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Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure

  • Toxicokinetics and Metabolism
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Abstract

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9 h under real-life conditions (2 mg/cm2 body surface area; double re-application; corresponding to 3.8 g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray–ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525 µg/g and 213 µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8 h after first application. First-phase terminal half-lives were 8–9 h. For 5OH-EHS, a second-phase terminal half-life could be determined (87 h). EHS and 5OH-EHS showed a faster elimination with 70–80% of the overall excretion occurring within 24 h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24 h reached up to 334 µg EHS and 124 µg of 5OH-EHS. Simulated real-life sunscreen use for 1 day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.

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Acknowledgements

The authors thank the Bavarian State Office for Health and Food Safety for the determination of the UV filter concentrations of the sunscreen product and all study subjects for their participation. We would also like to take this opportunity to thank the staff of the Institute of Occupational, Social and Environmental Medicine, Erlangen, for their support during the conduct of the field study.

Funding

This study was carried out with financial support by the Bavarian State Ministry for Health and Care. The sponsor was not involved in the study design, collection, analysis or interpretation of data and in the publication of the results.

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Authors and Affiliations

  1. Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestr. 9-11, 91054, Erlangen, Germany

    Julia Hiller, Katrin Klotz, Kerstin Hof, Annette Greiner, Thomas Göen & Hans Drexler

  2. Institute of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstr. 6, 91054, Erlangen, Germany

    Sebastian Meyer & Wolfgang Uter

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  1. Julia Hiller
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Correspondence to Julia Hiller.

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Ethical approval

The study protocol was approved by the local ethics committee of the University of Erlangen-Nürnberg (No. 122_17B) in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent was obtained from each participant prior to inclusion.

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Hiller, J., Klotz, K., Meyer, S. et al. Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure. Arch Toxicol 93, 2565–2574 (2019). https://doi.org/10.1007/s00204-019-02537-z

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