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ARS Home » Plains Area » Fargo, North Dakota » Edward T. Schafer Agricultural Research Center » Animal Metabolism-Agricultural Chemicals Research » Research » Publications at this Location » Publication #201327
Title: Toxicokinetics of Polybrominated Diphenyl Ether Congeners 47, 99, 100, and 153 in Mice

Author
item STASKAL, D - US EPA
item Hakk, Heldur
item BAUER, D - US EPA
item DILIBERTO, J - US EPA
item BIRNBAUM, L - US EPA

Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/22/2006
Publication Date: 8/25/2006
Citation: Staskal, D.F., Hakk, H., Bauer, D., Diliberto, J.J., Birnbaum, L.S. 2006. Toxicokinetics of Polybrominated Diphenyl Ether Congeners 47, 99, 100, and 153 in Mice. Toxicological Sciences 94(1):28-37.

Interpretive Summary: Polybrominated diphenyl ethers (PBDEs), used commonly as consumer product flame retardants, are bioaccumulative in human and wildlife samples, and are dominated by PBDE congeners 47, 99, 100, 153, and 154. No information is available on directly comparing the behavior of each BDE congener in mice. Therefore, the objective of this study was to compare the distribution, metabolism and excretion of BDEs 47, 99, 100 and 153. Four groups of female C57BL/6 mice were given a single iv dose of each BDE (1 mg/kg, respectively). Excretion was monitored daily and tissue disposition was determined at five days. All BDE congeners distributed with a similar pattern into fatty tissues, i.e. fat, muscle, skin, and liver. Tissue concentrations were much higher for BDE 153, than 100, 99, and 47, respectively. Excretion rates were inversely related to tissue concentrations; BDE 47 was the most rapidly excreted congener, followed by BDEs 99, 100, then 153. Each congener’s urinary elimination rate was governed by its ability to associate with a protein found in the urine. Metabolites were identified in both urine and feces samples, and BDE 99 was the most extensively metabolized congener in this study. The results of this study demonstrate that bromination pattern plays a role in the distribution, metabolism and excretion of PBDEs in mice, and future risk assessments need to consider the differential behavior of each congener when assessing the potential hazard of each PBDE congener to mammalian health.

Technical Abstract: The congener profiles of polybrominated diphenyl ethers (PBDEs) in biota samples are dominated by PBDE congeners 47, 99, 100, 153, and 154; all of which are components of the commercial pentaBDE mixtures commonly used in a variety of flammable consumer products. Very little information is available on the toxicokinetics of these congeners and no studies are available directly comparing these BDE congeners in mice. Therefore, the objective of this study was to compare the distribution, metabolism and excretion of BDEs 47, 99, 100 and 153. Female C57BL/6 mice were administered a single dose of BDE (1 mg/kg: 2.1, 1.9, 1.9 and 1.8 µmol/kg, respectively) intravenously. Excretion was monitored daily and terminal tissue disposition was examined five days following dosing. All BDE congeners in this study distribute with similar patterns into lipophilic tissues; tissue concentrations at five days were much higher for BDE 153, than 100, 99, and 47, respectively. Excretion rates were inversely related to tissue concentrations as BDE 47 was the most rapidly excreted congener, followed by BDEs 99, 100, and 153. Differences in tissue concentrations were largely driven by congener specific urinary elimination rates which appear to be associated with protein binding in the urine. Metabolites were identified in daily urine and feces samples; BDE 99 was the most rapidly metabolized congener in this study. The results of this study demonstrate that congener pattern plays a role in the distribution, metabolism and excretion of PBDEs in mice and it is therefore important to consider the differential toxicokinetic parameters associated with each congener when assessing the risk to human health from these PBDE congeners.