Tissue disposition, excretion and metabolism of 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100) in male Sprague-Dawley rats
Tissue disposition, excretion and metabolism of 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100) in male Sprague-Dawley rats
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DOI：
10.1080/00498250500491675
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发表时间：
2006-01-01
期刊：
影响因子：
1.8
通讯作者：
Larsen, G
中科院分区：
文献类型：
--
作者：
Hakk, H;Huwe, J;Larsen, G
本文研究了2，2‘，4，4’，6-五溴二苯醚(BDE-100)在常规和胆管插管雄性大鼠体内的吸收、处置、代谢和排泄规律。在常规大鼠中，放射性标记的口服剂量在72小时内保留了70%，亲脂组织是首选的处置部位，即脂肪组织、胃肠道、皮肤、肝脏和肺。尿中BDE-100的排泄量很低(为剂量的0.1%)。胆汁中BDE-100的排泄量略高于尿液中的排泄量，72小时时为1.7%，提示酚类代谢物发生了葡萄糖醛酸化反应。在胆汁中没有观察到硫醇代谢物，正如在其他多溴二苯醚代谢研究中所报道的那样。在常规雄性大鼠和胆管插管大鼠中，几乎20%的剂量和超过26%的剂量是从粪便中排出的，主要是作为未代谢的母体，尽管也观察到大量的不可提取的放射性标记。用质谱仪对粪便中的可提取代谢物进行了表征。检测到单羟基五溴二苯醚代谢物；还观察到伴随氧化脱溴的单羟基和双羟基代谢物作为粪便代谢物。[C-14]BDE-100在肝脏、胃肠道和脂肪组织中的组织残留仅含有母体物质。大部分0-72小时的胆汁放射性与一种未知的79 kDa蛋白或白蛋白有关。
The absorption, disposition, metabolism and excretion study of orally administered 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) was studied in conventional and bile-duct cannulated male rats. In conventional rats, > 70% of the radiolabelled oral dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, gastrointestinal tract, skin, liver and lungs. Urinary excretion of BDE-100 was very low (0.1% of the dose). Biliary excretion of BDE-100 was slightly greater than that observed in urine, i.e. 1.7% at 72 h, and glucuronidation of phenolic metabolites was suggested. Thiol metabolites were not observed in the bile as had been reported in other PBDE metabolism studies. Almost 20% of the dose in conventional male rats and over 26% in bile-duct cannulated rats was excreted in the faeces, mainly as the unmetabolized parent, although large amounts of non-extractable radiolabel were also observed. Extractable metabolites in faeces were characterized by mass spectrometry. Monohydroxylated pentabromodiphenyl ether metabolites were detected; mono-and di-hydroxylated metabolites with accompanying oxidative debromination were also observed as faecal metabolites. Tissue residues of [C-14] BDE-100 in liver, gastrointestinal tract and adipose tissue contained only parent material. The majority of the 0 - 72- h biliary radioactivity was associated with an unidentified 79-kDa protein or to albumin.