Stevens J T, Breckenridge C B, Wetzel L T, Gillis J H, Luempert L G, 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):139-53. doi: 10.1080/15287399409531911.
The symmetrical triazine herbicides have been used for the preemergence control of broadleaf weeds for nearly three decades. Recently, certain members of this class, primarily the chlorotriazines (substituted in the 2 position), have been shown to evoke an increased incidence of mammary tumors in female Sprague-Dawley rats. This response was noted when these chemicals were administered in the diet for 2 yr, and most often at dietary feeding levels at or above the maximum tolerated dose (MTD). At levels exceeding the MTD the health of these animals was compromised, as manifested by toxicity-related reduced survival that was not associated with the occurrence of mammary tumors. Mammary tumors in rats frequently occur as a result of the influence of endogenous estradiol and prolactin. Those hormones, as well as progesterone, growth-stimulating, luteinizing, and follicle-stimulating hormones, were measured after 24 mo of dietary administration of the chlorotriazine, simazine. The plasma hormone pattern seen in aged female Sprague-Dawley rats administered 1000 ppm simazine in the diet for 24 mo resembled that noted for aged female controls, except that the difference was more pronounced in the simazine-treated group. These results suggest that prolonged exposure of Sprague-Dawley females to excessive levels of triazines affects the neuroendocrine system, which in turn alters the pathology of the mammary gland. These changes are comparable to those that occur naturally as the rat ages. Changes in neuroendocrine control could result in the expression of an earlier onset and/or an increased incidence of mammary tumors, which already occur at a high spontaneous rate in aging Sprague-Dawley female rats.
对称三嗪类除草剂已用于苗前防除阔叶杂草近三十年。最近，这类除草剂中的某些成员，主要是氯代三嗪（在2位有取代基），已被证明可使雌性斯普拉格-道利大鼠乳腺肿瘤的发生率增加。当这些化学物质在饲料中投喂2年时观察到这种反应，而且最常出现在等于或高于最大耐受剂量（MTD）的饲料投喂水平。在超过MTD的水平时，这些动物的健康受到损害，表现为与毒性相关的存活率降低，但这与乳腺肿瘤的发生无关。大鼠乳腺肿瘤的发生常常是内源性雌二醇和催乳素影响的结果。在饲料中投喂氯代三嗪西玛津24个月后，对这些激素以及孕酮、生长刺激素、促黄体生成素和促卵泡激素进行了测量。在饲料中投喂1000 ppm西玛津24个月的老龄雌性斯普拉格-道利大鼠的血浆激素模式与老龄雌性对照组相似，只是在西玛津处理组中差异更为明显。这些结果表明，斯普拉格-道利雌性大鼠长期暴露于过量的三嗪会影响神经内分泌系统，进而改变乳腺的病理状况。这些变化与大鼠自然衰老时发生的变化相当。神经内分泌控制的改变可能导致乳腺肿瘤更早发生和/或发生率增加，而在衰老的斯普拉格-道利雌性大鼠中，乳腺肿瘤本来就有很高的自发发生率。
