Journal article
Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology
Konstanz University of Applied Sciences1
United States Food and Drug Administration2
Federal Institute for Risk Assessment3
Research Group for Chemical Risk Assessment and GMO, National Food Institute, Technical University of Denmark4
National Food Institute, Technical University of Denmark5
European Chemical Industry Council6
BASF7
National Institutes of Health8
S-IN Soluzioni Informatiche S.r.l.9
Johns Hopkins University10
Australian Government Department of Health11
Health Canada12
Pompeu Fabra University13
United States Environmental Protection Agency14
Innovatune S.r.l.15
Instituto Oswaldo Cruz-Fiocruz16
University Clinic Tübingen17
National Institute of Health Sciences Tokyo18
IRCCS Istituto di ricerche farmacologiche Mario Negri - Milano, Bergamo, Ranica19
Università degli Studi di Milano-Bicocca20
University of Windsor21
Biopredic International22
Liverpool John Moores University23
National Institute of Public Health and the Environment24
Fraunhofer Institute for Toxicology and Experimental Medicine25
...and 15 moreRead-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.
Language: | English |
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Year: | 2020 |
Pages: | 579-606 |
ISSN: | 18688551 , 09467785 and 1868596x |
Types: | Journal article |
DOI: | 10.14573/altex.1912181 |
ORCIDs: | Hougaard Bennekou, Susanne |