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.

JECFA previously assessed titanium dioxide at its 13^th meeting, at which time the expert committee assigned a “not specified” ADI for the additive due to an absence of significant absorption and a lack of toxicological effects in the available experimental animal and human studies. Since its original evaluation by JECFA, titanium dioxide has become a public point of contention, with its ban being introduced (and then subsequently withdrawn) in California legislation in 2023, a legal battle playing out in the EU over the additive’s ban and classification as a carcinogen in 2022, and the European Food Safety Authority (EFSA) calling titanium dioxide unsafe. However, supporters of titanium dioxide say that claims about its dangers are founded in unreliable studies, and some recent research has supported its safety as a food additive.