Further development of the EpiDerm™ 3D reconstructed human skin micronucleus (RSMN) assay

• Published in: Mutation research Vol. 673; no. 2; pp. 92 - 99
• Main Authors: Mun, Greg C., Aardema, Marilyn J., Hu, Ting, Barnett, Brenda, Kaluzhny, Yulia, Klausner, Mitchell, Karetsky, Viktor, Dahl, Erica L., Curren, Rodger D.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17-03-2009; Elsevier
• Subjects: 3D human skin model; Animal Testing Alternatives - methods; Biological and medical sciences; Calibration; Cytochalasin B - pharmacology; Dose-Response Relationship, Drug; Epidermis - drug effects; Epidermis - physiology; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotoxicity; Humans; In vitro skin micronucleus assay; Medical sciences; Micronucleus Tests - methods; Mutagens - pharmacology; Sensitivity and Specificity; Skin - cytology; Skin Irritancy Tests - methods; Time Factors; Tissue Engineering - methods; Toxicology; European Union; In vitro skin micronucleus assay; 3D human skin model; Genotoxicity; Human; Toxicity; Mutagenicity testing; In vitro; Toxicology; Micronucleus; Development; Genetics; Models; Skin
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/j.mrgentox.2008.12.004

The upcoming ban on testing of cosmetics in animals by the European Union's 7th Amendment to the Cosmetics Directive will require genotoxicity safety assessments of cosmetics ingredients and final formulations to be based primarily on
in vitro genotoxicity tests. The current
in vitro test battery produces an unacceptably high rate of false positives, and used by itself would effectively prevent the use and development of many ingredients that are actually safe for human use. To address the need for an
in vitro test that is more predictive of genotoxicity
in vivo, we have developed an
in vitro micronucleus assay using a three-dimensional human reconstructed skin model (EpiDerm™) that more closely mimics the normal dermal exposure route of chemicals. We have refined this model and assessed its ability to predict genotoxicity of a battery of chemicals that have been previously classified as genotoxins or non-genotoxins based on
in vivo rodent skin tests. Our reconstructed skin micronucleus assay correctly identified 7 genotoxins and 5 non-genotoxins, demonstrating its potential to have a higher predictive value than currently available
in vitro genotoxicity tests, and its utility as part of a comprehensive
in vitro genotoxicity testing strategy.