Nanoparticle Toxicology: Measurements of Pulmonary Hazard Effects Following Exposures to Nanoparticles
Nanoparticle Toxicology: Measurements of Pulmonary Hazard Effects Following Exposures to Nanoparticles
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DOI：
10.1007/978-1-61779-052-2_20
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Warheit, David B.
中科院分区：
文献类型：
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作者：
Sayes, Christie M.;Reed, Kenneth L.;Warheit, David B.
接触纳米颗粒类型后的健康风险取决于两个主要因素，即危害和接触潜力。本章描述了一种肺生物测定方法，用于评估纳米颗粒在气管内滴注暴露后对大鼠的危险影响；这些肺部暴露被用作更生理相关的吸入暴露途径的替代品。这种肺生物测定的基本特征是剂量反应评估和时间过程评估，以确定任何观察到的效果的可持续性。因此，该试验的主要终点如下：(1)肺部炎症和细胞毒性的时间过程和剂量反应强度，(2)气道和肺实质细胞增殖，(3)肺组织的组织病理学评估。该分析可以使用细（色素）或超细（纳米）尺寸的颗粒进行。在该实验中，将大鼠暴露于选定浓度的颗粒溶液或悬浮液中，并在注射后24小时、1周、1个月和3个月评估其对肺的影响。通过支气管肺泡灌洗（BAL）回收颗粒暴露动物和对照动物的细胞和液体，并评估炎症和细胞毒性终点。本方案还描述了颗粒灌注大鼠肺组织的制备和组织病理学分析。该试验表明，颗粒的滴注暴露产生的影响与先前在吸入相同颗粒的研究中测量到的影响相似。
Health risks following exposures to nanoparticle types arc dependent upon two primary factors, namely, hazard and exposure potential. This chapter describes a pulmonary bioassay methodology for assessing the hazardous effects of nanoparticulates in rats following intratracheal instillation exposures; these pulmonary exposures are utilized as surrogates for the more physiologically relevant inhalation route of exposure. The fundamental features of this pulmonary bioassay are dose response evaluations and time-course assessments to determine the sustainability of any observed effect. Thus, the major endpoints of this assay are the following: (1) time course and dose response intensity of pulmonary inflammation and cytotoxicity, (2) airway and lung parenchymal cell proliferation, and (3) histopathological evaluation of lung tissue. This assay can be performed using particles in the fine (pigmentary) or ultrafine (nano) size regimes.In this assay, rats are exposed to selected concentrations of particle solutions or suspensions and lung effects are evaluated at 24 h, 1 week, 1 month, and 3 months postinstillation exposure. Cells and fluids from groups of particle-exposed animals and control animals are recovered by bronchoalveolar lavage (BAL) and evaluated for inflammatory and cytotoxic endpoints. This protocol also describes the lung tissue preparation and histopathological analysis of the lung tissue of particle-instilled rats. This assay demonstrates that instillation exposures of particles produce effects similar to those previously measured in inhalation studies of the same particulates.