title: High-throughput models for exposure-based chemical prioritization in the ExpoCast project.
abstract: 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.
authors.affiliation: National Center for Computational Toxicology, United States Environmental Protection Agency , Research Triangle Park, North Carolina 27711, United States. wambaugh.john@epa.gov
authors.forename: John F
authors.initials: JF
authors.lastname: Wambaugh
authors.forename: R Woodrow
authors.initials: RW
authors.lastname: Setzer
authors.forename: David M
authors.initials: DM
authors.lastname: Reif
authors.forename: Sumit
authors.initials: S
authors.lastname: Gangwal
authors.forename: Jade
authors.initials: J
authors.lastname: Mitchell-Blackwood
authors.forename: Jon A
authors.initials: JA
authors.lastname: Arnot
authors.forename: Olivier
authors.initials: O
authors.lastname: Joliet
authors.forename: Alicia
authors.initials: A
authors.lastname: Frame
authors.forename: James
authors.initials: J
authors.lastname: Rabinowitz
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Knudsen
authors.forename: Richard S
authors.initials: RS
authors.lastname: Judson
authors.forename: Peter
authors.initials: P
authors.lastname: Egeghy
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallero
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Cohen Hubal
mesh_terms: D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000145:classification; D008962:Models, Theoretical
chemical_list: D004785:Environmental Pollutants