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首页> 外文会议>ACS Symposium Series 890; Symposium on Nanotechnology and the Environment: Applications and Implications; ; >Lung Toxicity Bioassay Study in Rats with Single-Wall Carbon Nanotubes
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Lung Toxicity Bioassay Study in Rats with Single-Wall Carbon Nanotubes

机译：单壁碳纳米管对大鼠的肺毒性生物测定研究

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The objective of this study was to evaluate the toxicity of intratracheally instilled single wall carbon nanotubes (SWCNT) in the lungs of rats. The pulmonary toxicity of intratracheally instilled carbon nanotubes was compared with a positive control particle-type, quartz, and carbonyl iron particles (a negative control particle-type). The lungs of rats were intratracheally instilled with either 1 or 5 mg/kg of the following control or particle-types: 1) carbon nanotubes; 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) and PBS + 1% Tween 80 instilled rats served as additional controls. After exposures, the lungs of PBS and particle-exposed rats were assessed both using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and by histopathological evaluation of lung tissue at 24 hrs, 1 week, 1 month and 3 months post-instillation exposure. High dose exposures to SWCNT produced mortality in ～15% of instilled rats within 24 hrs post-instillation. This mortality was due to mechanical blockage of the large airways by the instillate, and did not result from inherent lung toxicity of the instilled SWCNT particulate. Data from the bronchoalveolar lavage and cell proliferation studies demonstrated that lung exposures to quartz particles produced persistent enhancement in pulmonary inflammation, cytotoxicity, and lung cell parenchymal cell proliferation indices. Alternatively, single wall carbon nanotube exposures produced transient inflammatory and cell injury effects at 1 day postexposure, due primarily to the blockage of airways and resulting injury by the instillate. Histopathological analyses revealed that exposures to quartz particles (5 mg/kg) resulted in dose-dependent lung inflammatory responses, in association with accumulation of foamy alveolar macrophages and early lung fibrosis at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron particles produced no significant adverse effects. Lung exposures to SWCNT in rats produced a non dose-dependent foreign tissue body reaction, as evidenced by a series of muitifocal mononuclear granulomas. The granulomas were characterized by black SWCNT bolus material in the center, and surrounded by macrophage-like giant cells. The lesions did not appear to progress beyond 1 month postexposure. Surprisingly, the bronchoalveolar lavage and cell proliferation results were not predictive biomarkers of the SWCNT-induced granulomatous lesions, unlike pulmonary responses to quartz particles. The observation of a SWCNT dust-induced foreign tissue reaction is not consistent with the following: 1) lack of lung toxicity by assessing lavage parameters; 2) lack of lung toxicity by measuring cell proliferation parameters; 3) an apparent lack of a dose response relationship; 4) non-uniform distribution of lesions; 5) the paradigm of dust-related lung toxicity effects; 6) possible regression of effects over time. Moreover, recently reported data from two exposure assessment studies at the workplace indicate very low aerosol SWCNT exposure levels. Therefore, the physiological relevance of these findings remains to be determined. Thus, to reconcile the apparent discrepancies in this lung bioassay study, it is critical that the pulmonary effects of SWCNT soot in rats be assessed by generating SWCNT aerosols in an inhalation toxicity study.
机译：这项研究的目的是评估气管内滴注的单壁碳纳米管（SWCNT）对大鼠肺的毒性。将气管内滴注的碳纳米管的肺毒性与阳性对照颗粒类型，石英和羰基铁颗粒（阴性对照颗粒类型）进行了比较。气管内滴注1或5 mg / kg以下对照或颗粒类型的大鼠肺：1）碳纳米管； 2）石英颗粒，3）羰基铁颗粒。磷酸盐缓冲盐水（PBS）和PBS + 1％Tween 80滴注的大鼠作为其他对照。暴露后，使用支气管肺泡灌洗（BAL）流体生物标记物，细胞增殖方法以及滴注后24小时，1周，1个月和3个月的肺组织病理学评估来评估PBS和暴露于颗粒的大鼠的肺接触。高剂量暴露于SWCNT会在滴注后24小时内约有15％的滴注大鼠死亡。该死亡率是由于滴注物对大气道的机械阻塞所致，而不是由于滴注的SWCNT颗粒固有的肺毒性所致。支气管肺泡灌洗和细胞增殖研究的数据表明，肺部暴露于石英颗粒会持续增强肺部炎症，细胞毒性和肺实质细胞增殖指数。或者，单壁碳纳米管暴露在暴露后1天会产生短暂的炎症和细胞损伤作用，这主要是由于气道阻塞和注射液造成的损伤。组织病理学分析表明，暴露于石英颗粒（5 mg / kg）会导致剂量依赖性的肺部炎症反应，并伴有泡沫性肺泡巨噬细胞的积累和正常颗粒沉积部位的早期肺纤维化。肺暴露于羰基铁颗粒不会产生明显的不利影响。大鼠的肺部接触SWCNT会产生非剂量依赖性的异物组织体反应，一系列多灶性单核肉芽肿证明了这一点。肉芽肿的中心是黑色的SWCNT团块，周围是巨噬细胞样巨细胞。暴露后1个月以上，病变似乎没有进展。令人惊讶的是，与肺对石英颗粒的反应不同，支气管肺泡灌洗和细胞增殖结果不是SWCNT诱导的肉芽肿性病变的预测生物标志物。 SWCNT粉尘引起的异物组织反应的观察结果与以下情况不一致：1）通过评估灌洗参数，缺乏肺毒性； 2）通过测量细胞增殖参数缺乏肺毒性； 3）明显缺乏剂量反应关系； 4）病灶分布不均匀； 5）与粉尘有关的肺毒性作用的范例； 6）随着时间的流逝，效应可能会消退。此外，最近在工作场所进行的两次接触评估研究报告的数据表明，SWCNT的气溶胶暴露水平非常低。因此，这些发现的生理相关性尚待确定。因此，为了调和该肺生物测定研究中的明显差异，至关重要的是，在吸入毒性研究中通过产生SWCNT气雾剂来评估SWCNT烟尘对大鼠的肺部影响。

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