Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process

Summary Background Citronellol is a frequently used fragrance compound in consumer products. It is present in fragrance mix II, which is used for screening of contact allergy to fragrances. Because of its chemical structure, citronellol could be susceptible to autoxidation. Objectives To compare the behaviour of citronellol with that of the structurally similar compounds linalool and geraniol, in terms of ability to autoxidize, the products formed, and the sensitization potencies of these. Methods Citronellol was exposed to air, and autoxidation was followed by gas chromatography–mass spectrometry (GC–MS) analysis after derivatization of thermolabile compounds. The sensitizing potencies of the oxidation mixture and its major oxidation compounds were examined with the local lymph node assay. Results The concentration of citronellol decreased while the sensitization potency increased in air‐exposed samples over time, with hydroperoxides being identified as the major oxidation products and main skin sensitizers. Conclusions The present study shows the impact of the absence of the 2,3‐double bond in the citronellol structure on the oxidation pathways for formation of oxidation products. The study also shows the usefulness of our new GC–MS method for quantification of the citronellol oxidation products, especially the hydroperoxides. The investigated citronellol hydroperoxides could be important allergens, owing to the high concentrations detected and frequent exposure to citronellol in the population.