The in vivo studies for copper (Cu) and copper oxide (CuO) nanoparticles show different perturbations on liver, kidney or neuronal functions at high doses due to the release of copper ions.

 

Acute oral toxicity of copper particles has shown a significant correlation with its size distribution where micro-sized copper particles were classified as non-toxic (LD50 < 5000 mg/kg). On the contrary, nano-sized copper particles had a LD50 of about 400 mg/kg in mice and were classified as moderately toxic based on the Hodge and Sterner scale [1]. After oral gavage of nano- and micro-particles with a concentration of 70 mg/kg body weight in mice and an equivalent of soluble CuCl2 (147,6 mg/kg) only the nano-copper generated an accumulation of excessive alkalescent substance and copper ions that even culminated in a metabolic alkalosis and overload of copper ions similarly to the results obtained with copper chloride [1].

Another in vivo study conducted with rats analysing urine, serum, and extracts from liver and kidney tissues by metabolomic approach after up to 200 mg Cu NP/kg body weight treatment for 5 days showed the induction of severe hepatotoxicity (toxin-induced liver disease) and nephrotoxicity (poisonous effect on the kidneys) similar to copper overload [2]. The nephrotoxicity was mainly caused by an oxidative stress and at high doses (up to 600 mg/kg body weight) cell death (apoptosis) via both extrinsic and intrinsic pathway was observed [3].

Treatment of mice via inhalation (4 hr/day 5d/week for 2 weeks with 3,5 mg/m3) or instillation (24 hr post-exposure 3, 35, and 100 µg/mouse) resulted in both cases in an induction of inflammatory responses and the recruitment of neutrophils into the lung. The simultaneous administration of Cu NP and bacteria impaired the pulmonary clearance against Klebsiella pneumonia [4].

After intranasal instillation of Cu-NP in mice not only the tissue and cells in direct contact are affected but also systemic effects have been observed. After middle dose of 40 mg/kg body weight treatment significant changes in various neurotransmitter levels were measured in different brain regions, indicating a systemic effect in tissues were no particle or ion accumulation could be observed [5].

 

In General the described effects may be summarised in the following way: The particles determine the biodistribution and the release of copper ions, whereas the toxicity is comparable to cupper ions or other soluble nanomaterials.

 

Literature arrow down

  1. Meng, H et al. (2007), Toxicol Lett, 175(1-3): 102-110.
  2. Lei, R et al. (2008), Toxicol Appl Pharmacol, 232(2): 292-301.
  3. Sarkar, A et al. (2011), Toxicology, 290(2-3): 208-217.
  4. Kim, JS et al. (2011), Part Fibre Toxicol, 8(1): 29.
  5. Zhang, L et al. (2012), Nanotoxicology, 6(5): 562-575.

 

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