Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers
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 µg...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022005645 |
| _version_ | 1811316133323603968 |
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| author | Katharina E. Ebert Peter Griem Tobias Weiss Thomas Brüning Heiko Hayen Holger M. Koch Daniel Bury |
| author_facet | Katharina E. Ebert Peter Griem Tobias Weiss Thomas Brüning Heiko Hayen Holger M. Koch Daniel Bury |
| author_sort | Katharina E. Ebert |
| collection | DOAJ |
| description | 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 µg (kg body weight)−1) were investigated in four volunteers (two male, two female). As commercial products generally contain a mixture of cis- and trans-HMS, both cis-rich and 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 cis- and 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 cis-HMS was one order of magnitude below that of trans-HMS. Furthermore, the mean total urinary excretion fraction (Fue) for the metabolites derived from trans-HMS (6.4 %) was two orders of magnitude higher than for the metabolites derived from cis-HMS (0.045 %). Our data proves diastereoselectivity in toxicokinetics of cis- and trans-HMS, emphasizing the necessity to address isomer ratios in future studies including HMS exposure and risk assessments. |
| first_indexed | 2024-04-13T11:43:28Z |
| format | Article |
| id | doaj.art-ff18e76e2e28404a8077dd7a7637fa7b |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-13T11:43:28Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-ff18e76e2e28404a8077dd7a7637fa7b2022-12-22T02:48:14ZengElsevierEnvironment International0160-41202022-12-01170107637Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkersKatharina E. Ebert0Peter Griem1Tobias Weiss2Thomas Brüning3Heiko Hayen4Holger M. Koch5Daniel Bury6Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, GermanySymrise AG, Mühlenfeldstraße 1, 37603 Holzminden, GermanyInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, GermanyInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, GermanyInstitute of Inorganic and Analytical Chemistry, University of Münster, Corrensstrasse 48, 48149 Münster, GermanyInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, GermanyInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany; Corresponding author.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 µg (kg body weight)−1) were investigated in four volunteers (two male, two female). As commercial products generally contain a mixture of cis- and trans-HMS, both cis-rich and 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 cis- and 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 cis-HMS was one order of magnitude below that of trans-HMS. Furthermore, the mean total urinary excretion fraction (Fue) for the metabolites derived from trans-HMS (6.4 %) was two orders of magnitude higher than for the metabolites derived from cis-HMS (0.045 %). Our data proves diastereoselectivity in toxicokinetics of cis- and trans-HMS, emphasizing the necessity to address isomer ratios in future studies including HMS exposure and risk assessments.http://www.sciencedirect.com/science/article/pii/S0160412022005645HomosalateUltraviolet filterSunscreenHuman biomonitoringMetabolismOral dose |
| spellingShingle | Katharina E. Ebert Peter Griem Tobias Weiss Thomas Brüning Heiko Hayen Holger M. Koch Daniel Bury Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers Environment International Homosalate Ultraviolet filter Sunscreen Human biomonitoring Metabolism Oral dose |
| title | Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers |
| title_full | Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers |
| title_fullStr | Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers |
| title_full_unstemmed | Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers |
| title_short | Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers |
| title_sort | diastereoselective metabolism of homomenthyl salicylate homosalate identification of relevant human exposure biomarkers |
| topic | Homosalate Ultraviolet filter Sunscreen Human biomonitoring Metabolism Oral dose |
| url | http://www.sciencedirect.com/science/article/pii/S0160412022005645 |
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