New metabolites of 2-ethylhexyl salicylate in human urine after simulated real-life dermal sunscreen application

Toxicol Lett. 2024 Oct:400:1-8. doi: 10.1016/j.toxlet.2024.07.912. Epub 2024 Jul 20.

Abstract

2-Ethylhexyl salicylate (EHS) is an organic UV filter which is used in sunscreen and other personal care products. The dermal uptake of EHS was studied in several dermal-exposure experiments. This paper aims to coherently assess urine samples after dermal exposure for the biomarkers EHS, 5OH-EHS, 5oxo-EHS, and 5cx-EPS as well as further biomarkers of interest, specifically 4OH-EHS, 4oxo-EHS, 2OH-EHS, and 6OH-EHS, for the first time. Samples from 18 participants of a pre-existing dermal exposure study under real-life conditions were reassessed using a comprehensive LC-MS/MS method. EHS accounts for 34 % of the cumulative excretion of all analytes within 24 h after exposure, followed by 5OH-EHS (19 %), 5cx-EPS (18 %), 4OH-EHS (15 %) and 5oxo-EHS (11 %). Further metabolites were only quantified in minor amounts. EHS as the most prominent excretion parameter in this study demonstrates the missing first-pass effect after dermal absorption. Furthermore, the applied novel comprehensive analytical procedure revealed oxidation at the ω (5cx-EPS, 6OH-EHS), ω-1 (5OH-EHS, 5oxo-EHS), and ω-2 positions (4OH-EHS, 4oxo-EHS) in the main chain of the ethylhexyl group as well as oxidation in the side chain (2OH-EHS). The presented data are of high relevance for a reliable toxicological risk assessment of dermal exposure to EHS.

Keywords: Biomarker; Dermal exposure; Ethylhexyl salicylate; Human biomonitoring; LC-MS/MS; UV filter.

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Biomarkers* / urine
  • Chromatography, Liquid
  • Female
  • Humans
  • Male
  • Middle Aged
  • Salicylates* / pharmacokinetics
  • Salicylates* / urine
  • Skin / metabolism
  • Skin Absorption*
  • Sunscreening Agents* / metabolism
  • Sunscreening Agents* / pharmacokinetics
  • Tandem Mass Spectrometry*
  • Young Adult

Substances

  • Sunscreening Agents
  • 2-ethylhexyl salicylate
  • Salicylates
  • Biomarkers