Acute toxicity study in mice of orally administrated TiO₂ nanoparticles functionalized with caffeic acid

The acute toxicity of surface-modified TiO₂ nanoparticles (NPs) with caffeic acid (CA) was compared with those of its separate constituents (free CA and bare TiO₂ NPs) upon their oral administration in laboratory mice. Prior to in vivo experiments, the interfacial charge transfer (ICT) complex between surface Ti atoms and CA is thoroughly characterized. Composition and stability constants of ICT complex were determined using Job's method and Banesi-Hildebrand analysis, respectively. The experimental data were supported with quantum chemical calculations based on density functional theory (DFT). Acute toxicity signs, including biochemical alterations and extensive histopathological changes in the liver tissue of mice were detected 14 days after oral administration of bare TiO₂ NPs. However, the clinical signs of toxicity, the fractional contribution of organs, biochemical parameters of liver and kidney function, and histopathological changes in liver upon treatment with surface-modified TiO₂ NPs with CA were not observed. Also, the genotoxic potential of the ICT complex and its constituents were evaluated in leukocytes of whole blood cells in vivo by comet assay. Both, bare and surface-modified TiO₂ NPs did not display DNA damaging effect in time frame of 24 h upon their oral administration in mice.