Reproductive effects of tris(4-chlorophenyl)methanol in the rat
Reproductive effects of tris(4-chlorophenyl)methanol in the rat
复制标题
DOI：
10.1016/s0045-6535(98)00500-1
复制
发表时间：
1999-08-01
期刊：
影响因子：
8.8
通讯作者：
Chu, I
中科院分区：
文献类型：
--
作者：
Foster, WG;Desaulniers, D;Chu, I
三（4-氯苯基）甲醇（TCPM）是一种来源不明的全球性污染物，其结构与内分泌调节农药1,1,1 -三氯-2,2-双（对氯苯基）乙烷（DDT）和三敌畏有关。因此，本研究对性成熟雄性大鼠（n = 20）分别饲喂1.0、10.0或100 ppm的TCPM 28天，研究TCPM对生殖的潜在毒性作用。计算的TCPM采食量分别为0.0、0.1、1.2和12.4 mg/kg/d。与对照组相比，最高剂量组晚期血中促卵泡激素（FSH）浓度显著升高（P < 0.02）。相比之下，饮食中暴露于TCPM对黄体生成素（LH）、睾酮(T)和T/LH比值的循环水平没有影响。增加TCPM浓度的MCF-7细胞孵育既不能诱导增殖，也不能阻断雌二醇诱导的增殖作用，这表明TCPM既不是雌激素也不是抗雌激素。利用前列腺雄激素受体进行的相对结合亲和力研究表明，TCPM具有与滴滴涕的主要代谢物1,1-二氯-2,2-双（对氯苯基）乙烯（p,p'-DDE）相当的结合亲和力。此外，TCPM的Ki值（0.62 μ M）低于抗雄激素农药p、p′-DDE和vinclozolin的Ki值。尽管TCPM在体外与雄激素受体结合，但对血清T水平和睾丸形态变化均无影响，这表明在体内观察到的FSH水平升高的作用机制可能与本研究中使用的剂量水平下TCPM的抗雄激素作用无关。TCPM对生殖影响的无不良影响水平为10 ppm，相当于计算摄入量为1.2 mg/kg/天。1999爱思唯尔科学有限公司版权所有。
Tris(4-chlorophenyl)methanol (TCPM) is a global contaminant of unknown origin that is structurally related to the endocrine modulating pesticides 1,1,1 -trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and Dicofol. Therefore, the potential reproductive toxic effects of TCPM were investigated in sexually mature male Sprague Dawley rats (n = 20) treated with 1.0, 10.0 or 100 ppm of TCPM mixed in the diet for 28 days. The calculated TCPM intake was 0.0, 0.1, 1.2 and 12.4 mg/kg/day, respectively. Serum concentrations of follicle stimulating hormone (FSH) in terminal blood samples were significantly (P < 0.02) elevated in the highest dose group compared to the controls. In contrast, dietary exposure to TCPM had no effect on circulating levels of luteinizing hormone (LH), testosterone (T) and the T/LH ratio. Incubation of MCF-7 cells with increasing concentrations of TCPM failed to either induce proliferation or to block the proliferative effect induced by estradiol indicating that TCPM is neither estrogenic or anti-estrogenic. Relative binding affinity studies using androgen receptors from the prostate revealed that TCPM has a binding affinity comparable to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), the principle metabolite of DDT. In addition, the calculated Ki (0.62 mu M) for TCPM is lower than the reported Ki's for the antiandrogenic pesticides p,p'-DDE and vinclozolin. Although TCPM binds with the androgen receptor in vitro, the absence of both an effect on serum T levels and morphological changes in the testis suggests that the mechanism of action for elevated FSH levels seen in vivo may not involve an antiandrogenic effect of TCPM at the dose level used in this study. The no adverse effect level for reproductive effects of TCPM is 10 ppm which is equivalent to a calculated intake of 1.2 mg/kg/day. (C) 1999 Elsevier Science Ltd. All rights reserved.