Morck Anna, Hakk Heldur, Orn Ulrika, Klasson Wehler Eva
Department of Environmental Chemistry, Stockholm University, Sweden.
Drug Metab Dispos. 2003 Jul;31(7):900-7. doi: 10.1124/dmd.31.7.900.
Among the group of polybrominated diphenyl ethers used as flame-retardants, the fully brominated diphenyl ether, decabromodiphenyl ether (decaBDE), is the most commonly used. Despite the large usage of decaBDE, neither the metabolic pathways nor the absorption have been addressed, and there are very few studies on its toxicology. In this work, it is shown that after a single oral dose of 14C-labeled decaBDE to rats, at least 10% of the decaBDE dose is absorbed. The major excretion route in conventional rats is via feces that contained 90% of the decaBDE dose. The excretion in bile was close to 10% of the dose and represented mainly metabolites. It cannot be excluded that greater than 10% of the oral dose had been absorbed since 65% of the radioactivity excreted in feces was metabolites. The highest concentrations on a lipid weight basis were found in plasma and blood-rich tissues, and the adipose tissue had the lowest concentration of decaBDE. After derivatization of a phenolic fraction, gas chromatography-mass spectrometry (GC/MS) analyses indicated that metabolites with five to seven bromine atoms had formed, and they possessed a guaiacol structure (a hydroxy and a methoxy group) in one of the rings. In addition, traces of nonabrominated diphenyl ethers and monohydroxylated metabolites were found by GC/MS. Metabolites, characterized by their chemical properties, were interpreted to be covalently bound to macromolecules, either proteins or lipids. In addition, water solubility was suggested. The metabolic pathway was indicated to include a reactive intermediate.
在用作阻燃剂的多溴二苯醚组中，全溴化二苯醚十溴二苯醚（decaBDE）是最常用的。尽管十溴二苯醚的使用量很大，但代谢途径和吸收情况均未得到研究，关于其毒理学的研究也非常少。在这项研究中，结果表明，给大鼠单次口服14C标记的十溴二苯醚后，至少10%的十溴二苯醚剂量被吸收。常规大鼠的主要排泄途径是粪便，粪便中含有90%的十溴二苯醚剂量。胆汁排泄量接近剂量的10%，且主要为代谢产物。由于粪便中排泄的放射性物质65%是代谢产物，所以不能排除口服剂量超过10%已被吸收的可能性。以脂质重量计，血浆和富含血液的组织中浓度最高，而脂肪组织中十溴二苯醚的浓度最低。酚类部分衍生化后，气相色谱 - 质谱（GC/MS）分析表明，已形成含五至七个溴原子的代谢产物，且它们在其中一个环中具有愈创木酚结构（一个羟基和一个甲氧基）。此外，通过GC/MS还发现了痕量的九溴二苯醚和单羟基化代谢产物。根据其化学性质表征的代谢产物被解释为与蛋白质或脂质等大分子共价结合。此外，还表明了其水溶性。代谢途径表明包括一个反应性中间体。
