Wetzel L T, Luempert L G, Breckenridge C B, Tisdel M O, Stevens J T, Thakur A K, Extrom P J, Eldridge J C
Department of Toxicology, Ciba Crop Protection Division, Ciba-Geigy Corporation, Greensboro, North Carolina 27419-8300.
J Toxicol Environ Health. 1994 Oct;43(2):169-82. doi: 10.1080/15287399409531913.
The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague-Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague-Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of days in estrus or under the influence of exposure to estrogen, (3) earlier onset of galactocele formation, and (4) earlier onset of mammary and pituitary tumor formation but not an increased incidence of mammary and pituitary tumors when compared to concurrent control rats. Fischer 344 female rats fed atrazine at an MTD exhibited slightly lengthened estrous cycles, but no effects were observed on estradiol or progesterone levels, or on the onset or incidence of mammary tumors. These results support a hypothesis that high-dose atrazine administration in Sprague-Dawley females is related to an acceleration of age-related endocrine changes leading to an earlier onset and/or increased incidence of mammary tumors. This endocrine-mediated response, which appears to be unique to the Sprague-Dawley female rat, occurs only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, promoting prolonged exposure to endogenous estrogen.
在Fischer 344和Sprague-Dawley雌性大鼠中，评估了饮食中给予高达400 ppm阿特拉津对选定内分泌和肿瘤特征的慢性影响。研究表明，对Sprague-Dawley雌性大鼠终身给予最大耐受剂量（MTD）的阿特拉津会导致：（1）发情周期延长；（2）发情期或受雌激素暴露影响的天数增加；（3）乳腺囊肿形成提前；（4）乳腺和垂体肿瘤形成提前，但与同期对照大鼠相比，乳腺和垂体肿瘤的发生率并未增加。以MTD喂食阿特拉津的Fischer 344雌性大鼠发情周期略有延长，但未观察到对雌二醇或孕酮水平、乳腺肿瘤的发生或发生率有影响。这些结果支持了一个假设，即对Sprague-Dawley雌性大鼠高剂量给予阿特拉津与年龄相关的内分泌变化加速有关，导致乳腺肿瘤的发病提前和/或发生率增加。这种内分泌介导的反应似乎是Sprague-Dawley雌性大鼠特有的，仅在干扰正常发情周期的阈值剂量（MTD）及以上出现，从而促进了对内源性雌激素的长期暴露。
