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首页> 外文期刊>Environmental Science & Technology >Nanoscale and Fine Zinc Oxide Particles: Can in Vitro Assays Accurately Forecast Lung Hazards following Inhalation Exposures?
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Nanoscale and Fine Zinc Oxide Particles: Can in Vitro Assays Accurately Forecast Lung Hazards following Inhalation Exposures?

机译：纳米级和细小的氧化锌颗粒：体外分析能否准确预测吸入暴露后的肺部危害？

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摘要

The development of accurate in vitro screening assays to assess lung hazard potential of nanomaterials is a highly desirable goal. However, some studies have noted little correlation between in vitro and in vivo results. Moreover, a recent National Academy of Sciences report predicts that future hazard testing will be conducted primarily using cell culture assays. The three major objectives of this study were to compare lung toxicity impacts of nanoscale (NZnO) vs fine zinc oxide (FZnO) particulates, assess predictability of in vitro cell culture systems, and compare effects of instillation vs inhalation exposures in rats. Physicochemical aspects of ZnO particle types were rigorously characterized and did not agree with specifications provided by the supplier; i.e., the ZnO particle types were closer in size than advertised. Rats were exposed in vivo ether by intratracheal instillation to 1 or 5 mg/kg of nanoscale or fine size zinc oxide particle types or by inhalation to aerosols of 25 or 50 mg/m~3 for 1 or 3 h. Lung inflammation, cytotoxicity, and histopathological endpoints were assessed at several time points postexposure. Three different in vitro culture conditions were utilized. Cultures of (1) rat lung epithelial cells, (2) primary alveolar macrophages, and (3) alveolar macrophages-L2 lung epithelial cell cocultures were incubated with fine or nano ZnO particles and evaluated for cytotoxicity biomarkers (LDH) and proinflammatory cytokines (MIP-2 and TNF-a). In vivo exposures to instilled or inhaled fine or nanoscale ZnO produced "metal fume fever" responses, characterized by transient short-term lung inflammatory or cytotoxic responses. Alternatively, in vitro exposures to fine or nanoscale ZnO particles produced minor cytotoxic responses at 4 and 24 h, only in cocultures and at the highest (particle overload) dose with little detectable proinflammatory cytokine generation (MIP-2, and TNF-ot|. To summarize, the comparisons of in vivo and in vitro toxicity measurements following nano or fine ZnO particle exposures demonstrated little convergence and few differences in potency.
机译：开发精确的体外筛选测定法以评估纳米材料对肺部的潜在危害是一个非常理想的目标。但是，一些研究表明，体外和体内结果之间几乎没有相关性。此外，美国国家科学院最近的一份报告预测，未来的危险性测试将主要使用细胞培养测定法进行。这项研究的三个主要目标是比较纳米级（NZnO）与细氧化锌（FZnO）颗粒对肺部的毒性影响，评估体外细胞培养系统的可预测性，以及比较滴注与吸入暴露对大鼠的影响。 ZnO颗粒类型的理化特性经过严格表征，与供应商提供的规格不符；即ZnO颗粒的尺寸比广告中的尺寸更近。通过气管内滴注至1或5 mg / kg的纳米级或超细氧化锌颗粒类型或通过吸入25或50 mg / m〜3的气雾剂1或3 h，使大鼠体内暴露于乙醚中。在暴露后几个时间点评估肺部炎症，细胞毒性和组织病理学终点。利用了三种不同的体外培养条件。将（1）大鼠肺上皮细胞，（2）原发性肺泡巨噬细胞和（3）肺泡巨噬细胞-L2肺上皮细胞共培养物的培养物与ZnO细颗粒或纳米颗粒一起孵育，并评估其细胞毒性生物标志物（LDH）和促炎细胞因子（MIP） -2和TNF-a）。体内接触滴入或吸入的细或纳米级ZnO会产生“金属烟雾热”反应，其特征是短暂的短期肺部炎症或细胞毒性反应。或者，在体外暴露于细或纳米级的ZnO颗粒仅在共培养和最高（颗粒超载）剂量下于4和24 h产生较小的细胞毒性反应，几乎没有可检测的促炎细胞因子生成（MIP-2和TNF-ot |）。总而言之，纳米或细ZnO颗粒暴露后的体内和体外毒性测量结果的比较表明，收敛性很小，效力差异也很小。

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  • 来源
    《Environmental Science & Technology》 |2009年第20期|7939-7945|共7页
  • 作者

    D. B. WARHEIT; C. M. SAYES; K. L. REED;

  • 作者单位

    DuPont Haskeli Global Centers for Health and Environmental Sciences, Newark, DE;

    DuPont Haskeli Global Centers for Health and Environmental Sciences, Newark, DE Texas A&M University, College Station, TX;

    DuPont Haskeli Global Centers for Health and Environmental Sciences, Newark, DE;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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