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In 2021, the European Food Safety Authority concluded that titanium dioxide is no longer safe in foods due to the same concerns over nanoparticles. As a result, titanium dioxide is now banned as a food additive in the EU. Although studies have shown that the absorption of ingested titanium dioxide is low, evidence suggests that titanium dioxide nanoparticles can accumulate in the body over time. Health Canada deemed it safe in 2022 but noted concerns. Unlike their European counterparts, Canadian officials did not consider studies performed with titanium dioxide nanoparticles alone. 

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Duan et al. administered 125 mg/kg BW or 250 mg/kg BW of anatase TiO2 (5 nm) intragastrically to mice continuously for 30 days. The exposed mice lost body weight, whereas the relative liver, kidney, spleen and thymus weights increased. Particles seriously affected the haemostasis of the blood and the immune system. The decrease in the immune response could be the result of damage to the spleen, which is the largest immune organ in animals and plays an important role in the immune response. Powel et al. demonstrated that TiO2 NPs may trigger immune reactions of the intestine after oral intake. They showed that TiO2 NPs conjugated with bacterial lipopolysaccharide, but not TiO2 NPs or lipopolysaccharide alone, trigger the immune response in human peripheral blood mononuclear cells and in isolated intestinal tissue. This indicates that TiO2 NPs may be important mediators in overcoming normal gut-cell hyporesponsiveness to endogenous luminal molecules, which may be particularly relevant to patients with inflammatory bowel disease, which is characterized by an abnormal intestinal permeability.

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