Lung Toxicity of 16 Fine Particles on Intratracheal Instillation in a Bioassay Model Using F344 Male Rats
Lung Toxicity of 16 Fine Particles on Intratracheal Instillation in a Bioassay Model Using F344 Male Rats
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DOI：
10.1177/0192623308318214
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发表时间：
2008-06-01
影响因子：
1.5
通讯作者：
Imaida, Katsumi
中科院分区：
文献类型：
--
作者：
Yokohira, Masanao;Kuno, Toshiya;Imaida, Katsumi
我们开发了一种生物测定模型，以估计肺内滴注后早期肺中细颗粒的毒性（Yokohira等人，2005; Yokohira等人，2007）。进行本实验以通过基于作为阳性对照的滴注石英（4 mg至0 mg）的剂量依赖性毒性估计适当剂量并评估无悬浮液的粉末状颗粒的影响来改进模型（实验1）。此外，用开发的生物测定法（实验2A、2B和2C）检查一系列颗粒的毒性。所选择的材料是十六种颗粒，包括纳米颗粒和柴油粉。结果表明：2 mg石英混悬于0.2mL生理盐水中的剂量对急性和亚慢性炎症反应的敏感性最高。尽管包括纳米颗粒在内的一些材料表现出对于敏感性评估来说太强的毒性，但排序可以如下给出：CuO >石英>中和的Na 2 PdCl 4> NiO >水滑石> MnO 2>柴油>二氧化钛（在实验2B中）> β-环糊精>柴油标准物>二氧化钛（在实验2A中）> CaCO 3。
We have developed a bioassay model to estimate toxicity of fine particles in the lungs at an early stage after intratracheal instillation (Yokohira et al. 2005; Yokohira et al. 2007). The present experiment was conducted to improve the model by estimating appropriate doses based on dose-dependent toxicity of instilled quartz (4 mg to 0 mg) as a positive control and assessing the impact of powdered particles without suspension ( Experiment 1). In addition, examination of the toxicity of a series of particles was performed with the developed bioassay ( Experiments 2A, 2B, and 2C). The materials chosen were sixteen particles, including nanoparticles and diesel powder. Histopathological and immunohistochemical analysis of bromodeoxyuridine ( BrdU) incorporation and inducible nitric oxide synthase ( iNOS) were performed after exposure of the lungs.A dose of 2 mg quartz suspended in 0.2 mL saline was suggested to be most appropriate for sensitive detection of acute and subchronic inflammatory changes. Although some materials, including nanoparticles, demonstrated toxicity that was too strong for sensitive assessment, the ranking order could be given as follows: CuO > quartz > neutralized Na2PdCl4 > NiO > hydrotalcite > MnO2 > diesel > titanium dioxide ( in Experiment 2B) > beta-cyclodextrin > diesel standard > titanium dioxide ( in Experiment 2A) > CaCO3.