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Toxicological assessment of phthalates and their alternatives using human keratinocytes

机译:邻苯二甲酸盐的毒理学评估及其使用人角蛋白细胞的替代品

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摘要

Phthalates are mainly used as binders and plasticizers in various industrial products including detergents, surfactants, waxes, paints, pharmaceuticals, food products, and cosmetics. However, they have been reported to be endocrine disruptors, which are chemicals that can mimic or disturb endocrines, causing interference to the endocrine system. Recently, there have been numerous reports showing that phthalates have negative health impacts such as asthma, breast cancer, obesity, type II diabetes, and male infertility. Due to these effects, there is an urgent need for phthalate alternatives. In this study, the potential cytotoxicity of phthalates and their substitutes were screened in HaCaT cells, a human keratinocyte cell line, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) thiazolyl blue assay, immunocytochemistry, flow cytometric analysis, and western blotting. We confirmed that common phthalates such as butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP) have genotoxic effects, leading to cell death. Among the known phthalate substitutes, tributyl O-acetylcitrate (ATBC), triethyl 2-acetylcitrate (ATEC), and trihexyl O-acetylcitrate (ATHC) were tested for cytotoxicity. As a result, ATEC showed similar levels of cytotoxicity with the phthalates whereas ATBC and ATHC did not show significant cytotoxicity even in high doses (5 mg/ml).
机译:邻苯二甲酸酯主要用作各种工业产品的粘合剂和增塑剂,包括洗涤剂,表面活性剂,蜡,涂料,药品,食品和化妆品。然而,据报道,它们是内分泌破坏剂,其是可以模仿或扰乱内分泌的化学物质,导致对内分泌系统的干扰。最近,有许多报道显示邻苯二甲酸酯具有负面健康影响,例如哮喘,乳腺癌,肥胖症,II型糖尿病和男性不孕症。由于这些效果,迫切需要邻苯二甲酸酯替代品。在这项研究中,使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴铵(MTT)噻唑基,在HACAL细胞中筛选邻苯二甲酸盐和其替代物的潜在细胞毒性及其替代物在HACAT细胞中筛选蓝色测定,免疫细胞化学,流式细胞术分析和蛋白质印迹。我们证实,邻苯二甲酸丁酯(BBP),邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二丁酯(DEHP)的二丁基酯(DEHP)具有遗留毒性作用,导致细胞死亡,邻苯二甲酸苄酯(BBP),二 - 乙基己基苯甲酸酯等常见的邻苯二甲酸酯。在已知的邻苯二甲酸邻苯二甲酸邻苯二甲酸丁基酯(ATBC)中,对细胞毒性进行测试,对邻乙酸乙酯(ATBC),三乙基二乙酸三乙酯(ATEC)和三己酯(ATHC)进行测试。结果,Atec显示出与邻苯二甲酸盐的细胞毒性相似的细胞毒性,而ATBC和ATHC即使高剂量(5mg / ml)也没有显示出显着的细胞毒性。

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