Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats

Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n-butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of tetatogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects.