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离体人体皮肤对甲基氯异噻唑啉酮(MCI)和甲基异噻唑啉酮(MI)的渗透。

Ex vivo human skin permeation of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI).

机构信息

Institute for Work and Health (IST), University of Lausanne and Geneva, Lausanne, Switzerland.

Department of Dermatology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

出版信息

Arch Toxicol. 2017 Nov;91(11):3529-3542. doi: 10.1007/s00204-017-1978-x. Epub 2017 May 3.

Abstract

Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are biocides used in many types of products such as cosmetics, paints, and cleaning agents. Skin contact is often encountered when using these products. Although MCI and MI are strong allergens and cause skin irritation, no scientific skin permeation study has been reported except for some unpublished data. Therefore, this study assessed the permeation of MCI and MI both separately and as a mixture through freshly dermatomed human skin (800 µm) in a flow-through diffusion cell system. Different concentrations of aqueous standards (1.5/1, 70/50, 150/35, and 750/175 µg/mL of MCI/MI) and various commercial products were assessed after 15-20 h of exposure. In parallel, the dose-dependent irritant effects of MCI/MI and MI were estimated by histology following 6- or 24-h exposure. Overall results show that MI in formulations or in aqueous standard solutions quickly permeated the skin with time lags less than 15 min while MCI was much slower (>3.5 h). MCI in formulations had permeation rates up to five times greater than that for MI in the same product, and in two tested creams were not found to permeate skin. Some signs of irritation were observed by histology; especially at the highest MCI/MI concentrations (750/250 µg/mL) in aqueous solutions. This confirms that MCI reacts readily with skin and may induce local irritation. The MCI and MI permeations are also greatly influenced by the topical vehicle. It is, therefore, more relevant to test exposures to formulations than aqueous standard solutions.

摘要

甲基氯异噻唑啉酮(MCI)和甲基异噻唑啉酮(MI)是许多类型产品(如化妆品、油漆和清洁剂)中使用的杀菌剂。在使用这些产品时,经常会接触到皮肤。尽管 MCI 和 MI 是很强的过敏原,会引起皮肤刺激,但除了一些未发表的数据外,没有关于它们经皮渗透的科学研究报告。因此,本研究在流动扩散细胞系统中评估了 MCI 和 MI 单独以及混合物分别透过新鲜去皮人体皮肤(800 µm)的渗透情况。在 15-20 小时的暴露后,评估了不同浓度的水相标准品(1.5/1、70/50、150/35 和 750/175 µg/mL 的 MCI/MI)和各种商业产品。同时,通过组织学评估了 6 小时或 24 小时暴露后 MCI/MI 和 MI 的剂量依赖性刺激作用。总体结果表明,配方中的 MI 或水相标准溶液中的 MI 很快透过皮肤,时滞小于 15 分钟,而 MCI 则慢得多(>3.5 小时)。配方中的 MCI 渗透速率比同一产品中 MI 的渗透速率高五倍,并且在两种测试的乳膏中未发现 MCI 渗透皮肤。组织学观察到一些刺激迹象;特别是在水相溶液中 MCI/MI 浓度最高(750/250 µg/mL)时。这证实了 MCI 与皮肤迅速反应,并可能引起局部刺激。MCI 和 MI 的渗透也受到局部赋形剂的极大影响。因此,测试制剂暴露比水相标准溶液更相关。

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