SHORT-TERM EFFECTS OF CHLOROTRIAZINES ON ESTRUS IN FEMALE SPRAGUE-DAWLEY AND FISCHER-344 RATS

Atrazine or simazine (s-chlorotriazines) was administered by gavage da ily for 2 wk to female Sprague-Dawley and Fischer 344 rats at oral dos es of 100 or 300 mg/kg to evaluate effects on body, ovary, uterus, and adrenal weights, estrous cycle stages, vaginal cytology, and plasma h ormone (estradiol, progesterone, prolactin, and corticosterone) levels . Significant reductions in body weights of both Sprague-Dawley and Fi scher 344 female rats at both dose levels were accompanied by a signif icant reduction in ovarian and uterine weights, and a decrease in circ ulating estradiol levels. The magnitudes of the effects were less in F ischer 344 rats than in Sprague-Dawley rats, and the effects of simazi ne were less pronounced than those of atrazine at the same dose. A max imum tolerated dose (MTD: greater than or equal to 10% body weight red uction) was estimated to be 100 mg/kg for atrazine and 300 mg/kg for s imazine for both stains. The Sprague-Dawley female rats exhibited a tr eatment-related lengthening of the estrous cycle and an increased numb er of days characterized by cornified epithelial cells. This resulted in a greater percent of the cycle days spent in estrus and reduction i n the percent of the cycle days spent in diestrus. Atrazine-dosed Fisc her 344 females also exhibited a significant trend toward cycle length ening, but this was due to reduction in the percent of cycle spent in estrus and a concomitant increase in diestrual days. These findings su ggest that treatment with doses of triazine at or above the MTD may re sult in prolonged exposure to endogenous estrogen in the Sprague-Dawle y but not the Fischer 344 rat. These changes may account for the obser ved earlier onset and/or increased incidence of mammary tumors in chlo rotriazine-treated female Sprague-Dawley rats. This strain of rat is a lready known to be prone to a substantial development of mammary tumor s with advancing age, while the Fischer 344 strain is not as likely to exhibit this response.