The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methodsShow others and affiliations
Number of Authors: 452020 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 94, no 7, p. 2435-2461Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
2020. Vol. 94, no 7, p. 2435-2461
Keywords [en]
GIVIMP, In vitro toxicology, Nuclear receptor, Metadata, Data processing
National Category
Computer and Information Sciences
Identifiers
URN: urn:nbn:se:su:diva-184518DOI: 10.1007/s00204-020-02802-6ISI: 000545934500001PubMedID: 32632539OAI: oai:DiVA.org:su-184518DiVA, id: diva2:1467522
2020-09-152020-09-152022-02-25Bibliographically approved