Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats

Abstract

The tissue distribution and toxicity of intravenously administered nanoparticles of titanium dioxide (TiO₂) (>10 wt.% at <100 nm size) were investigated because of the fundamental importance to obtain information on the kinetics of this widely used nanoparticle in a situation of 100% bioavailability. Male Wistar rats were treated with single intravenous injections of a suspension of TiO₂ in serum (5 mg/kg body weight), and the tissue content of TiO₂ was determined 1, 14, and 28 days later. Biochemical parameters and antigens in serum were also assessed to determine potential pathological changes. The health and behavior of the animals were normal throughout the study. There were no detectable levels of TiO₂ in blood cells, plasma, brain, or lymph nodes. The TiO₂ levels were highest in the liver, followed in decreasing order by the levels in the spleen, lung, and kidney, and highest on day 1 in all organs. TiO₂ levels were retained in the liver for 28 days, there was a slight decrease in TiO₂ levels from day 1 to days 14 and 28 in the spleen, and a return to control levels by day 14 in the lung and kidney. There were no changes in the cytokines and enzymes measured in blood samples, indicating that there was no detectable inflammatory response or organ toxicity. Overall, rats exposed to TiO₂ nanoparticles by a route that allows immediate systemic availability showed expected tissue distribution, no obvious toxic health effects, no immune response, and no change in organ function. Therefore, even with 100% bioavailability of the 5 mg/kg TiO₂ dose afforded by the intravenous route of administration, there were no remarkable toxic effects evident in the experimental animals. These results indicate that TiO₂ nanoparticles could be used safely in low doses.