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Titanium dioxide is one of the many oxides formed naturally in our environment. Manufacturers source this mined mineral from rutile, brookite, and anatase. It is then processed and refined to meet stringent safety guidelines based on the end-use for the mineral. 

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.