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: > or = 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.