Twenty-Eight-Day Repeated-Dose Toxicity Studies for Detection of Weak Endocrine Disrupting Effects of Nonylphenol and Atrazine in Female Rats.

Abstract

To assess the risk evaluation of endocrine disrupting chemicals with weak estrogenic or anti-estrogenic effects in mammals, the suitability of 28-day repeated dosing test and the strain difference were investigated in adult female rats. In the study, 60 and 250 (150) mg/kg/day of nonylphenol and 5 and 50 mg/kg/day of atrazine were dosed to female SD, F344, and Donryu rats for 28 days. Abnormal estrous cyclicity was observed in both groups of SD rats given nonylphenol, in the high-dose nonylphenol and atrazine F344 rats, and in both groups of Donryu rats receiving the test compounds. A slight tendency for increase in numbers of uterine BrdU-positive cells was observed in F344 rats given high-dose nonylphenol, and elevation was noted in one animal each which showed persistent estrus in the groups of Donryu rats given atrazine. Organ weight, necropsy and histopathological findings did not point to any effects of these chemicals on the endocrine or reproductive systems except for ovarian atrophy in the atrazine treated Donryu rats with persistent estrus. These results indicate that severe morphological effects might not be induced in female reproductive organs of adult rats by short-term exposure to these chemicals, unless very high doses are given. Vaginal smear may be the most sensitive parameter for detection of estrogenic or anti-estrogenic effects of chemicals, when normal cycling animals are used for the study.