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通过体内角质层研究 UV 滤光剂乙基己基甲氧基肉桂酸酯顺反式异构体相关的皮肤毒代动力学。

Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

机构信息

Faculty of Science, RECETOX - Research Centre for Toxic Compounds in the Environment, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic.

出版信息

Environ Sci Pollut Res Int. 2017 Nov;24(32):25061-25070. doi: 10.1007/s11356-017-0172-2. Epub 2017 Sep 17.

DOI:10.1007/s11356-017-0172-2
PMID:28920186
Abstract

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

摘要

2-乙基己基甲氧基肉桂酸酯(EHMC)是个人护理产品中使用最广泛的紫外线滤光剂之一。它在阳光下会发生顺/反异构化,而对顺式异构体的毒性影响的了解有限。已知一种化合物的两个几何异构体可能具有不同的物理化学性质和作用。然而,由于其皮肤毒代动力学的差异,目前还没有研究关注 EHMC 异构化产物的毒代动力学,以比较它们在皮肤暴露于顺式-EHMC 和反式-EHMC 时的潜在差异。在这项研究中,研究了母体反式-EHMC 及其顺式异构体的皮肤吸收。将含有反式-EHMC 的市售防晒霜局部涂抹于两名志愿者的前臂皮肤上,并加入实验室制备的顺式-EHMC。皮肤暴露 8 小时后,用胶带剥离去除角质层(SC)。使用总蛋白测定法分光光度法测定去除的 SC 厚度。通过 HPLC-DAD 测量去除的 SC 中两种异构体的浓度。通过体内菲克第二定律扩散确定了两种 EHMC 异构体在 SC 中的新扩散和渗透系数。两种异构体之间的皮肤毒代动力学参数差异无统计学意义。然而,对异构体形式进行单独的毒理学研究并确定其皮肤毒代动力学参数对于人类风险评估的精细化至关重要。

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本文引用的文献

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Sci Total Environ. 2017 Sep 1;593-594:18-26. doi: 10.1016/j.scitotenv.2017.03.043. Epub 2017 Mar 21.
2
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Sci Total Environ. 2016 Dec 1;572:1092-1100. doi: 10.1016/j.scitotenv.2016.08.017. Epub 2016 Aug 13.
3
New probabilistic risk assessment of ethylhexyl methoxycinnamate: Comparing the genotoxic effects of trans- and cis-EHMC.甲氧基肉桂酸乙基己酯的新概率风险评估:比较反式和顺式EHMC的遗传毒性作用。
Environ Toxicol. 2017 Feb;32(2):569-580. doi: 10.1002/tox.22260. Epub 2016 Mar 30.
4
Variation in stratum corneum protein content as a function of anatomical site and ethnic group.角质层蛋白质含量随解剖部位和种族群体的变化。
Int J Cosmet Sci. 2016 Jun;38(3):224-31. doi: 10.1111/ics.12274. Epub 2015 Oct 12.
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Importance of a suitable working protocol for tape stripping experiments on porcine ear skin: Influence of lipophilic formulations and strip adhesion impairment.猪耳皮肤胶带剥离实验合适工作方案的重要性:亲脂性制剂的影响及胶带粘附损伤
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