ArticleMutagenesis2021
Validation of the 3D reconstructed human skin micronucleus (RSMN) assay: an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays.
Article in Mutagenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Evaluating the Suitability of HepaRG Cells for Regulatory Micronucleus Testing: Comparing Results for a Diverse Set of 28 Chemicals to Regulatory Accepted TK6 Cells.Environmental and molecular mutagenesis · 2026Article
- Application of the Comet Assay in Advanced In Vitro Models.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A framework for the safety evaluation of peptides in cosmetics.Current research in toxicology · 2026Article
- HepaRGNAM journal · 2025Article
- Current status and future challenges of genotoxicity OECD Test Guidelines for nanomaterials: a workshop report.Mutagenesis · 2023Article
- Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment.Mutagenesis · 2023Article
- High-throughput micronucleus assay using three-dimensional HepaRG spheroids for in vitro genotoxicity testing.Archives of toxicology · 2023Article
- Genotoxicity study of 2-methoxyethanol and benzalkonium chloride through Comet assay using 3D cultured HepG2 cells.Environmental analysis, health and toxicology · 2022Article
- Replacement of animal testing by integrated approaches to testing and assessment (IATA): a call for in vivitrosi.Archives of toxicology · 2022Review
- Article
- Use of the EpiDermTM 3D reconstructed skin micronucleus assay for fragrance materials.Mutagenesis · 2022Article
- The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.Mutagenesis · 2022Article
- Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of tobacco and other nicotine-containing products.Frontiers in toxicology · 2022Article
- Article
- A comparison of classical and 21st century genotoxicity tools: A proof of concept study of 18 chemicals comparing in vitro micronucleus, ToxTracker and genomics-based methods (TGx-DDI, whole genome clustering and connectivity mapping).Environmental and molecular mutagenesis · 2021Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro test batteries have become the standard approach to determine the genotoxic potential of substances of interest across industry sectors. While useful for hazard identification, standard in vitro genotoxicity assays in 2D cell cultures have limited capability to predict in vivo outcomes and may trigger unnecessary follow-up animal studies or the loss of promising substances where animal tests are prohibited or not desired. To address this problem, a team of regulatory, academia and industry scientists was established to develop and validate 3D in vitro human skin-based genotoxicity assays for use in testing substances with primarily topical exposure. Validation of the reconstructed human skin micronucleus (RSMN) assay in MatTek Epi-200™ skin models involved testing 43 coded chemicals selected by independent experts, in four US/European laboratories. The results were analysed by an independent statistician according to predefined criteria. The RSMN assay showed a reproducibly low background micronucleus frequency and exhibited sufficient capacity to metabolise pro-mutagens. The overall RSMN accuracy when compared to in vivo genotoxicity outcomes was 80%, with a sensitivity of 75% and a specificity of 84%, and the between- and within-laboratory reproducibility was 77 and 84%, respectively. A protocol involving a 72-h exposure showed increased sensitivity in detecting true positive chemicals compared to a 48-h exposure. An analysis of a test strategy using the RSMN assay as a follow-up test for substances positive in standard in vitro clastogenicity/aneugenicity assays and a reconstructed skin Comet assay for substances with positive results in standard gene mutation assays results in a sensitivity of 89%. Based on these results, the RSMN assay is considered sufficiently validated to establish it as a 'tier 2' assay for dermally exposed compounds and was recently accepted into the OECD's test guideline development program.
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