Sensitization potential and potency of terpene hydroperoxides in the COCAT method.

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.