Brown David J, Van Overmeire Ilse, Goeyens Leo, Denison Michael S, De Vito Michael J, Clark George C
Xenobiotic Detection Systems Inc., 1601 East Geer Street, Suite S, Durham, NC 27704, USA.
Chemosphere. 2004 Jun;55(11):1509-18. doi: 10.1016/j.chemosphere.2003.10.019.
Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2',4,4',5,5'-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2',4,4',5,5'-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.
溴化阻燃剂（BFRs）作为添加剂用于塑料中，以降低这些材料的燃烧速率，从而提高消费者安全性。随着塑料使用量的增加，阻燃剂的生产和使用也在增长。许多BFRs具有持久性，已在环境样品中被检测到，这引发了对其使用相关生物/毒理学风险的担忧。大多数BFRs似乎无毒，然而仍有人担心这些化合物或BFRs混合物中的可能污染物会与细胞受体相互作用。在本研究中，我们检测了十溴二苯醚、Firemaster BP4A（四溴双酚A）、Firemaster PHT4（四溴邻苯二甲酸酐）、六溴苯、五溴甲苯、十溴联苯、Firemaster BP-6（2,2',4,4',5,5'-六溴联苯）以及BFR混合物的可能污染物与芳烃受体（Ah受体）的相互作用。使用凝胶阻滞试验检测受体结合和激活情况，并使用基于报告基因的CALUX试验检测二噁英反应基因的表达增加情况。结果表明，使用这两种试验评估，BFRs在中高浓度下能够激活AhR信号转导途径。BFRs对AhR的依赖性激活可能部分归因于商业/工业混合物中存在的污染物。这通过我们对Firemaster BP-6与其主要成分2,2',4,4',5,5'-六溴联苯的比较分析得到了证实。一些溴化阻燃剂的工业混合物含有溴化联苯、二噁英或二苯并呋喃作为污染物。在CALUX试验中测试时，发现这些化合物等同于或比其氯化类似物更具活性。从这些溴化卤代芳烃的剂量反应曲线确定了相对有效效价。
