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Use of in vitro 3D tissue models in genotoxicity testing: Strategic fit, validation status and way forward. Report of the working group from the 7th International Workshop on Genotoxicity Testing (IWGT)

Stefan Pfuhler, Jan van Benthem, Rodger Curren, shareen Doak, Maria Dusinska, Makoto Hayashi, Robert H. Heflich, Darren Kidd, David Kirkland, Yang Luan, Gladys Ouedraogo, Kerstin Reisinger, Toshio Sofuni, Frédérique van Acker, Ying Yang, Raffaella Corvi

Mutation Research: Genetic Toxicology and Environmental Mutagenesis, Volume: 850-851, Start page: 503135

Swansea University Author: shareen Doak

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DOI (Published version): 10.1016/j.mrgentox.2020.503135

Abstract

Use of three-dimensional (3D) tissue equivalents in toxicology has been increasing over the last decade as novel preclinical test systems and as alternatives to animal testing. In the area of genetic toxicology, progress has been made with establishing robust protocols for skin, airway (lung) and li...

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Published in: Mutation Research: Genetic Toxicology and Environmental Mutagenesis
ISSN: 1383-5718 1879-3592
Published: Elsevier BV 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa53559
Abstract: Use of three-dimensional (3D) tissue equivalents in toxicology has been increasing over the last decade as novel preclinical test systems and as alternatives to animal testing. In the area of genetic toxicology, progress has been made with establishing robust protocols for skin, airway (lung) and liver tissue equivalents. In light of these advancements, a “Use of 3D Tissues in Genotoxicity Testing” working group (WG) met at the 7th IWGT meeting in Tokyo in November 2017 to discuss progress with these models and how they may fit into a genotoxicity testing strategy. The workshop demonstrated that skin models have reached an advanced state of validation following over 10 years of development, while liver and airway model-based genotoxicity assays show promise but are at an early stage of development. Further effort in liver and airway model-based assays is needed to address the lack of coverage of the three main endpoints of genotoxicity (mutagenicity, clastogenicity and aneugenicity), and information on metabolic competence. The IWGT WG believes that the 3D skin comet and micronucleus assays are now sufficiently validated to undergo an independent peer review of the validation study, followed by development of individual OECD Test Guidelines.
Keywords: In vitro genotoxicity testing; DNA damage; Comet assay; Micronucleus test; Reconstructed human skin; Liver spheroids; 3D airway models
College: Faculty of Medicine, Health and Life Sciences
Funders: The 3D skin comet and micronucleus validation outcome presented at IWGT was financially supported by the German Federal Ministry for Research and Technology (grant Nos. 0315226, 0316008) and by Cosmetics Europe, Belgium. The research on CeO2 nanoparticles presented in chapter 2b was financially supported by funds from TNO, The Netherlands.
Start Page: 503135

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