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

考察了几种含溴阻燃剂的内分泌干扰活性。1)在与甲状腺激素受体结合的实验中，观察到四溴双酚A、四氯双酚A、某些4-羟基多溴二苯醚对甲状腺激素的干扰作用。这些化学物质对GH3细胞也表现出甲状腺激素效应。而多溴二苯醚和双酚A则无此活性。其中，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‘，4-三溴二苯醚在人乳腺癌细胞株MCF-7的报告实验中显示出雌激素样活性。在这种情况下，3，5-二溴取代降低了雌激素活性。3)利用蝌蚪进行两栖动物变态实验，评价了这些化合物的作用。通过添加三碘甲腺原氨酸(T3)，他多洛尔的尾巴变短。这些化合物对T3诱导的蝌蚪尾巴退化表现出拮抗作用。这些事实表明，羟基溴化阻燃剂在世界范围内具有内分泌干扰作用。

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.