Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization.
Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.
Sköld
Maria
M
Department of Chemistry, Dermatochemistry and Skin Allergy, Göteborg University, SE-412 96 Göteborg, Sweden.
Börje
Anna
A
Harambasic
Elma
E
Karlberg
Ann-Therese
AT
D000080462:Acyclic Monoterpenes; D000485:Allergens / Q000737:chemistry* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis*; D023441:Local Lymph Node Assay; D039821:Monoterpenes / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D010476:Perfume / Q000737:chemistry; D013997:Time Factors
D000080462:Acyclic Monoterpenes; D000485:Allergens; D039821:Monoterpenes; D010476:Perfume; D006861:Hydrogen Peroxide; C018584:linalool