Title
The use of ex vivo human skin tissue for genotoxicity testing
Author
TNO Kwaliteit van Leven
Reus, A.A.
Usta, M.
Krul, C.A.M.
Publication year
2012
Abstract
As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air-liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. © 2012 Elsevier Inc.
Subject
Comet assay
Ex vivo human skin
Genotoxicity testing
Biomedical Innovation
Healthy Living
Triskelion BV Life
TAP - Toxicology and Applied Pharmacology RAPID - Risk Analysis for Products in Development
TNO Bedrijven
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DOI
https://doi.org/10.1016/j.taap.2012.03.019
TNO identifier
460442
ISSN
0041-008X
Source
Toxicology and Applied Pharmacology, 261 (261), 154-163
Document type
article