Adverse outcome pathways: opportunities, limitations and open questions
| Autor: | Alberto Mantovani, Tanja Waldmann, Bob van de Water, Cristina Cadenas, Hennicke Kamp, Thomas Braunbeck, Annemarie H. Meijer, Mathieu Vinken, Sylvia Escher, Domenico Gadaleta, Patricio Godoy, Anna Forsby, Stefan Schildknecht, Chris T. Evelo, Stefan Höhme, Rosemarie Marchan, Gerhard F. Ecker, Harry Vrieling, Susanne Hougaard Bennekou, Ciarán Fisher, Alice Limonciel, Enrico Mombelli, Rabea Graepel, Marcel Leist, Ahmed Ghallab, Michael Schwarz, Joost B. Beltman, Jens M. Kelm, Albert Braeuning, Olivier Taboureau, Bart van der Burg, Andrea Terron, Ferran Sanz, Frédéric Y. Bois, Steven Dooley, Dinant Kroese, Jan G. Hengstler, Paul Jennings, Egon Willighagen, Barbara Zdrazil, Barry Hardy, Erik H.J. Danen, Bjørn E. V. Koch, David A. Fluri, Christoph van Thriel, Dirk Drasdo, Ben van Ravenzwaay, Iain Gardner, Franz Oesch, Reham Hassan, Raymond Reif, Marvin Martens, Thomas Hartung |
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| Přispěvatelé: | University of Konstanz, Department of Forensic Medicine and Veterinary Toxicology [Qena], Faculty of Veterinary Medicine [Qena], South Valley University [Qena]-South Valley University [Qena], Universiteit Leiden, Leibniz Research Centre for Working Environment and Human Factors [Dortmund] (IFADO), Technische Universität Dortmund [Dortmund] (TU), The Danish Epidemiology Science Centre, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Vrije Universiteit Brussel (VUB), BASF [Ludwigshafen], SimCYP Ltd, Institut National de l'Environnement Industriel et des Risques (INERIS), Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig, Medical University Graz, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), University of Heidelberg, Medical Faculty, Universitat Pompeu Fabra [Barcelona] (UPF), Karolinska Institutet [Stockholm], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), InSphero [Schlieren], University of Vienna [Vienna], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BioDetection Systems, Universität Mannheim, Maastricht University [Maastricht], Institut National de la Santé et de la Recherche Médicale (INSERM), IT University of Copenhagen (ITU), Istituto Superiore di Sanità (ISS), Douglas Connect GmbH, Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Carl Zeiss SMT AG, Carl Zeiss, Oberkochen, Faculty of Biology, Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University [Austria] (IMU), BASF, DRC/VIVA/METO, Institut National de l'Environnement Industriel et des Risques, Department of Experimental and Clinical Pharmacology andToxicology [Tübingen], Eberhard Karls Universität Tübingen, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Institute for Health and Consumer Protection, European Commission - Joint Research Centre, Université Grenoble Alpes - UFR Médecine [ ?-2019] (UGA UFRM [ ?-2019]), Molecular Hepatology - Alcohol Associated Diseases, Department of Medicine II, University of Heidelberg, Medical Faculty of Mannheim-University of Heidelberg, Medical Faculty of Mannheim, BigCat - Bioinformatics and Systems Biology Research Group, UMR-S973, MTi, Université Paris Diderot - Paris 7 (UPD7), Department of Immunology and Cell Biology, Mario Negri Institute, Leiden University, Vrije Universiteit [Brussels] (VUB), Universiteit Leiden [Leiden], BASF SE, 67056 Ludwigshafen, Johannes Gutenberg - University of Mainz (JGU), Centre for Alternatives to Animal Testing (CAAT EU), Universitat Pompeu Fabra [Barcelona], European Food Safety Authority = Autorité européenne de sécurité des aliments, Université Grenoble Alpes (UGA), Universität Mannheim [Mannheim], Istituto Superiore di Sanita [Rome], Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Johannes Gutenberg - Universität Mainz (JGU), IT University of Copenhagen, Molecular and Computational Toxicology, AIMMS, Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - R4 - Gene-environment interaction, Promovendi NTM, RS: FHML MaCSBio, Publica, Pharmaceutical and Pharmacological Sciences, Connexin Signalling Research Group, Liver Connexin and Pannexin Research Group, Experimental in vitro toxicology and dermato-cosmetology |
| Rok vydání: | 2017 |
| Předmět: |
CCl4
0301 basic medicine Proof of non-toxicity Health Toxicology and Mutagenesis CCl RAPID - Risk Analysis for Products in Development Biomedical Innovation Signal transduction Ecotoxicology Toxicology NATURAL-KILLER-CELLS Prioritization of compounds Life Adverse Outcome Pathway ACTIVATED STELLATE CELLS ComputingMilieux_MISCELLANEOUS Risk assessment TUMOR-NECROSIS-FACTOR Event (computing) EVIDENCE-BASED TOXICOLOGY ENVIRONMENTAL CHEMICALS General Medicine Toxicokinetics Multiple hit events Proof of non-toxicity Evidence-based toxicology Identification (information) Paracetamol Risk analysis (engineering) Vinyl acetate RISK-ASSESSMENT Systems biology Construct (philosophy) Healthy Living Human Quality Control READ-ACROSS Vinyl Compounds Plasticity Liver fibrosis Nanotechnology Harmonization Multiple hit events Biology History 21st Century Risk Assessment Binning of events Adverse outcome 03 medical and health sciences Adverse outcome pathway SDG 3 - Good Health and Well-being ddc:570 Tumor promotion Journal Article Animals Humans Vinyl acetate Tumor promotion Regulatory toxicology Set (psychology) Epidemiological data Adverse Outcome Pathways Interspecies extrapolation 030111 toxicology SYSTEMS TOXICOLOGY Nonhuman Toxicity assay [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation Mice Inbred C57BL Multi-scale integration Metabolism 030104 developmental biology DEVELOPMENTAL NEUROTOXICITY Computational toxicology ELSS - Earth Life and Social Sciences Pathway unidirectionality |
| Zdroj: | Archives of Toxicology Archives of Toxicology, 2017, 91 (11), pp.3477-3505. ⟨10.1007/s00204-017-2045-3⟩ Archives of Toxicology, Springer Verlag, 2017, 91 (11), pp.3477-3505. ⟨10.1007/s00204-017-2045-3⟩ Archives of Toxicology, 91(11), 3477-3505. Springer Verlag Archives of Toxicology, 91(11), 3477-3505 Archives of Toxicology, 91(11), 3477-3505. Springer Archives of Toxicology, 11, 91, 3477-3505 Leist, M, Ghallab, A, Graepel, R, Marchan, R, Hassan, R, Bennekou, S H, Limonciel, A, Vinken, M, Schildknecht, S, Waldmann, T, Danen, E H J, van Ravenzwaay, B, Kamp, H, Gardner, I, Godoy, P, Bois, F Y, Braeuning, A, Reif, R, Oesch, F, Drasdo, D, Höhme, S, Schwarz, M, Hartung, T, Braunbeck, T, Beltman, J, Vrieling, H, Sanz, F, Forsby, A, Gadaleta, D, Fisher, C, Kelm, J, Fluri, D, Ecker, G F, Zdrazil, B, Terron, A, Jennings, P, van der Burg, B, Dooley, S, Meijer, A H, Willighagen, E, Martens, M, Evelo, C T, Mombelli, E, Taboureau, O, Mantovani, A, Hardy, B, Koch, B, Escher, S, van Thriel, C, Cadenas, C, Kroese, D, van de Water, B & Hengstler, J G 2017, ' Adverse outcome pathways : opportunities, limitations and open questions ', Archives of Toxicology, vol. 91, no. 11, pp. 3477-3505 . https://doi.org/10.1007/s00204-017-2045-3 |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-017-2045-3 |
| Popis: | Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field. © 2017, Springer-Verlag GmbH Germany. |
| Databáze: | OpenAIRE |
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