Effects of in utero through lactational exposure to dicyclohexyl phthalate and p,p'-DDE in Sprague-Dawley rats.
Anti-androgenic chemicals alter sexual differentiation by a variety of mechanisms, and the mechanisms between phthalate esters and p,p'-DDE are considered to be different. We performed an in utero through lactational exposure assay using dicyclohexyl phthalate and p,p'-DDE to investigate the sexual differentiation of these chemicals. Pregnant CD (SD) IGS rats were given dicyclohexyl phthalate or p,p'-DDE orally from gestational day (GD) 6 to postnatal day (PND) 20, and the endocrine-mediated effects in dams and their offspring were examined. The reproductive performance of offspring was also examined. The doses of dicyclohexyl phthalate were 0, 20, 100, and 500 mg/kg/day, and those of p,p'-DDE were 5, 15, and 50mg/kg/day. Using the dicyclohexyl phthalate, a dam in the 500 mg/kg group showed dystocia and died. The viability index of offspring on PND 4 decreased in the 500 mg/kg group. Prolonged preputial separation, reduced ano-genital distance, increased areolas/nipple retention, hypospadia, decreased ventral prostate and levator ani/bulbocavernosus muscle weights and decreased testicular germ cells were observed in male offspring in the 500 mg/kg group. In the assay using p,p'-DDE, decreased viability index of offspring on PND 21, prolonged preputial separation in male offspring and early vaginal opening in female offspring were observed in the 50mg/kg group. The copulation and fertility indices decreased in the reproductive performance of offspring in the 50mg/kg group. The endocrine-mediated effects were detected in offspring of dams given 100mg/kg dicyclohexyl phthalate, and in offspring of dams given 20mg/kg p,p'-DDE. Our results suggest that the in utero through lactational exposure assay is a useful method to detect endocrine-mediated effects and that further comparative study between this assay and two-generation reproductive test are necessary when this assay becomes one of the definitive tests.
Chemicals Evaluation and Research Institute, 1-4-25, Kouraku, Bunkyo-ku, Tokyo 112-0004, Japan. yamasaki-kanji@ceri.jp
Kanji
K
Yamasaki
Hirokazu
H
Okuda
Tetsuya
T
Takeuchi
Yasushi
Y
Minobe
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D005260:Female; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D000726:Androgen Antagonists; D010795:Phthalic Acids; D003633:Dichlorodiphenyl Dichloroethylene; C036042:dicyclohexyl phthalate