Effects of TRI-n-butyl phosphate on pregnancy in rats

A teratological study was carried out on the plasticizer tri-n-butyl phosphate (TBP). Pregnant Wistar rats were treated orally on days 7-17 of gestation with TBP at 0, 100, 200, 400 or 800 mg/kg/day in the dose-finding study and 0, 62.5, 125, 250 or 500 mg/kg/day in the subsequent teratological study. Caesarean sections were performed on day 20 of gestation. In the dose-finding study, all of the pregnant rats were killed by the treatment with TBP at 800 mg/kg/day. In the teratological study, salivation and depression of body weight gain, adjusted body weight gain and food consumption were observed at the higher doses of TBP. There were no significant differences between the groups in the incidence of dead or resorbed foetuses, the number of living foetuses and the body weights of living foetuses of both sexes. The incidence of rudimentary lumbar rib increased significantly at 500 mg/kg/day. There were two cases of malformation: a foetus with deformity of fore- and hind-limbs at 400 mg/kg/day in the dose-finding study and conjoined twins exhibiting three fore-limbs and four hind-limbs at 125 mg/kg/day in the teratological study. These malformations were rare in the background data of teratology, and the incidence of foetuses with malformations was not increased significantly. Therefore, TBP was considered not to be teratogenic in this study.