Metabolism and disposition of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) following a single or repeated administration to rats or mice

Abstract

The metabolism and disposition of ¹⁴C-labelled 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) were studied in F344 rats and B6C3F1 mice. Approximately 85% of a 1 µmol kg⁻¹ oral dose was absorbed by male rats and mice. Within 24 h following oral doses ranging from 0.1 to 1000 µmol kg⁻¹ to rats, 39–47% of the dose was excreted in the faeces (including 16% unabsorbed), up to 2% was excreted in the urine, and 34–38% remained in the tissues, mostly in adipose tissue. Mice excreted more in the urine and less in the faeces than rats. Tissue accumulation was observed following repeated dosing to rats. Two dihydrohydroxy-S-glutathionyl and two S-glutathionyl conjugates of BDE99, 2,4,5-tribromophenol glucuronide, two mono-hydroxylated BDE99 glucuronides, and three mono-hydroxylated tetrabromodiphenyl ether glucuronides were identified in male rat bile. 2,4,5-Tribromophenol and its glucuronide and sulfate conjugates, were identified in male rat urine. 2,4,5-Tribromophenol, one mono-hydroxylated tetrabromodiphenyl ether, and two mono-hydroxylated BDE99 were characterized in male rat faeces. BDE99 undergoes more extensive metabolism than does BDE47. Half of the absorbed oral dose in male rats was excreted in 10 days mostly as metabolites derived from arene oxide intermediates.

Key words::

• 2,2′,4,4′,5-Pentabromodiphenyl ether (BDE99)
• polybrominated diphenyl ether (PBDE)
• glutathione conjugation
• glucuronide conjugation
• sulfate conjugation

Acknowledgements

The authors thank A. C. Creech for excellent technical assistance. This research was supported by the Intramural Research Program of the NIH/NIEHS.