1 H NMR Based Metabolomics Studies of the Toxicity of Titanium Dioxide Nanoparticles in Zebrafish ( Danio rerio )

Titanium dioxide nanoparticles (TiO 2 ‐NPs) are widely used in foods, cosmetics, and pharmaceuticals. In the present study, male and female zebrafish ( Danio rerio ) were exposed to sub‐lethal concentrations of TiO 2 ‐NPs dosed at 0.1 mg/L (low) and 5.0 mg/L (high), respectively. 1 H–nuclear magnetic resonance (NMR) profiling combined with univariate and multivariate statistics was used to assess metabolic alterations in the TiO 2 ‐NP‐treated fish. Purine metabolism—including the anabolism/catabolism of ATP, ADP, AMP, xanthine, and inosine—was significantly influenced, which may indicate some genotoxicity resulting from TiO 2 ‐NP exposure. Increasing the dose and duration of TiO 2 ‐NP exposure led to additional metabolic disturbances in glycerophospholipid metabolism and the Krebs cycle. Our findings demonstrate the potential applicability of using a metabolomics approach to determine underlying metabolic disturbances caused by TiO 2 ‐NPs.