United States Environmental Protection Agency Office of Research and Development National Exposure Research Laboratory Research Abstract Government Performance Results Act (GPRA) Goal 8 Annual Performance Measure 28 Significant Research Findings: Framework for Modeling Aggregate Exposures to Arsenic from Source through Human Exposure to Dose Scientific Exposure to environmental contaminants is a complex process that may occur Problem and from several sources through a number of different pathways and routes. Policy Issues Aggregate exposure is the combined exposures to a single chemical from all sources across all routes and pathways. To conduct an aggregate exposure assessment, a comprehensive approach is required to understand and adequately characterize the chemical-specific exposures to the general population as well as to susceptible and highly-exposed subpopulations. In a 1995 report, EPA's Science Advisory Board (SAB) underscored the importance of strengthening the scientific technique for exposure assessment. The SAB also identified technical limitations that hamper current exposure assessments. To address recommendations made by the SAB and a number of other national scientific advisory groups, EPA's Office of Research and Development (ORD) identified research needed to strengthen the scientific foundation for human health risk assessment. 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, a scientifically robust multimedia, multipathway human exposure modeling framework is needed that incorporates models, databases, and analytic tools that can be used to probabilistically estimate exposures (and doses) to individuals, populations, and highly exposed subpopulations, as well as predict and investigate the complex relationships between source and dose, including variability and uncertainty. Research The EPA's National Exposure Research Laboratory (NERL) and its university Approach partners have developed a computational system called MENTOR (Modeling ENvironment for TOtal Risk studies) to enable source-to-dose predictions for pollutants of concern. MENTOR is a computational system or framework that enables the user to select from different models that simulate pollutants moving from sources to environmental concentrations, from environmental concentrations to human exposure (contact with chemicals), and from human exposure to dose (amount of chemical that enters into the body and then is distributed or eliminated). Currently, the main computational component of the MENTOR system for predicting human exposures is NERL's Stochastic Human Exposure ------- and Dose Simulation (SHEDS) model. SHEDS is a probabilistic model that predicts the range and distribution of aggregate personal exposures and doses within a population, as well as characterizing the uncertainty in the model estimates. The MENTOR system (including the SHEDS model) are being developed and evaluated through a series of targeted case studies. A MENTOR/SHEDS model application to the arsenic problem was conducted through three case studies in three counties in Ohio representing substantially different conditions of exposure. The MENTOR/SHEDS modeling framework for arsenic currently considers five exposure pathways: inhalation, drinking water consumption, food intake, non- dietary ingestion, and dermal absorption. These pathways, with the exception of dermal absorption, have been implemented in a population-based source-to-dose modeling framework. Different modules in MENTOR and SHEDS were also evaluated using available environmental and urinary biomarker measurements of arsenic. Results and Results of the MENTOR/SHEDS application to arsenic case studies demonstrate Impact the feasibility of characterizing multimedia/multipathway exposures/doses to arsenic. Initial findings indicate that food and drinking- water exposure pathways contributed more than the inhalation exposure pathway to the predicted dose of arsenic in the urine, with the food pathway contributing more to arsenic intakes than the drinking-water pathway. The results may be reversed in locations where drinking water has high arsenic levels. These case studies not only provided information on relative contributions of multipathway exposure routes to the total arsenic exposure estimates, but also provided internal target tissue dose estimates, which are important for improving our characterization of human health risks from exposures to environmental arsenic. Results of this work also demonstrate the feasibility of applying a similar framework to efficiently conduct probabilistic exposure assessments for other high-priority compounds. This research will benefit the risk assessment community, environmental regulatory decision-makers, susceptible subpopulations, and the general public by providing a comprehensive computational framework for developing and applying human exposure models. The MENTOR/SHEDS modeling project is being conducted by EPA/NERL in collaboration with the Environmental and Occupational Health Sciences Institute (EOHSI), a joint university organization. EOHSI led the MENTOR system development and its application to arsenic. EPA's Office of Pesticide Programs (OPP) has provided technical input on the dietary module development and evaluation. ManTech Environmental Technology, Inc. provided SHEDS model computer program development and quality assurance support. Research Collaboration and Research Products Recent publications related to this work, include the following: ------- Buck, R.J., Ozkaynak, EL, Xue, J., Zartarian, V.G., Hammerstrom, K. (2001). "Modeled Estimates of Chlorpyrifos Exposure and Dose for the Minnesota and Arizona NHEXAS Populations,"Journal of the Exposure Analysis and Environmental Epidemiology, (11), 253- 268. Georgopoulos P.G., Wang S.W, Yang Y.C., Xue, J., McCurdy T. and Ozkaynak H. (2003) Assessing Multimedia/Multipathway Exposures to Arsenic Using a Mechanistic Source-to- Dose Modeling Framework. Draft journal manuscript. (August 2003). Georgopoulos P.G., Wang S.W, Yang Y.C., Tan H.C., Vyas V.M., Ouyang M., Everett, L., Vowinkel W., Xue, J.,McCurdy T. and Ozkaynak H. (2003) Assessing Multimedia/Multipathway Exposures to Arsenic Using a Mechanistic Source-to-Dose Modeling Framework. Revised Technical Report (June 2003). Georgopoulos P.G., Wang S.W, Yang Y.C., Tan H.C., Vyas V.M., Ouyang M., Vowinkel W., McCurdy T. and Ozkaynak H. (2002) Assessing Multimedia/Multipathway Exposures to Arsenic Using a Mechanistic Source-to-Dose Modeling Framework. Technical Report (June 2002). Zartarian, V.G., Ozkaynak, EL, Burke, J.M., Zufall, M.J., Rigas, M.L., and Furtaw, E.J.,Jr. (2000). "A Modeling Framework for Estimating Children's Residential Exposure and Dose to Chlorpyrifos via Dermal Residue Contact and Non-Dietary Ingestion." Environmental Health Perspectives, 108(6), 505-514. Future Research Future research specific to arsenic will include application of the MENTOR/SHEDS framework to measurements collected in Millard County, Utah in order to evaluate the model performance against urinary arsenic data measured by scientists in EPA's National Health and Environmental Effects Research Laboratory (NHEERL). More generally, research will continue to improve the capabilities of the MENTOR/SHEDS framework to quickly and efficiently link models and databases to characterize exposures of the general population and highly exposed subpopulations from source to dose. Questions and inquiries can be directed to the principal investigator: Haluk Ozkaynak, Ph.D. U.S. EPA, Office of Research and Development National Exposure Research Laboratory Ariel Rios Building (MC-8601-D) 1200 Pennsylvania Avenue, NW Washington, DC 20460 Phone: 202-564-1531 E-mail:: ozkavnak,haluk@epa.gov Federal funding for this research was administered under EPA Contract #68-D- 00-206 to ManTech Environmental Technology, Inc., and EPA Cooperative Agreement #CR827033 to Environmental and Occupational Health Sciences Institute (EOHSI). Contacts for Additional Information ------- |