Toxic effects of low-level long-term inhalation exposures of rats to nickel oxide nanoparticles

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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.For modeling chronic intoxication development under low-level but long-term inhalation exposures to NiO nanoparticles, the experiments were carried out on outbred white female rats from our own breeding colony with an initial body weight of 150–220 g, with a minimum of 12 animals in exposed and control groups. Rats were housed in conventional conditions, breathed unfiltered air, and were fed standard balanced food. The experiments were planned and implemented in accordance with the “International guiding principles for biomedical research involving animals” developed by the Council for International Organizations of Medical Sciences (1985) and were approved by the Ethics Committee of the Ekaterinburg Medical Research Center Medical for Prophylaxis and Health Protection in Industrial Workers