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Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products

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Abstract

On prolonged exposure to air, linalool can form sensitizing hydroperoxides. Positive hydroperoxide patch tests in dermatitis patients have frequently been reported, but their relevance has not been established. Owing to a lack of analytical methods and data, it is unclear from which sources the public might be exposed to sufficient quantities of hydroperoxides for induction of sensitization to occur. To address this knowledge gap, we developed analytical methods and performed stability studies for fine fragrances and deodorants/antiperspirants. In parallel, products recalled from consumers were analysed to investigate exposure to products used in everyday life. Liquid chromatography–mass spectrometry with high mass resolution was found to be optimal for the selective and sensitive detection of the organic hydroperoxide in the complex product matrix. Linalool hydroperoxide was detected in natural linalool, but the amount was not elevated by storage in a perfume formulation exposed to air. No indication of hydroperoxide formation in fine fragrances was found in stability studies. Aged fine fragrances recalled from consumers contained a geometric mean linalool concentration of 1,888 μg/g and, corrected for matrix effects, linalool hydroperoxide at a concentration of around 14 μg/g. In antiperspirants, we detected no oxidation products. In conclusion, very low levels of linalool hydroperoxide in fragranced products may originate from raw materials, but we found no evidence for oxidation during storage of products. The levels detected are orders of magnitude below the levels inducing sensitization in experimental animals, and these results therefore do not substantiate a causal link between potential hydroperoxide formation in cosmetics and positive results of patch tests.

Formation of hydroperoxides from linalool and detection by LC-MS with high resolution

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Abbreviations

GC:

Gas chromatography

HR-MS:

High-resolution mass spectrometry

LC:

Liquid chromatography

LOD:

Limit of detection

LOQ:

Limit of quantification

MS:

Mass spectrometry

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Acknowledgments

We thank Thierry Granier for synthesizing linalool hydroperoxide and Tina Haupt for skilful laboratory assistance.

Conflict of interest

This work was funded entirely by Givaudan Schweiz and Givaudan France. The authors are all employees of Givaudan but have received no compensation other than their salaries for this work and declare no other conflict of interest.

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Authors and Affiliations

  1. Analytical Chemistry, Givaudan Schweiz AG, Ueberlandstrasse 138, 8600, Duebendorf, Switzerland

    Susanne Kern

  2. Perfume Analysis, Givaudan France SAS, 19-23 Voie des Bans, 95102, Argenteuil, France

    Hafida Dkhil & Prisca Hendarsa

  3. RAPS Fragrance Toxicology, Givaudan International SA, 5 Chemin de la Parfumerie, 1214, Vernier, Switzerland

    Graham Ellis

  4. Biosciences, Givaudan Schweiz AG, Ueberlandstrasse 138, 8600, Duebendorf, Switzerland

    Andreas Natsch

Authors
  1. Susanne Kern
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  2. Hafida Dkhil
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  3. Prisca Hendarsa
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  4. Graham Ellis
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Correspondence to Andreas Natsch.

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Kern, S., Dkhil, H., Hendarsa, P. et al. Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products. Anal Bioanal Chem 406, 6165–6178 (2014). https://doi.org/10.1007/s00216-014-8066-3

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  • DOI: https://doi.org/10.1007/s00216-014-8066-3

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