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J Appl Toxicol. 2016 May;36(5):669-84. doi: 10.1002/jat.3197. Epub 2015 Aug 7.

An in vitro human skin test for assessing sensitization potential.

Author information

1
Alcyomics Ltd, Bulman House, Regent Centre, Gosforth, Newcastle-upon-Tyne, NE3 3LS, UK.
2
Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK.
3
Faculty of Life Sciences, University of Manchester, Manchester, UK.

Abstract

Sensitization to chemicals resulting in an 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 the 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 skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were 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, which 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 IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process.

KEYWORDS:

T-cell proliferation; antigen-specific priming; in vitro alternative to animal testing; interferon-γ; local lymph node assay; potency; skin sensitization

PMID:
26251951
DOI:
10.1002/jat.3197
[Indexed for MEDLINE]

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