Diastereoselective metabolism of homomenthyl salicylate (homosalate)
- Homosalate (HMS) is a salicylate UV filter broadly used in sunscreens and personal care products. The aim of this study was the collection of human toxicokinetic data on HMS as a tool for risk assessment. For this purpose, metabolism and urinary excretion after a single oral HMS dose (98.2–149.1 \(\mu\)g (kg body weight)\(^{−1}\)) were investigated in four volunteers (two male, two female). As commercial products generally contain a mixture of \(\it cis-\) and \(\it trans\)-HMS, both \(\it cis-\)rich and \(\it trans\)-rich isomer mixtures were studied to investigate possible differences in metabolism. Initial metabolite screening tentatively identified six oxidative metabolite subgroups, of which hydroxylated and carboxylic acid metabolites were studied in more detail. Unchanged parent HMS and the previously identified HMS metabolites 5-((2-hydroxybenzoyl)oxy)-3,3-dimethylcyclohexane-1-carboxylic acid (HMS-CA) and 3-hydroxy-3,5,5-trimethylcyclohexyl 2-hydroxybenzoate (3OH-HMS), respectively, were quantified separately as \(\it cis-\) and \(\it trans\)-isomers via authentic standards by isotope dilution analysis. In addition, further alkyl-hydroxylated and carboxylic acid metabolites were investigated semi-quantitatively. Peak concentrations in urine were reached 1.5–6.3 h post-dose and more than 80 % of each of the quantitatively investigated metabolites (and at least 70 % of the semi-quantitatively investigated metabolites) was excreted within the first 24 h. Plasma and urine data indicated that oral bioavailability of \(\it cis-\)HMS was one order of magnitude below that of \(\it trans\)-HMS. Furthermore, the mean total urinary excretion fraction (\(F_{ue}\)) for the metabolites derived from \(\it trans\)-HMS (6.4 %) was two orders of magnitude higher than for the metabolites derived from \(\it cis-\)HMS (0.045 %). Our data proves diastereoselectivity in toxicokinetics of \(\it cis-\) and \(\it trans\)-HMS, emphasizing the necessity to address isomer ratios in future studies including HMS exposure and risk assessments.
Author: | Katharina E. EbertORCiDGND, Peter GriemGND, Tobias WeißORCiDGND, Thomas BrüningORCiDGND, Heiko HayenORCiDGND, Holger M. KochORCiDGND, Daniel BuryORCiDGND |
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URN: | urn:nbn:de:hbz:294-103717 |
DOI: | https://doi.org/10.1016/j.envint.2022.107637 |
Parent Title (English): | Environment international |
Subtitle (English): | identification of relevant human exposure biomarkers |
Publisher: | Elsevier Science |
Place of publication: | Amsterdam, Niederlande |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/11/10 |
Date of first Publication: | 2022/11/17 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds Homosalate; Human biomonitoring; Metabolism; Oral dose; Sunscreen; Ultraviolet filter |
Volume: | 170 |
Issue: | Article 107637 |
First Page: | 107637-1 |
Last Page: | 107637-14 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY-NC-ND 4.0 - Attribution-NonCommercial-NoDerivatives 4.0 International |