Assessment of contact allergens by dissociation of irritant and sensitizing properties
article
The human organotypic skin explant culture (hOSEC) model is a promising alternative in vitro model for screening contact allergens. In this model, the chemical-induced migration of Langerhans cells (LCs) out of the epidermis, evaluated after a 24-h exposure period, is used as a measure of sensitizer potential. As skin irritants can also induce LC migration it is essential that concentrations of test chemicals are used that are not even weakly irritant. Using the hOSEC irritation model chemicals are classified as weak irritants if they are toxic after a 48-h exposure period. Toxicity is determined by methyl green-pyronine (MGP) staining of hOSEC. We studied three frequently used non-sensitizing skin irritants and six potent or frequent human sensitizers in a dose-response. A complete discrimination between non-sensitizers and contact sensitizers was obtained for the chemicals tested when the concentrations used were lower than the weak irritant concentrations. Frequency of positive allergen reactions in patch test of human populations correlated with the difference between weak irritant concentrations and the lowest concentration inducing significant LC migration. Sensitizer potency correlated with chemical irritancy as determined by keratinocyte death. For the compounds tested, the hOSEC model predicted allergenicity in humans better than the guinea pig maximization test and the mouse local lymph node assay. © 2004 Elsevier Ltd. All rights reserved.
Topics
AEC, 3,3-amino-9-ethyl carbazoleAlternative methodAP, alkaline phosphataseBA, basal accumulationbLC, LC in the basal epidermal areaContact allergyLangerhans cell migrationOrganotypic skin explant cultureSkin irritationIrritant agentPyronineCell deathCell migrationConcentration responseExplantHumanHuman tissueKeratinocyteLangerhans cellPatch testSkin sensitizationToxicity testingAnimal Testing AlternativesCell MovementCells, CulturedDose-Response Relationship, DrugEpidermisFemaleImmunizationLangerhans CellsCavia porcellusSus scrofaMethyl green, 54327-10-5Pyronine, 92-32-0AllergensIrritants
TNO Identifier
238032
ISSN
08872333
Source
Toxicology in Vitro, 18(5), pp. 681-690.
Pages
681-690
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