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A new prediction model for distinguishing skin sensitisers based on IL-18 release from reconstructed epidermis: enhancing the assessment of a key event in the skin sensitisation adverse outcome pathway


Journal of Dermatology & Cosmetology
Eric Andres,1 Mouctar Barry,1 Alexander Hundt,1 Christophe Dini,1 Pierre-Jacques Ferret2

Abstract

1.1 Objective: The aim of this study was the evaluation of the prediction capacities of the rhe/IL-18 assay for the identification of contact sensitisers using the EpiCSTM reconstructed epidermis model by applying a newly developed prediction model.
1.2 Methods: 20 references substances were tested following the rhe/IL-18 protocol. Each batch of reconstructed epidermis was characterised with respect to its basal level of IL-18 release by the inclusion of unexposed and solvent only controls. The data were interpreted using a new prediction model based on the ratio of the IL-18 concentration at maximum response to test item concentration. The prediction performance was compared with that of previously published prediction models based on the differential release of IL-18 compared to the solvent control.
1.3 Results: The EpiCS test system provided remarkably low and stable levels of basal and solvent induced IL-18 release over 10 batches of epidermises. The performance of the newly developed prediction model was found to be comparable to previously published results and differences were examined in terms of balance between positive and negative substance identification between the tried prediction models.
1.4 Conclusion: The results indicate that the prediction model provides promising performance when applied to the data of the rhe/IL-18 assay, with levels of sensitivity, specificity and accuracy similar to OECD validated assays, albeit obtained with a reduced number of substances. Therefore, further testing of a wider range of substances type should be envisaged.

Keywords

animal testing alternatives, toxicity tests methods, allergens toxicity, epidermis, drug effects, skin, keratinocytes, skin tests, sensitisation, interleukin-18 immunology, haptens, toxicity, epidermis, immunology, humans

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