1. The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods
- Author
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Anja Wilmes, Tobias Strassfeld, Harry Vrieling, Manoj Kumar, Balázs Mihalik, Costanza Rovida, Giorgia Pallocca, Nanette G Vrijenhoek, Ciarán Fisher, Bart van der Burg, Thomas Braunbeck, Xenia Dolde, Alice Krebs, Zofia Janstova, Béla Z. Schmidt, Wiebke Albrecht, Jan G. Hengstler, Tim Brecklinghaus, David A. Fluri, J. J. W. A. Boei, Thomas Exner, Marcel Leist, Tanja Waldmann, Jaffar Kisitu, Anna-Katharina Holzer, Manuel Pastor, Joh Dokler, Andrea Paola Cediel Ulloa, Paul Jennings, Barbara M.A. van Vugt-Lussenburg, Bas ter Braak, Bob van de Water, Anna Forsby, Maja Brajnik, Wolfgang Moritz, Catherine M. Verfaillie, Johannes P Schimming, Rebecca von Hellfeld, Alice Limonciel, Francois Busquet, Julianna Kobolák, Ugis Sarkans, Regina Stöber, Jessica Lundqvist, Andras Dinnyes, Molecular and Computational Toxicology, and AIMMS
- Subjects
0301 basic medicine ,Test data generation ,Computer science ,Health, Toxicology and Mutagenesis ,Data validation ,HAZARD ASSESSMENT ,Toxicology ,CELL-CULTURE PRACTICE ,Documentation ,Policy Making ,Cells, Cultured ,Zebrafish ,media_common ,EPITHELIAL-CELLS ,General Medicine ,data processing ,GIVIMP ,in vitro toxicology ,metadata ,nuclear receptor ,Test (assessment) ,Strategy implementation ,Europe ,Data processing ,In Vitro Systems ,NEURAL CREST MIGRATION ,Life Sciences & Biomedicine ,REPRODUCTIVE TOXICITY ,Risk Assessment ,03 medical and health sciences ,SDG 17 - Partnerships for the Goals ,ddc:570 ,Terminology as Topic ,Toxicity Tests ,media_common.cataloged_instance ,Animals ,Humans ,European union ,Retrospective Studies ,In vitro toxicology ,Electronic Data Processing ,Metadata ,Science & Technology ,business.industry ,030111 toxicology ,Reproducibility of Results ,CALUX METHOD ,IN-VITRO ,Pipeline (software) ,DRUG DISCOVERY ,030104 developmental biology ,Nuclear receptor ,DEVELOPMENTAL NEUROTOXICITY DNT ,Government Regulation ,Software engineering ,business ,EMBRYONIC STEM-CELLS - 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. Electronic supplementary material The online version of this article (10.1007/s00204-020-02802-6) contains supplementary material, which is available to authorized users.
- Published
- 2020
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