Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization.
Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.
Hagvall
Lina
L
Department of Chemistry, Dermatochemistry and Skin Allergy, Göteborg University, SE-412 96 Göteborg, Sweden.
Bäcktorp
Carina
C
Svensson
Sophie
S
Nyman
Gunnar
G
Börje
Anna
A
Karlberg
Ann-Therese
AT
D000080462:Acyclic Monoterpenes; D000388:Air; D000485:Allergens / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000032:analysis / Q000633:toxicity; D007114:Immunization; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010084:Oxidation-Reduction; D010476:Perfume / Q000737:chemistry* / Q000633:toxicity*; D013729:Terpenes / Q000737:chemistry* / Q000633:toxicity*
D000080462:Acyclic Monoterpenes; D000485:Allergens; D010476:Perfume; D013729:Terpenes; D006861:Hydrogen Peroxide; C007836:geraniol