Seminar: Functional Exposomics and Mechanisms of Toxicity—Insights from Model Systems and NAMs
Yunjia Lai, Muhammet Ay, Carolina Duarte-Hospital, Gary W. Miller, Souvarish Sarkar
Abstract
BACKGROUND: Significant progress has been made over the past decade in measuring the chemical components of the exposome, providing transformative population-scale frameworks in probing the etiologic link between environmental factors and disease phenotypes. While the analytical technologies continue to evolve with reams of data being generated, there is an opportunity to complement exposome-wide association studies (ExWAS) with functional analyses to advance etiologic search at organismal, cellular, and molecular levels. OBJECTIVES: Exposomics is a transdisciplinary field aimed at enabling discovery-based analysis of the nongenetic factors that contribute to disease, including numerous environmental chemical stressors. While advances in exposure assessment are enhancing population-based discovery of exposome-wide effects and chemical exposure agents, functional screening and elucidation of biological effects of exposures represent the next logical step toward precision environmental health and medicine. In this work, we focus on the use, strategies, and prospects of alternative approaches and model systems to enhance the current human exposomics framework in biomarker search and causal understanding, spanning from bench-based nonmammalian organisms and cell culture to computational new approach methods (NAMs). DISCUSSION: extrapolation (IVIVE) and integrated approaches to testing and assessment (IATA) under the adverse outcome pathway (AOP) framework. Together, these alternatives offer a strong toolbox to support functional exposomics to study toxicity and causal mediators underpinning exposure-disease links. https://doi.org/10.1289/EHP13120.