title: Characterization of skin sensitizers from autoxidized citronellol - impact of the terpene structure on the autoxidation process.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, University of Gothenburg, 412 96, Gothenburg, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rudbäck
authors.forename: Lina
authors.initials: L
authors.lastname: Hagvall
authors.forename: Anna
authors.initials: A
authors.lastname: Börje
authors.forename: Ulrika
authors.initials: U
authors.lastname: Nilsson
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
mesh_terms: D000080462:Acyclic Monoterpenes; D000485:Allergens / Q000737:chemistry*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006861:Hydrogen Peroxide / Q000737:chemistry; D023441:Local Lymph Node Assay; D008808:Mice, Inbred CBA; D039821:Monoterpenes / Q000737:chemistry*; D010084:Oxidation-Reduction; D010476:Perfume / Q000737:chemistry*; D027826:Rosa / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry
chemical_list: D000080462:Acyclic Monoterpenes; D000485:Allergens; D039821:Monoterpenes; D010476:Perfume; D013729:Terpenes; D006861:Hydrogen Peroxide; C018584:linalool; C007836:geraniol; C007078:citronellol
keywords: FM II; GC-MS; autoxidation; citronellol; contact allergy; fragrances; prehapten; structure-activity relationships; trimethyl silyl (TMS) derivatives