Absorption and Effects of Patch Test Preparations of Hydroperoxides of Limonene and Hydroperoxides of Linalool in Human Ex Vivo Skin

Journal article, 2026

Background: Limonene and linalool are fragrance terpenes that undergo autoxidation to sensitizing hydroperoxides. This study assessed the penetration of limonene hydroperoxide and linalool hydroperoxide from patch test preparations in ex vivo human skin samples, alongside analysing the effects of the patch test preparations on the composition of skin lipids, using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Methods: NativeSkin Access human skin biopsies were treated with commercially available patch test preparations ‘hydroperoxides of linalool (1.0%)’ or ‘hydroperoxides of limonene (0.3%)’. ToF-SIMS analysis was performed to assess skin penetration of limonene hydroperoxide and linalool hydroperoxide and assess changes in endogenous lipids. Results: ToF-SIMS analysis showed that limonene hydroperoxide and linalool hydroperoxide remain mainly confined to the stratum corneum. Multivariate analysis indicated that the chemical composition of the stratum corneum differed in the patch test exposed skin in comparison to control samples. There were significant changes in the intensity of several lipid species upon exposure to the patch test exposed skin. Conclusion: Absorption of limonene hydroperoxide and linalool hydroperoxide occurs from patch test preparations. Skin exposure to these preparations can alter the skin lipidome.