Pathological features of different sizes of nickel oxide following intratracheal instillation in rats

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 μm) 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 μm), crystalline silica (Min-U-SIL-5; geometric mean diameter 1.6 μm, geometric standard deviation [GSD] 2.0), and TiO2 (geometric mean diameter 1.5 μm, 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.

[1]  R. Henderson,et al.  Biochemical responses of rat and mouse lung to inhaled nickel compounds. , 1989, Toxicology.

[2]  G. Oberdörster,et al.  Carcinogenicity assessment of selected nickel compounds. , 1997, Toxicology and applied pharmacology.

[3]  David Brown,et al.  The pulmonary toxicology of ultrafine particles. , 2002, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.

[4]  J. Finkelstein,et al.  Acute pulmonary effects of ultrafine particles in rats and mice. , 2000, Research report.

[5]  H. Yamato,et al.  Biopersistence of man-made fibers by animal inhalation experiments in recent reports. , 2001, Industrial health.

[6]  B. Lehnert,et al.  Correlation between particle size, in vivo particle persistence, and lung injury. , 1994, Environmental health perspectives.

[7]  Y. Cheng,et al.  Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[8]  NTP Toxicology and Carcinogenesis Studies of Nickel Oxide (CAS No. 1313-99-1) in F344 Rats and B6C3F1 Mice (Inhalation Studies). , 1996, National Toxicology Program technical report series.

[9]  H. Yamato,et al.  Effect of Particle Size of Intratracheally Instilled Crystalline Silica on Pulmonary Inflammation , 2007, Journal of occupational health.

[10]  I. Tanaka,et al.  Biological half-time in rats exposed to nickel monosulfide (amorphous) aerosol by inhalation , 1988, Biological Trace Element Research.

[11]  G. Oberdorster,et al.  Significance of particle parameters in the evaluation of exposure-dose-response relationships of inhaled particles. , 1996, Inhalation toxicology.

[12]  T. Webb,et al.  Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  David B Warheit,et al.  Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[14]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  W. MacNee,et al.  The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area , 2007, Occupational and Environmental Medicine.

[16]  Robert Gelein,et al.  PULMONARY INFLAMMATORY RESPONSE TO INHALED ULTRAFINE PARTICLES IS MODIFIED BY AGE, OZONE EXPOSURE, AND BACTERIAL TOXIN , 2000, Inhalation toxicology.

[17]  Jie Chen,et al.  Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats , 2004, Toxicology and industrial health.

[18]  K. Fukuda,et al.  Lung lesions induced by intratracheal instillation of nickel fumes and nickeloxide powder in rats. , 1997, Industrial health.

[19]  C. Cox,et al.  Intratracheal instillation versus intratracheal-inhalation of tracer particles for measuring lung clearance function. , 1997, Experimental lung research.

[20]  David M. Brown,et al.  Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components , 2000, Occupational and environmental medicine.

[21]  David M. Brown,et al.  Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black. , 2000, The European respiratory journal.

[22]  K. Tsuchiya,et al.  Lung burden of green nickel oxide aerosol and histopathological findings in rats after continuous inhalation , 1988, Biological Trace Element Research.

[23]  H. Yamato,et al.  Patterns of Histopathological Change Determined by the Point Counting Method and Its Application for the Hazard Assessment of Respirable Dust , 2004, Inhalation toxicology.