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人类暴露于紫外线过滤剂 2-乙基己基水杨酸酯的尿代谢产物作为生物标志物。

Urinary metabolites of the UV filter 2-Ethylhexyl salicylate as biomarkers of exposure in humans.

机构信息

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.

Symrise AG, Mühlenfeldstrasse 1, 37603, Holzminden, Germany.

出版信息

Toxicol Lett. 2019 Jul;309:35-41. doi: 10.1016/j.toxlet.2019.04.001. Epub 2019 Apr 3.

Abstract

The UV filter 2-ethylhexyl salicylate (EHS) is used in sunscreens and other personal care products worldwide and has been found in a variety of environmental media. We aimed to provide human toxicokinetic data on EHS as a tool for risk assessment. For that purpose, we investigated metabolism and urinary metabolite excretion after a single oral EHS dose (57.4-75.5 μg/(kg body weight)) in three male volunteers. In a suspect screening, we tentatively identified seven EHS metabolites. Three EHS specific metabolites were quantitatively investigated: 2-ethyl-5-hydroxyhexyl 2-hydroxybenzoate (5OH-EHS), 2-ethyl-5-oxohexyl 2-hydroxybenzoate (5oxo-EHS), and 5-(((2-hydroxybenzoyl)oxy)methyl)heptanoic acid (5cx-EPS). These metabolites were excreted with urinary excretion fractions of 0.28% (range: 0.13-0.54%), 0.11% (0.06-0.20%), and 0.24% (0.14-0.41%), respectively. The elimination was fast: peak urinary concentrations were found 1.6-2.6 h after dose and ≥95% of the total amounts were excreted within 24 h. Elimination kinetics were biphasic, with mean elimination half-lives of 0.8 h (first phase) and 6.6 h (second phase) for 5OH-EHS, 0.8 h and 6.3 h for 5oxo-EHS, and 1.1 h and 5.9 h for 5cx-EPS. After dermal exposure (sunscreen application), we found a considerably delayed EHS elimination. Based on urinary metabolite levels we calculated EHS exposure levels for a small pilot population.

摘要

紫外线滤光剂 2-乙基己基水杨酸酯(EHS)被广泛用于防晒霜和其他个人护理产品中,已在多种环境介质中被检出。我们旨在提供 EHS 的人类毒代动力学数据,作为风险评估的工具。为此,我们在 3 名男性志愿者中单次口服 EHS 剂量(57.4-75.5μg/(kg 体重))后,研究了其代谢和尿代谢产物排泄情况。在疑似筛查中,我们暂定鉴定了 7 种 EHS 代谢物。我们对 3 种 EHS 特异性代谢物进行了定量研究:2-乙基-5-羟基己基 2-羟基苯甲酸酯(5OH-EHS)、2-乙基-5-氧代己基 2-羟基苯甲酸酯(5oxo-EHS)和 5-(((2-羟基苯甲酰基)氧基)甲基)庚酸(5cx-EPS)。这些代谢物的排泄率分别为 0.28%(范围:0.13-0.54%)、0.11%(0.06-0.20%)和 0.24%(0.14-0.41%)。排泄速度很快:在剂量后 1.6-2.6 小时即可检测到尿液中的峰值浓度,95%以上的总量在 24 小时内排出。消除呈双相性,5OH-EHS 的平均消除半衰期分别为 0.8 小时(第一相)和 6.6 小时(第二相),5oxo-EHS 分别为 0.8 小时和 6.3 小时,5cx-EPS 分别为 1.1 小时和 5.9 小时。经皮肤暴露(防晒霜应用)后,我们发现 EHS 的消除明显延迟。根据尿液代谢物水平,我们计算了一个小型试点人群的 EHS 暴露水平。

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