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.

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When E171 isn’t combined with other ingredients and administered in water, some studies suggest that under these artificial conditions, E171 may be processed differently in the body resulting in some biological changes in experimental animals that are poorly understood.

The precipitation of titanium dioxide involves the reaction of titanium sulfate with an alkaline solution to form titanium hydroxide, which is then calcined to produce titanium dioxide. The precipitation process is crucial for achieving the desired particle size distribution, crystallinity, and purity of the final product.

Lithopone is rather nontoxic, due to the insolubility of its components. It has been used in medicine as a radiocontrast agent. Lithopone is allowed to be in contact with foodstuffs in the US and Europe.

In their role as risk managers, the European Commission and Member States will now reflect on EFSA’s scientific advice and decide upon any appropriate regulatory measures or advice for consumers.

In 2021, the European Food Safety Authority concluded that titanium dioxide is no longer safe in foods due to the same concerns over nanoparticles. As a result, titanium dioxide is now banned as a food additive in the EU. Although studies have shown that the absorption of ingested titanium dioxide is low, evidence suggests that titanium dioxide nanoparticles can accumulate in the body over time. Health Canada deemed it safe in 2022 but noted concerns. Unlike their European counterparts, Canadian officials did not consider studies performed with titanium dioxide nanoparticles alone. 

In a statement sent to USA TODAY on Sunday, Justin Comes, vice president of research and development for Skittles maker Mars Wrigley North America, said the company couldn't comment on pending litigation – but that its use of titanium dioxide and all Mars Wrigley ingredients are safe and manufactured in compliance with strict quality and safety requirements established by food safety regulators, including the FDA.

Food-grade titanium dioxide differs from what’s added to plastics and paints to enhance whiteness. However, there have been concerns about the environmental impact of titanium dioxide production and the potential health risks from exposure to its particles.

EU ban on titanium dioxide

Prof Matthew Wright, both a member of the FAF Panel and chair of EFSA’s working group on E 171, said: “Although the evidence for general toxic effects was not conclusive, on the basis of the new data and strengthened methods we could not rule out a concern for genotoxicity and consequently we could not establish a safe level for daily intake of the food additive.”