Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats.
Perinatal di(2-ethylhexyl) phthalate (DEHP) exposure was examined in time-mated Wistar rats gavaged from gestation day 7 to postnatal day 16 with doses from 3 to 900 mg/kg-d. These doses covered the whole dose-response curve for the demasculinizing effects of DEHP including low-dose effects. At a relatively low dose of 10 mg/kg-d, DEHP caused adverse anti-androgenic effects on male rat development as male anogenital distance was decreased, the incidence of nipple retention was increased, weight of levator ani/bulbocavernosus muscles and prostate was reduced and mild external genitalia dysgenesis was observed. Higher doses of DEHP induced histopathological effects on the testes, reduced testis weight, and expression of androgen-regulated genes in the prostate. The results provide new evidence of low-dose effects of DEHP and are consistent with the EU NOAEL of 5 mg/kg for DEHP. Our results also indicate a reason for concern about human exposure to DEHP.
Christiansen
Sofie
S
National Food Institute, Technical University of Denmark, Department of Toxicology and Risk Assessment, Søborg, Denmark. sochr@food.dtu.dk
Boberg
Julie
J
Axelstad
Marta
M
Dalgaard
Majken
M
Vinggaard
Anne Marie
AM
Metzdorff
Stine Broeng
SB
Hass
Ulla
U
D001003:Anal Canal / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology
D000726:Androgen Antagonists; D010968:Plasticizers; D004051:Diethylhexyl Phthalate