The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods
Archives of Toxicology, vol. 94, pp. 2435–2461
Abstract
Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.
Authors 44
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BioDetection Systems (Netherlands)
Affiliation as printed
BioDetection Systems BV, Science Park 406, 1098 XH, Amsterdam, The Netherlands
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Affiliation as printed
In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany
trenzyme GmbH, Byk-Gulden-Str. 2, 78467, Konstanz, Germany
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Leibniz Research Centre for Working Environment and Human Factors
Affiliation as printed
Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Leibniz Research Center for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139, Dortmund, Germany
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Jan Boei Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
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Affiliation as printed
Division of Drug Discovery and Safety, Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
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Edelweiss Connect (Switzerland)
Affiliation as printed
Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057, Basel, Switzerland
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Affiliation as printed
Aquatic Ecology and Toxicology Group, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 504, 69120, Heidelberg, Germany
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Leibniz Research Centre for Working Environment and Human Factors
Affiliation as printed
Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Leibniz Research Center for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139, Dortmund, Germany
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Affiliation as printed
CAAT Europe, University of Konstanz, Steinbeis SU-1866, 78457, Konstanz, Germany
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Affiliation as printed
BioTalentum Ltd., Aulich Lajos str. 26, Gödöllő, 2100, Hungary
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Edelweiss Connect (Switzerland)
Affiliation as printed
Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057, Basel, Switzerland
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Affiliation as printed
In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany
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Edelweiss Connect (Switzerland)
Affiliation as printed
Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, 4057, Basel, Switzerland
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Affiliation as printed
Simcyp Division, Certara UK Limited, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK
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Affiliation as printed
InSphero AG, Wagistrasse 27, 8952, Schlieren, Switzerland
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Stockholm University · Karolinska Institutet
Affiliation as printed
Department of Biochemistry and Biophysics, Stockholm University, 10691, Stockholm, Sweden
Unit of Toxicology Sciences, Swedish Toxicology Sciences Research Center (Swetox), Karolinska Institutet, Forskargatan 20, 151 36, Södertälje, Sweden
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Leibniz Research Centre for Working Environment and Human Factors
Affiliation as printed
Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Leibniz Research Center for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139, Dortmund, Germany
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Affiliation as printed
In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany
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Affiliation as printed
BioTalentum Ltd., Aulich Lajos str. 26, Gödöllő, 2100, Hungary
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Affiliation as printed
Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
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Affiliation as printed
In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany
Konstanz Research School Chemical Biology, University of Konstanz, 78457, Konstanz, Germany
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Affiliation as printed
BioTalentum Ltd., Aulich Lajos str. 26, Gödöllő, 2100, Hungary
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Leuven Stem Cell Institute · KU Leuven
Affiliation as printed
Department of Development and Regeneration, Stem Cell Biology and Embryology, Stem Cell Institute Leuven, KU Leuven, O&N IV Herestraat 49, 3000, Leuven, Belgium
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Affiliation as printed
Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
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Stockholm University · Karolinska Institutet
Affiliation as printed
Department of Biochemistry and Biophysics, Stockholm University, 10691, Stockholm, Sweden
Unit of Toxicology Sciences, Swedish Toxicology Sciences Research Center (Swetox), Karolinska Institutet, Forskargatan 20, 151 36, Södertälje, Sweden
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Affiliation as printed
BioTalentum Ltd., Aulich Lajos str. 26, Gödöllő, 2100, Hungary
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Affiliation as printed
InSphero AG, Wagistrasse 27, 8952, Schlieren, Switzerland
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Affiliation as printed
CAAT Europe, University of Konstanz, Steinbeis SU-1866, 78457, Konstanz, Germany
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Affiliation as printed
Unit of Toxicology Sciences, Swedish Toxicology Sciences Research Center (Swetox), Karolinska Institutet, Forskargatan 20, 151 36, Södertälje, Sweden
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Universitat Pompeu Fabra · Hospital del Mar Research Institute
Affiliation as printed
Department of Experimental and Health Sciences, Research Programme on Biomedical Informatics (GRIB), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, 08003, Barcelona, Spain
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Affiliation as printed
CAAT Europe, University of Konstanz, Steinbeis SU-1866, 78457, Konstanz, Germany
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European Bioinformatics Institute
Affiliation as printed
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK
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Affiliation as printed
Leiden Academic Center for Drug Research, LACDR/Toxicology, Leiden University, PO Box 9500, 2300 RA, Leiden, The Netherlands
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VIB-KU Leuven Center for Brain & Disease Research · KU Leuven
Affiliation as printed
Switch Laboratory, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Brain and Disease Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
Switch Laboratory, Department of Cellular and Molecular Medicine, VIB‐KU Leuven Center for Brain and Disease Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
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Leibniz Research Centre for Working Environment and Human Factors
Affiliation as printed
Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Leibniz Research Center for Working Environment and Human Factors (IfADo), Ardeystraße 67, 44139, Dortmund, Germany
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Affiliation as printed
InSphero AG, Wagistrasse 27, 8952, Schlieren, Switzerland
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Affiliation as printed
Leiden Academic Center for Drug Research, LACDR/Toxicology, Leiden University, PO Box 9500, 2300 RA, Leiden, The Netherlands
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Affiliation as printed
Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
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BioDetection Systems (Netherlands)
Affiliation as printed
BioDetection Systems BV, Science Park 406, 1098 XH, Amsterdam, The Netherlands
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Leuven Stem Cell Institute · KU Leuven
Affiliation as printed
Department of Development and Regeneration, Stem Cell Biology and Embryology, Stem Cell Institute Leuven, KU Leuven, O&N IV Herestraat 49, 3000, Leuven, Belgium
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Affiliation as printed
Aquatic Ecology and Toxicology Group, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 504, 69120, Heidelberg, Germany
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Harry Vrieling Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands
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Affiliation as printed
Leiden Academic Center for Drug Research, LACDR/Toxicology, Leiden University, PO Box 9500, 2300 RA, Leiden, The Netherlands
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Marcel Leist corresponding
Affiliation as printed
CAAT Europe, University of Konstanz, Steinbeis SU-1866, 78457, Konstanz, Germany. marcel.leist@uni-konstanz.de
In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany. marcel.leist@uni-konstanz.de
CAAT Europe, University of Konstanz, Steinbeis SU-1866, 78457, Konstanz, Germany
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