Decreased anogenital distance and increased incidence of undescended testes in fetuses of rats given monobenzyl phthalate, a major metabolite of butyl benzyl phthalate.
The objective of this study was to determine the adverse effects of monobenzyl phthalate (MBeP), a major metabolite of butyl benzyl phthalate (BBP), on the development of the reproductive system, and to assess the role of MBeP in the antiandrogenic effects of BBP. Pregnant rats were given MBeP by gavage at 167, 250, or 375 mg/kg on days 15-17 of pregnancy. Fetuses were examined on day 21 of pregnancy. Maternal body weight gain and food consumption were significantly decreased at 167 mg/kg and higher. Fetal weight was significantly decreased at 375 mg/kg. A significant increase in the incidence of undescended testes and decrease in the anogenital distance (AGD) and ratio of AGD to the cube root of body weight was found in male fetuses at 250 mg/kg and higher. The AGD and ratio of AGD to the cube root of body weight of female fetuses in the MBeP-treated groups were comparable to those in the control group. The present data indicate that MBeP produces adverse effects on the development of the reproductive system in male offspring and suggest that MBeP may be responsible for the antiandrogenic effects of BBP.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501 Tokyo, Japan. ema@nihs.go.jp
Miyawaki
Emiko
E
Hirose
Akihiko
A
Kamata
Eiichi
E
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D003456:Cryptorchidism / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D020964:Embryo Loss / Q000139:chemically induced; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D010795:Phthalic Acids / Q000378:metabolism* / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects
D000726:Androgen Antagonists; D010795:Phthalic Acids; D010968:Plasticizers; C027561:butylbenzyl phthalate