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PREDICTION OF SATURABLE URINARY ELIMINATION OF 2,2’,4,4’-TETRABROMODIPHENYL ETHER (BDE-47) USING A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL IN MICE
Citation:
EMOND, C., D. STASKAL, AND L. S. BIRNBAUM. PREDICTION OF SATURABLE URINARY ELIMINATION OF 2,2’,4,4’-TETRABROMODIPHENYL ETHER (BDE-47) USING A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL IN MICE. Presented at International Congress of Toxicology, Montreal, QC, CANADA, July 15 - 19, 2007.
Impact/Purpose:
The aim of this work was to propose a mode of action that describes the urinary elimination of BDE-47 in mice using a physiologically based pharmacokinetic model.
Description:
Polybrominated diphenyl ethers (PBDE) are used as additive flame-retardants. Global uses increased greatly over the past 30 years, which increases human exposure and body burden. Our laboratory has shown that urinary elimination is saturable and dose dependent in adult mice for 4 of the major BDE congeners present in biota (i.e. BDEs 47, 99, 100, and 153). However, saturation was not found in rats or immature mice. That suggests a role for active renal excretion of PBDEs. The aim of this work was to propose a mode of action that describes the urinary elimination of BDE-47 in mice using a physiologically based pharmacokinetic model (PBPK). The model contained 5 compartments built and validated using data from rats and extrapolated to the mouse. Physiological, physicochemical and biochemical parameters came from the literature. An extensive description of kidney and blood compartments was applied related to the experimental observations. Comparison between experiments and simulated data show accurate predictions. At low doses, the model shows a relative higher elimination as compared to higher doses, consistent with the experimental data. This work may have a major impact to explain physiological observations of urinary transport suggested by our earlier results. In addition, this approach may be applicable to humans if urinary elimination of PBDEs occurs in humans. (This abstract does not reflect Agency policy.)