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Updated: Feb 3, 2026

Contact Hypersensitivity as a Murine Model of Allergic Contact Dermatitis
Published on: September 26, 2022
Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open
Niels H Bennike1, Lina Palangi2, Johanna Bråred Christensson3,4
1National Allergy Research Centre, Department of Dermatology and Allergy, Copenhagen University Hospital Herlev-Gentofte, Hellerup, Denmark.
Background:
Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported.
Objectives:
To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet.
Methods:
A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 μg/cm2 , was performed.
Results:
Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls).
Conclusions:
Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance.
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