Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology

Costanza Rovida, Tara Barton-Maclaren, Emilio Benfenati, Francesca Caloni, Charu Chandrasekera, Christophe Chesne, Mark T D Cronin, Joop De Knecht, Daniel R Dietrich, Sylvia E Escher, Suzanne Fitzpatrick, Brenna Flannery, Matthias Herzler, Susanne Hougaard Bennekou, Bruno Hubesch, Hennicke Kamp, Jaffar Kisitu, Nicole Kleinstreuer, Simona Kovarich, Marcel LeistAlexandra Maertens, Kerry Nugent, Giorgia Pallocca, Manuel Pastor, Grace Patlewicz, Manuela Pavan, Octavio Presgrave, Lena Smirnova, Michael Schwarz, Takashi Yamada, Thomas Hartung

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Abstract

Read-across (RAx) translates available information from well-characterized chemicals to the substance for which there is a toxicological data gap. The OECD is working on case studies to probe general applicability of RAx, and several regulations (e.g. EU-REACH) already allow this procedure to be used to waive new in vivo tests. The decision to prepare a review on the state of the art of RAx as a tool for risk assessment for regulatory purposes was taken during a workshop with international experts in Ranco, Italy in July 2018. Three major issues were identified that need optimisation to allow a higher regulatory acceptance rate of the RAx procedure: (i) the definition of similarity of source and target, (ii) the translation of biological/toxicological activity of source to target, in the RAx procedure, and (iii) how to deal with issues of ADME that may differ between source and target. The use of new approach methodologies (NAM) was discussed as one of the most important innovations to improve the acceptability of RAx. At present, NAM data may be used to confirm chemical and toxicological similarity. In the future, the use of NAM may be broadened to fully characterize the hazard and toxicokinetic properties of RAx compounds. Concerning available guidance, documents on Good Read-Across Practice (GRAP) and on best practices to perform and evaluate the RAx process were identified. Here, in particular the RAx guidance, being worked out by the European Commission's H2020 project EU-ToxRisk, together with many external partners with regulatory experience, is given.

Original languageEnglish
JournalA L T E X. Alternatives to Animal Experimentation
Volume37
Issue number4
Pages (from-to)579-606
ISSN1868-596X
DOIs
Publication statusPublished - 2020

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