TiO₂ comes in many different forms. However, only a few of these forms are considered food-grade (acceptable to be added to food). Many studies that raised concern about the safety of TiO₂, including the concern for genotoxicity, used forms of TiO₂ that are not considered acceptable for use in food and have different properties than food-grade TiO₂. Other studies did use food-grade TiO₂, but took steps to break the material down into smaller particles than what would normally be found in food.

In a 2017 study published in Scientific Reports, researchers exposed rats to human-relevant levels of E171 to examine the effects of intestinal inflammation and carcinogenesis. They saw that “a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model.” They continued: “Stimulation of immune cells isolated from Peyer’s Patches [which are clusters of lymphoid follicles found in the intestine] showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased,” researchers wrote. “A 100-day titanium dioxide treatment promoted colon microinflammation and initiated preneoplastic lesions.” The scientists concluded: “These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.”