三氧化钨纳米颗粒在吸入研究和气管内滴注研究中的肺部毒性。
Pulmonary toxicity of tungsten trioxide nanoparticles in an inhalation study and an intratracheal instillation study.
机构信息
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Fukuoka, Japan.
Center for Stress-related Disease control and Prevention, University of Occupational and Environmental Health, Fukuoka, Japan.
出版信息
J Occup Health. 2022 Jan;64(1):e12367. doi: 10.1002/1348-9585.12367.
OBJECTIVES
We conducted inhalation and intratracheal instillation studies in order to examine the effects of tungsten trioxide (WO ) nanoparticles on the lung, and evaluated whether or not the nanoparticles would cause persistent lung inflammation.
METHODS
In the inhalation study, male 10-week-old Fischer 334 rats were classified into 3 groups. The control, low-dose, and high-dose groups inhaled clean air, 2, and 10 mg/m WO nanoparticles, respectively, for 6 h each day for 4 weeks. The rats were dissected at 3 days, 1 month, and 3 months after the inhalation, and the bronchoalveolar lavage fluid (BALF) and lung tissue were examined. In the intratracheal instillation study, male 12-week-old Fischer 334 rats were divided into 3 subgroups. The control, low-dose, and high-dose groups were intratracheally instilled 0.4 ml distilled water, 0.2, and 1.0 mg WO nanoparticles, respectively, dissolved in 0.4 ml distilled water. The rats were sacrificed at 3 days, 1 week, and 1 month after the intratracheal instillation, and the BALF and lung tissue were analyzed as in the inhalation study.
RESULTS
The inhalation and instillation of WO nanoparticles caused transient increases in the number and rate of neutrophils, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-2 in BALF, but no histopathological changes or upregulation of heme oxygenase (HO)-1 in the lung tissue.
CONCLUSION
Our results suggest that WO nanoparticles have low toxicity to the lung. According to the results of the inhalation study, we also propose that the no observed adverse effect level (NOAEL) of WO nanoparticles is 2 mg/m .
目的
我们进行了吸入和气管内滴注研究,以研究三氧化钨(WO )纳米颗粒对肺部的影响,并评估纳米颗粒是否会引起持续的肺部炎症。
方法
在吸入研究中,将 10 周龄雄性 Fischer 334 大鼠分为 3 组。对照组、低剂量组和高剂量组分别吸入清洁空气、2 和 10 mg/m WO 纳米颗粒,每天吸入 6 小时,持续 4 周。在吸入后 3 天、1 个月和 3 个月对大鼠进行解剖,检查支气管肺泡灌洗液(BALF)和肺组织。在气管内滴注研究中,将 12 周龄雄性 Fischer 334 大鼠分为 3 个亚组。对照组、低剂量组和高剂量组分别气管内滴注 0.4 ml 蒸馏水、0.2 和 1.0 mg WO 纳米颗粒,溶于 0.4 ml 蒸馏水中。在气管内滴注后 3 天、1 周和 1 个月处死大鼠,分析 BALF 和肺组织,与吸入研究相同。
结果
吸入和气管内滴注 WO 纳米颗粒导致 BALF 中中性粒细胞数量和中性粒细胞比率、细胞因子诱导的中性粒细胞趋化因子(CINC)-1 和 CINC-2一过性增加,但肺组织中无组织病理学改变或血红素加氧酶(HO)-1 上调。
结论
我们的结果表明 WO 纳米颗粒对肺部的毒性较低。根据吸入研究的结果,我们还提出 WO 纳米颗粒的无观察到不良效应水平(NOAEL)为 2 mg/m 。