In a 2017 study published in Scientific Reports, researchers exposed rats to human-relevant levels of E171 to examine the effects of intestinal inflammation and carcinogenesis. They saw that “a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model.” They continued: “Stimulation of immune cells isolated from Peyer’s Patches [which are clusters of lymphoid follicles found in the intestine] showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased,” researchers wrote. “A 100-day titanium dioxide treatment promoted colon microinflammation and initiated preneoplastic lesions.” The scientists concluded: “These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.”
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Freshwater algae show low-to-moderate susceptibility to TiO2 exposure, with more pronounced toxic effects in the presence of UV irradiation. It has also been shown that nano-sized TiO2 is significantly more toxic to algae Pseudokirchneriella sub-capitata than submicron-sized TiO2. Hund-Rinke and Simon reported that UV irradiated 25 nm TiO2 NPs are more toxic to green freshwater algae Desmodesmus subspicatus than UV irradiated 50 nm particles, which is in agreement with Hartmann et al. UV irradiated TiO2 NPs also inactivated other algae species such as Anabaena, Microcystis, Melsoira and Chroococcus. It was demonstrated that smaller particles have a greater potential to penetrate the cell interior than submicron-sized particles and larger aggregates. Studies have shown that the amount of TiO2 adsorbed on algal cells can be up to 2.3 times their own weight.
TiO2 is also used in oral pharmaceutical formulations, and the Pharmaceutical Excipients handbook considers nano-sized TiO2 a non-irritant and non-toxic excipient. Despite the fact that TiO2 submicron- and nano-sized particles are widely used as food and pharmaceutical additives, information on their toxicity and distribution upon oral exposure is very limited.
In a 2019 study published in the journal Nanotoxicology, researchers recreated the first phase of digestion in mice and fed them titanium dioxide, then examined whether accumulation occurred in the organs. Researchers wrote: “Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO2 particles was also measured. Titanium accumulation in the liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine. Overall, [this] indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered.”