Observation of preputial separation is a useful tool for evaluating endocrine active chemicals

Abstract

Flutamide, p,p′-dichlorodiphenyldichloroethylene, vinclozolin, diethylstilbestrol, ethynylestradiol and tamoxifen were administered by gavage to pregnant Sprague-Dawley rats on gestational days 14-17 or 18-21, and to male offspring on postnatal days 1-5, 17-21 or 35-39. The influence on the sexual maturation was assessed by preputial separation. Cleft phallus with hypospadias was induced by prenatal exposure to 10 mg/ kg flutamide on gestational days 14-17 and 18-21, or administration of 100 mg/kg vinclozolin on gestational days 14-17 to the dams. The day of preputial separation in these offspring could not be determined, because complete separation did not occur. Prenatal exposure of males to other chemicals did not affect the preputial separation. Postnatal exposure of 10 and 30 mg/kg flutamide and 30 mg/kg vinclozolin led to delays of preputial separation. A marked delay was observed in males exposed to 100 μg/kg of ethynylestradiol or 3 mg/kg of tamoxifen on postnatal days 1-5. Diethylstilbestrol, 300 μg/kg, administration on postnatal days 1-5 and 35-39 caused a delay in preputial separation. These results indicate that observing preputial separation is useful for evaluating anti-androgen treatment in the prepubertal period, and estrogen-related chemical treatment from the neonatal period. 2005 © The Japanese Society of Toxicologic Pathology.