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High-Throughput Models for Exposure-Based Chemical Prioritization in the ExpoCast Project
Citation:
WAMBAUGH, J. F., R. W. SETZER, D. REIF, S. GANGWAL, J. MITCHELLBLACKWOOD, J. A. ARNOT, O. JOLIET, A. FRAME, J. R. RABINOWITZ, T. B. KNUDSEN, R. S. JUDSON, P. P. EGEGHY, D. A. VALLERO, AND E. A. COHEN HUBAL. High-Throughput Models for Exposure-Based Chemical Prioritization in the ExpoCast Project . Jerald Schnoor (ed.), ENVIRONMENTAL SCIENCE AND TECHNOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 47(15):8479-8488, (2013).
Impact/Purpose:
The ExpoCast exposure prioritization framework is designed to apply to large numbers of chemicals, to incorporate new models as they become available, to weight model components appropriately, and to make predictions of human (and in due course ecological) exposure, all with an appropriate characterization of uncertainty. This framework meets the mandate of the NRC for an objective, standardized, and transparent approach to high-throughput exposure modeling. As new models are incorporated into the ExpoCast framework, the results reported here will serve as a baseline. There is a clear need to develop screening tools for near-field human exposures. We hope that the value of future exposure prioritization work can now be quantitatively demonstrated by reducing the large uncertainties currently associated with predicting human exposure to environmental chemicals.
Description:
The United States Environmental Protection Agency (U.S. EPA) must characterize potential risks to human health and the environment associated with manufacture and use of thousands of chemicals. High-throughput screening (HTS) for biological activity allows the ToxCast research program to prioritize chemical inventories for potential hazard. Similar capabilities for estimating exposure potential would support rapid risk-based prioritization for chemicals with limited information; here, we propose a framework for high-throughput exposure assessment. To demonstrate application, an analysis was conducted that predicts human exposure potential for chemicals and estimates uncertainty in these predictions by comparison to biomonitoring data. We evaluated 1936 chemicals using far-field mass balance human exposure models (USEtox and RAIDAR) and an indicator for indoor and/or consumer use. These predictions were compared to exposures inferred by Bayesian analysis from urine concentrations for 82 chemicals reported in the National Health and Nutrition Examination Survey (NHANES). Joint regression on all factors provided a calibrated consensus prediction, the variance of which serves as an empirical determination of uncertainty for prioritization on absolute exposure potential. Information on use was found to be most predictive; generally, chemicals above the limit of detection in NHANES had consumer/indoor use. Coupled with hazard HTS, exposure HTS can place risk earlier in decision processes. High-priority chemicals become targets for further data collection.
