The need for strategic development of safety sciences.

The practice of risk assessment and regulation of substances has largely developed as a patchwork of circumstantial additions to a nowadays more or less shared international toolbox. The dominant drivers from the US and Europe have pursued remarkably different approaches in the use of these tools for regulation, i.e., a more risk-based approach in the US and a more precautionary approach in Europe. We argue that there is need for scientific developments not only for the tools but also for their application, i.e., a need for Regulatory Science or, perhaps better, Safety Science. While some of this is emerging on the US side as strategic reports, e.g., from the National Academies, the NIH and the regulatory agencies, especially the EPA and the FDA, such strategic developments beyond technological developments are largely lacking in Europe or have started only recently at EFSA, ECHA or within the flagship project EU-ToxRisk. This article provides a rationale for the creation of a European Safety Sciences Institute (ESSI) based on regulatory and scientific needs, political context and current EU missions. Moreover, the possible modus operandi of ESSI will be described along with possible working formats as well as anticipated main tasks and duties. This mirrors the triple alliance on the American side (US EPA, NIH and FDA) in revamping regulatory sciences. Moreover, this could fit the political agenda of the European Commission for better implementation of existing EU legislation rather than creating new laws.

[1]  A. Boobis,et al.  A framework for cumulative risk assessment in the 21st century , 2017, Critical reviews in toxicology.

[2]  S. Rappaport Implications of the exposome for exposure science , 2011, Journal of Exposure Science and Environmental Epidemiology.

[3]  Thomas Hartung,et al.  Food for Thought ... on mapping the human toxome. , 2011, ALTEX.

[4]  T. Hartung Evolution of toxicological science: the need for change , 2017 .

[5]  T. Hartung Evidence-based toxicology - the toolbox of validation for the 21st century? , 2010, ALTEX.

[6]  Thomas Hartung,et al.  Pathway-Based Approaches for Environmental Monitoring and Risk Assessment. , 2016, Environmental science & technology.

[7]  Harvey J Clewell,et al.  Can case study approaches speed implementation of the NRC report: "toxicity testing in the 21st century: a vision and a strategy?". , 2011, ALTEX.

[8]  Anton Simeonov,et al.  Good Cell Culture Practice for stem cells and stem-cell-derived models. , 2016, ALTEX.

[9]  Thomas Hartung,et al.  Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies , 2007, Environmental health perspectives.

[10]  Grace Patlewicz,et al.  Current and Future Perspectives on the Development, Evaluation, and Application of in Silico Approaches for Predicting Toxicity. , 2016, Chemical research in toxicology.

[11]  Angelo Moretto,et al.  Risk assessment in the 21st century: Roadmap and matrix , 2014, Critical reviews in toxicology.

[12]  C. Wild Complementing the Genome with an “Exposome”: The Outstanding Challenge of Environmental Exposure Measurement in Molecular Epidemiology , 2005, Cancer Epidemiology Biomarkers & Prevention.

[13]  David M. Reif,et al.  Toxicity Testing in the 21st Century Beyond Environmental Chemicals , 2018, ALTEX.

[14]  Richard A Becker,et al.  Read-across approaches--misconceptions, promises and challenges ahead. , 2014, ALTEX.

[15]  Thomas B Knudsen,et al.  Systems Toxicology , 2015, International journal of toxicology.

[16]  Valérie Zuang,et al.  A Modular Approach to the ECVAM Principles on Test Validity , 2004, Alternatives to laboratory animals : ATLA.

[17]  T Hartung,et al.  Toward an evidence-based toxicology , 2006, Human & experimental toxicology.

[18]  Thomas Hartung,et al.  E-cigarettes and the need and opportunities for alternatives to animal testing. , 2016, ALTEX.

[19]  D. Demortain Scientists and the Regulation of Risk: Standardising Control , 2011 .

[20]  Stephen M. Rappaport,et al.  Building Exposure Biology Centers to Put the E into “G × E” Interaction Studies , 2009, Environmental health perspectives.

[21]  M. Dellarco,et al.  A 21st century roadmap for human health risk assessment , 2014, Critical reviews in toxicology.

[22]  Uwe Marx,et al.  Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. , 2016, ALTEX.

[23]  Melvin E Andersen,et al.  The Human Toxome Project , 2015, ALTEX.

[24]  Melvin E. Andersen,et al.  The Human Toxome Collaboratorium: A Shared Environment for Multi-Omic Computational Collaboration within a Consortium , 2016, Front. Pharmacol..

[25]  Sangeeta Khare,et al.  Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology. , 2015, ALTEX.

[26]  Thomas Hartung,et al.  Food for thought...on alternative methods for chemical safety testing. , 2010, ALTEX.

[27]  Martin Stephens,et al.  Mechanistic validation. , 2013, ALTEX.

[28]  Mardas Daneshian,et al.  Current approaches and future role of high content imaging in safety sciences and drug discovery. , 2014, ALTEX.

[29]  Michael S Victoroff,et al.  Evidence-based toxicology: a comprehensive framework for causation , 2005, Human & experimental toxicology.

[30]  Alan R. Boobis,et al.  The use of mode of action information in risk assessment: Quantitative key events/dose-response framework for modeling the dose-response for key events , 2014, Critical reviews in toxicology.

[31]  T. Knudsen,et al.  A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing. , 2012, ALTEX.

[32]  Emilio Benfenati,et al.  Novel chemical hazard characterisation approaches , 2016 .

[33]  Thomas Hartung,et al.  Toward a New Toxicology — Evolution or Revolution? , 2008, Alternatives to laboratory animals : ATLA.

[34]  Alexandra Maertens,et al.  MPTP’s Pathway of Toxicity Indicates Central Role of Transcription Factor SP1 , 2015, Archives of Toxicology.

[35]  D. Blacker Food for thought. , 2013, JAMA neurology.

[36]  Melvin E. Andersen,et al.  Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing , 2015, Toxicological sciences : an official journal of the Society of Toxicology.

[37]  T. Hartung Toxicology for the twenty-first century , 2009, Nature.

[38]  Alexandra Maertens,et al.  Integrated testing strategies for safety assessments. , 2013, ALTEX.

[39]  Mardas Daneshian,et al.  Highlight report: Launch of a large integrated European in vitro toxicology project: EU-ToxRisk , 2016, Archives of Toxicology.

[40]  Michael Balls,et al.  Guidance on Good Cell Culture Practice , 2005, Alternatives to laboratory animals : ATLA.

[41]  M. Kogevinas,et al.  The exposome in practice: Design of the EXPOsOMICS project , 2017, International journal of hygiene and environmental health.

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

[43]  Nicole Kleinstreuer,et al.  Supporting read-across using biological data. , 2016, ALTEX.

[44]  Thomas Hartung,et al.  Lessons Learned from Alternative Methods and their Validation for a New Toxicology in the 21st Century , 2010, Journal of toxicology and environmental health. Part B, Critical reviews.

[45]  Melvin E. Andersen,et al.  Developing tools for defining and establishing pathways of toxicity , 2015, Archives of Toxicology.

[46]  Thomas Hartung,et al.  Utility of the adverse outcome pathway concept in drug development , 2017, Expert opinion on drug metabolism & toxicology.

[47]  Thomas Hartung,et al.  21st Century Cell Culture for 21st Century Toxicology. , 2017, Chemical research in toxicology.

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

[49]  D. Krewski,et al.  A Framework for the Next Generation of Risk Science , 2014, Environmental health perspectives.

[50]  Hector C. Keun,et al.  The Human Early-Life Exposome (HELIX): Project Rationale and Design , 2013, Environmental health perspectives.

[51]  Thomas Hartung,et al.  A Toxicology for the 21st Century—Mapping the Road Ahead , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[52]  Division on Earth Toxicity Testing in the 21st Century: A Vision and a Strategy , 2007 .

[53]  Thomas Hartung,et al.  Comparative analysis of the revised Directive 2010/63/EU for the protection of laboratory animals with its predecessor 86/609/EEC - a t4 report. , 2010, ALTEX.

[54]  Antony J. Williams,et al.  ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology. , 2016, Chemical research in toxicology.

[55]  Sebastian Hoffmann,et al.  The Emergence of Systematic Review in Toxicology , 2016, Toxicological sciences : an official journal of the Society of Toxicology.

[56]  Rick A. Fasani,et al.  Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity , 2016, Archives of Toxicology.

[57]  Mardas Daneshian,et al.  Consensus report on the future of animal-free systemic toxicity testing. , 2014, ALTEX.

[58]  Sebastian Hoffmann,et al.  Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review. , 2016, Environment international.

[59]  Imran Shah,et al.  Toxicokinetic Triage for Environmental Chemicals. , 2015, Toxicological sciences : an official journal of the Society of Toxicology.

[60]  T. Hartung,et al.  Metabolomic network analysis of estrogen-stimulated MCF-7 cells: a comparison of overrepresentation analysis, quantitative enrichment analysis and pathway analysis versus metabolite network analysis , 2016, Archives of Toxicology.

[61]  Alexandra Maertens,et al.  t4 report: Toward Good Read-Across Practice (GRAP) Guidance , 2016, ALTEX.

[62]  Ewen Callaway Daily dose of toxics to be tracked , 2012, Nature.

[63]  Thomas Hartung,et al.  Integrated Testing Strategies (ITS) for safety assessment. , 2015, ALTEX.

[64]  Angelo Moretto,et al.  Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans , 2016, Critical reviews in toxicology.