Pre-natal Exposures of Children to Polybrominated Diphenyl Ethers: The Collection of Animal and Human Data along with the Development and Validation of a PBPK ModelEPA Grant Number: R830756
Title: Pre-natal Exposures of Children to Polybrominated Diphenyl Ethers: The Collection of Animal and Human Data along with the Development and Validation of a PBPK Model
Investigators: Raymer, James H.
Current Investigators: Raymer, James H. , Birnbaum, Linda , Emond, C. , Garner, C. Edwin , Studabaker, W.
Institution: RTI International
EPA Project Officer: Hahn, Intaek
Project Period: January 1, 2003 through December 31, 2006 (Extended to December 31, 2007)
Project Amount: $749,654
RFA: Children's Vulnerability to Toxic Substances in the Environment (2002) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Health
Little is known about in-utero exposures to most environmental chemicals, including the polybrominated diphenyl ethers (PBDEs). These PBDEs are known to have neurological effects and are suspected of having endocrine disruption capability. Work proposed in this study will lead to a physiologically-based pharmacokinetic (PBPK) model for PBDEs in an animal model system (rats).
Objective:The overall objectives are: 1. Develop a Physiologically Based Pharmacokinetic Model (PBPK) animal model for the Polybrominateddiphenyl ethers (PBDEs) 2,2',4,4'-tetrabromomodiphenyl ether and 2,2',4,4',5-pentabromodiphenyl ether (PBDEs) that can be used to estimate fetal exposures to PBDEs in humans. The parameters necessary to develop the model for PBDEs will be measured. 2. Analytical methods for PBDEs in human blood and meconium will be developed/installed and applied to samples collected during this project both to estimate the utility of the model and to determine if chemical analysis of cord blood and meconium are appropriate media for measurement of cumulative exposures of newborn babies to PBDEs. Specific hypotheses include: 1. A rodent PBPK model for PBDEs can be scaled to be applicable to humans. 2. The PBDE concentrations in cord blood and meconium from newborns are proportional. 3. Mother's blood concentrations of PBDEs are predictive of the cord blood and/or meconium concentrations in newborn babies. 4. Meconium is a useful medium for assessing cumulative dose of the developing fetus.
A PBPK model will be developed and validated for the target PBDEs that includes the gestational component. A chronic exposure scenario akin to that anticipated in humans will be used. Necessary partitioning and metabolic parameters will be measured using in-vivo and in-vitro experiments. Analytical methods for the PBDEs in all matrices under study will be validated. The model will be scaled to humans and the applicability will be tested using biological samples collected from mothers and newborn infants.
This work will provide a PBPK model that can be used to estimate exposures of unborn children to the target PBDEs. The most appropriate matrix for the assessment of in-utero exposure will be obtained. The developed PBPK model can be used in future work to study different aspects of exposure, including the impact of chronic and intermittent exposures on time-sensitive, developmental events. The exposures of a group of mothers and their newborn children to the target analytes will be determined.