title: From the exposome to mechanistic understanding of chemical-induced adverse effects.
abstract: The exposome encompasses an individual's exposure to exogenous chemicals, as well as endogenous chemicals that are produced or altered in response to external stressors. While the exposome concept 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. Here, 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 that structures and organizes the sequence of biological events from an initial molecular interaction of a chemical with a biological target to an adverse outcome. Complementing exposome research with the AOP concept may facilitate a mechanistic understanding of stress-induced adverse effects, examine the relative contributions from various components of the exposome, determine the primary risk drivers in complex mixtures, and promote an integrative assessment of chemical risks for both human and environmental health.
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany. Electronic address: beate.escher@ufz.de.
authors.forename: Beate I
authors.initials: BI
authors.lastname: Escher
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hackermüller
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Polte
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.affiliation: Leipzig University, Rudolf Boehm Institute for Pharmacology & Toxicology, Clinical Pharmacology, Haertelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Altenburger
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Böhme
authors.affiliation: European Commission Joint Research Centre, Directorate F - Health, Consumers and Reference Materials, Via E. Fermi 2749, 21027 Ispra, VA, Italy.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Bopp
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Brack
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Busch
authors.affiliation: University London, Imperial College, Department Epidemiology & Biostatistics, School of Public Health, St Marys Campus, Norfolk Place, London W2 1PG, England, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Chadeau-Hyam
authors.affiliation: Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
authors.affiliation: German Environment Agency UBA, Dessau-Roßlau, Germany.
authors.forename: Adolf
authors.initials: A
authors.lastname: Eisenträger
authors.affiliation: Vanderbilt University, School of Medicine, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department Biochemistry, Nashville, TN 37232, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
authors.affiliation: US Army Engineer Research & Development Center, Vicksburg, MS, USA; Mississippi State University, Starkville, MS, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.affiliation: Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA; University of Konstanz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Hein
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Gunda
authors.initials: G
authors.lastname: Herberth
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Jahnke
authors.affiliation: Maastricht University, Department Toxicogenomics, 6200 MD Maastricht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Kleinjans
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Klüver
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Krauss
authors.affiliation: Vrije Universiteit, Faculty of Earth & Life Sciences, Institute for Environmental Studies, 1081 HV Amsterdam, The Netherlands.
authors.forename: Marja
authors.initials: M
authors.lastname: Lamoree
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Lehmann
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Luckenbach
authors.affiliation: Dept of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Miller
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Müller
authors.affiliation: King's College London, MRC-PHE Centre for Environment & Health, Analytical & Environmental Sciences Division, London SE1 9NH, England, United Kingdom.
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Reemtsma
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Rolle-Kampczyk
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany; Technical University Bergakademie Freiberg, Institute for Organic Chemistry, 09596 Freiberg, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Schüürmann
authors.affiliation: Institute Pasteur, Systems Biology Laboratory, Paris, France.
authors.forename: Benno
authors.initials: B
authors.lastname: Schwikowski
authors.affiliation: US EPA, National Exposure Research Laboratory, Research Triangle Park, NC 27711, USA.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Tan
authors.affiliation: Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Trump
authors.affiliation: German Environment Agency UBA, Dessau-Roßlau, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walter-Rohde
authors.affiliation: US EPA, National Center for Computational Toxicology, Research Triangle Park, NC 27711, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Wambaugh
mesh_terms: D000818:Animals; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D018570:Risk Assessment
chemical_list: D004785:Environmental Pollutants
keywords: AOP; Exposome; Risk assessment; Systems biology; Systems chemistry; Systems toxicology