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

Krebs, A.; Vugt-Lussenburg, B.M.A. van; Waldmann, T.; Albrecht, W.; Boei, J.; Braak, B. ter; Brajnik, M.; Braunbeck, T.; Brecklinghaus, T.; Busquet, F.; Dinnyes, A.; Dokler, J.; Dolde, X.; Exner, T.E.; Fisher, C.; Fluri, D.; Forsby, A.; Hengstler, J.G.; Holzer, A.K.; Janstova, Z.; Jennings, P.; Kisitu, J.; Kobolak, J.; Kumar, M.; Limonciel, A.; Lundqvist, J.; Mihalik, B.; Moritz, W.; Pallocca, G.; Ulloa, A.P.C.; Pastor, M.; Rovida, C.; Sarkans, U.; Schimming, J.P.; Schmidt, B.Z.; Stober, R.; Strassfeld, T.; Water, B. van de; Wilmes, A.; Burg, B. van der; Verfaillie, C.M.; Hellfeld, R. von; Vrieling, H.; Vrijenhoek, N.G.; Leist, M.

doi:doi:10.1007/s00204-020-02802-6

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...Show moreHazard 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.Show less

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