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ToxSci Advance Access published online on August 25, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl091
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 24, 2006
Accepted August 1, 2006

Biotransformation and Toxicokinetics

Toxicokinetics of Polybrominated Diphenyl Ether Congeners 47, 99, 100, and 153 in Mice

D. F. Staskal 1 *, H. Hakk 2, D. Bauer 3, J. J. Diliberto 4, and L. S. Birnbaum 4

1 UNC Curriculum in Toxicology, US EPA, MD B143-01, 109 TW Alexander Dr., Research Triangle Park, NC 27711; Current Affiliation, ChemRisk, 3420 Executive Center Drive, Austin, TX 78731
2 USDA, ARS, Biosciences Research Laboratory, PO Box 5674, Fargo, ND 58105-5647
3 UNC Curriculum in Toxicology, US EPA, MD B143-01, 109 TW Alexander Dr., Research Triangle Park, NC 27711
4 US EPA, ORD, NHEERL, ETD, US EPA, MD B143-01, 109 TW Alexander Dr., Research Triangle Park, NC 27711

* To whom correspondence should be addressed.
D. F. Staskal, E-mail: dstaskal{at}chemrisk.com


  Abstract

The congener profiles of polybrominated diphenyl ethers (PBDEs) in human and wildlife samples are dominated by brominated diphyenyl ether (BDE) 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 exposure. All BDE congeners in this study distribute with similar patterns into lipophilic tissues; however, tissue concentrations five days following exposure 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 were associated with protein binding in the urine. While the overall rate of metabolism appeared to be low, analysis of metabolites in daily feces samples revealed that BDE 99 was the most rapidly metabolized congener in this study. The results of this study demonstrate that congener substitution 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.


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