Sex-Specific Effects of Short-Term Oral Administration of Food-Grade Titanium Dioxide Nanoparticles in the Liver and Kidneys of Adult Rats.

Titanium dioxide (TiO₂) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO₂ is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO₂ nanoparticles (NPs) (primary size < 25 nm) in male and female rats that were orally exposed for 5 days to 0, 1, and 2 mg/kg body weight per day (comparable with daily E171 consumption). Selected liver and kidney toxicity endpoints included serum biomarkers, histopathological analysis and expression of osteopontin (SPP1), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and neuropeptide Y (NPY). Although TiO₂ NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO₂ NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO₂ NPs in other items that can lead to human exposure. [ABSTRACT FROM AUTHOR]