title: Pathological features of different sizes of nickel oxide following intratracheal instillation in rats.
abstract: Focusing on the "size" impact of particles, the objective of this study was to analyze morphological and qualitative changes over time in the development of inflammation and collagen deposition in lung tissue after intratracheal instillation of two sizes of nickel oxide in rats, in comparison with the results of instillation of crystalline silica and titanium dioxide. The fine-sized nickel oxide sample (nNiOm: median diameter of agglomerated particles 0.8 microm) was prepared from crude particles of nickel oxide (median diameter of primary particle 27 nm) by liquid-phase separation. Another samples of micrometer-sized nickel oxide (NiO: median diameter of particles 4.8 microm), crystalline silica (Min-U-SIL-5; geometric mean diameter 1.6 microm, geometric standard deviation [GSD] 2.0), and TiO(2) (geometric mean diameter 1.5 microm, GSD 1.8) were also used. Well-sonicated samples of 2 mg per 0.4 ml saline or saline alone (control) were intratracheally instilled into Wistar rats (males, 10 wk old). Bronchoalveolar lavage fluid (BAL)F and lung tissue were examined at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo after instillation, from 5 rats of each group. Histopathological findings showed that the infiltration of macrophages or polymorphonuclear cells and the alveolitis in rats treated with nNiOm were remarkable over time and similar to the effects of crystalline silica. The numbers of total cells in BALF and the percentage of plymorphonuclear leukocytes (PMNs) also increased in the nNiOm group and silica group. The point counting method (PCM) showed a significant increase of inflammatory area, with the peak at 3 mo after instillation in the nNiOm group. In contrast, NiO treatment showed only a slight inflammatory change. Collagen deposition in two regions in the lung tissue (alveolar duct and pleura) showed an increasing collagen deposition rate in nNiOm at 6 mo. Our results suggest that submicrometer nano-nickel oxide is associated with greater toxicity, as for crystalline silica, than micrometer-sized nickel oxide. Biological effects of factors of particle size reduction, when dealing with finer particles such as nanoparticles, were reconfirmed to be important in the evaluation of respirable particle toxicity.
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan. gamisan@med.uoeh-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ogami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.forename: Motoi
authors.initials: M
authors.lastname: Todoroki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nishi
authors.forename: Chikara
authors.initials: C
authors.lastname: Kadoya
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Isamu
authors.initials: I
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D008855:Microscopy, Electron, Scanning; D009532:Nickel / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D052638:Particulate Matter; D012822:Silicon Dioxide; D009532:Nickel; D003094:Collagen; C028007:nickel monoxide