Limonene hydroperoxide analogues differ in allergenic activity
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Updated: Jun 27, 2026

Humanized Mediator Release Assay as a Read-Out for Allergen Potency
Published on: June 29, 2021
Johanna Bråred Christensson1, Staffan Johansson, Lina Hagvall
1Dermatochemistry and Skin Allergy, Department of Chemistry, University of Gothenburg, SE-412 96 Gothenburg, Sweden. jacpth01@geh.regionh.dk
Background:
The fragrance terpene R-limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing.
Objectives:
This study investigates the sensitizing potencies of ox. and non-ox. limonene and of structurally closely related limonene hydroperoxides. The clinical importance of the difference in sensitizing potency of two hydroperoxides in autoxidized limonene was studied.
Patients/Methods:
Ox. and non-ox. limonene were investigated in the murine local lymph node assay (LLNA). Limonene hydroperoxides were investigated using a modified LLNA involving non-pooled lymph nodes and statistical calculations; patch testing of patients with known contact allergy to ox. limonene was performed.
Results:
A marked increase in the sensitizing potency of ox. limonene compared with that of pure limonene was observed in the LLNA. One analogue, limonene-1-hydroperoxide, was a significantly more potent sensitizer than the other hydroperoxides and gave more positive test reactions in the allergic patients.
Conclusions:
The results support that hydroperoxides have a specific reactivity indicating that oxygen-centred radicals are important in hapten-protein complex formation of hydroperoxides. The primary oxidation products of ox. limonene, the hydroperoxides, have an important impact on the sensitizing capacity of the oxidation mixture.
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