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A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR DEVELOPMENTAL EXPOSURE TO PBDE-47 IN RODENTS
Citation:
EMOND, C., J. H. RAYMER, E. GARNER, J. J. DILIBERTO, D. STASKAL, AND L. S. BIRNBAUM. A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL FOR DEVELOPMENTAL EXPOSURE TO PBDE-47 IN RODENTS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments where they have the potential to bioaccumulate in wildlife and in people. These compounds have been detected in blood and other human tissue collected from populations around the world. Although there are 209 PBDE congeners, approximately five dominate the profiles measured in humans, particularly 2,2′,4,4′-tetrabromodiphenyl either (BDE 47), demonstrating a need to understand the toxicokinetic properties associated with this class of chemicals. A small subset of the PBDES have been investigated in toxicokinetic studies; these studies have shown that binding proteins, elimination, adipose tissue mass, and placenta transfer may all play roles in the distribution of PBDEs. The aim of this work was to develop a developmental PBPK model for BDE-47 in mice and rats with the perspective of extrapolating the model to humans. The model consists of seven compartment including liver, brain, fat, kidney, placenta/foetus, blood and rest of the body. Parameters such as tissue volumes, blow flows, and partition coefficients were extracted from previously reported studies. Optimization was performed using mouse exposure data for adult female and neonates determined in our laboratory. The optimized model was extrapolated to rats and validated using single and repetitive exposure scenario data from the literature. The model validation used experimental data from acute and subchronic exposures prior to and during gestation. The simulations predict that BDE-47 tissue concentrations in the maternal compartments are within the standard deviation of the experimental data. This PBPK model presented here is the first reported for any PBDE. This model may provide a framework for the development of a human PBPK model to predict both adult and developmental PBDE concentrations for use in risk assessments. (This abstract does not reflect Agency policy. Supported in part by EPA cooperative agreements CR830756 and DESE CT 826513.)