Developmental toxic effects of diisobutyl phthalate, the methyl-branched analogue of di- n-butyl phthalate, administered by gavage to rats

Abstract

The developmental toxicity of diisobutyl phthalate (DIBP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given DIBP at doses of 0 (olive oil), 250, 500, 750, and 1000 mg/kg/day, by gavage (5 ml/kg), on gestational days (GD) 6 through 20. Maternal toxicity, as evidenced by reduction in body weight gain, was observed at the beginning of treatment (GD 6–9), at 500 mg/kg and higher doses. The incidence of resorptions was significantly increased at 750 mg/kg, and reached 60% at 1000 mg/kg. There was a dose-related decrease in fetal weight, which was significantly lower than control from 500 mg/kg. A significant increase in the incidence of fetuses with visceral and skeletal malformations was seen at 750 and 1000 mg/kg. In particular, fused sternebrae occurred at a significantly higher frequency. Two skeletal variations were increased at 750 and 1000 mg/kg: retarded ossification of vertebrae, and predominantly, supernumerary ribs. The incidence of male fetuses with undescended testes was also significantly elevated at the two highest doses. In conclusion, DIBP administered by gavage is embryotoxic and teratogenic, and affects the developing male reproductive tract, at maternal toxic doses.