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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.

Numerous studies have linked titanium dioxide to genotoxicity and cytotoxicity. Genotoxicity refers to a chemical’s potential to cause DNA damage, which can, in turn, lead to cancer. Cytotoxicity is a general term that refers to a characteristic of being harmful to cells.  

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