Lung Toxicity of 16 Fine Particles on Intratracheal Instillation in a Bioassay Model Using F344 Male Rats

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 to...

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Bibliographic Details
Published in:Toxicologic pathology 2008-06, Vol.36 (4), p.620-631
Main Authors: Yokohira, Masanao, Kuno, Toshiya, Yamakawa, Keiko, Hosokawa, Kyoko, Matsuda, Yoko, Hashimoto, Nozomi, Suzuki, Satoshi, Saoo, Kousuke, Imaida, Katsumi
Format: Article
Language:English
Subjects:
Air Pollutants - toxicity
Animals
Biological and medical sciences
Biological Assay
Immunohistochemistry
Intubation, Intratracheal
Lung - drug effects
Lung - pathology
Male
Medical sciences
Particle Size
Particulate Matter - toxicity
Pneumonia - chemically induced
Pneumonia - pathology
Rats
Rats, Inbred F344
Toxicology
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Summary: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) > β-cyclodextrin > diesel standard > titanium dioxide (in Experiment 2A) > CaCO3.
ISSN:0192-6233
1533-1601
DOI:10.1177/0192623308318214