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MODELS AND MODELING METHODS FOR ASSESSING HUMAN EXPOSURE AND DOSE TO TOXIC CHEMICALS AND POLLUTANTS

Contact

http://cfpub.epa.gov/si/si_public_comments.cfm

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:

This project aims to strengthen the general scientific foundation of EPA's exposure and risk assessment, management, and policy processes by developing state-of-the-art exposure to dose mathematical models and solution methods. The results of this research will be to produce a modeling framework and integrated group of physiologically-based pharmacokinetic (PBPK) models.

This system called the Exposure Related Dose Estimating Model (ERDEM) can be easily modified for a variety of exposure assessment and risk characterization problems. The models interpret uptake into the body by multiple routes of entry (e.g., dermal, ingestion, and inhalation). Also, the modeling framework will be capable of incorporating the physiological changes of differing activity levels as well as the anatomic and physiological differences between infants and children during growth and development.

The development of mathematical methods includes parameter estimation methods and uncertainty analysis. These source-to-exposure-to-dose models provide the essential linkage between experimental data and assumptions established by regulation to dose-response models designed by toxicologists.

Record Details:

Record Type:PROJECT
Start Date:10/01/1994
Completion Date:09/01/2004
Record ID: 29217