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United States Department of Agriculture

Agricultural Research Service

Title: Tissue Disposition, Excretion, and Metabolism of 2,2',4,4',5-Pentabromodiphenyl Ether (Bde-99)in the Male Sprague-Dawley Rat.

Authors
item Hakk, Heldur
item Larsen, Gerald
item Klasson-Wehler, Eva - ASTRAZENECA

Submitted to: Xenobiotica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 15, 2001
Publication Date: January 1, 2002
Citation: Hakk, H., Larsen, G.L., Klasson-Wehler, E. 2002. Tissue disposition, excretion, and metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99)in the male Sprague-Dawley rat. Xenobiotica 32(5):369-382.

Interpretive Summary: One of the most abundant brominated flame retardants is the brominated diphenyl ether (BDE) family. The tetra- and penta-bromo diphenyl ethers are the most common BDE congeners found in environmental analyses. The purpose of this study was to measure the metabolic behavior of [14C]2,2',4,4',5-pentabromodiphenyl ether (BDE-99) in male rats for 3, 6, and 12 days. BDE-99 was absorbed reasonably well, but was not excreted to a large extent in either the urine or bile. Fecal excretion was the major route of elimination, and it contained a significant level of non- extractable BDE-99. BDE-99 preferentially deposited in lipophilic tissues, i.e. adipose tissue, GI tract, adrenal gland, and skin, although it could be found in every tissue sampled. The BDE-99 was readily extracted from fat, kidney, and lungs as the parent compound, but in liver a large portion of these BDE-99 residues were non-extractable or were metabolites. Metabolites identified in bile and feces indicated that hydroxylation, debromination, and thiol formation were characteristic of rat metabolism of BDE-99. Total plasma thyroid hormone levels increased about 2-fold soon after receiving the dose, but returned to normal levels within 12 days.

Technical Abstract: One of the most abundant brominated flame retardants in use for consumer products is the brominated diphenyl ether (BDE) family. 2,2',4,4'-tetra- and 2,2',4,4',5-penta-bromo diphenyl ether (BDE-47 and 99, respectively) are the most common BDEs identified in environmental analyses. The purpose of this study was to measure the metabolic behavior of [14C]2,2',4,4',5- pentabromodiphenyl ether (BDE-99) in male rats for 3, 6, and 12 days. BDE 99 was absorbed reasonably well after a single oral dose, but less than 1% was excreted via the urine, and less than 4% was excreted in the bile after 3 days. Fecal excretion was the major route of elimination (43% at 3 days), and it contained a significant portion of non-extractable BDE-99 residues (19-52%). BDE-99 preferentially deposited in lipophilic tissues, i.e. epididymal fat (3.8%), carcass fat (17%), GI tract (6.1%), adrenals (0.1%), and skin (21%), although it could be found in every tissue sampled. .The whole body half-life of BDE-99 in male rats was slightly less than 6 days, and therefore, it was concluded that it had a reasonable potential to bioaccumulate. The BDE-99 was readily extracted from fat, kidney, and lungs as the parent compound, but in liver, a large portion of the deposit- ed radioactivity was non-extractable, & the extractable portion contained hydroxylated metabolites. Metabolites identified in bile and feces were monohydroxylated, monohydroxylated with an accompanying loss of a bromine, dihydroxylated, and thiols (probably formed via the mercapturic acid pathway). Total plasma thyroid hormone levels increased approximately 2- fold at 3 and 6 days, but returned to normal levels within 12 days.

Last Modified: 4/19/2014
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