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The most significant uncertainty identified by the EU experts was the concern that TiO₂ particles may have genotoxic effects. Genotoxicity refers to the ability of a chemical to directly damage genetic material within a cell (DNA), which may lead to cancer in certain situations. Although the experts did not conclude that TiO₂ particles in E171 are genotoxic, they could not rule out the concern that they might be.

From studies deemed relevant, the experts found that titanium dioxide as a food additive is poorly absorbed by the gastrointestinal tract of mice and rats, with no adverse effects observed in short-term studies in rodents receiving titanium dioxide in their diets. No observed adverse effect levels (NOAELs) of 15,000 milligrams per kilogram of bodyweight (mg/kg BW) per day and 5,000 mg/kg BW per day—the highest doses tested—were established for mice and rats, respectively.