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

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.

Key words::

• Polybrominated diphenyl ether (PBDE)
• metabolism and disposition
• persistent organic pollutant

Acknowledgements

The authors thank A. C. Creech for excellent technical assistance and Drs M. L. Cunningham and U. Hoffler of NIEHS for reviewing the manuscript. Research was supported by the Intramural Research Program of the NIH and NIEHS.