Eldridge J C, Fleenor-Heyser D G, Extrom P C, Wetzel L T, Breckenridge C B, Gillis J H, Luempert L G, Stevens J T
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
J Toxicol Environ Health. 1994 Oct;43(2):155-67. doi: 10.1080/15287399409531912.
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.
将阿特拉津或西玛津（s-氯三嗪）以100或300mg/kg的口服剂量每日经口灌胃给予雌性斯普拉格-道利大鼠和费希尔344大鼠2周，以评估对体重、卵巢、子宫和肾上腺重量、发情周期阶段、阴道细胞学以及血浆激素（雌二醇、孕酮、催乳素和皮质酮）水平的影响。在两个剂量水平下，斯普拉格-道利大鼠和费希尔344雌性大鼠的体重均显著降低，同时卵巢和子宫重量显著减少，循环雌二醇水平降低。费希尔344大鼠的效应程度低于斯普拉格-道利大鼠，且在相同剂量下，西玛津的效应不如阿特拉津明显。对于两种品系，阿特拉津的最大耐受剂量（MTD：体重减轻≥10%）估计为100mg/kg，西玛津为300mg/kg。斯普拉格-道利雌性大鼠表现出与治疗相关的发情周期延长以及以角质化上皮细胞为特征的天数增加。这导致发情期在整个周期天数中所占百分比增加，而间情期在整个周期天数中所占百分比减少。给予阿特拉津的费希尔344雌性大鼠也表现出明显的周期延长趋势，但这是由于发情期在周期中所占百分比降低以及间情期天数相应增加所致。这些发现表明，以MTD或高于MTD的剂量使用三嗪进行治疗，可能会使斯普拉格-道利大鼠而非费希尔344大鼠长时间暴露于内源性雌激素中。这些变化可能解释了在经氯三嗪处理的雌性斯普拉格-道利大鼠中观察到的乳腺肿瘤发病较早和/或发病率增加的现象。已知这种品系的大鼠随着年龄增长易患大量乳腺肿瘤，而费希尔344品系则不太可能出现这种反应。
