Toxicokinetics of polybrominated diphenyl ether congeners 47, 99, 100, and 153 in mice.
The congener profiles of polybrominated diphenyl ethers (PBDEs) in human and wildlife samples are dominated by brominated diphenyl 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 mumol/kg, respectively) intravenously. Excretion was monitored daily, and terminal tissue disposition was examined 5 days following exposure. All BDE congeners in this study distribute with similar patterns into lipophilic tissues; however, tissue concentrations 5 days following exposure were much higher for BDE-153 than for 100, 99, and 47, respectively. Excretion rates were inversely related to tissue concentrations as BDE-47 was the most rapidly excreted congener, followed by BDE-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.
Staskal
Daniele F
DF
UNC Curriculum in Toxicology, US EPA, MD B143-01, Research Triangle Park, North Carolina 27711, USA. dstaskal@chemrisk.com
Hakk
Heldur
H
Bauer
Daniel
D
Diliberto
Janet J
JJ
Birnbaum
Linda S
LS
D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D005260:Female; D055768:Halogenated Diphenyl Ethers; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry
C477694:2,2',4,4',5-brominated diphenyl ether; D002250:Carbon Radioisotopes; D055768:Halogenated Diphenyl Ethers; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C517828:hexabrominated diphenyl ether 153; C517827:pentabrominated diphenyl ether 100; C511295:2,2',4,4'-tetrabromodiphenyl ether