Acute toxicity and biodistribution of different sized copper nano-particles in rats after oral administration

In order to compare the detailed toxicity of nano‑copper and CuCl2·2H2O (Cu ions) in vivo, the oral toxicity of four differently sized Cu particles (30 nm, 50 nm, 80 nm and 1 μm) on rats was investigated compared with CuCl2·2H2O in acute exposure scenarios. We compared the acute LD50 values and evaluated the kinetics of Cu following a single equivalent dose (200 mg/kg) of five Cu materials. Continuous gavage of nano‑copper for 7 days, the mortality rates, relative organ weights, and hematological, biochemical, and histopathologic characteristics of rats were examined. The results showed that the LD50 values of Cu ions, 30 nm, 50 nm, 80 nm, and 1 μm copper particles were 359.6, 1022, 1750, 2075, and >5000 mg/kg, respectively. Physiological and biochemical indexes indicated that 80 nm nano‑copper (Cu NPs) produced the highest degrees of toxicity in short term. The liver and kidneys were the major organs most affected by Cu NPs, and also the target organs for Cu accumulation. The toxic effects of Cu ions are similar to those of nano‑copper, but they were not the same. Therefore, the toxic effect of nano‑copper is likely to be the result of the dual action of nano‑copper particles and copper ions. Collectively, the acute toxic effects produced by Cu NPs were highly correlated with particle size. Moreover, the toxic effects produced by repeated dosing differed from those produced by a single dose, and this may be due to organ targeting effects that are dependent on the size of the nano-particles.