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.

Additionally, the committee noted that the available data did not provide convincing evidence of genotoxicity for titanium dioxide as a food additive, but recognized the limitations in current methodologies with respect to the testing of poorly soluble particulate materials. Although there were uncertainties in the genotoxicity data, the experts took into account the fact that the additive was not carcinogenic in adequately conducted two-year studies in mice and rats at doses of up to 7,500 mg/kg BW per day for mice, and 2,500 mg/kg BW per day for rats, the highest doses tested. There was also no evidence of reproductive or developmental toxicity in studies in rats at doses up to 1,000 mg/kg BW per day, the highest doses tested.