Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late pregnancy

The objective of this study was to determine the adverse effects of monobut yl phthalate (MBuP), a major metabolite of dibutyl phthalate (DBP), on deve lopment of the reproductive system in offspring following maternal administ ration during late pregnancy, and to assess the role of MBuP in the antiand rogenic effects of DBP. Pregnant rats were given MBuP by gastric intubation at 250, 500, or 750 mg/kg on days 15 through 17 of pregnancy. Maternal bod y weight gain and food consumption during the administration period were si gnificantly decreased at 500 mg/kg and higher and at 750 mg/kg, respectivel y. A significant increase in the incidence of postimplantation embryonic lo ss was found at 500 mg/kg and higher. The body weights of male and female f etuses were significantly lower at 750 mg/kg. A significant increase in the incidence of fetuses with undescended testes was found at 250 mg/kg and hi gher. A significant decrease in the anogenital distance (AGD) of male fetus es was observed at 250 mg/kg and higher. The AGD/body weight ratio and AGD/ cube root of body weight ratio in male fetuses was also significantly reduc ed at 250 mg/kg and higher. The AGD, AGD/body weight ratio and AGD/cube roo t of body weight ratio in female fetuses in the MBuP-treated groups were co mparable to those in the control group. The present study indicates that MB uP on days 15 to 17 of pregnancy produced adverse effects on the developmen t of reproductive system in male offspring and suggest that MBuP may be res ponsible for the induction of the antiandrogenic effects of DBP. (C) 2001 E lsevier Science Inc. All rights reserved.