Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open application test (ROAT) study

Contact Dermatitis. 2019 Apr;80(4):208-216. doi: 10.1111/cod.13168. Epub 2018 Dec 12.

Abstract

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.

Keywords: ROAT; allergic contact dermatitis; clinical relevance; contact allergy; dose-response relationship; fragrance substance; limonene hydroperoxides; oxidized limonene.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Allergens / administration & dosage
  • Allergens / adverse effects*
  • Dermatitis, Allergic Contact / diagnosis
  • Dermatitis, Allergic Contact / etiology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hydrogen Peroxide / administration & dosage
  • Hydrogen Peroxide / adverse effects*
  • Male
  • Middle Aged
  • Monoterpenes / administration & dosage
  • Monoterpenes / adverse effects*
  • Patch Tests
  • Perfume / administration & dosage
  • Perfume / adverse effects*

Substances

  • Allergens
  • Monoterpenes
  • Perfume
  • Hydrogen Peroxide