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A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the human biomonitoring of non-occupational exposure to the fragrance 2-(4-tert-butylbenzyl)propionaldehyde (lysmeral)

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Abstract

2-(4-tert-Butylbenzyl)propionaldehyde also known as lysmeral, lilial, or lily aldehyde (CAS No. 80-54-6) is a synthetic odorant mainly used as a fragrance in a variety of consumer products like cleaning agents, fine fragrances, cosmetics, and air fresheners. Due to its broad application in various fields, lysmeral was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). A method based on ultra-high pressure liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of potential biomarkers of lysmeral in human urine samples. Sample cleanup was performed by liquid-liquid extraction (LLE). Quantification was achieved by standard addition using stable isotope-labeled, authentic reference standards. The method is characterized by its robustness, reliability, and excellent sensitivity as proven during method validation according to approved standard guidelines. The following five lysmeral metabolites were identified as potential biomarkers of exposure for lysmeral in human urine samples: lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, tert-butylbenzoic acid (TBBA), and tert-butylhippuric acid (TBHA). The determination of lysmerol required derivatization with 3-nitrophthalic acid anhydride and showed the lowest limit of detection (LOD) and limit of quantification (LOQ) in urine (0.035 and 0.10 μg/L, respectively). LOD and LOQ for the other metabolites were in the range of 0.12–0.15 and 0.36–0.45 μg/L, respectively. Accuracy for all analytes was in the range of 90–110 %. Intra- and inter-day precision was in the range of 5–10 %, except for TBHA, for which the coefficient of variation was unacceptably high (>20 %) and therefore excluded from the method. The method was applied to urine samples of 40 adult volunteers. The four remaining lysmeral metabolites were detectable in most of the 40 urine samples in the following order according to quantity excreted: TBBA >> lysmerol ≈ lysmerylic acid > hydroxy-lysmerylic acid. In conclusion, we successfully developed a biomonitoring method for the assessment of the exposure to lysmeral in the general population. The method is characterized by its precision, robustness, and accuracy. The metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, and TBBA turned out to be suitable biomarkers of exposure to lysmeral, either alone or in combination with one or more of the other metabolites. Sensitivity was found to be sufficient for assessing the background exposure to this chemical in the general population.

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References

  1. Fráter G, Bajgrowicz JA, Kraft P. Fragrance chemistry. Tetrahedron. 1998;54(27):7633–703.

    Article  Google Scholar 

  2. Sgorbini B, Ruosi MR, Cordero C, Liberto E, Rubiolo P, Bicchi C. Quantitative determination of some volatile suspected allergens in cosmetic creams spread on skin by direct contact sorptive tape extraction-gas chromatography-mass spectrometry. J Chromatogr A. 2010;1217(16):2599–605.

    Article  CAS  Google Scholar 

  3. Heisterberg MV, Menné T, Johansen JD. Contact allergy to the 26 specific fragrance ingredients to be declared on cosmetic products in accordance with the EU cosmetics directive. Contact Dermatitis. 2011;65(5):266–75.

    Article  CAS  Google Scholar 

  4. ECHA (European Chemicals Agency). 2-(4-tert-butylbenzyl)propionaldehyde. 2016. Available from http://echa.europa.eu/substance-information/-)substanceinfor/100.001.173. Last assessed 19 May 2016.

  5. Buckley DA. Fragrance ingredient labelling in products on sale in the U.K. Br J Dermatol. 2007;157(2):295–300.

    Article  CAS  Google Scholar 

  6. Rastogi SC, Johansen JD, Frosch P, Menne T, Bruze M, Lepoittevin JP, et al. Deodorants on the European market: quantitative chemical analysis of 21 fragrances. Contact Dermatitis. 1998;38(1):29–35.

    Article  CAS  Google Scholar 

  7. Schnuch A, Uter W, Dickel H, Szliska C, Schliemann S, Eben R, et al. Quantitative patch and repeated open application testing in hydroxyisohexyl 3-cyclohexene carboxaldehyde sensitive-patients. Contact Dermatitis. 2009;61(3):152–62.

    Article  CAS  Google Scholar 

  8. Bader M, Barr D, Goen T, Schaller KH, Scherer G, Angerer J. Reliability criteria for analytical methods. In: Hartwig A, Angerer J, editors. Biomonitoring methods (part IV). The MAK-collection for occupational health and safety. Weinheim: Wiley-VCH; 2010. p. 55–101.

    Google Scholar 

  9. Food and Drug Administration (FDA). Guidance for industry—bioanalytical method validation. 2001 http://www.fdagov/downloads/Drugs/Guidances/ucm070107pdf. Accessed 22 Jul 2014.

  10. Blaszkewicz M, Liesenhoff-Henze K. Creatinine in urine. In: Hartwig A, Angerer J, editors. Biomonitoring methods (part IV). The MAK-collection for occupational health and safety. Weinheim: Wiley-VCH; 2010. p. 169–84.

    Google Scholar 

  11. Quirke JM, Adams CL, van Berkel GJ. Chemical derivatization for electrospray ionization mass spectrometry. 1. Alkyl halides, alcohols, phenols, thiols, and amines. Anal Chem. 1994;66(8):1302–15.

    Article  CAS  Google Scholar 

  12. Di Sotto A, Maffei F, Hrelia P, Di Giacomo S, Pagano E, Borrelli F, et al. Genotoxicity assessment of some cosmetic and food additives. Regul Toxicol Pharmacol. 2014;68(1):16–22.

    Article  Google Scholar 

  13. Larsen WG. Allergic contact dermatitis to the fragrance material lilial. Contact Dermatitis. 1983;9(2):158–9.

    Article  CAS  Google Scholar 

  14. Diel F, Fischer M, Kamsteeg J, Schubert H, Weber KM. List of REACH allergens. Umwelt Gesundheit. 2006;2:47–53.

    Google Scholar 

  15. del Nogal Sanchez M, Perez-Pavon JL, Moreno CB. Determination of suspected allergens in cosmetic products by headspace-programmed temperature vaporization-fast gas chromatography-quadrupole mass spectrometry. Anal Bioanal Chem. 2010;397(6):2579–91.

    Article  Google Scholar 

  16. Klaschka U, von der Ohe PC, Bschorer A, Krezmer S, Sengl M, Letzel M. Occurrences and potential risks of 16 fragrances in five German sewage treatment plants and their receiving waters. Environ Sci Pollut Res Int. 2013;20(4):2456–71.

    Article  CAS  Google Scholar 

  17. Leijs H, Broekhans J, van Pelt L, Mussinan C. Quantitative analysis of the 26 allergens for cosmetic labeling in fragrance raw materials and perfume oils. J Agric Food Chem. 2005;53(14):5487–91.

    Article  CAS  Google Scholar 

  18. Villa C, Gambaro R, Mariani E, Dorato S. High-performance liquid chromatographic method for the simultaneous determination of 24 fragrance allergens to study scented products. J Pharm Biomed. 2007;44(3):755–62.

    Article  CAS  Google Scholar 

  19. National Institute of Health (NIH) TDNT. p-tert-Butylbenzoic acid. 2016. http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+98-73-7. Accessed 25 Apr 2016.

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Acknowledgments

The development of this method of analyzing lysmeral metabolites in human urine (including the synthesis of reference compounds) was funded by the German chemical industry. The method was developed during an ongoing 10-year project on human biomonitoring. The project is a cooperation agreed in 2010 between the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the Verband der chemischen Industrie e.V. (German Chemical Industry Association (VCI)); it is administered by the Federal Environment Agency (UBA). Experts from government authorities, industry, and science accompany the project in selecting substances and developing methods. We thank Dr. Holger Koch for directing the human study and providing corresponding samples.

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Authors and Affiliations

  1. Analytisch-Biologisches Forschungslabor GmbH, Goethestrasse 20, 80336, Munich, Germany

    Nikola Pluym, Dusan Krnac, Gerhard Gilch, Max Scherer & Gerhard Scherer

  2. BASF SE, GUP/P - Z570, 67056, Ludwigshafen, Germany

    Edgar Leibold

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  1. Nikola Pluym
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  2. Dusan Krnac
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  3. Gerhard Gilch
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  4. Max Scherer
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  5. Edgar Leibold
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  6. Gerhard Scherer
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Correspondence to Gerhard Scherer.

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Pluym, N., Krnac, D., Gilch, G. et al. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the human biomonitoring of non-occupational exposure to the fragrance 2-(4-tert-butylbenzyl)propionaldehyde (lysmeral). Anal Bioanal Chem 408, 5873–5882 (2016). https://doi.org/10.1007/s00216-016-9702-x

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  • DOI: https://doi.org/10.1007/s00216-016-9702-x

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