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.

Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters. The researchers wrote: “Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.” After reviewing dozens of studies, the scientists concluded: “Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”

The FDA has issued guidance clarifying the safe use of titanium dioxide pigment as a food colorant and has stated that titanium dioxide may be safely used in cosmetics, including those intended for use around the eye. FDA also regulates the safety and effectiveness of sunscreen active ingredients, including nanoscale titanium dioxide.

The vitaminC@P25TiO₂NPs, on the other side, did not have any effect on cell protection against ROS. This might be due to the fact that vitamin C, a well-known scavenger of ROS, could behave as prooxidant and even promote ROS and lipid peroxidation [39]. It was recently described that at small concentrations of vitamin C, the prooxidant effects dominate; while in large concentrations the antioxidant ones predominate [40]. The effect also depends on the cell state and the interaction of vitamin C with light. In this case, ascorbic acid may act as an antenna to harvest visible light when conjugated to P25TiO₂NPs. Indeed, it was previously found that this combination (in some ratios) could have an improved photocatalytic activity, possibly due to a red shift in its light absorbance [41]. Further studies on vitaminC@P25TiO₂NPs were not conducted, because of the poor antioxidant capacity [42].

Synonyms and Related Terms

However, humans are not exposed to E171 in drinking water at any significant quantity over a long duration, so this potential effect is irrelevant to the human experience. It’s important to understand that a potential hazard is not the same thing as an actual risk. 

Following the EU’s ban on E171, the FDA told the Guardian that, based on current evidence, titanium dioxide as a food additive is safe.  “The available safety studies do not demonstrate safety concerns connected to the use of titanium dioxide as a color additive.”

Titanium dioxide (TiO2) is renowned for its brightness, high refractive index, and stability. It comes in two primary crystalline forms rutile and anatase. Rutile is predominantly used in the production of tires due to its superior characteristics, including high UV resistance, durability, and excellent pigmentary properties. These features make TiO2 an ideal choice for enhancing the performance and longevity of tire products.

In the same year (2019), the Netherlands Food and Consumer Product Safety Authority (NVWA) also delivered an opinion on possible health effects of food additive titanium dioxide, which highlighted the importance of examining immunotoxicological effects in addition to potential reprotoxicological effects.