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Below 20% substitution, it is recommended to replace 1 kg of TiO2 with 1 kg of lithopone supplier.  

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How we’re exposed to an ingredient matters greatly in terms of our long-term health. 
  
Research shows that inhaling titanium dioxide particles in significant quantities over time can cause adverse health outcomes. Unless you work in an industrial setting, inhaling substantial amounts of titanium dioxide is highly unlikely. 

While the FDA maintains that the regulated use of titanium dioxide is safe, the European Food Safety Authority and some other experts warn of potential, serious health risks.

For research published in Archives of Toxicology in 2020, scientists fed one group of mice a solution containing titanium dioxide for one month, and compared it to those that did not receive the additive. They found “the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed” in the titanium dioxide group when compared with the control group. The tests also revealed that the titanium dioxide exposure could cause locomotor dysfunction, or mobility issues “by elevating the excitement of enteric neurons, which might spread to the brain via gut-brain communication by vagal pathway.” The researchers concluded: “These findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.”

A few non-dietary studies have reported adverse effects in the gastrointestinal tract of laboratory animals given food-grade TiO₂. However, these same effects were not seen when the same or higher doses of food-grade TiO₂ were administered in the animals' diet. Dietary studies best reflect how humans are exposed to TiO₂ from food. Thus, the Food Directorate placed the most emphasis on the results of these studies in the state of the science report.

Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters. The researchers wrote: “Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.” After reviewing dozens of studies, the scientists concluded: “Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”

Nano-sized TiO₂ generally shows low or no acute toxicity in both invertebrates and vertebrates. However, exposure of Daphnia magna to 20 ppm TiO₂ for 8 consecutive days was found to cause 40 % mortality. Zhu et al. showed minimal toxicity to D. magna after 48 h exposure, while upon chronic exposure for 21 days, D. magna suffered severe growth retardation and mortality. A significant amount of nano-sized TiO₂ was found also accumulated in the body of the animals. Similar findings with coated nano-sized TiO₂ (T-Lite™ SF, T-Lite™ SF-S and T-Lite™ MAX; BASF SE) were reported by Wiench et al. Biochemical measurements showed that exposure to TiO₂ NPs induces significant concentration-dependent antioxidant enzyme activities in D. magna. Lee et al. showed that 7 and 20 nm-sized TiO₂ induced no genotoxic effect in D. magna and in the larva of the aquatic midge Chironomus riparius.

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.    

The morphology of vitaminB2@P25TiO₂NPs is coherent with the description of Degussa P25 typical population. Size distribution histograms were made from manual measures of the nanoparticles observed in SEM micrographs using ImageJ®. This data showed that more than 70% is anatase (between 20 and 60 nm) with a minor amount of rutile characteristic bars (between 80 and 100 nm) and a small amount of amorphous phase (<40 nm) [36]. Further analysis of the same sample areas with an EDS probe demonstrated the presence of organic material composed of C and O (Fig. 2). This material was found homogeneously distributed on the surface of the different shapes of P25TiO₂NP, not in the background, indicating a specific interaction that could be attributed to the functionalization of the P25TiO₂NPs with vitamin B2.