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 monobutyl phthalate (MBuP), a major metabolite of dibutyl phthalate (DBP), on development of the reproductive system in offspring following maternal administration during late pregnancy, and to assess the role of MBuP in the antiandrogenic 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 body weight gain and food consumption during the administration period were significantly decreased at 500 mg/kg and higher and at 750 mg/kg, respectively. A significant increase in the incidence of postimplantation embryonic loss was found at 500 mg/kg and higher. The body weights of male and female fetuses 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 higher. A significant decrease in the anogenital distance (AGD) of male fetuses 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 reduced at 250 mg/kg and higher. The AGD, AGD/body weight ratio and AGD/cube root of body weight ratio in female fetuses in the MBuP-treated groups were comparable to those in the control group. The present study indicates that MBuP on days 15 to 17 of pregnancy produced adverse effects on the development of reproductive system in male offspring and suggest that MBuP may be responsible for the induction of the antiandrogenic effects of DBP.
Ema
M
M
National Institute of Health Sciences, Osaka Branch, 1-1-43 Hoenzaka, Chuo-ku, 540-0006, Osaka, Japan. ema@nihs.go.jp
Miyawaki
E
E
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D003456:Cryptorchidism / Q000139:chemically induced / Q000473:pathology; D003993:Dibutyl Phthalate / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D020964:Embryo Loss / Q000139:chemically induced; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D015430:Weight Gain / Q000187:drug effects
D010795:Phthalic Acids; D003993:Dibutyl Phthalate; C028577:monobutyl phthalate