Toxicokinetics of homosalate in humans after dermal application: applicability of oral-route data for exposure assessment by human biomonitoring

Arch Toxicol. 2024 May;98(5):1383-1398. doi: 10.1007/s00204-024-03704-7. Epub 2024 Mar 14.

Abstract

Homosalate (HMS) is a UV filter used in sunscreens and personal care products as a mixture of cis- and trans-isomers. Systemic absorption after sunscreen use has been demonstrated in humans, and concerns have been raised about possible endocrine activity of HMS, making a general population exposure assessment desirable. In a previous study, it was shown that the oral bioavailability of cis-HMS (cHMS) is lower than that of trans-HMS (tHMS) by a factor of 10, calling for a separate evaluation of both isomers in exposure and risk assessment. The aim of the current study is the investigation of HMS toxicokinetics after dermal exposure. Four volunteers applied a commercial sunscreen containing 10% HMS to their whole body under regular-use conditions (18-40 mg HMS (kg bw)-1). Parent HMS isomers and hydroxylated and carboxylic acid metabolites were quantified using authentic standards and isotope dilution analysis. Further metabolites were investigated semi-quantitatively. Elimination was delayed and slower compared to the oral route, and terminal elimination half-times were around 24 h. After dermal exposure, the bioavailability of cHMS was a factor of 2 lower than that of tHMS. However, metabolite ratios in relation to the respective parent isomer were very similar to the oral route, supporting the applicability of the oral-route urinary excretion fractions for dermal-route exposure assessments. Exemplary calculations of intake doses showed margins of safety between 11 and 92 (depending on the approach) after single whole-body sunscreen application. Human biomonitoring can reliably quantify oral and dermal HMS exposures and support the monitoring of exposure reduction measures.

Keywords: Homosalate; Human biomonitoring; Sunscreen; Toxicokinetics; Ultraviolet filter.

MeSH terms

  • Administration, Cutaneous
  • Biological Monitoring*
  • Humans
  • Salicylates*
  • Sunscreening Agents*
  • Toxicokinetics

Substances

  • homosalate
  • Sunscreening Agents
  • Salicylates