diazepam on palate formation in the Sprague-Dawley rat. Five groups of dams received subcutaneous doses of either 10, 20, 30, 40, or 50 mg/kg body weight of diazepam. Control dams received propylene glycol (vehicle). Dams in each dosage group were killed at 16.9 (16 d 9 h); 16.16, and 17.9 days of gestation, respectively, to assess delay in palatal shelf elevation. Crown rump length (CRL) of 1,283 fetuses collected from 105 dams was measured. Fetuses in each time/dosage group showed a reduction in CRL (P less than .01). With increasing dosage the number of fetuses showing delayed palatal shelf elevation was significantly increased (P less than .01). These results demonstrate that with an increase in dose there is an increased delay in palatal shelf elevation and a decrease in CRL. However, in this strain there seems to be a rapid prenatal recovery, resulting in a marked reduction in the incidence of delayed palatal shelf elevation.