Teratogenicity of 13-cis retinoic acid and phenobarbital sodium in CF-1 mice

The teratogenicity of 13-cis-retinoic acid (RA) either administered alone or following pretreatment with phenobarbital sodium (PB), was assessed. Groups of gravid CF-1 mice were administered dosages of either 10, 100, 200, or 400 mg/kg of RA orally on either days 11, 12 or 13 of gestation, in order to determine structural alterations. In addition, separate groups of mice were orally pretreated with 80 mg/kg/day of PB on days 7 through 10 of gestation prior to the administration of RA. Skeletal alterations attributed to maternal administration of either 100, 200 or 400 mg/kg of RA on days 11-13 included delayed ossification of the limbs and supraoccipital bone, the presence of extra ribs, and various sternebral defects. Soft tissue alterations included cleft palate and dilation of the renal pelves which occurred following maternal exposure on days 11 and 12-13, respectively. Significant decreases in the incidence of cleft palate and delayed ossification of the limbs were observed in those dams administered RA on days 11 or 12, respectively, following prior treatment with PB. These data suggest that administration of PB, a prototypical hepatic microsomal enzyme inducer, may partially antagonize the teratogenicity of RA.