A few non-dietary studies have reported adverse effects in the gastrointestinal tract of laboratory animals given food-grade TiO₂. However, these same effects were not seen when the same or higher doses of food-grade TiO₂ were administered in the animals' diet. Dietary studies best reflect how humans are exposed to TiO₂ from food. Thus, the Food Directorate placed the most emphasis on the results of these studies in the state of the science report.

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Relative to a lot of other things that people should be concerned about, titanium dioxide in my mind, is really low on the list. I would be more worried about some substitutes that people are using for titanium dioxide that don't have decades of research associated with it, said Westerhoff.

A significant body of research, mostly from rodent models and in vitro studies, has linked titanium dioxide with health risks related to the gut, including intestinal inflammation, alterations to the gut microbiota, and more. It is classified by the International Agency for Research on Cancer (IARC) in Group 2B, as possibly carcinogenic to humans.