The use of ex vivo human skin tissue for genotoxicity testing

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• 作者：Astrid A. Reus^a ; Mustafa Usta^a ; Cyrille A.M. Krul^b ; ^{cyrille.krul@tno.nl}
• 关键词：Genotoxicity testing ; Ex vivo human skin ; Comet assay
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2012
• 期刊代码：58_0041008x
• 类别：pha
• 出版时间：1 June, 2012
• 卷：261
• 期：2
• 页码：154-163
• 文件大小：473 K

摘要

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.