title: Assessment of contact allergens by dissociation of irritant and sensitizing properties.
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.
authors.affiliation: AmCOGG, AMC, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. jjljacobs@yahoo.com
authors.forename: John J L
authors.initials: JJ
authors.lastname: Jacobs
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Lehé
authors.forename: Keith D A
authors.initials: KD
authors.lastname: Cammans
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Das
authors.forename: Graham R
authors.initials: GR
authors.lastname: Elliott
mesh_terms: D000485:Allergens / Q000145:classification / Q000633:toxicity*; D000826:Animal Testing Alternatives; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007114:Immunization; D007509:Irritants / Q000145:classification / Q000633:toxicity*; D007801:Langerhans Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D000485:Allergens; D007509:Irritants