The fragrance chemical β-caryophyllene—air oxidation and skin sensitization

Fragrances are common causes of allergic contact dermatitis. β-Caryophyllene is a sesquiterpene that is used as a fragrance chemical. Analogous to the monoterpenes R-limonene and linalool, it can be expected to autoxidize when air exposed. The aim of the present study was to investigate the autoxidation of β-caryophyllene and to evaluate the effect on the contact allergenic activity. β-Caryophyllene started to oxidize immediately when air exposed and after 5 weeks almost 50% of the original compound was consumed. Caryophyllene oxide was found to be the major oxidation product. Hydroperoxides of β-caryophyllene could not be detected in the oxidation mixture. Caryophyllene oxide was shown to be an allergen of moderate strength and β-caryophyllene air exposed for 10 weeks showed a weak sensitizing capacity in the local lymph node assay. The study reveals that the allergenic activity of β-caryophyllene is affected by autoxidation, but to a lesser extent when compared to R-limonene and linalool. The present findings support our results in clinical studies showing oxidized β-caryophyllene to be a rather rare sensitizer compared to oxidized R-limonene and linalool.