Male CD1 mice were subjected to nose-inhalation exposure of CeO2 nanoparticles (NPs) for 0, 7, 14 or 28 days with 14 or 28 days of recovery time at an aerosol concentration of 2 mg/m(3). Markers of lung injury and pro-inflammatory cytokines (interleukin-1beta, tumour necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid (BALF), oxidative stress in lungs, bio-accumulation, and histopathology of pulmonary and extrapulmonary tissues were assessed. BALF analysis revealed the induction of pulmonary inflammation, as evident by an increase in the influx of neutrophils with a significant secretion of pro-inflammatory cytokines that lead to generation of oxidative stress and cytotoxicity, as is evident by induction of lipid peroxidation, depletion of glutathione and increased BALF lactate dehydrogenase and protein. The histopathological examination revealed that these inhaled CeO2 NPs were located all over the pulmonary parenchyma, inducing a severe, chronic, active inflammatory response characterised by necrosis, proteinosis, fibrosis and well-formed discrete granulomas in the pulmonary tissue and tubular degeneration leading to coagulative necrosis in kidneys. Inductively coupled plasma optical emission spectrometer results showed a significant bio-accumulation of these particles in the pulmonary and extrapulmonary tissues, even after one month of post-inhalation exposure. Together, these findings suggest that inhalation exposure of CeO2 NPs can induce pulmonary and extrapulmonary toxicity.

This experiment was aimed to determine the significance of dose by comparing acute oral toxicological potential of nano-sized zinc oxide (20 nm) with its micro-sized zinc oxide. Sprague Dawley rats, 8 to 9 weeks old, were administered with 5, 50, 300, 1000 and 2000 mg/kg body weight (b.w.) of nano- and micro-sized zinc oxide suspended in distilled water once through oral gavage. The effects of the micro- and nano-sized zinc oxide on biochemical and hematological parameters were analyzed on day 14 of administration. The organs were collected for histopathology. Interestingly, inverse dose-dependent increase was noted in aspartate aminotransferase, alanine aminotransferase serum levels of nano-size zinc oxide groups when compared with their micro-sized zinc oxide. Clotting time was effected in all the male groups of nano-size zinc oxide, except in 1000 mg/kg b.w. The incidences of microscopic lesions in liver, pancreas, heart and stomach were higher in lower doses of nano-size zinc oxide compared to higher dose. However, the incidences of above lesions were higher in rats treated with a high dose of micro-sized zinc oxide. We conclude that nano-size zinc oxide exhibited toxicity at lower doses, thus alarming future nanotoxicology research needs to be focused on importance of dose metrics rather following the conventional methods while conducting in vivo experiments.

We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-α and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure.

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