In a 2020 study published in the Journal of Trace Elements in Medicine and Biology, researchers conducted an in vitro experiment to analyze the effects of TiO2 nanoparticles on a human neuroblastoma (SH-SY5Y) cell line. The scientists evaluated “reactive oxygen species (ROS) generation, apoptosis, cellular antioxidant response, endoplasmic reticulum stress and autophagy.” The results showed that exposure to the nanoparticles “induced ROS generation in a dose dependent manner, with values reaching up to 10 fold those of controls. Nrf2 nuclear localization and autophagy also increased in a dose dependent manner. Apoptosis increased by 4- to 10-fold compared to the control group, depending on the dose employed.” 

In an early study Jani et al. administred rutile TiO₂ (500 nm) as a 0.1 ml of 2.5 % w/v suspension (12.5 mg/kg BW) to female Sprague Dawley rats, by oral gavage daily for 10 days and detected presence of particles in all the major gut associated lymphoid tissue as well as in distant organs such as the liver, spleen, lung and peritoneal tissue, but not in heart and kidney. The distribution and toxicity of nano- (25 nm, 80 nm) and submicron-sized (155 nm) TiO₂ particles were evaluated in mice administered a large, single, oral dosing (5 g/kg BW) by gavage. In the animals that were sacrificed two weeks later, ICP-MS analysis showed that the particles were retained mainly in liver, spleen, kidney, and lung tissues, indicating that they can be transported to other tissues and organs after uptake by the gastrointestinal tract. Interestingly, although an extremely high dose was administrated, no acute toxicity was observed. In groups exposed to 80 nm and 155 nm particles, histopathological changes were observed in the liver, kidney and in the brain. The biochemical serum parameters also indicated liver, kidney and cardiovascular damage and were higher in mice treated with nano-sized (25 or 80 nm) TiO₂ compared to submicron-sized (155 nm) TiO₂. However, the main weaknesses of this study are the use of extremely high single dose and insufficient characterisation of the particles.