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

The metabolism and disposition of (14)C-labelled 2,2',4,4'-tetrabromodiphenyl ether (BDE47) were investigated in F344 rats and B6C3F1 mice. Approximately 75-85% of 1 micromol 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 (14)C to major tissues were dose-proportional in male rats from 0.1 to 1,000 micromol kg(-1). BDE47-derived radioactivity increased in all rat and mouse tissues examined following repeated daily doses of 1 micromol kg(-1). Accumulation of (14)C 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.