Citation:

Kryak, D D. DEMONSTRATION OF HUMAN EXPOSURE TOOLS. Presented at EPA Science Forum 2004, Washington, DC, June 1-3, 2004.

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 Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientifically based regulatory decisions. For this exposition, the following four (4) major HEASD research projects are presented and demonstrated.

HEDS. The major focus of the Human Exposure Database System (HEDS) is the dissemination of human exposure databases via the World Wide Web. These data collected by HEASD, or its contractors and collaborators will provide needed information on human exposure to researchers, exposure and risk assessors, and the public. HEDS will ensure that data sets on human exposure measurements, activity patterns, and exposure factors are available, easily understood, and readily accessible for exposure analysts and modelers.

CHAD. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and predicting variation in exposure and intake dose from all media. NERL has undertaken a number of activity surveys, including the National Human Activity Pattern Survey (NHAPS), and has combined its data and others into the Consolidated Human Activity Database (CHAD). CHAD facilitates queries by the public and exposure modelers needing activity information. Since inhalation, water consumption, and food ingestion can be related to a personal energy expenditure indicator in CHAD, this database facilitates multi-route exposure and uptake dose modeling.

SHEDS. Risk assessors and managers need realistic exposure and dose prediction tools. NERL has developed Stochastic Human Exposure and Dose Simulation (SHEDS) model to improve the scientific basis of exposure assessments. The primary objectives for the SHEDS model are: (1) to provide a refined and evaluated exposure model tool with the capability to address exposures for cumulative risk assessments; and (2) to apply the model to conduct reliable probabilistic population exposure assessments for specific case studies of importance to the Agency (e.g., pesticides, wood preservatives, particulate matter, air toxics).

ERDEM. The Exposure-Related Dose-Estimating Model (ERDEM) is a physiologically based pharmacokinetic (PBPK) modeling framework and a set of applied PBPK models for several different chemicals or groups of related chemicals. ERDEM simulates absorption into the body by multiple routes of entry (e.g., dermal absorption, ingestion, and inhalation), and the distribution, metabolism, and elimination of chemicals. These exposure-to-dose models provide the essential linkage between experimental data and assumptions established by regulation, and dose-response models designed by toxicologists.

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