Harvesting the promise of AOPs: An assessment and recommendations

Highlights • The AOP framework aims to increase efficiency of chemical safety assessments.• The stakeholder community for AOPs, however, is broader than chemical risk assessors.• There are scientific and social challenges to successfully engage all stakeholders.• Multi-faceted communication and governance strategies will address these challenges.

[1]  Andrew Worth,et al.  Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA). , 2014, Regulatory toxicology and pharmacology : RTP.

[2]  Patricia A Weideman,et al.  Point of departure (PoD) selection for the derivation of acceptable daily exposures (ADEs) for active pharmaceutical ingredients (APIs). , 2016, Regulatory toxicology and pharmacology : RTP.

[3]  Edward J. Perkins,et al.  The Adverse Outcome Pathway: A Conceptual Framework to Support Toxicity Testing in the Twenty-First Century , 2015 .

[4]  Neil Benson,et al.  Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is. , 2015, Drug discovery today. Technologies.

[5]  Tobias Schulze,et al.  Effect-directed analysis supporting monitoring of aquatic environments--An in-depth overview. , 2016, The Science of the total environment.

[6]  S. Funtowicz,et al.  Science for the PostNormal Age , 2001 .

[7]  Annemarie P van Wezel,et al.  Towards the review of the European Union Water Framework Directive: Recommendations for more efficient assessment and management of chemical contamination in European surface water resources. , 2017, The Science of the total environment.

[8]  Sharon Munn,et al.  Adverse outcome pathway development II: best practices. , 2014, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  J. Stilgoe,et al.  Developing a framework for responsible innovation* , 2013, The Ethics of Nanotechnology, Geoengineering and Clean Energy.

[10]  René von Schomberg,et al.  From the Ethics of Technology Towards an Ethics of Knowledge Policy & Knowledge Assessment , 2007 .

[11]  Jan G. Hengstler,et al.  Adverse outcome pathways: a concise introduction for toxicologists , 2017, Archives of Toxicology.

[12]  Winston A Hide,et al.  Big data: The future of biocuration , 2008, Nature.

[13]  Gary R. Mirams,et al.  Prediction of Thorough QT study results using action potential simulations based on ion channel screens , 2014, Journal of pharmacological and toxicological methods.

[14]  Icilio Cavero,et al.  15th Annual Meeting of the Safety Pharmacology Society: Focus on traditional sensory systems. , 2017, Journal of pharmacological and toxicological methods.

[15]  Martin Hofmann-Apitius,et al.  Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations. , 2017, Drug discovery today.

[16]  Torsten Reimer,et al.  Virtual Research Environment Collaborative Landscape Study , 2010 .

[17]  Other.  Directive 2000/60/EC of the European Parliament and of The Council of 23 October 2000 establishing a Framework for Community Action in the Field of Water Policy (Water Framework Directive) , 2000 .

[18]  Gary R. Mirams,et al.  Recent developments in using mechanistic cardiac modelling for drug safety evaluation , 2016, Drug discovery today.

[19]  S. Funtowicz,et al.  Science for the Post-Normal Age , 1993, Commonplace.

[20]  Melvin E Andersen,et al.  Adverse Outcome Pathways can drive non-animal approaches for safety assessment , 2015, Journal of applied toxicology : JAT.

[21]  R Charles Coombes,et al.  Stratified, precision or personalised medicine? Cancer services in the 'real world' of a London hospital. , 2017, Sociology of Health and Illness.

[22]  Jingbo Zhu,et al.  A systems-level approach for investigating organophosphorus pesticide toxicity. , 2018, Ecotoxicology and environmental safety.

[23]  Division on Earth,et al.  A Framework to Guide Selection of Chemical Alternatives , 2014 .

[24]  Igor Linkov,et al.  Increasing Scientific Confidence in Adverse Outcome Pathways: Application of Tailored Bradford-Hill Considerations for Evaluating Weight of Evidence. , 2015, Regulatory toxicology and pharmacology : RTP.

[25]  Users' Handbook supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways , 2019 .

[26]  Jeremy K Nicholson,et al.  Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism. , 2015, Drug discovery today. Technologies.

[27]  Maurice Whelan,et al.  How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology , 2016, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  Gavin Maxwell,et al.  From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment. , 2013, ALTEX.

[29]  Rolf Altenburger,et al.  Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays. , 2014, Environmental science & technology.

[30]  Joop L. M. Hermens,et al.  Quantitative structure‐activity relationships in aquatic toxicity studies of chemicals and complex mixtures of chemicals , 1985 .

[31]  R. V. Schomberg.  A Vision of Responsible Research and Innovation , 2013 .

[32]  Manuel C. Peitsch,et al.  Systems Toxicology: From Basic Research to Risk Assessment , 2014, Chemical research in toxicology.

[33]  Daniel L Villeneuve,et al.  Environmental surveillance and monitoring—The next frontiers for high‐throughput toxicology , 2016, Environmental toxicology and chemistry.

[34]  Sharon Munn,et al.  Advancing the adverse outcome pathway framework—An international horizon scanning approach , 2017, Environmental toxicology and chemistry.

[35]  David H. Guston,et al.  Real-time technology assessment , 2020, Emerging Technologies: Ethics, Law and Governance.

[36]  Icilio Cavero,et al.  14th Annual Meeting of the Safety Pharmacology Society: Threading through peripheral and central nervous system presentations. , 2015, Journal of pharmacological and toxicological methods.

[37]  P. Graaf,et al.  Towards integrative systems pharmacology models in oncology drug development. , 2015 .

[38]  Helmut Segner,et al.  The SOLUTIONS project: challenges and responses for present and future emerging pollutants in land and water resources management. , 2015, The Science of the total environment.

[39]  Icilio Cavero,et al.  14th Annual Meeting of the Safety Pharmacology Society: threading through scientific sessions for originality and novelty , 2015, Expert opinion on drug safety.

[40]  J. Ziman,et al.  Getting scientists to think about what they are doing , 2001, Science and engineering ethics.

[41]  R. Judson,et al.  Estimating toxicity-related biological pathway altering doses for high-throughput chemical risk assessment. , 2011, Chemical research in toxicology.

[42]  G. Langley,et al.  Estimates for Worldwide Laboratory Animal Use in 2005 , 2008 .

[43]  Giovanni De Grandis,et al.  Practical integration: The art of balancing values, institutions and knowledge - lessons from the History of British Public Health and Town Planning. , 2016, Studies in history and philosophy of biological and biomedical sciences.

[44]  Rolf Altenburger,et al.  Development of a bioanalytical test battery for water quality monitoring: Fingerprinting identified micropollutants and their contribution to effects in surface water. , 2017, Water research.

[45]  Martin Krauss,et al.  Linking in Vitro Effects and Detected Organic Micropollutants in Surface Water Using Mixture-Toxicity Modeling. , 2015, Environmental science & technology.

[46]  Frederic D.L. Leusch,et al.  Bioanalytical Tools in Water Quality Assessment , 2011 .

[47]  Hong Wang,et al.  Environmental policy, legislation and management of persistent organic pollutants (POPs) in China. , 2012, Environmental pollution.

[48]  Benno Schwikowski,et al.  From the exposome to mechanistic understanding of chemical-induced adverse effects. , 2017, Environment international.

[49]  J. Hermens,et al.  Modes of action in ecotoxicology: their role in body burdens, species sensitivity, QSARs, and mixture effects. , 2002, Environmental science & technology.

[50]  Patience Browne,et al.  Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program , 2017, Environmental health perspectives.

[51]  J. Bailar,et al.  Toxicity Testing in the 21st Century: A Vision and a Strategy , 2010, Journal of toxicology and environmental health. Part B, Critical reviews.

[52]  A. Vinggaard,et al.  A computational approach to mechanistic and predictive toxicology of pesticides. , 2014, ALTEX.

[53]  Stephen W. Edwards,et al.  The Adverse Outcome Pathway: A Multifaceted Framework Supporting 21st Century Toxicology. , 2018, Current opinion in toxicology.

[54]  Rachael P. Huntley,et al.  Gene regulation knowledge commons: community action takes care of DNA binding transcription factors , 2016, Database J. Biol. Databases Curation.

[55]  Hiroaki Kitano,et al.  Lessons from Toxicology: Developing a 21st-Century Paradigm for Medical Research , 2015, Environmental health perspectives.

[56]  Daniel L Villeneuve,et al.  Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment , 2010, Environmental toxicology and chemistry.

[57]  A. V. van Wezel,et al.  Narcosis due to environmental pollutants in aquatic organisms: residue-based toxicity, mechanisms, and membrane burdens. , 1995, Critical reviews in toxicology.

[58]  Raymond L Woosley,et al.  Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes. , 2016, Journal of the American College of Cardiology.

[59]  Richard Cubberley,et al.  Applying the skin sensitisation adverse outcome pathway (AOP) to quantitative risk assessment. , 2014, Toxicology in vitro : an international journal published in association with BIBRA.

[60]  Rebecca A. B. Burton,et al.  Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop , 2015, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[61]  S. Bradbury,et al.  Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment. , 1987, Environmental health perspectives.

[62]  Helmut Segner,et al.  Future water quality monitoring--adapting tools to deal with mixtures of pollutants in water resource management. , 2015, The Science of the total environment.

[63]  Sharon Munn,et al.  Adverse outcome pathway (AOP) development I: strategies and principles. , 2014, Toxicological sciences : an official journal of the Society of Toxicology.

[64]  Kenneth M Y Leung,et al.  Progress of environmental management and risk assessment of industrial chemicals in China. , 2012, Environmental pollution.

[65]  Kellie A Fay,et al.  Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies , 2017, Environmental toxicology and chemistry.

[66]  R Bruno,et al.  Simulations to Predict Clinical Trial Outcome of Bevacizumab Plus Chemotherapy vs. Chemotherapy Alone in Patients With First‐Line Gastric Cancer and Elevated Plasma VEGF‐A , 2016, CPT: pharmacometrics & systems pharmacology.

[67]  M. Gibbons,et al.  Re-Thinking Science: Knowledge and the Public in an Age of Uncertainty , 2003 .

[68]  S. Marshall,et al.  Good Practices in Model‐Informed Drug Discovery and Development: Practice, Application, and Documentation , 2016, CPT: pharmacometrics & systems pharmacology.

[69]  N. Vermeulen,et al.  Mercapturic acids, protein adducts, and DNA adducts as biomarkers of electrophilic chemicals. , 1992, Critical reviews in toxicology.

[70]  S. Visser,et al.  Implementation of Quantitative and Systems Pharmacology in Large Pharma , 2014, CPT: pharmacometrics & systems pharmacology.

[71]  Melanie Gross,et al.  Current Limitations and Recommendations to Improve Testing for the Environmental Assessment of Endocrine Active Substances , 2017 .

[72]  D Benton,et al.  Recent changes in the GenBank On-line Service. , 1990, Nucleic acids research.

[73]  Sharon Munn,et al.  Adverse outcome pathway development from protein alkylation to liver fibrosis , 2016, Archives of Toxicology.

[74]  Revised Guidance Document on Developing and Assessing Adverse Outcome Pathways , 2013 .

[75]  Daniel L Villeneuve,et al.  Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death. , 2017, The Science of the total environment.

[76]  Paul B Watkins,et al.  The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury. , 2017, Drug metabolism and pharmacokinetics.

[77]  Leonardo Candela.  Virtual Research Environment , 2019, Definitions.

[78]  A. Hedgecoe,et al.  The Politics of Personalised Medicine: Pharmacogenetics in the Clinic , 2004 .