多溴二苯醚及其代谢物的内分泌干扰活性和构效关系研究进展

Study on Endocrine Disruption and Structure-Activity Relationship of PBDEs and Their Metabolites

多溴二苯醚(Polybrominated diphenyl ethers,PBDEs)作为一种良好的防火溴系阻燃剂(Brominated flame retardants,BFRs)广泛应用于各种家用和工业产品.研究表明,PBDEs容易从产品中溢出而进入环境.近年来,PBDEs及其代谢物已在各种环境介质和生物体中被广泛检出.毒理学研究发现,PBDEs及其代谢物具有生殖毒性、免疫毒性、神经毒性和内分泌干扰作用.在总结国内外相关研究基础上,论文综述了PBDEs及其代谢物的内分泌干扰活性,重点集中在对甲状腺激素活性、雌激素活性、雄激素活性及影响性激素转化和代谢的芳香化酶、CYP17酶、雌二醇磺基转移酶(E2SULT)活性的影响;分析了具有不同测试终点内分泌干扰活性的化合物的结构特征.研究发现,在内分泌干扰活性方面,PBDEs母体化合物的影响较小,主要是PBDEs代谢物产生的影响,特别是羟基化代谢物引起了较严重的内分泌干扰作用,即PBDEs化合物是一类通过代谢而被活化的内分泌干扰前趋物.为评价PBDEs及其代谢物对人和其他生物的健康危害,应加强其内分泌干扰活性机制的研究,以及具有同类型作用模式的PBDEs及其代谢物定量结构-活性关系的研究.

Polybrominated diphenyl ethers （PBDEs）, a specific group of brominated flame retardants （BFRs）, are widely used in household and industrial products, including electronics and household furnishings. PBDEs and their metabolites have recently been reported to be present in various environmental and biotic samples. PBDEs have reproductive and developmental toxicity, immunity toxicity, neurotoxicity and endocrine disruption toxicity. This paper summarizes the endocrine disrupting activity of PBDEs and their metabolites, mainly focusing on disrupting thyroid hormone, estrogen hormone, androgen hormone and various enzyme activities （e.g. aromatase CYP19, CYP17 enzyme and estradiol sulfotransferase E2SULT, which affect the transformation and metabolism of sex hormone）, and analyzes the structure feature of PBDE compounds corresponding to different endpoints. It is found that PBDEs metabolites exhibit higher endocrine disrupting activity than PBDEs parent compounds do, especially HO-PBDEs induce serious endocrine disrupting interaction. The endocrine disrupting activities of PBDEs need metabolism in vitro. In order to evaluate environmental and human health risks from PBDEs exposure, their toxicity action mechanisms and quantitative structure-activity relationship （QSAR） should be investigated further.