Louis Gwendolyn W, Hallinger Daniel R, Braxton M Janay, Kamel Alaa, Stoker Tammy E
a Endocrine Toxicology Branch, Toxicity Assessment Division , National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA , Research Triangle Park , NC , USA.
b Oak Ridge Institute for Science and Education (ORISE) , US Department of Energy , Oak Ridge , TN , USA.
J Toxicol Environ Health A. 2017;80(4):236-249. doi: 10.1080/15287394.2017.1287029. Epub 2017 Jun 1.
Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. Previously, subchronic TCS treatment to female rats was found to advance puberty and potentiate the effect of ethinyl estradiol (EE) on uterine growth when EE and TCS were co-administered prior to weaning. In the pubertal study, a decrease in serum thyroxine (T) concentrations with no significant change in serum thyroid-stimulating hormone (TSH) was also observed. The purpose of the present study was to further characterize the influence of TCS on the reproductive and thyroid axes of the female rat using a chronic exposure regimen. Female Wistar rats were exposed by oral gavage to vehicle control, EE (1 μg/kg), or TCS (2.35, 4.69, 9.375 or 37.5 mg/kg) for 8 months and estrous cyclicity monitored. Although a divergent pattern of reproductive senescence appeared to emerge from 5 to 11 months of age between controls and EE-treated females, no significant difference in cyclicity was noted between TCS-treated and control females. A higher % control females displayed persistent diestrus (PD) by the end of the study, whereas animals administered with positive control (EE) were predominately persistent estrus (PE). Thyroxine concentration was significantly decreased in TCS-administered 9.375 and 37.5 mg/kg groups, with no marked effects on TSH levels, thyroid tissue weight, or histology. Results demonstrate that a long-term exposure to TCS did not significantly alter estrous cyclicity or timing of reproductive senescence in females but suppressed T levels at a lower dose than previously observed.
三氯生（TCS）是一种抗菌剂，已被证明在大鼠中是一种内分泌干扰物。此前，研究发现，在雌性大鼠断奶前同时给予乙炔雌二醇（EE）和三氯生（TCS）进行亚慢性处理，可使青春期提前，并增强EE对子宫生长的影响。在青春期研究中，还观察到血清甲状腺素（T4）浓度降低，而血清促甲状腺激素（TSH）无显著变化。本研究的目的是使用慢性暴露方案进一步表征TCS对雌性大鼠生殖轴和甲状腺轴的影响。通过口服灌胃将雌性Wistar大鼠暴露于溶剂对照组、EE（1μg/kg）或TCS（2.35、4.69、9.375或37.5mg/kg）中8个月，并监测发情周期。尽管在5至11月龄时，对照组和EE处理组雌性大鼠的生殖衰老模式出现了差异，但TCS处理组和对照组雌性大鼠的发情周期没有显著差异。到研究结束时，较高比例的对照组雌性大鼠表现为持续性静止期（PD），而给予阳性对照（EE）的动物主要表现为持续性发情期（PE）。在给予TCS的9.375和37.5mg/kg组中，甲状腺素浓度显著降低，对TSH水平、甲状腺组织重量或组织学没有明显影响。结果表明，长期暴露于TCS不会显著改变雌性大鼠的发情周期或生殖衰老时间，但在比先前观察到的更低剂量下会抑制T4水平。
