Enhanced teratogenic activity of di- n-butyltin diacetate by carbon tetrachloride pretreatment in rats

Abstract

Di- n-butyltin diacetate (DBTA) has been shown previously to cause malformations such as cleft mandible, ankyloglossia and fused ribs in rat foetuses after oral treatment of dams on day 8 of gestation. In this study, effects of pretreatment with carbon tetrachloride (CCl 4) on the teratogenic activity of DBTA were examined in Wistar rats. Pregnant rats were pretreated sc with CCl 4 (0.5 ml/kg) on days 6 and 7 of gestation and were treated orally with DBTA on day 8 of gestation at doses of 0, 4.5, 10 or 22 mg/kg. Caesarean sections were performed on day 20 of gestation, and foetuses were examined for external and skeletal anomalies. Pretreatment with CCl 4 enhanced the incidence of external and skeletal malformations caused by DBTA. Concentrations of di- n-butyltin in embryos, maternal liver and maternal blood on day 9 of gestation were increased by CCl 4 pretreatment, which inhibited the activity of maternal hepatic microsomal drug-metabolizing enzymes. These results suggest that there is little probability that metabolites of DBTA make a critical contribution to the teratogenicity of DBTA.