Short‐term effects of chlorotriazines on estrus in female Sprague‐Dawley and Fischer 344 rats

Abstract

Atrazine or simazine (s‐chlorotriazines) was administered by gavage daily for 2 wk to female Sprague‐Dawley and Fischer 344 rats at oral doses of 100 or 300 mg/kg to evaluate effects on body, ovary, uterus, and adrenal weights, estrous cycle stages, vaginal cytology, and plasma hormone (estradiol, progesterone, prolactin, and corticosterone) levels. Significant reductions in body weights of both Sprague‐Dawley and Fischer 344 female rats at both dose levels were accompanied by a significant reduction in ovarian and uterine weights, and a decrease in circulating estradiol levels. The magnitudes of the effects were less in Fischer 344 rats than in Sprague‐Dawley rats, and the effects of simazine were less pronounced than those of atrazine at the same dose. A maximum tolerated dose (MTD: ≥10% body weight reduction) was estimated to be 100 mg/kg for atrazine and 300 mg/kg for simazine for both stains. The Sprague‐Dawley female rats exhibited a treatment‐related lengthening of the estrous cycle and an increased number of days characterized by cornified epithelial cells. This resulted in a greater percent of the cycle days spent in estrus and reduction in the percent of the cycle days spent in diestrus. Atrazine‐dosed Fischer 344 females also exhibited a significant trend toward cycle lengthening, but this was due to reduction in the percent of cycle spent in estrus and a concomitant increase in diestrual days. These findings suggest that treatment with doses of triazine at or above the MTD may result in prolonged exposure to endogenous estrogen in the Sprague‐Dawley but not the Fischer 344 rat. These changes may account for the observed earlier onset and/or increased incidence of mammary tumors in chlorotriazine‐treated female Sprague‐Dawley rats. This strain of rat is already known to be prone to a substantial development of mammary tumors with advancing age, while the Fischer 344 strain is not as likely to exhibit this response.