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INTEGRATED PROBABILISTIC AND DETERMINISTIC MODELING TECHNIQUES IN ESTIMATING EXPOSURE TO WATER-BORNE CONTAMINANTS: PART 2 PHARMACOKINETIC MODELING
Citation:
Blancato, J N., F W. Power, C. R. Wilkes, A. M. Tsang, S C. Hern, AND S. S. Olin. INTEGRATED PROBABILISTIC AND DETERMINISTIC MODELING TECHNIQUES IN ESTIMATING EXPOSURE TO WATER-BORNE CONTAMINANTS: PART 2 PHARMACOKINETIC MODELING. Presented at Indoor Air 2002, Monterey, CA, June 30-July 5, 2002.
Impact/Purpose:
Research will be conducted to develop and apply integrated microenvironmental, and physiologically-based pharmacokinetic (PBPK) exposure-dose models and methods (that account for all media, routes, pathways and endpoints). Specific efforts will focus on the following areas:
1) Develop the Exposure Related Dose Estimating Model (ERDEM) System.
Includes: Updating the subsystems and compartments of the ERDEM models with those features needed for modeling chemicals of interest to risk assessors;
Designing and implementing the graphical user interface for added features.
Refining the exposure interface to handle various sources of exposure information;
Providing tools for post processing as well as for uncertainty and variability analyses;
Research on numerical and symbolic mathematical/statistical solution methods and computational algorithms/software for deterministic and stochastic systems analysis.
2) Apply ERDEM and other quantitative models to understand pharmacokinetics (PK) and significantly reduce the uncertainty in the dosimetry of specific compounds of regulatory interest.
Examples of the applications are:
exposure of children to pesticides
study design
route-to-route extrapolation
species extrapolation
experimental data analysis
relationship between parametric uncertainty and the distribution of model results
validity of scaling methods within species
validity of scaling methods from one species to another species
reduction of uncertainty factors for risk assessment
Description:
The Total Exposure Model (TEM) uses deterministic and stochastic methods to estimate the exposure of a person performing daily activities of eating, drinking, showering, and bathing. There were 250 time histories generated, by subject with activities, for the three exposure routes, oral, dermal, and inhalation,and these were input to the physiologically based pharmacokinetic (PBPK) model, via ERDEM (Exposure Related Dose Estimating model). The chemicals modeled were trichloroethylene (TCE), trichloroacetic acid (TCA), an dichloroacetic acid (DCA). Time histories of concentrations and Areas Under the Curve (AUC) were determined for the liver, kidney, and venous blood. They were combined to determine the distribution at each time step and hence define the 5th, 50th, and the 95th percentiles. The important pathways and the basis for their predominance are shown. Thus highly variable exposures can be related to actual dose to various organs of the human body.
The United States Environmental Protection Agency through its Office of Research and Development collaborated in the research described here and the Office of Water partially funded the work under Cooperatie Agreement CX-822663-01. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.