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Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

机译:氧化锌纳米粒子:大鼠90天重复剂量皮肤毒性研究

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Abstract: Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411?using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90?days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.
机译:摘要:氧化锌(ZnO)是一种持久的,广谱的物理防晒剂,可预防皮肤癌,晒伤和光老化。由于消费者偏爱较大尺寸的较大尺寸的ZnO颗粒,因此经常在防晒霜中使用,而较大尺寸的ZnO颗粒在皮肤上使用时不透明。尽管1999年美国食品药品监督管理局批准了在防晒剂中使用纳米颗粒(NPs),但仍存在安全隐患。这项研究的目的是根据《经济合作与发展组织测试指南411》的《良好实验室规范》评估皮肤应用后ZnO NPs的亚慢性毒性。将Sprague Dawley大鼠随机分为八组(一个对照组,一个媒介对照,三个实验组和三个恢复组)。将不同浓度的ZnO NPs皮下施用至实验组大鼠90天。每天测量并记录临床观察以及体重和食物消耗。确定血液学和生化参数。对所有动物的选定组织进行大体病理学和组织病理学检查。进行组织分析以确定靶器官组织分布。实验组的死亡率没有增加。尽管在施用部位有剂量依赖性刺激,但在其他器官中未发现与ZnO NPs有关的异常发现。肝脏,小肠,大肠和粪便中ZnO浓度的增加被认为是通过舔食口服摄入ZnO NP引起的。经由皮肤途径似乎限制了ZnO NPs通过皮肤的渗透。这项研究表明,皮下施用最高至1000 mg / kg体重的ZnO NP并没有观察到不利影响。

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