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Sensitization potential and potency of terpene hydroperoxides in the cocultured activation test method
Author(s) -
Hennen Jennifer,
Silva e Sousa Marta,
Sahli Fatma,
Lichter Jutta,
Lepoittevin JeanPierre,
GiménezArnau Elena,
Blömeke Brunhilde
Publication year - 2019
Publication title -
contact dermatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.524
H-Index - 96
eISSN - 1600-0536
pISSN - 0105-1873
DOI - 10.1111/cod.13286
Subject(s) - potency , chemistry , sensitization , local lymph node assay , cumene hydroperoxide , cd86 , hacat , citronellol , allergic contact dermatitis , limonene , in vitro , biochemistry , stereochemistry , pharmacology , immunology , biology , chromatography , allergy , geraniol , gene , essential oil , phenotype , catalysis
Abstract Background Positive patch test reactions to mixtures of oxidized terpenes containing allergenic hydroperoxides are frequently reported. However, human sensitization data for these hydroperoxides are not available. Objectives To analyse and evaluate the human sensitization potential and potency of hydroperoxides in vitro by using human cells. Materials/Methods Limonene‐1‐hydroperoxide, limonene‐2‐hydroperoxide, citronellol‐7‐hydroperoxide, cumene hydroperoxide, 1‐(1‐hydroperoxy‐1‐methylethyl)cyclohexene and mixtures of citronellol hydroperoxides (isomers at positions 6 and 7) and linalool hydroperoxides (isomers at positions 6 and 7) were studied. All compounds were synthesized except for cumene hydroperoxide, which was commercially available. Their potential and potency to activate dendritic cells (DCs) was evaluated by measuring the upregulation of CD86 and CD54 on THP‐1 cells upon exposure in the cocultured activation test (COCAT) consisting of HaCaT cells (human keratinocyte cell line) and THP‐1 monocytes (as a surrogate for DCs). Results Hydroperoxides upregulated CD86 and/or CD54 on cocultured THP‐1 cells in a concentration‐dependent manner. The results are comparable with their sensitization potency ranking in predictive animal models. Conclusions For the first time, the human sensitization potential and potency of several hydroperoxides were determined by the use of human cells and the COCAT method.