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Toxicologic Pathology
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Articles

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

Masanao Yokohira1, Toshiya Kuno1, Keiko Yamakawa1, Kyoko Hosokawa1, Yoko Matsuda1, Nozomi Hashimoto1, Satoshi Suzuki1, Kousuke Saoo1 and Katsumi Imaida1,2

1 Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan
2 Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan

Correspondence: Katsumi Imaida, Prof. Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750–1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761–0793, Japan; E-mail:imaida{at}med.kagawa-u.ac.jp.

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.

Key Words: particulates • nanoparticles • respiratory toxicology • fine particle • intratracheal instillation

This version was published on June 1, 2008

Toxicologic Pathology, Vol. 36, No. 4, 620-631 (2008)
DOI: 10.1177/0192623308318214
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