title: Relevance of xenobiotic enzymes in human skin in vitro models to activate pro-sensitizers.
abstract: Skin exposure to sensitizing chemicals can induce allergic reactions. Certain chemicals, so called pro-sensitizers, need metabolic activation to become allergenic. Their metabolic activation occurs in skin cells such as keratinocytes or dendritic cells. These cell types are also incorporated into dermal in vitro test systems used to assess the sensitizing potential of chemicals for humans. In vitrosystems range from single cell cultures to organotypic multi-cellular reconstructed skin models. Until now, their metabolic competence to unmask sensitizing potential of pro-sensitizers was rarely investigated. This review aims to summarize current information on available skin in vitro models and the relevance of xenobiotic metabolizing enzymes for the activation of pro-sensitizers such as eugenol, 4-allylanisole, and ethylendiamine. Among others, these chemicals are discussed as performance standards to validate new coming in vitro systems for their potential to identify pro-sensitizers.
authors.affiliation: BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Jäckh
authors.forename: Eric
authors.initials: E
authors.lastname: Fabian
authors.forename: Bennard
authors.initials: B
authors.lastname: van Ravenzwaay
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis / Q000201:enzymology* / Q000276:immunology; D005054:Eugenol / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D009924:Organ Culture Techniques / Q000379:methods; D010088:Oxidoreductases / Q000276:immunology / Q000378:metabolism*; D057089:Pathology, Molecular / Q000639:trends; D012867:Skin / Q000201:enzymology* / Q000276:immunology*; D015262:Xenobiotics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000485:Allergens; D006241:Haptens; D015262:Xenobiotics; D005054:Eugenol; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases