Biodistribution and toxicity of inhaled nickel oxide nanoparticles: Potential application to realistic exposure

As industrial applications of nickel oxide nanoparticles (NiONPs) increase due to their high surface energy and magnetic properties, their potential adverse health effects are emerging as a public concern. We administered NiONPs to mice via pharyngeal aspiration for 90 days and investigated their biodistribution and toxicity. NiONPs were primarily deposited in lung tissues, with translocation into other tissues. Blood triglyceride levels decreased significantly in male mice but increased in female mice, and glucose levels were elevated in both male and female mice. NiONPs increased the total number of pulmonary immune cells, accompanied by increases in the proportions of neutrophils and lymphocytes. Similarly, the concentrations of proinflammatory cytokines and tissue damage-related mediators increased notably in the lungs of male and female mice exposed to NiONPs (50 μg/mouse) compared with controls. Collagen fibers, lamellar body-like structures, and tubular myelin were frequently observed in the lung tissues of mice exposed to NiONPs. Given that toxicity test results at unrealistic doses are used only to a limited extent in setting permissible exposure limits, we also compared differences across exposure frequencies for the same amount. The lung burden was 2.51-fold higher in mice administered a 50 μg single dose than in mice administered 10 μg five times, and the pulmonary level of inflammatory mediators and the proportion of neutrophils were also higher in mice administered a 50 μg single dose. Meanwhile, the effects on each test item showed a similar trend between the two groups. Collectively, we conclude that chronic airway exposure to NiONPs may cause lung tissue damage by activating inflammatory mediators and may also result in systemic adverse health effects, depending on their distribution. Considering the unique lamellar body-like structures observed in the lungs, we also believe that further study is needed to elucidate their formation process and chronic health effects.