Despite its many advantages, the production of lithopone is not without its challenges. The raw materials used to make lithopone, particularly zinc sulfide, can be expensive and difficult to source. In addition, the production process itself can be complex and energy-intensive, requiring specialized equipment and skilled workers to operate. As a result, lithopone manufacturers must carefully manage their operations to ensure they remain competitive in the market.

In 2017, French researchers from the Institut National de la Recherche Agronomique (INRAE) were among the first to examine the effects of E171 nanoparticles on the body. They fed rats a dose of 10mg of E171 per kilogram of body weight per day, which was similar to human exposure in food. The research, which was published in Scientific Reports, showed that E171 was able to traverse the intestinal barrier, pass into the bloodstream, and reach other areas of the body in rats. Researchers also found a link between immune system disorders and the absorption of titanium dioxide nanoparticles. 

Titanium dioxide is considered safe for use in cosmetics products by expert bodies around the world, including Europe's Scientific Committee on Consumer Safety (SCCS) and the U.S. Food and Drug Administration (FDA). Nano grade titanium dioxide has been assessed by the SCCS and is approved by the European Commission for use as a UV filter.

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The Scientific Committee on Consumer Safety issued an opinion of the safety of titanium dioxide in food, stating that it should no longer be considered as safe when used as a food additive.