Limonene and linalool hydroperoxides review: Pros and cons for routine patch testing

Abstract

Limonene and linalool are among the most common fragrance terpenes used in everyday products. They are pre‐haptens, forming hydroperoxides (Lim‐OOHs, Lin‐OOHs) upon oxidation and inducing frequent positive patch test reactions in patients with dermatitis, and yet they are not routinely tested in Europe. This review evaluates current patch testing with Lim‐OOHs and Lin‐OOHs by asking whether hydroperoxide patch testing is warranted, examining the difficulties or challenges related to reading and interpreting hydroperoxide patch test results with currently available material, and assessing their relevance. Studies are increasingly pointing to high percentages of positive reactions in patients consecutively patch tested with these oxidized products. An association between a positive clinical history and a strong patch test reaction has been described, but problems with doubtful/irritant reactions have also been reported. Considering the high frequency of relevant positive reactions, the incorporation of Lim‐OOHs 0.3% and Lin‐OOHs 1% in the baseline series may be justified. Since exposure, sensitization, and elicitation limits of Lim‐OOHs and Lin‐OOHs in the products still need to be better determined, an assessment of previous exposure, possible sensitizations, and reactions may help to improve the clinical assessment.

Patch testing hydroperoxides of limonene and linalool in consecutive patients—Results of the IVDK 2018–2020

“…In the single centre analysis of our data presented in the online supplement, the share of positive and doubtful or irritant reactions to Lim‐OOHs and Lin‐OOHs was found to be very divergent (Tables S1 and S2). Similar heterogeneity of reaction scores had been reported frequently in the literature 6–8,10,11,13–16,29,34 . This circumstance can hardly be explained by local exposure variation to ubiquitous allergens like linalool and limonene 1,2 .…”

“…Similar heterogeneity of reaction scores had been reported frequently in the literature. [6][7][8]10,11,[13][14][15][16]29,34 This circumstance can hardly be explained by local exposure variation to ubiquitous allergens like linalool and limonene. 1,2 Technical and interindividual differences in the interpretations of reaction strengths among different investigators is a more comprehensive explanation, 34 and instability of the test preparations might be another one.…”

The European baseline series and recommended additions: 2023

“…In view of the known skin irritancy of the patch test formulations, difficulties in interpretation and the need for, ideally, a single patch test concentration it was agreed after debate to keep these allergens in the recommended additions to the EBS. 30 The inclusion of two concentrations of each allergen was felt to be important to aid interpretation. Of note, whilst an exposure source to these hydroperoxides remains unclear, 31 challenge in sensitized individuals has shown relevance even in those with doubtful reactions.…”

“…Reactions to both linalool 28 and limonene 29 hydroperoxides have been reviewed and in the group audit produced frequent positive reactions 3,5 leading some members to recommend inclusion in the EBS. In view of the known skin irritancy of the patch test formulations, difficulties in interpretation and the need for, ideally, a single patch test concentration it was agreed after debate to keep these allergens in the recommended additions to the EBS 30 . The inclusion of two concentrations of each allergen was felt to be important to aid interpretation.…”

Contact sensitizations in massage therapists with occupational contact dermatitis: Patch test data of the Information Network of Departments of Dermatology, 2008–2020

“…However, a standardized test preparation of oxidized lavender oil is currently not commercially available. In addition, also patch testing hydroperoxides of limonene and linalool might be important to identify even more fragrance‐sensitized individuals, despite some uncertainties related to their irritant potential and not completely understood clinical relevance in case of positive reactions 48–50 . During the presented study period, however, they were not part of the DKG test series and had hence only been tested in a small number of patients.…”