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

研究了某些溴化阻燃剂的内分泌干扰活性。1)在甲状腺激素受体结合试验中，观察到四溴双酚A、四氯双酚A和某些4-羟基化多溴二苯醚的甲状腺激素干扰活性。这些化合物对GH 3细胞也有甲状腺激素效应。然而，多溴二苯醚和双酚A没有表现出活性。特别是，四溴双酚A表现出最高的甲状腺激素活性。3，5-取代溴是甲状腺激素活性的重要因素。2)4-羟基-2，2 '，4-三溴二苯醚在使用人乳腺癌细胞系MCF-7的报告基因试验中显示出雌激素活性。在这种情况下，3，5-二溴取代降低雌激素活性。3)这些化学品的行动也估计了两栖类变态蝌蚪。三碘甲腺原氨酸（T3）的加入缩短了蝌蚪的尾巴。这些化合物对T3诱导的蝌蚪尾退化有拮抗作用。这些事实表明，羟基溴化阻燃剂在世界范围内的生活中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.