Metabolism and disposition of 2,2′,4,4′- tetrabromodiphenyl ether following administration of single or multiple doses to rats and mice

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Abstract
The metabolism and disposition of 14C-labelled 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) were investigated in F344 rats and B6C3F1 mice. Approximately 75–85% of 1 µmol BDE47 kg−1 was absorbed following oral administration to either rats or mice. Sex and species differences were observed in tissue distribution and excretion of BDE47-derived radioactivity. Absorption and distribution of 14C to major tissues were dose-proportional in male rats from 0.1 to 1000 µmol kg−1. BDE47-derived radioactivity increased in all rat and mouse tissues examined following repeated daily doses of 1 µmol kg−1. Accumulation of 14C in tissues of mice was less than in corresponding rat tissues. Glutathione conjugates of BDE47 were excreted in rat bile. A glucuronide and a sulfate conjugate of 2,4-dibromophenol were detected in the urine of BDE47-treated rats. BDE47 appears to induce its own metabolism. Increased formation of reactive metabolites over time may correlate with toxicological effects in BDE47-treated rodents.