Abstract
Titanium dioxide (TiO2) is considered to have a low impact on the human body; however, the safety of TiO2 nanoparticles (NPs) has attracted attention. Our previous study showed that the toxicity of silver NPs varies depending on their size, with 10 nm particles exhibiting fatal toxicity in mice. In this study, the toxicological effects of TiO2 NPs with a crystallite size of 6 nm were investigated in male and female F344/DuCrlCrlj rats by repeated oral administration for 90 days. No mortality or treatment-related adverse effects including body weight, urinalysis, hematology, serum biochemistry, or organ weights were observed. Histopathological examination showed deposition of yellowish-brown material in the gastrointestinal lumen, nasal cavity, trachea, Peyer's patches of the ileum, cervical and mediastinal lymph nodes, and bronchus-associated lymphoid tissue; however, no biological responses including inflammation were observed around the deposits. Titanium concentration analysis in the liver, kidneys, and spleen indicated that TiO2 NPs were not accumulated in these tissues. Immunohistochemical analysis of colonic crypts showed no abnormality or preneoplastic translocation of β-catenin. With regards to DNA damaging potential, no significant increase in micronucleated or γ-H2AX positive hepatocytes was observed in the liver specimen of the 28-day repeated oral study. The deposition site of yellowish-brown materials in the 90-day study also did not show the induction of γ-H2AX. These results indicated that the repeated oral administration of TiO2 NPs with a crystallite size of 6 nm at up to 1,000 mg/kg bw/day did not exhibit any toxic effects in rats, as determined by general toxicity, titanium accumulation, and potential colonic crypt abnormality and DNA damage.
