Toxicokinetics of 2-ethylhexyl salicylate (EHS) and its seven metabolites in humans after controlled single dermal exposure to EHS

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-12 DOI:10.1007/s00204-024-03827-x
Laura Kuhlmann, Thomas Göen, Julia Hiller
{"title":"Toxicokinetics of 2-ethylhexyl salicylate (EHS) and its seven metabolites in humans after controlled single dermal exposure to EHS","authors":"Laura Kuhlmann,&nbsp;Thomas Göen,&nbsp;Julia Hiller","doi":"10.1007/s00204-024-03827-x","DOIUrl":null,"url":null,"abstract":"<div><p>The chemical UV filter 2-ethylhexyl salicylate (EHS) is used in various personal-care products. The dermal and oral metabolism of EHS have already been targeted by different studies. However, toxicokinetic data after a single dermal exposure to EHS was missing. In our study, three volunteers were dermally exposed to a commercial EHS-containing sunscreen for 9 h with an application dose of 2 mg sunscreen per cm<sup>2</sup> body surface area. The exposure was performed indoors, and sunscreen was applied on about 75% of the total skin area. Complete urine voids were collected over 72 h and eight blood samples were drawn from each subject. Urine samples were analyzed for EHS and seven known metabolites (5OH-EHS, 4OH-EHS, 2OH-EHS, 6OH-EHS, 4oxo-EHS, 5oxo-EHS, and 5cx-EPS) by online-SPE UPLC MS/MS. The peaks of urinary elimination occurred 10–11 h after application. The elimination half-lives (Phase 1) were between 6.6 and 9.7 h. The dominant urinary biomarkers were EHS itself, followed by 5OH-EHS, 5cx-EPS, 5oxo-EHS, and 4OH-EHS. 2OH-EHS, 6OH-EHS, and 4oxo-EHS were detected only in minor amounts. An enhanced analysis of conjugation species revealed marginal amounts of unconjugated metabolites and up to 40% share of sulfate conjugates for 5OH-EHS, 5oxo-EHS, and 5cx-EPS. The results demonstrated a delayed systemic resorption of EHS via the dermal route. Despite an extensive metabolism, the parent compound occurred as main urinary parameter. The delayed dermal resorption as well as the slow elimination of EHS indicate an accumulation up to toxicological relevant doses during daily repeated dermal application to large skin areas.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402844/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00204-024-03827-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The chemical UV filter 2-ethylhexyl salicylate (EHS) is used in various personal-care products. The dermal and oral metabolism of EHS have already been targeted by different studies. However, toxicokinetic data after a single dermal exposure to EHS was missing. In our study, three volunteers were dermally exposed to a commercial EHS-containing sunscreen for 9 h with an application dose of 2 mg sunscreen per cm2 body surface area. The exposure was performed indoors, and sunscreen was applied on about 75% of the total skin area. Complete urine voids were collected over 72 h and eight blood samples were drawn from each subject. Urine samples were analyzed for EHS and seven known metabolites (5OH-EHS, 4OH-EHS, 2OH-EHS, 6OH-EHS, 4oxo-EHS, 5oxo-EHS, and 5cx-EPS) by online-SPE UPLC MS/MS. The peaks of urinary elimination occurred 10–11 h after application. The elimination half-lives (Phase 1) were between 6.6 and 9.7 h. The dominant urinary biomarkers were EHS itself, followed by 5OH-EHS, 5cx-EPS, 5oxo-EHS, and 4OH-EHS. 2OH-EHS, 6OH-EHS, and 4oxo-EHS were detected only in minor amounts. An enhanced analysis of conjugation species revealed marginal amounts of unconjugated metabolites and up to 40% share of sulfate conjugates for 5OH-EHS, 5oxo-EHS, and 5cx-EPS. The results demonstrated a delayed systemic resorption of EHS via the dermal route. Despite an extensive metabolism, the parent compound occurred as main urinary parameter. The delayed dermal resorption as well as the slow elimination of EHS indicate an accumulation up to toxicological relevant doses during daily repeated dermal application to large skin areas.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
控制人体单次皮肤接触水杨酸 2-乙基己酯 (EHS) 及其七种代谢物的毒物动力学。
化学紫外线过滤剂 2-乙基己基水杨酸酯(EHS)被用于各种个人护理产品中。不同的研究已经针对 EHS 的皮肤和口腔代谢进行了研究。然而,目前还缺少单次皮肤接触 EHS 后的毒物动力学数据。在我们的研究中,三名志愿者皮肤接触了含有 EHS 的商用防晒霜 9 小时,使用剂量为每平方厘米体表面积 2 毫克防晒霜。暴露是在室内进行的,防晒霜的涂抹面积约为皮肤总面积的 75%。在 72 小时内收集完整的尿液,并从每个受试者身上抽取 8 份血液样本。通过在线-SPE UPLC MS/MS 分析了尿样中的 EHS 和七种已知代谢物(5OH-EHS、4OH-EHS、2OH-EHS、6OH-EHS、4oxo-EHS、5oxo-EHS 和 5cx-EPS)。尿液消除峰出现在施药后 10-11 小时。消除半衰期(第一阶段)在 6.6 至 9.7 小时之间。尿液中最主要的生物标记物是 EHS 本身,其次是 5OH-EHS、5cx-EPS、5oxo-EHS 和 4OH-EHS。只检测到少量的 2OH-EHS、6OH-EHS 和 4oxo-EHS 。对共轭物种类的强化分析表明,5OH-EHS、5oxo-EHS 和 5cx-EPS 只含有少量未共轭的代谢物,而硫酸盐共轭物的比例高达 40%。结果表明,EHS 通过皮肤途径被全身吸收的时间较晚。尽管存在广泛的新陈代谢,但母体化合物仍是主要的尿液参数。EHS 的延迟皮肤再吸收和缓慢消除表明,在每天对大面积皮肤反复施用过程中,其累积量可达到毒理学相关剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
期刊最新文献
Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening. The emerging role of alternatively activated macrophages to treat acute liver injury. Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure. Telmisartan potentiates the ITE-induced aryl hydrocarbon receptor activity in human liver cell line. Therapeutic potential of 4-phenylbutyric acid against methylmercury-induced neuronal cell death in mice.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1