Title
Assessment of contact allergens by dissociation of irritant and sensitizing properties
Author
Jacobs, J.J.L.
Lehé, C.L.
Cammans, K.D.A.
Das, P.K.
Elliott, G.R.
Publication year
2004
Abstract
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.
Subject
AEC, 3,3-amino-9-ethyl carbazole
Alternative method
AP, alkaline phosphatase
BA, basal accumulation
bLC, LC in the basal epidermal area
Contact allergy
Langerhans cell migration
Organotypic skin explant culture
Skin irritation
Irritant agent
Pyronine
Cell death
Cell migration
Concentration response
Explant
Human
Human tissue
Keratinocyte
Langerhans cell
Patch test
Skin sensitization
Toxicity testing
Animal Testing Alternatives
Cell Movement
Cells, Cultured
Dose-Response Relationship, Drug
Epidermis
Female
Immunization
Langerhans Cells
Cavia porcellus
Sus scrofa
Methyl green, 54327-10-5
Pyronine, 92-32-0
Allergens
Irritants
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DOI
https://doi.org/10.1016/j.tiv.2004.03.007
TNO identifier
238032
ISSN
0887-2333
Source
Toxicology in Vitro, 18 (18), 681-690
Document type
article