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.

That came after a 2021 report from an expert panel at the European Food Safety Authority, which reviewed data on titanium dioxide safety. The panel said it couldn’t rule out concerns that the food additive might be able to damage DNA and possibly lead to cancer. They explained that after you eat something that has titanium dioxide in it, your body absorbs low levels of its particles – but the particles can build up as you eat more foods with this additive.

In a study published in the journal Food and Chemical Toxicology in 2016, researchers investigated whether titanium dioxide exposure led to an increase in colorectal tumor creation in mice by using a colitis associated cancer model. By measuring tumor progression markers, the researchers found that mice given titanium dioxide experienced enhanced tumor formation in the distal colon.  There was also a decrease of cells that act as a protective barrier in the colon. The researchers wrote: “These results suggest that E171 could worsen pre-existent intestinal diseases.”