Toxic Effects of Low-Level Long-Term Inhalation Exposures of Rats to Nickel Oxide Nanoparticles

Int J Mol Sci. 2019 Apr 10;20(7):1778. doi: 10.3390/ijms20071778.


Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical characteristics of the bronchoalveolar lavage fluid along with a paradoxically little pronounced pulmonary pathology associated with a rather low chronic retention of nanoparticles in the lungs. There were various manifestations of systemic toxicity, including damage to the liver and kidneys; a likely allergic syndrome as indicated by some cytological signs; transient stimulation of erythropoiesis; and penetration of nickel into the brain from the nasal mucous membrane along the olfactory pathway. Against a picture of mild to moderate chronic toxicity of nickel, its in vivo genotoxic effect assessed by the degree of DNA fragmentation in nucleated blood cells (the RAPD test) was pronounced, tending to increasing with the length of the exposure period. When rats were given orally, in parallel with the toxic exposure, a set of innocuous substances with differing mechanisms of expected bioprotective action, the genotoxic effect of NiO-NPs was found to be substantially attenuated.

Keywords: bioprotectors; genotoxicity; inhalation exposure; nickel oxide nanoparticles; pulmonary responses; systemic toxicity.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Inhalation Exposure / adverse effects*
  • Liver / pathology
  • Liver / ultrastructure
  • Lung / metabolism
  • Lung / ultrastructure
  • Male
  • Nanoparticles / toxicity*
  • Nickel / toxicity*
  • Organ Specificity
  • Rats
  • Time Factors


  • Nickel
  • nickel monoxide