Tissue disposition, excretion and metabolism of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE-99) in the male Sprague-Dawley rat

Abstract

1. A disposition, metabolism and excretion study of orally administered 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) was conducted in the conventional and bile duct-cannulated male rat. 2. In the conventional rat, >50% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, adrenals, gastrointestinal tract and skin. 3. Urinary excretion of BDE-99 was very low (<1% of dose), and glucuronidation of phenolic metabolites was suggested. 4. Biliary excretion of BDE-99 was slightly greater than observed in urine, i.e. 3.6% at 72h. 5. Over 43% of the dose in the conventional male rat and 86% in the bile duct-cannulated rat was excreted in the faeces, mainly as the unmetabolized parent compound. 6. Metabolites in bile and faeces were not conjugated. Mono- and di-hydroxylated pentabromodiphenyl ether metabolites were characterized by mass spectrometry. Two thiol metabolites were characterized in the bile. Oxidative debromination was also observed in the faecal metabolites. 7. Tissue BDE-99 was readily extractable, except for in the liver. The tissue ¹⁴C was not associated with lipids and was mainly the unmetabolized parent compound. 8. Total thyroxine (T4) plasma levels were elevated at 3 and 6 days, and returned to control levels by day 12.