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.

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When E171 isn’t combined with other ingredients and administered in water, some studies suggest that under these artificial conditions, E171 may be processed differently in the body resulting in some biological changes in experimental animals that are poorly understood.

The main concern with nanoparticles is that they are so tiny that they are absorbed into the skin more than we want them (ideally sunscreen should remain on the surface of the skin). Once absorbed they might form unwanted complexes with proteins and they might promote the formation of evil free radicals. But do not panic, these are concerns under investigation. A 2009 review article about the safety of nanoparticles summarizes this, to date, in-vivo and in-vitro studies have not demonstrated percutaneous penetration of nanosized particles in titanium dioxide and zinc oxide sunscreens. The English translation is, so far it looks like sunscreens with nanoparticles do stay on the surface of the skin where they should be.