Zhao Jian, Cai Leiming, Wang Jie, Wu Yingliang, Yao Baoyu, Zhang Le
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning Province, PR China.
Exp Toxicol Pathol. 2011 Jan;63(1-2):143-9. doi: 10.1016/j.etp.2009.11.001. Epub 2009 Dec 5.
To evaluate the endocrine-mediated effects of flumorph, we performed the uterotrophic assay, the Hershberger assay, and the repeated 28-day oral toxicity study based on the OECD draft protocols. In the uterotrophic assay, female ovariectomized SD rats were subcutaneously injected with flumorph at doses of 0, 50, 150, and 500 mg/kg on each of 3 days, and no changes were observed. In the Hershberger assay, castrated male SD rats were administered with flumorph by oral gavage at doses of 0, 50, 150, and 500 mg/kg/day for 10 consecutive days, and no abnormal changes were observed. However, in the repeated 28-day oral toxicity study , flumorph was orally administered at doses 0, 30, 100, and 300 mg/kg/day for at least 28 days, a significantly increase in T(4) value in male rats and TSH value in female rats were detected in the highest dosage group, respectively. Besides, the flumorph administration increase liver weights, produce hepatocellular diffuse fatty degeneration, and effect biochemical parameters related to liver function in male and/or female rats in dosed groups. Therefore, flumorph is concluded to have thyroid disruption effects and is likely a thyroid disrupter, but the further studies are needed for hazard identification.
为评估氟吗啉的内分泌介导效应，我们根据经合组织草案方案进行了子宫增重试验、赫什伯格试验以及重复28天的口服毒性研究。在子宫增重试验中，对雌性去卵巢SD大鼠连续3天每天皮下注射剂量为0、50、150和500 mg/kg的氟吗啉，未观察到变化。在赫什伯格试验中，对去势雄性SD大鼠连续10天每天经口灌胃给予剂量为0、50、150和500 mg/kg的氟吗啉，未观察到异常变化。然而，在重复28天的口服毒性研究中，以0、30、100和300 mg/kg/天的剂量对大鼠进行至少28天的口服给药，在最高剂量组分别检测到雄性大鼠T(4)值和雌性大鼠促甲状腺激素（TSH）值显著升高。此外，氟吗啉给药使肝脏重量增加，导致肝细胞弥漫性脂肪变性，并影响给药组雄性和/或雌性大鼠与肝功能相关的生化参数。因此，得出结论，氟吗啉具有甲状腺干扰效应，可能是一种甲状腺干扰物，但需要进一步研究以进行危害识别。
