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

Arch Toxicol. 2020 Jul;94(7):2435-2461. doi: 10.1007/s00204-020-02802-6. Epub 2020 Jul 6.

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.

Keywords: Data processing; GIVIMP; In vitro toxicology; Metadata; Nuclear receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Documentation*
  • Electronic Data Processing / legislation & jurisprudence*
  • Europe
  • Government Regulation*
  • Humans
  • Policy Making
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Terminology as Topic
  • Toxicity Tests*
  • Toxicology / legislation & jurisprudence*
  • Zebrafish / embryology