A geospatial modeling approach to quantifying the risk of exposure to environmental chemical mixtures via a common molecular target

• DOI: 10.1016/j.scitotenv.2022.158905
• Publication Date: 2022-09-21T16:22:46Z
• Authors: Kristin M. Eccles; Agnes L. Karmaus; Nicole C. Kleinst...; Fred Parham; Cynthia V. Rider; John F. Wambaugh; Kyle P. Messier
• Keywords: Chemical space

In the real world, individuals are exposed to chemicals from sources that vary over space and time. However, traditional risk assessments based on in vivo animal studies typically use a chemical-by-chemical approach apical disease endpoints. New methodologies (NAMs) toxicology, such as vitro high-throughput (HTS) assays generated Tox21 ToxCast, can more readily provide mechanistic chemical hazard information for with no existing data than methods. this paper, we establish workflow assess joint action of 41 modeled ambient exposures air USA-wide National Air Toxics Assessment by integrating human curated HTS (cHTS) identify counties where exposure local mixture may perturb common biological target. We exemplify proof-of-concept using CYP1A1 mRNA up-regulation. first estimate internal then convert inhaled concentration steady state plasma physiologically toxicokinetic modeling parameterized county-specific ages body weights. estimated blood concentration-response curve cHTS assay determine chemical-specific effects components. Three methods were used effect activity levels, which geospatially mapped. Finally, Monte Carlo uncertainty analysis was performed quantify influence each parameter combined effects. This demonstrates how NAMs be predict early-stage perturbations lead adverse health outcomes result mixtures. As result, work will advance assessment other early events chemicals.