Valentini et al. investigated the toxicity of TiO₂-NP to the cortical neuron cultures and in the brain of rats, reported the clear impact of TiO₂-NP on the neuronal cells and rat brain, and indicated the new evidences of TiO₂-NP toxicity in CNS.

While there have been reports of titanium toxicity in animal models, Fabian et al. and Warheit et al. reported that the risk of titanium toxicity was not significantly high. In a low-dose TiO₂ experiment, Fabian et al. reported no obvious toxic health effects and no detectable inflammatory response or organ toxicity in the rats intravenously injected with suspension of TiO₂ in serum (5 mg/kg body weight), despite of the expected biodistribution. In addition, Warheit et al. introduced ten different toxicity studies to form a base set of hazard test for TiO₂ ultrafine particle and found that most of the studies indicated low hazard potential in mammals or aquatic species.

The effects of TiO₂ nanoparticle toxicity in the cultured human cell were also studied. There have been a variety of human cell lines used in TiO₂ toxicity assessment experiments, including mesothelial cell, epithelial cell, trophoblast cell, and lymphoblastoid cell. In vitro studies reported by Wang et al. showed UF-TiO₂ genotoxicity and cytotoxicity in human lymphoblastic cells, with the induction of apoptosis following exposure to UF-TiO₂. Kuku and Culha used surface-enhanced Raman spectroscopy (SERS) for the multidimensional cellular dynamic information to exam the toxic response to TiO₂-NP of three cell lines of vein (HUVEC), lung carcinoma (A549), and fibroblast in skin (L929). The results pointed out that L929 is the most resistant cell line, while the HUVEC and A549 cell lines showed the collagen and lipid deformative phenomenon, respectively. Even though the pathological changes such as apoptosis and fibro-proliferative expression of the epithelial cells have been studied in several animal models, its precise mechanism is still not determined.