United States Environmental Protection Agency (USEPA) researchers are developing a strategy for high-throughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologically relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. Based on probabilistic methods and algorithms developed for The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals (SHEDS-MM), a new mechanistic modeling approach has been developed to accommodate high-throughput (HT) assessment of exposure potential. In this SHEDS-HT model, the residential and dietary modules of SHEDS-MM have been operationally modified to reduce the user burden, input data demands, and run times of the higher-tier model, while maintaining critical features and inputs that influence exposure. The model has been implemented in R; the modeling framework links chemicals to consumer product categories or food groups (and thus exposure scenarios) to predict HT exposures and intake doses. Initially, SHEDS-HT has been applied to 2507 organic chemicals associated with consumer products and agricultural pesticides. These evaluations employ data from recent USEPA efforts to characterize usage (prevalence, frequency, and magnitude), chemical composition, and exposure scenarios for a wide range of consumer products. In modeling indirect exposures from near-field sources, SHEDS-HT employs a fugacity-based module to estimate concentrations in indoor environmental media. The concentration estimates, along with relevant exposure factors and human activity data, are then used by the model to rapidly generate probabilistic population distributions of near-field indirect exposures via dermal, nondietary ingestion, and inhalation pathways. Pathway-specific estimates of near-field direct exposures from consumer products are also modeled. Population dietary exposures for a variety of chemicals found in foods are combined with the corresponding chemical-specific near-field exposure predictions to produce aggregate population exposure estimates. The estimated intake dose rates (mg/kg/day) for the 2507 chemical case-study spanned 13 orders of magnitude. SHEDS-HT successfully reproduced the pathway-specific exposure results of the higher-tier SHEDS-MM for a case-study pesticide and produced median intake doses significantly correlated (p<0.0001, R2=0.39) with medians inferred using biomonitoring data for 39 chemicals from the National Health and Nutrition Examination Survey (NHANES). Based on the favorable performance of SHEDS-HT with respect to these initial evaluations, we believe this new tool will be useful for HT prediction of chemical exposure potential.