人体丙二醇醚代谢的体外和体内评价

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-08-18 DOI:10.1016/j.etap.2025.104795

Hélène P. De Luca , Myriam Borgatta , Sophie Werner , Pascal Wild , Sylvain Le Gludic , Laura Suter-Dick , Nancy B. Hopf

{"title":"人体丙二醇醚代谢的体外和体内评价","authors":"Hélène P. De Luca , Myriam Borgatta , Sophie Werner , Pascal Wild , Sylvain Le Gludic , Laura Suter-Dick , Nancy B. Hopf","doi":"10.1016/j.etap.2025.104795","DOIUrl":null,"url":null,"abstract":"<div><div>Propylene glycol ethers (PGEs) consist of a major α-isomer (secondary alcohol group) and a minor β-isomer (primary alcohol group). Animal studies have reported toxic effects of the β-isomer metabolites, but human metabolism of PGEs remains poorly understood. We aimed to characterize the metabolism of two common PGEs in humans. Nine participants were exposed under controlled conditions (4 h) to propylene glycol ethyl ether (PGEE) or propylene glycol propyl ether (PGPE) (<35 ppm). Blood and urine samples were collected, and the respective β-isomers metabolites; 2-ethoxypropanoic acid (2-EPA) and 2-propoxypropanoic acid (2-PPA) were quantified. The 2-PPA blood absorption rate was 0.0005 ± 0.0002 µg/mL/h*ppm followed by rapid urinary elimination (half-life: 2 h) and slower secondary elimination (half-life: 10 h). No dose-response was observed for 2-EPA; therefore, β-PGEE metabolism was investigated <em>in vitro</em> using human liver S9 fractions. We provide 2-EPA hepatic kinetic and enzyme kinetic parameters. We recommend using of 2-PPA as a biomarker for PGPE exposures.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104795"},"PeriodicalIF":4.2000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vitro and in vivo evaluation of propylene glycol ethers metabolism in humans\",\"authors\":\"Hélène P. De Luca , Myriam Borgatta , Sophie Werner , Pascal Wild , Sylvain Le Gludic , Laura Suter-Dick , Nancy B. Hopf\",\"doi\":\"10.1016/j.etap.2025.104795\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Propylene glycol ethers (PGEs) consist of a major α-isomer (secondary alcohol group) and a minor β-isomer (primary alcohol group). Animal studies have reported toxic effects of the β-isomer metabolites, but human metabolism of PGEs remains poorly understood. We aimed to characterize the metabolism of two common PGEs in humans. Nine participants were exposed under controlled conditions (4 h) to propylene glycol ethyl ether (PGEE) or propylene glycol propyl ether (PGPE) (<35 ppm). Blood and urine samples were collected, and the respective β-isomers metabolites; 2-ethoxypropanoic acid (2-EPA) and 2-propoxypropanoic acid (2-PPA) were quantified. The 2-PPA blood absorption rate was 0.0005 ± 0.0002 µg/mL/h*ppm followed by rapid urinary elimination (half-life: 2 h) and slower secondary elimination (half-life: 10 h). No dose-response was observed for 2-EPA; therefore, β-PGEE metabolism was investigated <em>in vitro</em> using human liver S9 fractions. We provide 2-EPA hepatic kinetic and enzyme kinetic parameters. We recommend using of 2-PPA as a biomarker for PGPE exposures.</div></div>\",\"PeriodicalId\":11775,\"journal\":{\"name\":\"Environmental toxicology and pharmacology\",\"volume\":\"118 \",\"pages\":\"Article 104795\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environmental toxicology and pharmacology\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S138266892500170X\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental toxicology and pharmacology","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S138266892500170X","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

丙二醇醚（PGEs）由主要的α-异构体（仲醇基）和次要的β-异构体（伯醇基）组成。动物研究已经报道了β-异构体代谢物的毒性作用，但人类对PGEs的代谢仍然知之甚少。我们的目的是表征人类两种常见的PGEs的代谢。九名参与者在受控条件下（4 h）暴露于丙二醇乙醚（PGEE）或丙二醇丙醚（PGPE）（<35 ppm）。采集血样和尿样，分别检测β-异构体代谢产物；定量测定2-乙氧基丙烷酸（2-EPA）和2-丙氧基丙烷酸（2-PPA）。2- ppa血吸收率为0.0005 ± 0.0002 µg/mL/h*ppm，其次为快速尿消除（半衰期2 h）和较慢的二次消除（半衰期10 h）。2-EPA未见剂量反应；因此，利用人肝脏S9组分体外研究β-PGEE代谢。我们提供了2-EPA肝动力学和酶动力学参数。我们建议使用2-PPA作为PGPE暴露的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

In vitro and in vivo evaluation of propylene glycol ethers metabolism in humans

Propylene glycol ethers (PGEs) consist of a major α-isomer (secondary alcohol group) and a minor β-isomer (primary alcohol group). Animal studies have reported toxic effects of the β-isomer metabolites, but human metabolism of PGEs remains poorly understood. We aimed to characterize the metabolism of two common PGEs in humans. Nine participants were exposed under controlled conditions (4 h) to propylene glycol ethyl ether (PGEE) or propylene glycol propyl ether (PGPE) (<35 ppm). Blood and urine samples were collected, and the respective β-isomers metabolites; 2-ethoxypropanoic acid (2-EPA) and 2-propoxypropanoic acid (2-PPA) were quantified. The 2-PPA blood absorption rate was 0.0005 ± 0.0002 µg/mL/h*ppm followed by rapid urinary elimination (half-life: 2 h) and slower secondary elimination (half-life: 10 h). No dose-response was observed for 2-EPA; therefore, β-PGEE metabolism was investigated in vitro using human liver S9 fractions. We provide 2-EPA hepatic kinetic and enzyme kinetic parameters. We recommend using of 2-PPA as a biomarker for PGPE exposures.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.