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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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We've used titanium dioxide safely for decades. However, recently its safety was called into question. 
 
At CRIS, we've explored the safety of titanium dioxide for nearly half a decade, including conducting double-blind research to test the safety of food-grade titanium dioxide (E171). Our study shows that when exposed to food-grade titanium dioxide in normal conditions, research animals did not experience adverse health outcomes.
 
It's important to emphasize that in a National Institutes of Health study, experimental animals were exposed to titanium dioxide in amounts as high as 5% of their diet for a lifetime and showed no evidence of adverse effects. 
 
A handful of studies greatly influenced the decisions made by the European Food Safety Authority (EFSA). Unfortunately, these studies did not consider that titanium dioxide exposure comes from food, not drinking water. Additionally, CRIS researchers could not reproduce the adverse outcomes identified by the studies through typical food ingestion. Regardless, the EFSA banned E171 as a food ingredient and for use in other capacities in the summer of 2022.
 
In 2022, the United States, United Kingdom, and Canada maintained that the scientific evidence supports that titanium dioxide (E171) is safe for humans to use and consume.

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