Applicability of Human Oral Toxicokinetic Data for Human Biomonitoring of Dermal Exposure to 2-Ethylhexyl Salicylate (EHS).

Abstract

2-Ethylhexyl salicylate (EHS) is a UV filter used in sunscreens and personal care products. Mixed-route exposure via both dermal and oral pathways is considered likely, and specific oxidative metabolites of EHS (i.e., 5OH-EHS and 5cx-EPS) in urine have been successfully established as exposure biomarkers for robust human-biomonitoring-based exposure and risk assessments. Previous studies after sunscreen application have reported that EHS itself contributes to the total excretion of specific metabolites. To exclude the possibility of pathway-specific relevant differences in EHS metabolism, in this study, we provide the missing link, i.e., reliable quantitative toxicokinetic data for EHS after oral dose. For this purpose, we re-analyzed samples of a human toxicokinetics study in three volunteers. We found the urinary excretion fraction of EHS after oral uptake to be 0.28% (0.12%-0.51%), similar to 5OH-EHS (on average 0.28%) and 5cx-EPS (0.24%). In the sunscreen application studies, the relative excretion share of EHS was in the same order of magnitude as the oxidative metabolites, about a factor of two higher than 5OH-EHS and 5cx-EPS. Our study provides new quantitative excretion data for EHS itself in urine and confirms the applicability of the oral-route data also for dermal and mixed-route exposure scenarios. It further underlines the validity of the oxidative metabolites as the most sensitive and most robust biomarkers of EHS exposure, which, in contrast to EHS, are not susceptible to external contamination.