The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods

Alice Krebs, Barbara M A van Vugt-Lussenburg, Tanja Waldmann, Wiebke Albrecht, Jan Boei, Bas Ter Braak, Maja Brajnik, Thomas Braunbeck, Tim Brecklinghaus, Francois Busquet, Andras Dinnyes, Joh Dokler, Xenia Dolde, Thomas E Exner, Ciarán Fisher, David Fluri, Anna Forsby, Jan G Hengstler, Anna-Katharina Holzer, Zofia JanstovaPaul Jennings, Jaffar Kisitu, Julianna Kobolak, Manoj Kumar, Alice Limonciel, Jessica Lundqvist, Balázs Mihalik, Wolfgang Moritz, Giorgia Pallocca, Andrea Paola Cediel Ulloa, Manuel Pastor, Costanza Rovida, Ugis Sarkans, Johannes P Schimming, Bela Z Schmidt, Regina Stöber, Tobias Strassfeld, Bob van de Water, Anja Wilmes, Bart van der Burg, Catherine M Verfaillie, Rebecca von Hellfeld, Harry Vrieling, Nanette G Vrijenhoek, Marcel Leist*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2435-2461
Number of pages27
JournalArchives of Toxicology
Volume94
Issue number7
Early online date6 Jul 2020
DOIs
Publication statusPublished - Jul 2020

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