The most significant uncertainty identified by the EU experts was the concern that TiO₂ particles may have genotoxic effects. Genotoxicity refers to the ability of a chemical to directly damage genetic material within a cell (DNA), which may lead to cancer in certain situations. Although the experts did not conclude that TiO₂ particles in E171 are genotoxic, they could not rule out the concern that they might be.

The FDA categorized titanium dioxide as “Generally Recognized as Safe,” but there are warnings about its potential dangers from other organizations.

JECFA previously assessed titanium dioxide at its 13^th meeting, at which time the expert committee assigned a “not specified” ADI for the additive due to an absence of significant absorption and a lack of toxicological effects in the available experimental animal and human studies. Since its original evaluation by JECFA, titanium dioxide has become a public point of contention, with its ban being introduced (and then subsequently withdrawn) in California legislation in 2023, a legal battle playing out in the EU over the additive’s ban and classification as a carcinogen in 2022, and the European Food Safety Authority (EFSA) calling titanium dioxide unsafe. However, supporters of titanium dioxide say that claims about its dangers are founded in unreliable studies, and some recent research has supported its safety as a food additive.

In a review published in 2022 in the journal Archives of Toxicology, researchers found that the ingestion of E171 is a “a definite health risk for consumers and their progeny.” After reviewing dozens of in vivo, ex vivo and in vitro studies on the toxicity of E171, the researchers wrote that two facts must be noted: “First, reprotoxicity studies show that animals of both sexes are impacted by the toxicity of these nanoparticles, underlining the importance of conducting in vivo studies using both male and female animals. Second, human exposure begins in utero via maternal-fetal transfer and continues after birth by breastfeeding. Children are then chronically re-exposed due to their food preferences. To be relevant to the human in vivo situation, experimental studies should therefore consider nanoparticle exposure with respect to the age or life period of the studied population.”

After conducting a review of all the relevant available scientific evidence, EFSA concluded that a concern for genotoxicity of TiO₂ particles cannot be ruled out. Based on this concern, EFSA’s experts no longer consider titanium dioxide safe when used as a food additive. This means that an Acceptable Daily Intake (ADI ) cannot be established for E171.