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Fragrance Compound Geraniol Forms Contact Allergens on Air Exposure. Identification and Quantification of Oxidation Products and Effect on Skin Sensitization

Lina Hagvall,^† Carina Bäcktorp,^‡ Sophie Svensson,^§ Gunnar Nyman,^‡ Anna Börje,^† and Ann-Therese Karlberg*^†

Department of Chemistry, Dermatochemistry and Skin Allergy, Gteborg University, SE-412 96 Gteborg, Sweden, Computational Chemistry, Department of Chemistry, Gteborg University, SE-412 96 Gteborg, Sweden, and Occupational and Environmental Medicine, Sahlgrenska Academy and University Hospital, SE-405 30 Gteborg, Sweden

Chem. Res. Toxicol., 2007, 20 (5), pp 807–814

DOI: 10.1021/tx700017v

Publication Date (Web): April 12, 2007

†

Dermatochemistry and Skin Allergy, Göteborg University.

‡

Computational Chemistry, Göteborg University.

Sahlgrenska Academy and University Hospital.

To whom correspondence should be addressed. E-mail: karlberg@chem.gu.se.

Abstract

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.

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