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

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Costanza Rovida
Tara Barton-Maclaren
Emilio Benfenati
Francesca Caloni
P. Charukeshi Chandrasekera
Christophe Chesné
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 Leist
Alexandra Maertens
Kerry Nugent
Giorgia Pallocca
Manuel Pastor
Grace Patlewicz
Manuela Pavan
Octavio Presgrave
Lena Smirnova
Michael Schwarz
Takashi Yamada
Thomas Hartung

Abstract

Read-across (RAx) translates available information from well-characterized chemicals to a 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 optimization 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.

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How to Cite
Rovida, C., Barton-Maclaren, T., Benfenati, E., Caloni, F., Chandrasekera, P. C., Chesné, C., Cronin, M. T. D., De Knecht, J., Dietrich, D. R., Escher, S. E., Fitzpatrick, S., Flannery, B., Herzler, M., Hougaard Bennekou, S., Hubesch, B., Kamp, H., Kisitu, J., Kleinstreuer, N., Kovarich, S., Leist, M., Maertens, A., Nugent, K., Pallocca, G., Pastor, M., Patlewicz, G., Pavan, M., Presgrave, O., Smirnova, L., Schwarz, M., Yamada, T. and Hartung, T. (2020) “Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology”, ALTEX - Alternatives to animal experimentation, 37(4), pp. 579-606. doi: 10.14573/altex.1912181.
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