A two-dimensional non-comprehensive reversed/normal phase high-performance liquid chromatography/tandem mass spectrometry system for determination of limonene and linalool hydroperoxides

Ramzi, Ahmed Ibrahim; Ahmadi, Seyyed Hamid; Sadiktsis, Ioannis; Nilsson, Ulrika

doi:10.1016/j.chroma.2018.06.056

Cited by 24 publications

(27 citation statements)

References 31 publications

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“…25 A recently published study using a method for selective analysis of hydroperoxides in perfumes investigated the content of limonene-2-hydroperoxide in 10 fine fragrances kept and used under normal conditions by consumers for 1 to 5 years after purchase. 26 In four of these fine fragrances, limonene-2-hydroperoxide was detected at concentrations up to 56 ppm, but the levels of the more sensitizing limonene-1-hydroperoxide were not determined. In the current study, we estimated the dose, following repeated exposure in the ROAT, that will elicit allergic contact dermatitis in 10% of sensitized individuals to be 0.20 μg of Lim-OOHs/cm 2 The challenges encountered in quantifying the contents of Lim-OOHs in both the added limonene and the finished consumer product are reflected in the current legislation and industry guidelines.…”

Section: Discussionmentioning

confidence: 96%

“…The selected concentrations and doses were chosen to simulate real‐life daily exposure to limonene in a hydroalcoholic leave‐on cosmetic product; however, quantitative assessment of exposure to Lim‐OOHs in commercial fragranced consumer products containing limonene is challenging . A recently published study using a method for selective analysis of hydroperoxides in perfumes investigated the content of limonene‐2‐hydroperoxide in 10 fine fragrances kept and used under normal conditions by consumers for 1 to 5 years after purchase . In four of these fine fragrances, limonene‐2‐hydroperoxide was detected at concentrations up to 56 ppm, but the levels of the more sensitizing limonene‐1‐hydroperoxide were not determined.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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/cm 2 , 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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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…The quantification of hydroperoxides in consumer products is challenging, owing to low thermal stability and their lack of chromophores. [18][19][20][21] The link between exposure to the hydroperoxides and allergic contact dermatitis has been well documented in only a few cases. For example, a 7-year-old girl developed severe eyelid dermatitis after using a shampoo that contained linalool and low levels (0.2 μg/g) of linalool hydroperoxides.…”

Section: Introductionmentioning

confidence: 99%

Sensitization potential and potency of terpene hydroperoxides in the cocultured activation test method

et al. 2019

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“…We did complete this study by analysing an aftershave sample, which was received from the University of Stockholm. It had previously been analyzed by a novel heart-cut 2D LC-MS method 32 . This sample (labelled Sample 6 in the publication; aged > 5 years) was selected as it contained the highest HP level from a series of market products by this previous analysis and the highest ever reported terpene HP concentration in a commercial sample, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, one sample of an aftershave was received from the University of Stockholm. This sample had recently been found to contain a significant level of linalool-6-OOH by a new twodimensional LC-MS method 32 , and it was reanalysed by the four different methods from our method evaluation and validation studies to link our investigations with those published data on the same sample. However, this sample does not form part of the 'random' sample collection, as it was selected from a larger number of random samples based on a previous analytical result.…”

Section: Methodsmentioning

confidence: 99%

Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: An analytical market surveillance

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Nägelin²,

Leijs³

et al. 2019

Food and Chemical Toxicology

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et al.. Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: an analytical market surveillance. Food and Chemical Toxicology, Elsevier, 2019, 127, pp. AbstractReports about positive patch test reactions to oxidized linalool and limonene remain frequent. These terpenes are fragrance ingredients widely present in consumer products. The main sensitizing ingredients in the oxidation mixtures of these terpenes are hydroperoxides (HP). Currently, it is not clear whether fragranced consumer products are a relevant exposure source for HP. Analytical methodologies had been developed and validated in blind-coded ring-trials in multiple laboratories allowing quantification of the HP in different consumer products. The analytical approach had been successfully transferred to an independent third party laboratory and was now used in the analytical investigation of consumer products. In total, 104 products were analysed with a method based on hydroperoxide reduction followed by GC-MS. Samples included aged and new samples from the same brand, products which were suspected by patch test positive patients to elicit their symptoms and some products containing high levels of essential oils. Only four samples contained > 50 µg/g of at least one of four analysed HP by the reduction method. Confirmatory analysis by LC-MS methods directly testing for presence of the hydroperoxide indicated that levels are even below those observed by the conservative reduction method. The samples retrieved from patch-test positive samples were below detection limit for all four target analytes by GC-MS, and LC analysis with three methods confirmed this negative result. This independent market surveillance indicates that concentrations of HP in investigated consumer products and patient products are orders of magnitude below reported sensitizing or elicitating doses. No evidence for hydroperoxide accumulation in aged products or products used by patients could be found. The nature and source of the inducing agent responsible for the frequent positive patch test reactions to oxidized terpenes remains elusive. The analytical work with GC-MS at SOLVIAS was funded by IDEA. The analysis by LC-MS was funded by the three participating laboratories (Firmenich, IFF and Givaudan). The study management was funded by IDEA. Manuscript writing was funded by Givaudan Schweiz AG. The synthesis of reference standards and sample collection was funded by the IDEA project. We thankfully acknowledge all donors of samples, in particular the Spanish dermatological network collecting samples from patients (GEIDAC, Grupo Español de Investigación en Dermatitis Alérgica de Contacto). Other members of the IDEA HP taskforce are gratefully acknowledged for fruitful discussions during various workshops. IDEA management team: Hans J. Bender; Industry scientists: Alain Chaintreau, Hugues Brévard and Neil Owen; Scientists from Academia:

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A two-dimensional non-comprehensive reversed/normal phase high-performance liquid chromatography/tandem mass spectrometry system for determination of limonene and linalool hydroperoxides

Cited by 24 publications

References 31 publications

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

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

Sensitization potential and potency of terpene hydroperoxides in the cocultured activation test method

Exposure source for skin sensitizing hydroperoxides of limonene and linalool remains elusive: An analytical market surveillance

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