Titanium dioxide (TiO₂) is considered as an inert and safe material and has been used in many applications for decades. However, with the development of nanotechnologies TiO₂ nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. Therefore increased human and environmental exposure can be expected, which has put TiO₂ nanoparticles under toxicological scrutiny. Mechanistic toxicological studies show that TiO₂ nanoparticles predominantly cause adverse effects via induction of oxidative stress resulting in cell damage, genotoxicity, inflammation, immune response etc. The extent and type of damage strongly depends on physical and chemical characteristics of TiO₂ nanoparticles, which govern their bioavailability and reactivity. Based on the experimental evidence from animal inhalation studies TiO₂ nanoparticles are classified as “possible carcinogenic to humans” by the International Agency for Research on Cancer and as occupational carcinogen by the National Institute for Occupational Safety and Health. The studies on dermal exposure to TiO₂ nanoparticles, which is in humans substantial through the use of sunscreens, generally indicate negligible transdermal penetration; however data are needed on long-term exposure and potential adverse effects of photo-oxidation products. Although TiO₂ is permitted as an additive (E171) in food and pharmaceutical products we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure. TiO₂ may also enter environment, and while it exerts low acute toxicity to aquatic organisms, upon long-term exposure it induces a range of sub-lethal effects.

For a review published in 2023 in the journal Environmental Pollution, researchers examined E171 as a possible factor promoting obesity-related metabolic disorders. Because gut microbiota play an important role in immune function maintenance and development, and because titanium dioxide as a food additive has been shown to alter gut microbiota, researchers wanted to review “the dysregulations along the gut microbiota-immune system axis after oral TiO2 exposure compared to those reported in obese or diabetic patients, and to highlight potential mechanisms by which foodborne TiO2 nanoparticles may increase the susceptibility to develop obesity-related metabolic disorders.” The study authors discovered recurrent changes in the gut microbiota composition when exposed to titanium dioxide nanoparticles, with an imbalance of intestinal symbiotic microbiota. These changes and imbalances were also reported and played a role in the development of obesity, the authors wrote. This highlights “foodborne TiO2 nanoparticles as an endocrine disruptor-like chemical promoting obesity-related disorders,” the authors concluded.

The principal natural source of titanium dioxide is mined ilmenite ore, which contains 45-60 percent TiO₂. From this, or an enriched derivative (known as titanium slag), pure TiO₂ can be produced using the sulphate or chloride process.

It should also be considered that due to the low pH in the stomach, the increased dissolution of the TiO₂ particles may increase its bioavailability and may facilitate the entry of titanium ions into the blood circulation. Despite the relatively large consumption of TiO₂ as a food additive, no studies on the effect of pH on its absorption and bioavailability have been found in the literature. This can be attributed to a general belief that TiO₂is completely insoluble. However, this is not completely true, as TiO₂ particles show a certain degree of solubility.