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From the exposome to mechanistic understanding of chemical-induced adverse effects
Citation:
Escher, B., J. Hackermüller, T. Polte, S. Scholz, A. Aigner, R. Altenburger, A. Bohme, S. Bopp, W. Brack, W. Busch, M. Chadeau-Hyam, A. Covaci, A. Eisentrager, J. Galligan, N. Garcia-Reyero, T. Hartung, M. Hein, G. Herberth, A. Jahnke, J. Kleinjans, N. Kluever, M. Krauss, M. Lamoree, I. Lehmann, T. Luckenbach, G. Miller, A. Mueller, D. Phillips, T. Reemtsma, U. Rolle-Kampczyk, G. Schuurmann, B. Schwikowski, C. Tan, S. Trump, S. Walter-Rohde, AND J. Wambaugh. From the exposome to mechanistic understanding of chemical-induced adverse effects. ENVIRONMENT INTERNATIONAL. Elsevier Science Ltd, New York, NY, 99:97-106, (2017).
Impact/Purpose:
• Agency Research Drivers - The Toxic Substances Control Act (TSCA) requires the Agency to provide strategies to reduce, refine, or replace vertebrate animal testing for assessing risks from chemical substances or mixtures. • Science Challenge - Exposure is a critical component of risk assessment. Strategies to reduce animal toxicity testing require consideration of exposure and pharmacokinetic properties or behaviors of chemicals. • Research Approach - This article examines if links between chemicals and adverse outcomes can be improved by integrating the exposure considerations with the adverse outcome pathway (AOP) framework. This review was informed by a Workshop organized by the Integrated Project EXPOSOME at the UFZ Helmholtz Centre for Environmental Research in Leipzig, Germany. • Results - The AOP framework organizes events from an initial response to chemical exposure to an health outcome. By complementing the exposome research with the AOP concept, we can achieve a better mechanistic understanding, weigh the importance of various components of the exposome, and determine primary risk drivers. The ability to interpret multiple exposures and mixture effects at the mechanistic level requires a more holistic approach facilitated by the exposome concept. Findings in the workshops demonstrate how available exposure and pharmacokinetic information can be organized to inform regulatory decisions. • Anticipated Impact/Expected Use - Incorporating the AOP concept into the exposome will advance a mechanistic understanding of stress-induced adverse effects, and promote an integrative assessment of chemical risks for human and environmental health.
Description:
BACKGROUND: Current definitions of the exposome expand beyond the initial idea to consider the totality of exposure and aim to relate to biological effects. While the exposome has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. OBJECTIVES: We explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept - a framework to structure and organize the sequence of toxicological events from an initial molecular interaction of a chemical to an adverse outcome.METHODS: This review was informed by a Workshop organized by the Integrated Project EXPOSOME at the UFZ Helmholtz Centre for Environmental Research in Leipzig, Germany. DISCUSSION: The exposome encompasses all chemicals, including exogenous chemicals and endogenous compounds that are produced in response to external factors. By complementing the exposome research with the AOP concept, we can achieve a better mechanistic understanding, weigh the importance of various components of the exposome, and determine primary risk drivers. The ability to interpret multiple exposures and mixture effects at the mechanistic level requires a more holistic approach facilitated by the exposome concept.CONCLUSION: Incorporating the AOP concept into the exposome will advance a mechanistic understanding of stress-induced adverse effects, and promote an integrative assessment of chemical risks for human and environmental health.
