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DIFFERENTIAL URINARY PROTEIN BINDING OF PBDES IN MICE
Citation:
DILIBERTO, J. J., D. STASKAL, H. HAKK, AND L. S. BIRNBAUM. DIFFERENTIAL URINARY PROTEIN BINDING OF PBDES IN MICE. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Polybrominated diphenyl ethers (PBDEs), commercial chemicals used as flame retardants in consumer goods, have become the focus of increasing scientific research due to their persistent detection in humans and the environment in conjunction with their potential for toxicity. PBDE congeners 47, 99, 100, 153, and 154, the primary congeners detected in human and wildlife samples, have different pharmacokinetic behaviors in rodents which appear to be species-, sex-, and congener-dependent. Many of these differences appear to be driven by urinary excretion. Therefore, this study investigated urinary excretion in C56BL/6 mice of PBDE congeners 47, 99, 100, and 153 in an effort to characterize mechanisms responsible for their excretion. Female mice were administered a single intravenous (iv) dose of PBDE 47, 99, 100, or 153 and urinary excretion was monitored for 5 days. Urine was analyzed for protein binding by Sephadex G-75 columns, gel electrophoresis and Western blotting. Analyses of 0-24h urine for PBDEs 47 and 99 dosed mice and pooled 0-120h urine (pooled due to limited amounts of urinary radioactivity) for PBDEs 100 and 153 dosed mice showed that the majority of PBDE in urine was protein-bound (>65%). All the PBDEs investigated were bound to three mouse Major Urinary Protein (mMUP) isoforms, and were readily excreted via urine. These results suggest that the physiological parameters associated with MUP, such as increased MUP secretion in male mice versus females, could therefore contribute to understanding of the different pharmacokinetic parameters observed in rodents. In conclusion, urinary binding proteins could affect the pharmacokinetics of PBDEs in rodents. (This abstract does not reflect EPA policy. Work partially funded by EPA DESE CT 826513.)