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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 #129795
Title: BINDING OF BROMINATED DIPHENYL ETHERS TO MALE RAT CARRIER PROTEINS.

Author
item Hakk, Heldur
item Larsen, Gerald
item BERGMAN, A - UNIV OF STOCKHOLM, SWEDEN
item ORN, U - UNIV OF STOCKHOLM, SWEDEN

Submitted to: Xenobiotica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2002
Publication Date: 11/1/2002
Citation: Hakk, H., Larsen, G.L., Bergman, A., Orn, U. 2002. Binding of brominated diphenyl ethers to male rat carrier proteins. Xenobiotica 32(12):1079-1091.

Interpretive Summary: One of the most important brominated flame retardant families is the brominated diphenyl ether (BDE) family. BDE-99 and 209 are among the most abundant BDE congeners in use today. The purpose of this study was to measure the amount of excretion of each congener in urine and bile of rats, study whether proteins were involved in the excretion, and quantitate where each congener was located within the cells of selected tissues. BDE-99 and 209 were excreted at a very low rate in the urine (<1% after 72h). In both groups, a small portion of the urinary 14C(6 and 18%, respectively) was protein bound to carrier proteins. BDE-99 bound to a small urine protein, à2u-globulin, normally involved in pheromone transport and maintaining spermatogenesis. BDE-209 bound in the urine to albumin, but not à2u-globulin. Both parent material and metabolites were bound to these urinary proteins. In the bile, 28-47% of BDE-99 was bound to an unknown 79 kDa protein. Nearly all of the biliary BDE-209 was bound to the same unidentified protein. Both congeners were found to deposit in the liver, lung, kidney, and GI mucosal cells at 72h. A portion of each congener was in the soluble portion of the cell, and, in the case of BDE-209 treated liver, fatty acid binding protein was involved in solubilizing the BDE-209 intracellularly. The binding of a ligand to a protein often results in a conformational change in the protein, which in some cases can be detrimental. It is uncertain whether the ligand-protein interactions described here in the rat are to facilitate excretion of BDE-99 and 209, or toxic to the animal.

Technical Abstract: 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is the major component of commercial penta-BDE formulations used as flame retardants in polyurethane foam, and an abundant BDE congener found in environmental samples. Decabromodiphenyl ether (BDE-209) is currently the most abundant BDE flame retardant in use for protecting high-impact polystrene. Both BDE-99 and 209 are highly lipophilic, and almost nothing is known about how these compounds are absorbed or excreted. The purpose of the present study was to measure urinary and biliary excretion of both congeners, study the binding of these congeners to proteins found in the excreta, and determine the subcellular location of each congener in male rats. Less than 1% of the dose of BDE-99 and 209 was excreted in the urine of male rats. Over 6% of the protein-bound BDE-99 was bound to à2u-globulin, a pheromone transport protein. Approximately 18% of the urinary BDE-209 was bound to albumin; none to à2u-globulin. In both cases, metabolites and parent were bound to the identified proteins. In the bile, an unidentified 79 kDa protein bound to both BDE-99 and 209 and their metabolites. The bile protein was N- terminal blocked, had an isoelectric point of 5.7, and was monomeric. The subcellular localization of BDE-99 and 209 was quantitated in the liver, lung, kidney and gastrointestinal epithileal cells. In the case of liver cytosol, BDE-209 was bound to liver fatty acid binding protein. Protein-ligand binding events can lead to protein conformational changes, which may result in toxicity. However, it is unknown whether BDE-99 or 209 toxicity may be protein mediated, or whether the presently