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The FDA has not updated its general guidance on safety assessments since 2007. Within that time, there has been a significant increase in research on the confluence of toxicology, nanotechnology and human health. The EU updates its guidance regularly with new science available to offer proper safety assessments, with its most recent update published in 2021.

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.