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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.

The aim of this work was to examine particularly the Degussa P25 titanium dioxide nanoparticles (P25TiO₂NPs) because they are among the most employed ones in cosmetics. In fact, all kinds of titanium dioxide nanoparticles (TiO₂NPs) have gained widespread commercialization over recent decades. This white pigment (TiO₂NPs) is used in a broad range of applications, including food, personal care products (toothpaste, lotions, sunscreens, face creams), drugs, plastics, ceramics, and paints. The original source is abundant in Earth as a chemically inert amphoteric oxide, which is thermally stable, corrosion-resistant, and water-insoluble. This oxide is found in three different forms: rutile (the most stable and substantial form), brookite (rhombohedral), and anatase (tetragonal as rutile), of these, both rutile and anatase are of significant commercial importance in a wide range of applications [3]. Additionally, the nano-sized oxide exhibits interesting physical properties, one of them is the ability to act as semiconducting material under UV exposure. In fact, TiO₂NPs are the most well-known and useful photocatalytic material, because of their relatively low price and photo-stability [4]. Although, this photoactivity could also cause undesired molecular damage in biological tissues and needs to be urgently assessed, due to their worldwide use. However, not all nanosized titanium dioxide have the same behavior. In 2007, Rampaul A and Parkin I questioned: “whether the anatase/rutile crystal form of titanium dioxide with an organosilane or dimethicone coat, a common titania type identified in sunscreens, is appropriate to use in sunscreen lotions” [5]. They also suggested that with further study, other types of functionalized titanium dioxide could potentially be safer alternatives. Later, Damiani found that the anatase form of TiO₂NPs was the more photoactive one, and stated that it should be avoided for sunscreen formulations, in agreement with Barker and Branch (2008) [6,7].

The European Food Safety Authority updated its safety assessment of the mineral in March 2020, stating that titanium dioxide can no longer be considered safe as a food additive. This was due to evidence of potentially harmful effects after consumption of the mineral, which may accumulate in the body over time.