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To investigate the endocrine-mediated effects of neonatal administration of the weak estrogenic compounds, bisphenol A, nonylphenol and genistein, were subcutaneously injected with these compounds at doses of 0.1, 1, and 10 μg/rat/day for 5 days starting on postnatal day 1. Rats were autopsied at 47-50 days. Positive control groups were given diethylstilbestrol (DES) at the same dose levels as the other chemicals. The ano-genital distance, age of vaginal opening and preputial separation, and estrus cyclicity for all living offspring were examined. No abnormalities by the injection of nonylphenol and genistein were detected in this study. In the BPA groups, ano-genital distance in the females in the 1 and 10 μg BPA groups was shorter than in the control group, and the ventral prostate weight was higher in the 10 μg BPA group than in the control group. On the other hand, in the DES groups, delayed preputial separation occurred later in the 0.1 and 1 μg groups than in the control group, and in the 10 μg groups, preputial separation was not completed. Also the estrous stage persisted in female of all DES groups. Underdevelopment of the seminal vesicle and prostate were observed in males of the 1 and 10 μg DES groups, and fewer ovarian corpus lutea, ovarian follicular cysts, and uterine glands, as well as increased uterine epithelial height and squamous metaplasia of the epithelium in the uterus were observed in females of all DES groups. We concluded that the findings observed in the weak estrogenic compound groups were not toxicologically relevant changes and that the present data provide valuable information for the neonatal exposure assay using weak estrogenic compounds.

Reproductive Toxicity Study of Bisphenol A, Nonylphenol, and Genistein in Neonatally Exposed Rats