The tissue distribution and toxicity of intravenously administered nanoparticles of titanium dioxide (TiO
2) (>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 TiO
2 in serum (5 mg/kg body weight), and the tissue content of TiO
2 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 TiO
2 in blood cells, plasma, brain, or lymph nodes. The TiO
2 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. TiO
2 levels were retained in the liver for 28 days, there was a slight decrease in TiO
2 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 TiO
2 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
TiO
2 dose afforded by the intravenous route of administration, there were no remarkable toxic effects evident in the experimental
animals. These results indicate that TiO
2 nanoparticles could be used safely in low doses.