In a study published in the journal Environmental Toxicology and Pharmacology in 2020, researchers examined the effects of food additives titanium dioxide and silica on the intestinal tract by grouping and feeding mice three different food-grade particles — micro-TiO2, nano-TiO2, and nano-SiO2.  With all three groups, researchers observed changes in the gut microbiota, particularly mucus-associated bacteria. Furthermore, all three groups experienced inflammatory damage to the intestine, but the nano-TiO2 displayed the most pronounced changes. The researchers wrote: “Our results suggest that the toxic effects on the intestine were due to reduced intestinal mucus barrier function and an increase in metabolite lipopolysaccharides which activated the expression of inflammatory factors downstream. In mice exposed to nano-TiO2, the intestinal PKC/TLR4/NF-κB signaling pathway was activated. These findings will raise awareness of toxicities associated with the use of food-grade TiO2 and SiO2.”

In a study published in the journal Toxicology, researchers examined the effects of exposing human colon cancer cell line (HTC116) titanium dioxide food additives in vitro. “In the absence of cytotoxicity, E171 was accumulated in the cells after 24 hours of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization,” the scientists wrote. Researchers removed the additive from the culture, then examined the results 48 hours later. They found, “The removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.”