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通过体外方法组合评估三氯生和三氯卡班的遗传毒性、诱变性及内分泌干扰潜力。

The Potential for Genotoxicity, Mutagenicity and Endocrine Disruption in Triclosan and Triclocarban Assessed through a Combination of In Vitro Methods.

作者信息

Chrz Jan, Dvořáková Markéta, Kejlová Kristina, Očadlíková Danuše, Svobodová Lada, Malina Lukáš, Hošíková Barbora, Jírová Dagmar, Bendová Hana, Kolářová Hana

机构信息

Centre of Toxicology and Health Safety, National Institute of Public Health, Šrobárova 49/48, 100 00 Prague, Czech Republic.

Department of Medical Biophysics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc, 779 00 Olomouc, Czech Republic.

出版信息

J Xenobiot. 2023 Dec 21;14(1):15-30. doi: 10.3390/jox14010002.

Abstract

Triclosan and Triclocarban, preservatives widely used in cosmetics and other consumer products, underwent evaluation using a battery of new-approach methodologies in vitro (NAMs). Specifically, the Microplate Ames Test (MPF™ Test, Xenometrix, Allschwil, Switzerland) was employed to assess mutagenicity, the Comet assay in vitro on the HaCat cell line and the Mammalian Chromosome Aberration Test were utilized to evaluate genotoxicity, and the XenoScreen YES/YAS assay was applied to investigate endocrine disruption. The chemicals did not exhibit any positive responses for mutagenicity. However, the mammalian chromosome aberration test identified both chemicals as being positive for genotoxicity at 10 µg/mL. In the Comet assay, the percentage of DNA in the tail significantly increased in a concentration-dependent manner (at 5 and 10 µg/mL for Triclosan, at 2.5, 5, and 10 µg/mL for Triclocarban). The positive response depended on the increasing concentration and the duration of exposure. Triclosan, but not Triclocarban in any of the endocrine assays performed, indicated a potential for endocrine activity in the anti-estrogenic and anti-androgenic assays. The positive in vitro results detected were obtained for concentrations relevant to final products. The alarming findings obtained with the use of new-approach methodologies (NAMs) justify the current precautionary regulatory approach, limiting the use of these preservatives.

摘要

三氯生和三氯卡班是广泛用于化妆品及其他消费品的防腐剂,使用一系列体外新方法学(NAMs)对其进行了评估。具体而言,采用微孔板艾姆斯试验(MPF™试验,Xenometrix公司,瑞士阿尔施维尔)评估致突变性,利用体外彗星试验检测HaCat细胞系以及哺乳动物染色体畸变试验评估遗传毒性,并应用XenoScreen YES/YAS试验研究内分泌干扰情况。这些化学物质在致突变性方面未表现出任何阳性反应。然而,哺乳动物染色体畸变试验确定这两种化学物质在10μg/mL时均具有遗传毒性阳性结果。在彗星试验中,尾端DNA百分比呈浓度依赖性显著增加(三氯生在5μg/mL和10μg/mL时,三氯卡班在2.5μg/mL、5μg/mL和10μg/mL时)。阳性反应取决于浓度增加和暴露持续时间。在进行的任何内分泌试验中,三氯生显示出在抗雌激素和抗雄激素试验中有内分泌活性的可能性,而三氯卡班则未显示。检测到的体外阳性结果是在与最终产品相关的浓度下获得的。使用新方法学(NAMs)获得的这些令人担忧的结果证明了当前限制这些防腐剂使用的预防性监管方法的合理性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0224/10971739/c186c9f7dbf6/jox-14-00002-g001.jpg

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