Teratogenic effects of various di-n-butyltins with different anions and butyl(3-hydroxybutyl)tin dilaurate in rats.

In our previous study, di-n-butyltin diacetate has been shown to cause malformations such as cleft mandible, ankyloglossia, fused ribs, etc. in rat fetuses after oral treatment of maternal rats on day 8 of gestation. In this study, teratogenic effects of five di-n-butyltin compounds with different anions and also butyl(3-hydroxybutyl)tin dilaurate (3-OHDBTL) were examined in Wistar rats. Anion groups of these compounds were as follows: diacetate (DBTA), dichloride (DBTC), maleate (DBTM), oxide (DBTO) and dilaurate (DBTL). On day 8 of gestation, pregnant rats were treated orally with these compounds at 80 mumol/kg, or with 3-OHDBTL at 80 or 160 mumol/kg. Cesarean sections were performed on day 20 of gestation and fetuses were examined for their external and skeletal anomalies. Types of the observed malformations were similar to those in the previous study with DBTA except 3-OHDBTL, though the incidence of fetuses with malformations was different. In the DBTC-treated group, skeletal anomalies were predominant to external ones, especially with the higher incidence of fused ribs than in the other groups. In the 3-OHDBTL-treated group, no external and skeletal anomalies were observed at 80 mumol/kg and cleft lower lip and ankyloglossia were observed in only one fetus, but peaked mandible (the tip of lower jaw with acute angle) was specific at 160 mumol/kg. From these results, the di-n-butyl group rather than anionic group was found to be important in the teratogenicity of di-n-butyltin compounds as well as in the other kinds of toxicities and 3-OHDBTL, one of the main metabolites of DBTL, is not the critical substance of teratogenicity because of a very low teratogenic potency.