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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.

In a 2021, Chinese researchers examined the impact of E171 on lipid digestion and vitamin D3 bioaccessibility in a simulated human gastrointestinal tract model. They examined Vitamin D’s bioaccessibility, or the amount it was released in the gastrointestinal tract, becoming available for absorption, and found it “significantly decreased from 80% to 74%” with the addition of E171. In the experiment, E171 decreased lipid digestion dose-dependently. Researchers wrote: “The findings of this study enhance our understanding toward the potential impact of E171 on the nutritional attributes of foods for human digestion health.”  The study was published in the Journal of Agricultural and Food Chemistry,