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An in vitro human skin test for assessing sensitization potential

Lookup NU author(s): Dr Shaheda Ahmed, Dr Xiao Wang, Michael FIELDING, Andrew Kerry, Iain Dickinson, Revathy Munuswamy, Professor Anne Dickinson

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Abstract

Sensitization to chemicals resulting in allergy is an important health issue. The current gold-standard method for identification and characterization of skin sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals, (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA the explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity was achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, a chemical that was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFN╬│ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could providethe basis for a robust, reliable and entirely novel approach for characterization of sensitizing activity as a first step in the risk assessment process.


Publication metadata

Author(s): Ahmed SS, Wang XN, Fielding M, Kerry A, Dickinson I, Munuswamy R, Kimber I, Dickinson AM

Publication type: Article

Publication status: Published

Journal: Journal of Applied Toxicology

Year: 2016

Volume: 36

Issue: 5

Pages: 669-684

Print publication date: 01/05/2016

Online publication date: 07/08/2015

Acceptance date: 22/05/2015

ISSN (print): 0260-437X

ISSN (electronic): 1099-1263

Publisher: John Wiley & Sons Ltd

URL: http://dx.doi.org/10.1002/jat.3197

DOI: 10.1002/jat.3197

PubMed id: 26251951


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