The use of ex vivo human skin tissue for genotoxicity testing

Reus, Astrid A.; Usta, Mustafa

doi:10.1016/J.TAAP.2012.03.019

Title: The use of ex vivo human skin tissue for genotoxicity testing

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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 reflectedmore »« less

Authors:

Reus, Astrid A.; Usta, Mustafa ^[1]

TNO Triskelion BV, Utrechtseweg 48, 3704 HE, Zeist (Netherlands)

Publication Date:: Fri Jun 01 00:00:00 EDT 2012

OSTI Identifier:: 22215324

Resource Type:: Journal Article

Journal Name:: Toxicology and Applied Pharmacology

Additional Journal Information:: Journal Volume: 261; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; ACCURACY; ANIMAL TISSUES; EVALUATION; IN VITRO; IN VIVO; SAFETY ANALYSIS; SENSITIVITY; SKIN; SPECIFICITY; SURGERY; TOXICITY

Citation Formats


                    Reus, Astrid A., Usta, Mustafa, and Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl. The use of ex vivo human skin tissue for genotoxicity testing.  United States: N. p., 2012. 
        Web.  doi:10.1016/J.TAAP.2012.03.019.

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                    Reus, Astrid A., Usta, Mustafa, & Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl. The use of ex vivo human skin tissue for genotoxicity testing.  United States.  https://doi.org/10.1016/J.TAAP.2012.03.019

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                    Reus, Astrid A., Usta, Mustafa, and Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl. 2012.  
        "The use of ex vivo human skin tissue for genotoxicity testing".  United States.  https://doi.org/10.1016/J.TAAP.2012.03.019.

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@article{osti_22215324,

  title        = {The use of ex vivo human skin tissue for genotoxicity testing},

  author       = {Reus, Astrid A. and Usta, Mustafa and Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl},

  abstractNote = {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. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method is suitable for evaluation of chemicals that are in contact with skin.},

  doi          = {10.1016/J.TAAP.2012.03.019},

  url          = {https://www.osti.gov/biblio/22215324},
  journal      = {Toxicology and Applied Pharmacology},

  issn         = {0041-008X},

  number       = 2,

  volume       = 261,

  place        = {United States},

  year         = {Fri Jun 01 00:00:00 EDT 2012},

  month        = {Fri Jun 01 00:00:00 EDT 2012}

}

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