In an early study Jani et al. administred rutile TiO2 (500 nm) as a 0.1 ml of 2.5 % w/v suspension (12.5 mg/kg BW) to female Sprague Dawley rats, by oral gavage daily for 10 days and detected presence of particles in all the major gut associated lymphoid tissue as well as in distant organs such as the liver, spleen, lung and peritoneal tissue, but not in heart and kidney. The distribution and toxicity of nano- (25 nm, 80 nm) and submicron-sized (155 nm) TiO2 particles were evaluated in mice administered a large, single, oral dosing (5 g/kg BW) by gavage. In the animals that were sacrificed two weeks later, ICP-MS analysis showed that the particles were retained mainly in liver, spleen, kidney, and lung tissues, indicating that they can be transported to other tissues and organs after uptake by the gastrointestinal tract. Interestingly, although an extremely high dose was administrated, no acute toxicity was observed. In groups exposed to 80 nm and 155 nm particles, histopathological changes were observed in the liver, kidney and in the brain. The biochemical serum parameters also indicated liver, kidney and cardiovascular damage and were higher in mice treated with nano-sized (25 or 80 nm) TiO2 compared to submicron-sized (155 nm) TiO2. However, the main weaknesses of this study are the use of extremely high single dose and insufficient characterisation of the particles.
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For a mini-review published in the journal Particle and Fibre Technology in 2021, scientists wanted to evaluate whether Ti02 particles contributed to the development and/or exacerbation of irritable bowel disease, and whether they altered the four elements of intestinal barrier function: the intestinal microbiota, the immune system, the mucus layer, and the epithelium. The breakdown of these four elements can contribute to autoimmune, neurological, inflammatory, infectious, and metabolic diseases. Following their review, the researchers concluded: “Data indicate that TiO2 is able to alter the four compartments of IBF and to induce a low-grade intestinal inflammation associated or not with pre-neoplastic lesions.”