Impact/Purpose:

The objective of this task is to conduct cooperative research to implement a source-to-dose human exposure modeling framework to increase understanding of the exposure-to-dose system and to improve the risk assessment process. Research will address application of the modeling framework to address specific agency problems, evaluation of the modeling framework, and further development work that may be required based on application and evaluation of the human exposure source-to-dose modeling framework and tools.

Description:

In 1998 EPA's Office of Research and Development (ORD) identified necessary research to strengthen the scientific foundation for human health risk assessment as one of its six high priority areas for long-term research support. In addition, ORD identified three strategic research directions including that of reducing uncertainty in the mathematical modeling of human exposure. To address this priority research area, National Exposure Research Laboratory (NERL) of ORD set a long-term goal of developing and demonstrating a scientifically robust multimedia, multipathway human exposure modeling environment that incorporates models, databases, and analytic tools which can probabilistically estimate exposures (and doses) to individuals, populations, and susceptible sub-populations as well as predict and diagnose the complex relationships between source and dose. NERL then issued a solicitation and subsequently awarded two five-year agreements to provide support, stimulation, and collaboration in research to address this goal. One agreement was awarded to the Environmental and Occupational Health Sciences Institute (EOHSI), Piscataway, New Jersey. The other agreement was awarded to DOE-Lawrence Berkeley National Laboratory (LBNL). These agreements are referred to as the "University Partnership Agreements (UPAs)" and have been used to augment the existing capability of NERL's in-house Human Exposure Modeling Research Program.

In NERL's Human Exposure Modeling Research Program we apply a systems approach to study, characterize, and computationally describe exposure of individuals and populations to environmental pollutants. The objective of NERL's Human Exposure Modeling Research Program is to develop exposure and exposure-related modeling tools and conduct modeling analyses to help our clients address priority Agency needs in the following areas:

(1) Improving the scientific basis of risk assessment (screening and prioritizing compounds and potential exposures; identifying important stressors, sources, and pathways; identifying determinants of exposure; characterizing potential exposure);

(2) Predicting and classifying exposure and dose for human health studies (tox, clinical, epi);

(3) Predicting and assessing exposure and dose to design and test intervention and regulation.

Given the recent advances in human exposure source-to-dose modeling resulting from these initial collaborations as well as from research conducted by the scientific community at large, the next step is to implement the frameworks and tools to improve the science of, and reduce the uncertainties in, risk assessment. This task will involve a collaborative effort to apply a currently available human exposure source-to-dose modeling framework to assess exposure, dose, and risk from a variety of industrial, dietary, and residential pollutant sources. We will apply this framework and the associated modeling tools to a variety of pollutants including arsenic, pesticides, water-borne pollutants, and others. The source-to-dose model development and application conducted under this task will address Agency priorities in the areas of cumulative risk assessment, computational toxicology, and homeland security. In addition to addressing important Agency needs, the application of the latest advances in human exposure modeling under this task will greatly advance the science of exposure and dose assessment.

Record Details:

Record Type:PROJECT

Start Date:10/01/2003

Projected Completion Date:09/01/2009

OMB Category:Other

Record ID: 131983

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Project Information:

Progress :The University Partnership Agreements awarded 5 years ago have conducted collaborative research with NERL to advance the state of the science in human exposure source-to-dose modeling. In the first five year period of the UPAs, research focused on development of the modeling tools required to implement a source-to-dose human exposure framework. Research under these agreements has resulted in development of a range of tools for assessing exposure and dose to a variety of environmental contaminants of importance to the Agency. The cooperative agreement with EOHSI has focused on the development of the computational exposure modeling framework, MENTOR (Modeling Environment for Total Risk Studies). Significant progress has been made in the development and refinement of important framework modules for estimating human exposures to particulate matter (PM), pesticides and multimedia pollutants. The MENTOR system incorporates a range of tools for environmental and biological process and data analysis, system sensitivity and uncertainty analysis, and formal model reduction. Approaches and techniques of the SHEDS (Stochastic Simulation of Human Exposure and Dose) system have also been incorporated into MENTOR The MENTOR system and NERL exposure and dose modeling tools (e.g., ERDEM and SHEDS) have been applied (or are in the process of being applied) to address important Agency needs. These applications include modeling of source-to-dose population exposures to fine and ultrafine atmospheric particulate matter; arsenic, and; selected pesticides, air toxics and other multimedia pollutants. Under the agreement with LBNL, tools and computational approaches have been developed to reconstruct exposure from available biomonitoring data for selected multimedia pollutants; to evaluate the performance of complex source-to-dose models; to assess dermal exposures from contact with surfaces contaminated with pesticide residues; and to apply fugacity modeling techniques to predict pesticide distributions following residential applications. A list of publications resulting from the first set of agreements can be found in the 2003 description for Task #3957.

Relevance :There are two major drivers for the research being conducted under this task over the next 5 years: (1) models and tools developed over the last 5 years are ready to be applied to assess exposures to priority compounds; and (2) Agency goals for quantitatively assessing cumulative risks from exposures to multiple compounds require continued core research in human exposure modeling.

Given the recent advances in human exposure source-to-dose modeling resulting from research conducted in-house at NERL, through the UPAs, and by the scientific community at large, the next step is to implement the frameworks and tools to improve the science of, and reduce the uncertainties in, risk assessment. A significant effort is required to apply a currently available human exposure models and computational tools to assess exposure, dose, and risk from a variety of industrial, dietary, and residential pollutant sources. There is also a need for research to apply model frameworks and the associated modeling tools to a variety of pollutants including arsenic, pesticides, water-borne pollutants, and others. The application of the latest advances in human exposure modeling will greatly advance the science of exposure and dose assessment.

The research conducted under this task as part of the NERL Human Exposure Modeling program will support three areas that have been identified by ORD as high priority research areas: (1) human health cumulative risk assessment, computational toxicology, and homeland security.

Human health cumulative risk assessment

The goal of ORD is to conduct research using a systems approach to understand and characterize health effects resulting from exposures to multiple chemicals across lifestages. Research under this task will contribute to addressing Agency goals in human health cumulative risk assessment in the following areas:

(1) developing computational tools to facilitate assessment of cumulative risks,

(2) developing approaches for address time-patterns of exposure,

(3) developing approaches for incorporate mechanistic information on toxicity into dose models,

(4) applying models to assess highly-exposed and susceptible populations.

Computational toxicology initiative

Research conducted under this task will contribute to addressing 2 of the 3 objectives identified in the ORD CompTox Framework: (1) improve links in source-to-outcome paradigm, and (2) enhance quantitative risk assessment through application of computational chemistry, computational biology, and systems biology. Under the first goal, collaborative research will be conducted under this task to apply advanced computational techniques and a systems biology approach to link measures or estimates from source to effects to assess and predict risk. Under the second goal, collaborative research will be conducted to: 1) apply computational chemistry approaches to estimate model parameters; (2) combine a systems approach with computational chemistry tools to develop semi-quantitative methods for screening and prioritizing chemicals and exposures, and (3) investigate computational approaches for incorporating mechanistic information to address variability in exposure and dose models.

Homeland security

Research under this task will support work being conducted by ORD National Homeland Security Research Center to develop tools for rapid risk assessment. Collaborative research under this task will provide increased scientific understanding of the pathway of toxic pollutants from source to human exposure in urban areas and residential environments. In addition, research under this task will provide a sound scientific basis for modeling exposure in urban areas and residential environments.

Project IDs:

ID Code :20706

Project type :OMIS