Embryotoxicity and teratogenicity of thalidomide in rats

Abstract

The teratogenicity of thalidomide in Wistar rats was investigated after a single maternal intravenous injection during the organogenetic period. Thalidomide was administered at 45 mg/kg in 0.5 ml dimethylformamide (DMF) on day 10, 11, or 12 of the pregnancy. Thalidomide induced skeletal deformities of thoracic ribs and of the spinal column in 33 and 56 percent of the fetuses upon maternal administration of the drug on day 11 or 12, respectively. As compared to the solvent (DMF) control, thalidomide caused two‐ to three‐fold higher skeletally malformed fetuses. Deformities of the eyeball in fetuses (ophthalmorrhexis and microphthalmia) were induced by the maternal administration of the drug on day 10 and 12. The solvent (DMF) failed to induce organ deformities. Thalidomide induced embryotoxicity (as measured by percent dead and resorbed fetuses), at a rate three to eight times higher than the DMF control and represented 11 to 24 percent of dead and resorbed fetuses in thalidomide treated groups as compared to three percent in the DMF control group. Mean fetal weight was significantly reduced after maternal administration of thalidomide on day 11 of pregnancy, as compared to the DMF control. These studies conclude that thalidomide is teratogenic and embryotoxic in rats, when administered intravenously at 45 mg/kg bw.