Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate.
Di(2-ethylhexyl) phthalate (DEHP) is a well-known testicular toxicant inducing adverse effects in androgen responsive tissues. Therefore, di(2-ethylhexyl) adipate (DEHA) is currently being evaluated as a potential substitute for DEHP. Similarities in structure and metabolism of DEHP and DEHA have led to the hypothesis that DEHA can modulate the effects of DEHP. Wistar rats were gavaged with either vehicle, DEHP (300 or 750mg/kg bw/day) or DEHP (750mg/kg bw/day) in combination with DEHA (400mg/kg bw/day) from gestation day (GD) 7 to postnatal day (PND) 17. Decreased anogenital distance (AGD) and retention of nipples in male offspring were found in all three exposed groups. Dosed males exhibited decreased weights of ventral prostate and m. levator ani/bulbocavernosus. Histopathological investigations revealed alterations in testis morphology in both juvenile and adult animals. The litter size was decreased and postnatal mortality was increased in the combination group only, which is likely a combined effect of DEHP and DEHA. However, no combination effect was seen with respect to antiandrogenic effects, as males receiving DEHP in combination with DEHA did not exhibit more pronounced effects in the reproductive system than males receiving DEHP alone.
Jarfelt
Kirsten
K
Danish Institute for Food and Veterinary Research, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
Dalgaard
Majken
M
Hass
Ulla
U
Borch
Julie
J
Jacobsen
Helene
H
Ladefoged
Ole
O
D000272:Adipates / Q000633:toxicity*; D000284:Administration, Oral; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D005865:Gestational Age; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects
D000272:Adipates; D000726:Androgen Antagonists; C013966:dioctyl adipate; D004051:Diethylhexyl Phthalate