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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.

One of the main challenges that manufacturers face when it comes to buff percentage is ensuring consistency. Variations in the level of coating on titanium dioxide particles can lead to differences in color, opacity, and other properties in the final product. This can be especially problematic in industries such as paint and coatings, where consistency is critical for achieving the desired results.