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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 #158660

Title: DECABROMODIPHENYL ETHER IN THE RAT: ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION.

Author
item MORCK, A - STOCKHOLM UNIV.
item Hakk, Heldur
item ORN, U - STOCKHOLM UNIV.
item KLASSON-WEHLER, E - ASTRA-ZENECA

Submitted to: Drug Metabolism and Disposition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2003
Publication Date: 1/1/2003
Citation: Morck, A., Hakk, H., Orn, U., Klasson-Wehler, E. 2003. Decabromodiphenyl ether in the rat: absorption, distribution, metabolism, and excretion. Drug Metabolism and Disposition. 31:900-907.

Interpretive Summary: One of the most abundant groups of brominated flame retardant is the brominated diphenyl ether (BDE) family. The fully brominated decabromodiphenyl ether (BDE-209)is the most common BDE congener in use today worldwide. The purpose of this study was to measure the metabolic behavior of carbon-14 radiolabelled decabromodiphenyl ether (BDE-209) in male rats for 3 and 7 days. At least 10% of the BDE-209 dose was absorbed, but the great majority of the dose was excreted in the feces as both unchanged parent compound (35%) and metabolites (65%). Biliary excretion was nearly 10%, and it represented mainly metabolites of BDE-209. BDE-209 preferentially deposited in plasma and highly blood profused tissues, such as liver, kidney, heart, and intestinal wall, while its concentration in adipose tissue was the lowest of the measured tissues. The metabolites of BDE-209 were found to be bound to lipids and/or proteins in both the feces and in the tissues, and a small amount of water-soluble metabolites were also present. Absorbed parent compound was readily metabolized through a reactive intermediate. Metabolites identified in bile and feces indicated that hydroxylation, debromination, and methoxy/hydroxy formation were characteristic of rat metabolism of BDE-209.

Technical Abstract: One of the most important groups of brominated flame retardant is the brominated diphenyl ether (BDE) family. The fully brominated decabromodiphenyl ether (BDE-209)is the most common BDE congener in use today worldwide. The purpose of this study was to measure the metabolic behavior of [14C]2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) in male rats for 3 and 7 days. At least 10% of the BDE-209 dose was absorbed, as was indicated by biliary excretion of 14C, and it was composed mainly of metabolites. Greater than 90% of the dose was excreted in the feces as both unchanged parent compound (35%) and metabolites (65%). Less than 0.1% of the dose was excreted in the urine. Absorbed parent compound was readily metabolized via a putative reactive intermediate. Many metabolites of BDE-209 in both the feces and in the tissues (17-69% of resident 14C)were found to be covalently bound to lipids and/or proteins, and a small amount of water-soluble metabolites were also present (0-11% of resident 14C). The neutral and phenolic metabolites identified in bile and feces indicated that monohydroxylation, debromination, and guaiacol formation were characteristic of rat metabolism of BDE-209. BDE-209 preferentially deposited in highly perfused tissues, i.e. plasma, liver, heart and adrenals (4.8-22 nmole/g fresh-weight), while its concentration in adipose tissue was the lowest of the measured tissues (0.17 nmole/g fresh-weight). Very few differences in tissue disposition were observed between rats at 3 or 7 days.