An in vitro human skin test for assessing sensitization potential. Issue 5 (7th August 2015)

• Record Type: Journal Article
• Authors: Ahmed, S. S.; Wang, X. N.; Fielding, M.; Kerry, A.; Dickinson, I.; Munuswamy, R.; Kimber, I.; Dickinson, A. M.
• Is Part Of: Journal of applied toxicology. Volume 36:Issue 5(2016)
• Page Start: 669
• Page End: 684
• Publication Date: 2015-08-07
• Subjects: skin sensitization -- local lymph node assay -- in vitro alternative to animal testing -- potency -- T‐cell proliferation -- interferon‐γ -- antigen‐specific priming; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3197
• Languages: English
• ISSNs: 0260-437X

Abstract

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. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : Chemical sensitization resulting in allergy is an important health issue. Here we describe a human in‐vitro skin explant test for sensitization hazard assessment as an alternative approach to using animal models. This method measures histological damage in human skin as a readout of the immune response induced by the test material. We tested 44 chemicals and compared results to the mouse local lymph node assay LLNA and published human sensitization data with a correlation coefficient of 0.90 and 0.91, respectively.