Formation of Hydroxylated Metabolites Responsible for the Toxicity of Brominated Flame Retardants and Thyroid Hormone Disrupting Action

对几种溴化阻燃剂的内分泌干扰活性进行了研究。1)四溴双酚A、四氯双酚A和一些4-羟基化多溴联苯醚与甲状腺激素受体的结合试验中，观察了其对甲状腺激素的干扰活性。这些化学物质对GH3细胞也表现出甲状腺激素效应。然而，多溴联苯醚和双酚A没有表现出活性。其中四溴双酚A的甲状腺激素活性最高。3,5 -取代溴是甲状腺激素活性的重要因素。2) 4-羟基- 2,2′，4-三溴联苯醚在人乳腺癌细胞系MCF-7的报告细胞实验中显示出雌激素活性。在这种情况下，3,5 -二溴取代降低了雌激素活性。3)以蝌蚪为实验对象，对这些化学物质的作用进行了评价。三碘甲状腺原氨酸（T3）的加入使tadopole的尾部缩短。这些化学物质对t3诱导的蝌蚪尾退有拮抗作用。这些事实表明，羟基溴化阻燃剂在世界范围内表现出内分泌干扰作用。

Endocrine-disrupting activity of some brominated flame retardants was examined. 1) The thyroid hormone-disrupting activity of tetrabromobisphenol A, tetrachlorobisphenol A, some 4-hydroxylated polybromodiphenyl ethers was observed in the assay of binding to thyroid hormone receptor. These chemicals also showed thyroid hormonal effect on GH3 cell. However, polybrominated diphenyl ethers and bisphenol A did not exhibit the activity. Especially, tetrabromobisphenol A exhibited the highest thyroid hormonal activity. 3, 5-Substituted bromide is an essential factor for the thyroid hormonal activity. 2) 4-Hydroxy-2, 2', 4-tribromodiphenyl ether exhibited estrogenic activity in the reporter assay using human breast cancer cell line MCF-7. In this case, 3, 5-dibromo substitution decreased the estrogenic activity. 3) The action of these chemicals was also estimated by amphibian metamorphosis using tadpole. The tail of tadopole was shortened by the addition of triiodothyronine (T3). These chemicals showed antagonistic effect against the T3-induced tadpole tail regression. These facts suggest that hydroxylated brominated flame retardants exhibited endocrine-disrupting effect in the worldwide life.