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An international multicentre study on the allergenic activity of air‐oxidized R‐limonene
Authors:Johanna Bråred Christensson  Klaus E. Andersen  Magnus Bruze  Jeanne D. Johansen  Begoña Garcia‐Bravo  Ana Giménez‐Arnau  Chee‐Leok Goh  Rosemary Nixon  Ian R. White
Affiliation:1. Department of Dermatology, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden;2. Dermatochemistry and Skin Allergy, Department of Chemistry and Molecular Biology, University of Gothenburg, 412 96 Gothenburg, Sweden;3. Department of Dermatology, Odense University Hospital, University of Southern Denmark, DK‐5000 Odense, Denmark;4. Department of Occupational and Environmental Dermatology, Sk?ne University Hospital, Lund University, 205 02 Malm?, Sweden;5. The National Allergy Research Centre, Department of Dermato‐Allergology, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark;6. Department of Dermatology, University Hospital Virgen Macarena, 41007 Seville, Spain;7. Department of Dermatology, Hospital del Mar, Universitat Autònoma, 08003 Barcelona, Spain;8. National Skin Centre, 308205 Singapore, Singapore;9. Occupational Dermatology Research and Education Centre, Skin and Cancer Foundation, Melbourne 3053, Australia;10. Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK
Abstract:Background. Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R‐limonene has previously been patch tested in multicentre studies, giving 2–3% positive patch test reactions in consecutive patients. Objectives. To investigate whether oxidized R‐limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim‐OOHs), could be a useful tool for the detection of contact allergy in an international setting. Methods. Oxidized R‐limonene 3.0% (Lim‐OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. Results. Overall, 5.2% (range 2.3–12.1%) of the patients showed a positive patch test reaction to oxidized R‐limonene. Doubtful reactions were found in 7.0% of the patients (range 0–24%). Few irritant reactions were seen. Conclusions. Oxidized R‐limonene at 3.0% pet. with a specified content of Lim‐OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R‐limonene would not be informed of their fragrance allergy if this specific test had not been performed.
Keywords:allergic contact dermatitis  autoxidation  CAS 5989‐27‐5  dose per unit area  fragrance allergy  hydroperoxides  limonene  oxidation products  patch test concentration  patch testing  terpenes
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