Maternal and Fetal Toxicity of Dimethyltin in Rats

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The maternal and fetal toxicity of dimethltin chloride(DMTC) was examined in two teratological studies in pregnant Wistar rats. In one study, the animals were treated by oral gavage with DMTC at doses of 0, 5, 10, 15, or 20 mg/kg/day on gestational days 7-17. In the second study, animals were treated by oral gavage at doses of 0, 20 or 40 mg/kg/day DMTC on two or three consecutive days at one of four different periods of gestation (gestational days 7-9, 10-12, 13-15 or 16-17). Caesarean sections were performed on day 20 of gestation in both studies. In the first study, vaginal bleeding, tremor and convulsions were observed in animals treated at 20 mg/kg/day after day 15 of gestation. Of ten dams treated with 20mg/kg/day DMTC, two died and one exhibited total resorption. While a increase in the incidence of cleft palate was found in the fetuses of animals treated with 20 mg/kg/day DMTC, the dams so treated exhibited severe clinical signs of toxicity. Animals treated in the second study with doses of 20 or 40 mg/kg/day at one of four periods of gestation had a reduction in the adjusted body weight gain but not in gravid uterus weight and did not show any evidence of teratogenic effect at either dose and period tested. These studies suggest that DMTC did not produce teratogenic effects at dose levels where no maternal toxicity was observed. It was suggested that under the conditions of the first study, since no signs of maternal or fetal toxicity could be detected up 10 mg/kg/day DMTC, this dose was chosen to represent the no-observed-adverse-effect level(NOAEL).
公益社団法人日本薬学会の論文
2001-12-01

著者

NODA Tsutomu
Osaka City Institute of Public Health and Environmental Sciences

Maternal and Fetal Toxicity of Dimethyltin in Rats

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