Absorption, distribution, metabolism and excretion (ADME) study with 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154) in male Sprague-Dawley rats
Absorption, distribution, metabolism and excretion (ADME) study with 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154) in male Sprague-Dawley rats
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DOI：
10.1080/00498250802546853
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发表时间：
2009-01-01
期刊：
影响因子：
1.8
通讯作者：
Larsen, G. L.
中科院分区：
文献类型：
--
作者：
Hakk, H.;Huwe, J. K.;Larsen, G. L.
在常规和胆管插管雄性sd大鼠中进行了口服2,2',4,4',5,6'-六溴联苯醚（BDE-154, 11.3 mol kg-1）的代谢研究。在常规大鼠中，约31%的放射性标记剂量在72小时被保留，亲脂组织是首选的处置部位。尿中BDE-154的排泄量极低（1.0%），检出母体化合物。累积胆汁排泄量为1.3%，建议使用谷胱甘肽偶联物。常规雄性大鼠62%以上的剂量通过粪便排出，由母体化合物（7.3%）、游离代谢物（13.1%）和共价结合残基（41.4%）组成。通过气相色谱/质谱分析表征的粪便代谢物包括单羟基化六/五/四溴联苯醚和二羟基化六/五溴联苯醚的多个异构体。脂肪组织14C是可提取的BDE-154，但40%的肝脏14C与大分子结合。该研究证明了进行个体多溴联苯醚（PBDE）代谢研究对于充分了解PBDE药代动力学的重要性。
A metabolism study of orally administered 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154; 11.3 moles kg-1) was conducted in conventional and bile duct-cannulated male Sprague-Dawley rats. In conventional rats, approximately 31% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition. Urinary excretion of BDE-154 was very low (1.0%), and parent compound was detected. Cumulative biliary excretion was 1.3%, and glutathione conjugates were suggested. Over 62% of the dose in conventional male rats was excreted in faeces, and was composed of parent compound (7.3%), free metabolites (13.1%), and covalently bound residues (41.4%). Faecal metabolites characterized by gas chromatography/mass spectrometry included multiple isomers of monohydroxylated hexa-/penta-/tetrabromodiphenyl ethers, and di-hydroxylated hexa/pentabromodiphenyl ethers. The adipose tissue 14C was extractable BDE-154, but 40% of liver 14C was bound to macromolecules. The study demonstrated the importance of performing individual polybrominated diphenyl ether (PBDE) metabolism studies to understand fully PBDE pharmacokinetics.