Tissue disposition, excretion and metabolism of 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100) in male Sprague–Dawley rats

Abstract

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 [14C]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.