Developmental toxicity of triphenyltin hydroxide in mice

Triphenyltin-hydroxide (TPTH) is used as agricultural fungicide in Brazil and elsewhere. This study was undertaken to evaluate the developmental toxicity of TPTH in mice. Swiss Webster mice were treated by gavage with TPTH (0, 3.75, 7.5, 15 and 30 mg/kg bw/day) on gestation days (GD) 6-17. Caesarean sections were performed on GD 18, and implantations, resorptions and live and dead fetuses were counted. Half of each litter was fixed and examined for visceral anomalies while the remaining fetuses were cleared and stained with Alizarin Red S for skeleton evaluation. A reduced pregnancy weight gain (after subtraction of uterine weights), smaller thymus, spleen and liver, and deaths indicated that doses > or = 7.5mg/kg body wt/day were toxic to mothers. At the two highest doses, TPTH enhanced embryolethality and reduced fetal body weight. The incidence of cleft palate (not seen in controls) was augmented (36.8%) at the highest dose of TPTH, while palatine bone defects were increased at the lowest dose (3.75 mg/kg bw/day). Soft-tissue anomalies, such as misshapened thymus, and malpositioned testes and uteri, were more frequent at doses of TPTH > or = 7.5 mg/kg bw/day. TPTH also caused a dose-related increase of fetal skeleton variations (e.g. poorly ossified skull bones) and malformations (misshapened Axis and skull bones). In conclusion, TPTH was toxic to the embryos (NOAEL <3.75 mg/kg bw/day) at doses that were not overtly toxic to their mothers.