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.

In a study published in the journal Toxicology, researchers examined the effects of exposing human colon cancer cell line (HTC116) titanium dioxide food additives in vitro. “In the absence of cytotoxicity, E171 was accumulated in the cells after 24 hours of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization,” the scientists wrote. Researchers removed the additive from the culture, then examined the results 48 hours later. They found, “The removal of E171 was unable to revert the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.”

It's hard to determine the total amount of food products that have titanium dioxide because federal regulations don't require all producers to list its use on ingredient labels, but the list of foods containing the substance certainly doesn't end with Skittles.