Krivoshiev Boris V, Dardenne Freddy, Covaci Adrian, Blust Ronny, Husson Steven J
Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium.
Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium.
Toxicol In Vitro. 2016 Jun;33:153-62. doi: 10.1016/j.tiv.2016.03.006. Epub 2016 Mar 12.
Flame retardants are chemicals that are added to nearly all manufactured materials. Additionally, there has been a steady increase in diseases resulting from endocrine-disruption with an aligned increase in use of chemicals. Given the persistence, potential bioaccumulation, limited toxicological understanding, and vast use of flame retardants, there is a need to investigate potential endocrine-disruptive activity associated with these compounds in an effort for better risk assessment. We therefore used the MCF-7 flow-cytometric proliferation assay in an effort to establish potential estrogen-disrupting effects of twelve currently-used flame retardants. Triphenyl phosphate, tris(1,3-dichloro-2-propyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, and tetrabromobisphenol A showed statistically significant estrogenic activity, with hexabromocyclododecane being the most potent of the five (EC20 of 5.5 μM). Tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, tri(2-chloroethyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, tetrabromobisphenol A, and tris(2,3,-dibromopropyl) isocyanurate harboured anti-estrogenic activity when co-treating with 17β-estradiol, with hexabromocyclododecane showing the highest potency (IC20 of 17.6 μM). Interestingly, some compounds showed both estrogenic and anti-estrogenic effects, indicating both receptor-dependant and -independent mechanisms attributed to some of these compounds, in line with other studies. Multiple currently-used flame retardants may therefore act as xenoestrogens and anti-estrogens, or alter estrogen homeostasis, which could affect endocrine function.
阻燃剂是添加到几乎所有人造材料中的化学物质。此外,因内分泌干扰导致的疾病一直在稳步增加,与此同时化学物质的使用量也在增加。鉴于阻燃剂具有持久性、潜在生物累积性、毒理学认识有限且使用广泛,有必要研究与这些化合物相关的潜在内分泌干扰活性,以便进行更好的风险评估。因此,我们使用MCF-7流式细胞术增殖试验来确定十二种目前使用的阻燃剂的潜在雌激素干扰作用。磷酸三苯酯、磷酸三(1,3-二氯-2-丙基)酯、磷酸三丁酯、六溴环十二烷和四溴双酚A显示出具有统计学意义的雌激素活性,其中六溴环十二烷是这五种中活性最强的(EC20为5.5 μM)。当与17β-雌二醇共同处理时,磷酸三(2-丁氧基乙基)酯、磷酸三(1,3-二氯-2-丙基)酯、磷酸三(2-氯乙基)酯、磷酸三丁酯、六溴环十二烷、四溴双酚A和三(2,3-二溴丙基)异氰脲酸酯具有抗雌激素活性,其中六溴环十二烷的效力最高(IC20为17.6 μM)。有趣的是,一些化合物同时显示出雌激素和抗雌激素作用,这表明这些化合物中的一些存在受体依赖性和非依赖性机制,这与其他研究一致。因此,多种目前使用的阻燃剂可能充当外源性雌激素和抗雌激素,或改变雌激素稳态,进而可能影响内分泌功能。