Time-course comparison of pulmonary inflammation induced by intratracheal
instillation of four different nickel oxide nanoparticles in male Fischer
rats |
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| Authors: | Toshio Kobayashi Yutaka Oshima Yasuhiro Tsubokura Takako Muroi Shozo Ajimi Makoto Nakai Kenji Kawaguchi Takeshi Sasaki Naohide Shinohara Nobuya Imatanaka |
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| Institution: | 1.CERI Hita, Chemicals Evaluation and Research Institute, Japan, 3-822 Ishii-machi, Hita-shi, Oita 877-0061, Japan;2.The United Graduate School of Veterinary Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi-shi, Yamaguchi 753-8511, Japan;3.National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8560, Japan |
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| Abstract: | Occupational exposure to nickel oxide (NiO) is an important cause of respiratory tract cancer. Toxicity is known to be associated with the dissociated component, i.e. nickel (II) ions. To address the relationship between physicochemical properties, including solubility in artificial lysosomal fluid, of NiO and time-course changes in the pulmonary response, we conducted an intratracheal instillation study in male Fischer rats using four different well-characterized NiO products, US3352 (NiO A), NovaWireNi01 (NiO B), I small particle (NiO C), and 637130 (NiO D). The NiOs were suspended in purified water and instilled once intratracheally into male F344 rats (12 weeks old) at 0 (vehicle control), 0.67, 2, and 6 mg/kg body weight. The animals were euthanized on days 3, 28, or 91 after instillation, and blood analysis, bronchoalveolar lavage fluid (BALF) testing, and histopathological examination were performed. The most soluble product, NiO B, caused the most severe systemic toxicity, leading to a high mortality rate, but the response was transient and surviving animals recovered. The second-most-soluble material, NiO D, and the third, NiO A, caused evident pulmonary inflammation, and the responses persisted for at least 91 days with collagen proliferation. In contrast, NiO C induced barely detectable inflammation in the BALF examination, and no marked changes were noted on histopathology. These results indicate that the early phase toxic potential of NiO products, but not the persistence of pulmonary inflammation, is associated with their solubility. |
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| Keywords: | intratracheal instillation nanomaterial nickel oxide pulmonary toxicity rat |
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