A sensitive method for determination of allergenic fragrance terpene hydroperoxides using liquid chromatography coupled with tandem mass spectrometry

Rudbäck, Johanna; Islam, M. Nurul; Nilsson, Ulrika; Karlberg, Ann‐Therése

doi:10.1002/jssc.201200855

Cited by 31 publications

(46 citation statements)

References 28 publications

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“…These autoxidation by‐products can be very difficult to identify through traditional analytical techniques. Methods for the detection of some monoterpene hydroperoxides has been recently developed, which usually involve the derivatization of the hydroperoxide species to stable detectable species (Kern et al, ; Rudbaeck, Islam, Nilsson, & Karlberg, ; Rudbaeck, Ramzy, Karlberg, & Nilsson, ).…”

Section: Resultsmentioning

confidence: 99%

In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients

Avonto

Wang

Chittiboyina

et al. 2018

J of Applied Toxicology

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Twenty‐four pure fragrance ingredients of concern as potential skin sensitizers were previously subjected to degradation studies and evaluated using the high throughput with dansyl cysteamine (HTS‐DCYA) method. The experimental results showed that two‐thirds of the 24 fragrance ingredients underwent chemical degradation. In some cases, such degradation was accompanied by an increase in thio‐reactivity. These results prompted us to investigate the reactivity of the same ingredients using the direct peptide reactivity assay (DPRA). In the present work, the 24 chemicals were subjected to forced degradation for 150 days, and evaluated with both DPRA and HTS‐DCYA methods. At the end of the study, four and eight compounds remained non‐reactive in the DPRA and DCYA assay, respectively. Coumarin, benzyl salicylate, benzyl cinnamate and hexyl cinnamal were found unreactive in both assays, while cinnamal, cinnamyl alcohol, hydroxycitronellal and lilial were found negative in the DCYA but positive in the DPRA method. The incongruity in reactivity of these four compounds was attributed to a possible role of pro‐oxidants formed upon degradation, resulting in depletion of peptide without formation of apparent covalent adducts with the test chemical. To validate this hypothesis, the effect of hydrogen peroxide as model pro‐oxidant on both lysine‐ and cysteine‐heptapeptide depletion in the DPRA method was thus investigated. The obtained results showed little effect of oxidative conditions on lysine depletion, while cysteine depletion was significantly affected by concentrations above 1.1 mg/L of hydrogen peroxide. Overall, both in chemico methods confirmed chemical instability should be considered when assessing the skin sensitization potential of (un)known chemicals with alternative methods.

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Section: Resultsmentioning

confidence: 99%

In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients

Avonto

Wang

Chittiboyina

et al. 2018

J of Applied Toxicology

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“…Terpene hydroperoxides are difficult to detect in products, as the chemical structures of terpenes provide only weak chromophores and also low thermostability. We have previously developed a sensitive method using liquid chromatography/electrospray ionization-MS/MS for the quantification of specific hydroperoxides (38). However, in the case of air-exposed citronellol, the separation efficiency of this method was insufficient for accurate determination of all oxidation products.…”

Section: Discussionmentioning

confidence: 99%

Characterization of skin sensitizers from autoxidized citronellol – impact of the terpene structure on the autoxidation process

et al. 2014

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The present study shows the impact of the absence of the 2,3-double bond in the citronellol structure on the oxidation pathways for formation of oxidation products. The study also shows the usefulness of our new GC-MS method for quantification of the citronellol oxidation products, especially the hydroperoxides. The investigated citronellol hydroperoxides could be important allergens, owing to the high concentrations detected and frequent exposure to citronellol in the population.

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“…However, the possibilities for identification of the hydroperoxides have recently improved. A new analytical method has been developed by which it is possible to detect limonene hydroperoxides, linalool hydroperoxides and linalyl acetate hydroperoxides in concentrations from 0.3 µg/ml (0.3 ppm).…”

Section: Prehaptensmentioning

confidence: 99%

Activation of non‐sensitizing or low‐sensitizing fragrance substances into potent sensitizers – prehaptens and prohaptens

et al. 2013

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SummaryExperimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety.Key words: abiotic and biotic activation; autoxidation; directive 76/768/ECC; fragrance allergens; prehaptens; prohaptens; SCCS; scientific opinion.Many fragrance substances act as haptens, that is, low molecular weight chemicals that are immunogenic when attached to a carrier protein in the skin. This means that the substances can directly react with skin proteins, owing to inherent chemical properties. Experimental and clinical studies have shown that there are also fragrance substances that act as prehaptens or prohaptens, forming Accepted for publication 29 June 2013 allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, and thus increasing the risk of sensitization.A prehapten is a chemical that is itself non-sensitizing or low-sensitizing, but that is transformed into a hapten outside the skin by chemical transformation (air

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A sensitive method for determination of allergenic fragrance terpene hydroperoxides using liquid chromatography coupled with tandem mass spectrometry

Cited by 31 publications

References 28 publications

In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients

In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients

Characterization of skin sensitizers from autoxidized citronellol – impact of the terpene structure on the autoxidation process

Activation of non‐sensitizing or low‐sensitizing fragrance substances into potent sensitizers – prehaptens and prohaptens

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