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0090-9556/03/3107-900-907$20.00
DMD 31:900-907, 2003

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

Anna Mörck, Heldur Hakk, Ulrika Örn, and Eva Klasson Wehler

Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden (A.M., U.O., E.K.W.); and U.S. Department of Agriculture, Agricultural Research Science, Bioscience Research Laboratory, Fargo, North Dakota (H.H.)

Among the group of polybrominated diphenyl ethers used as flame-retardants, the fully brominated diphenyl ether, decabromodiphenyl ether (decaBDE), is the most commonly used. Despite the large usage of decaBDE, neither the metabolic pathways nor the absorption have been addressed, and there are very few studies on its toxicology. In this work, it is shown that after a single oral dose of 14C-labeled decaBDE to rats, at least 10% of the decaBDE dose is absorbed. The major excretion route in conventional rats is via feces that contained 90% of the decaBDE dose. The excretion in bile was close to 10% of the dose and represented mainly metabolites. It cannot be excluded that greater than 10% of the oral dose had been absorbed since 65% of the radioactivity excreted in feces was metabolites. The highest concentrations on a lipid weight basis were found in plasma and blood-rich tissues, and the adipose tissue had the lowest concentration of decaBDE. After derivatization of a phenolic fraction, gas chromatography-mass spectrometry (GC/MS) analyses indicated that metabolites with five to seven bromine atoms had formed, and they possessed a guaiacol structure (a hydroxy and a methoxy group) in one of the rings. In addition, traces of nonabrominated diphenyl ethers and monohydroxylated metabolites were found by GC/MS. Metabolites, characterized by their chemical properties, were interpreted to be covalently bound to macromolecules, either proteins or lipids. In addition, water solubility was suggested. The metabolic pathway was indicated to include a reactive intermediate.


Address correspondence to: Eva Klasson Wehler, AstraZeneca R&D, S-15 185 Södertälje, Sweden. E-mail: eva.klassonwehler{at}astrazeneca.com




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