Distribution of the parent compound and its metabolites in serum, urine, and feces of mice administered 2,2′,4,4′-tetrabromodiphenyl ether

Abstract

2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is a predominant polybromodiphenyl ether congener in the environment. Its absorption, excretion, and metabolism in animals have been investigated; however, the distribution of BDE-47 and its metabolites in excreta and blood at steady-state conditions has been unclear. In the present study, we addressed the issue by determining the amounts of BDE-47, eight monohydroxylated metabolites (OH-BDEs), and 2,4-dibromophenol (2,4-DBP) in serum, urine, and feces of gpt delta transgenic mice orally administered BDE-47 at 1.5, 10, and 30 mg/kg/d for 6 weeks during the 24 h period (for urine and feces) or at 24 h (for blood) post-last dosing. The distribution profiles in the three matrices showed that BDE-47, OH-BDEs, and 2,4-DBP were mostly distributed in urine (59–70%), feces (95–96%), and urine (51–80%), respectively. In each matrix, BDE-47 was the predominant compound under all doses, which accounted for 84–96% in serum, 68–98% in urine, and 37–92% in feces. However, exclusive of BDE-47, OH-BDEs were the predominant class of metabolites in serum (72–86%) and feces (67–87%), whereas 2,4-DBP was the major metabolite in urine (98–99%). Among monohydroxylated metabolites, the dominant compounds were 4-hydroxy-2,2′,3,4′-tetrabromodiphenyl ether (4-OH-BDE-42) and 4′-hydroxy-2,2′,4,5′-tetrabromodiphenyl ether (4′-OH-BDE-49) in feces (27–33% and 25–43%, respectively), and 3-hydroxy-2,2′,4,4′-tetrabromodiphenyl ether (3-OH-BDE-47) in serum (26–43%). Thus, BDE-47 and 2,4-DBP were mostly present in urine, and OH-BDEs were primarily found in feces. Blood was not an important carrier for either BDE-47 or its metabolites. The data provide information for distribution and elimination of BDE-47 and its metabolites in mice at steady-state conditions.