Geospatial modeling approaches to link in vitro data with geographic exposure
Traditional risk assessments based on in vivo animal studies typically use a chemical-by-chemical approach and apical disease endpoints. However, in the real world, individuals are exposed to chemicals from sources that vary over space and time. EPA and NIEHS scientists collaborated to develop a workflow (Eccles et al. 2022) to integrate human exposure data for 41 chemicals in the EPA National Air Toxics Assessment with curated high-throughput screening (cHTS) assays to identify counties where exposure to the local chemical mixture may perturb a common biological target. The workflow used the estimated blood plasma concentration and the concentration–response curve from the cHTS data to determine the chemical-specific effects of the mixture components. Three mixture modeling methods were used to estimate the joint effect from exposure to the chemical mixture on the activity levels, which were geospatially mapped. This workflow demonstrates how new approach methodologies (NAMs) can be used to predict early-stage biological perturbations that can lead to adverse health outcomes that result from exposure to chemical mixtures. As a result, this work will advance mixture risk assessment and other early events in the effects of chemicals.