TiO2 itself was officially first named and created in a laboratory in the late 1800s. It wasn’t mass manufactured until the early 20th century, when it started to take over as a safer alternative to other white pigments.
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.