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Metabolism of alcohol ethoxylates (AEs) in rat, hamster, and human hepatocytes and liver S9: a pilot study for metabolic stability, metabolic pathway, and metabolites identification in vitro and in silico

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Název: Metabolism of alcohol ethoxylates (AEs) in rat, hamster, and human hepatocytes and liver S9: a pilot study for metabolic stability, metabolic pathway, and metabolites identification in vitro and in silico
Autoři: Shi, Quan, Moors, Stefan, Dawick, James, Kavanagh, Lauren, Neely, Theresa, Tian, Yuan, Dreeßen, Birte, Carrillo, Juan Carlos, Hein, Holger, Boogaard, Peter J.
Zdroj: Arch Toxicol
Informace o vydavateli: Springer Science and Business Media LLC, 2024.
Rok vydání: 2024
Témata: Male, OECD QSAR toolbox, Alcohol ethoxylates (AEs), Pilot Projects, Metabolites profiles, Biotransformation pathways, Rats, 3. Good health, Rats, Sprague-Dawley, Liver S9, Surface-Active Agents, Species Specificity, Liver, Half-Life [MeSH], Liver/metabolism [MeSH], Ethylene Glycols/toxicity [MeSH], Rats, Sprague-Dawley [MeSH], Computer Simulation [MeSH], Male [MeSH], Metabolic Networks and Pathways [MeSH], Toxicokinetics and Metabolism, Species Specificity [MeSH], Hepatocytes/drug effects [MeSH], Cricetinae [MeSH], Ethylene Glycols/metabolism [MeSH], Humans [MeSH], Rats [MeSH], Surface-Active Agents/metabolism [MeSH], Animals [MeSH], Hepatocytes/metabolism [MeSH], Hepatocytes, Chromatography, Liquid [MeSH], Surface-Active Agents/toxicity [MeSH], Pilot Projects [MeSH], Cricetinae, Animals, Humans, Computer Simulation, Ethylene Glycols, Metabolic Networks and Pathways, Half-Life, Chromatography, Liquid
Popis: Alcohol ethoxylates (AEs) are a well-known class of non-ionic surfactants widely used by the personal care market. The aim of this study was to evaluate and characterize the in vitro metabolism of AEs and identify metabolites. Five selected individual homologue AEs (C8EO4, C10EO5, C12EO4, C16EO8, and C18EO3) were incubated using human, rat, and hamster liver S9 fraction and cryopreserved hepatocytes. LC–MS was used to identify metabolites following the incubation of AEs by liver S9 and hepatocytes of all three species. All AEs were metabolized in these systems with a half-life ranging from 2 to 139 min. In general, incubation of AE with human liver S9 showed a shorter half-life compared to rat liver S9. While rat hepatocytes metabolized AEs faster than human hepatocytes. Both hydrophobic alkyl chain and hydrophilic EO head group groups of AEs were found to be target sites of metabolism. Metabolites were identified that show primary hydroxylation and dehydrogenation, followed by O-dealkylation (shortening of EO head groups) and glucuronidation. Additionally, the detection of whole EO groups indicates the cleavage of the ether bond between the alkyl chain and the EO groups as a minor metabolic pathway in the current testing system. Furthermore, no difference in metabolic patterns of each individual homologue AE investigated was observed, regardless of alkyl chain length or the number of EO groups. Moreover, there is an excellent agreement between the in vitro experimental data and the metabolite profile simulations using in silico approaches (OECD QSAR Toolbox). Altogether, these data indicate fast metabolism of all AEs with a qualitatively similar metabolic pathway with some quantitative differences observed in the metabolite profiles. These metabolic studies using different species can provide important reference values for further safety evaluation.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-0738
0340-5761
DOI: 10.1007/s00204-024-03761-y
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38844554
https://repository.publisso.de/resource/frl:6499935
https://research.wur.nl/en/publications/metabolism-of-alcohol-ethoxylates-aes-in-rat-hamster-and-human-he
https://doi.org/10.1007/s00204-024-03761-y
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....e67a11a4b2dc49280b9818da26d79bec
Databáze: OpenAIRE
Popis
Abstrakt:Alcohol ethoxylates (AEs) are a well-known class of non-ionic surfactants widely used by the personal care market. The aim of this study was to evaluate and characterize the in vitro metabolism of AEs and identify metabolites. Five selected individual homologue AEs (C8EO4, C10EO5, C12EO4, C16EO8, and C18EO3) were incubated using human, rat, and hamster liver S9 fraction and cryopreserved hepatocytes. LC–MS was used to identify metabolites following the incubation of AEs by liver S9 and hepatocytes of all three species. All AEs were metabolized in these systems with a half-life ranging from 2 to 139 min. In general, incubation of AE with human liver S9 showed a shorter half-life compared to rat liver S9. While rat hepatocytes metabolized AEs faster than human hepatocytes. Both hydrophobic alkyl chain and hydrophilic EO head group groups of AEs were found to be target sites of metabolism. Metabolites were identified that show primary hydroxylation and dehydrogenation, followed by O-dealkylation (shortening of EO head groups) and glucuronidation. Additionally, the detection of whole EO groups indicates the cleavage of the ether bond between the alkyl chain and the EO groups as a minor metabolic pathway in the current testing system. Furthermore, no difference in metabolic patterns of each individual homologue AE investigated was observed, regardless of alkyl chain length or the number of EO groups. Moreover, there is an excellent agreement between the in vitro experimental data and the metabolite profile simulations using in silico approaches (OECD QSAR Toolbox). Altogether, these data indicate fast metabolism of all AEs with a qualitatively similar metabolic pathway with some quantitative differences observed in the metabolite profiles. These metabolic studies using different species can provide important reference values for further safety evaluation.
ISSN:14320738
03405761
DOI:10.1007/s00204-024-03761-y