Most notably, a European Food Safety Authority safety assessment published in May 2021 pointed to genotoxicity concerns, as suggested by previous research. Genotoxicity is the ability of chemicals to damage genetic information such as DNA, which may lead to cancer.

Drobne et al. used the terrestrial arthropod Porcellio scaber as a test organism for determining the cytotoxic effect of TiO₂ NPs (anatase). The animals were exposed to TiO₂ NPs of two different sizes (25 nm and 75 nm) in the concentration range 10–1000 μg TiO₂/g dry food for 3 to 14 days. No adverse effects, such as mortality, body weight changes or reduced feeding, were observed. In fact, quite the opposite, an enhanced feeding rate, food absorption efficiency and increase in catalase activity were observed. The intensity of these responses appeared to be time- but not dose-dependent. It should also be noted that the concentrations tested in this study were much higher than the predicted concentration (4.8 μg/g soil) at high emission scenario of nano-sized TiO₂. Using the same test organism another group showed that exposure to TiO₂ NPs induced destabilization of cell membrane in the epithelium of digestive glands isolated from exposed animals. They also showed that this effect can be observed after just 30 minutes of exposure.

FAQ – EFSA 2021 safety assessment of titanium dioxide (E171)

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.”

While the conclusions of the EU expert panel were considered in this report, Health Canada's Food Directorate conducted its own comprehensive review of the available science. This included evaluating new scientific data that addressed some of the uncertainties identified by the EU expert panel and were not available at the time of their review.