In addition to consistency, manufacturers must also consider the cost implications of buff percentage. Higher levels of coating on titanium dioxide particles can increase production costs, as more coating materials are required. However, a lower buff percentage may lead to a lower quality product that does not meet the needs of customers. Balancing the cost and quality considerations of buff percentage is a key challenge for manufacturers in the titanium dioxide industry.

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.