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A significant body of research, mostly from rodent models and in vitro studies, has linked titanium dioxide with health risks related to the gut, including intestinal inflammation, alterations to the gut microbiota, and more. It is classified by the International Agency for Research on Cancer (IARC) in Group 2B, as possibly carcinogenic to humans.

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.”

Still, in 2016 Skittles publicly declared it would get rid of the chemical compound in its products, according to a press release at the time from the Center for Food Safety, which called the substance harmful and potentially poisonous. But the ingredient remains, according to the lawsuit, which alleges the candy company is misleading consumers by not having eliminated titanium dioxide.