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

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 9h under real-life conditions (2mg/cm2 body surface area; double re-application; corresponding to 3.8g 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 525µg/g and 213µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8h after first application. First-phase terminal half-lives were 8-9h. For 5OH-EHS, a second-phase terminal half-life could be determined (87h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24h reached up to 334µg EHS and 124µg of 5OH-EHS. Simulated real-life sunscreen use for 1day 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.