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.

CSPI’s Chemical Cuisine is the web’s definitive rating of the chemicals used to preserve foods and affect their taste, texture, or appearance. Besides titanium dioxide, the group recommends avoiding artificial sweeteners like aspartame, acesulfame potassium, and sucralose, as well as synthetic food dyes like Yellow 5 and Red 3. CSPI and others have recently asked the Food and Drug Administration to ban the latter dye in foods and ingested drugs because the FDA has already determined that it is a carcinogen unsafe for use in cosmetics.

The gastrointestinal tract is a complex barrier/exchange system, and is the most important route by which macromolecules can enter the body. The main absorption takes place through villi and microvilli of the epithelium of the small and large intestines, which have an overall surface of about 200 m². Already in 1922, it was recognized by Kumagai, that particles can translocate from the lumen of the intestinal tract via aggregation of intestinal lymphatic tissue (Peyer’s patch, containing M-cells (phagocytic enterocytes)). Uptake can also occur via the normal intestinal enterocytes. Solid particles, once in the sub-mucosal tissue, are able to enter both the lymphatic and blood circulation.