Titanium Dioxide vs Caramel Color IV: which is worse?

What is Titanium Dioxide?

Titanium dioxide (TiO2) is a naturally occurring white mineral used as a food colorant, whitening agent, and opacity enhancer. In food applications, it exists as nano-sized and micro-sized particles. It is one of the most widely produced industrial minerals globally, used in paints, plastics, sunscreens, and food products.

What is Caramel Color IV?

Caramel Color IV (Class IV caramel, E150d) is a food coloring made by heating sugar with both ammonium and sulfite compounds. This production method creates a unique set of reactive byproducts, notably 4-methylimidazole (4-MEI), which has been linked to cancer in animal studies. It is the most widely used caramel coloring in beverages like Coca-Cola and Pepsi.

Documented risks

Titanium Dioxide: The EU banned titanium dioxide as a food additive in 2022 following EFSA's landmark 2021 safety assessment (EFSA Journal 2021;19(5):6585), which concluded that titanium dioxide 'can no longer be considered safe as a food additive.' The primary concern is genotoxicity from nanoparticles: EFSA determined it was impossible to rule out the risk of DNA damage (genotoxicity) from TiO2 nanoparticles at typical food use exposure levels. In vitro studies have demonstrated that TiO2 nanoparticles cause DNA strand breaks in intestinal epithelial cells and induce oxidative stress. A 2019 study in Nature Communications found TiO2 nanoparticles could disrupt gut microbiome balance and intestinal barrier function in mice models. Multiple studies have suggested effects on gut permeability and immune function. IARC classifies titanium dioxide as Group 2B (possible human carcinogen) for inhalation exposure in occupational settings — primarily relevant to workers handling TiO2 dust, based on rat lung cancer studies. While inhalation and oral exposure are different routes, EFSA determined that the genotoxicity concerns from nanoparticles applied to oral food use as well. Following the EU ban, California attempted to pass legislation banning TiO2 in candy (along with other additives) in 2022. The bill was signed in modified form. Mars reformulated EU Skittles to remove TiO2. The US FDA has not announced specific action on food-grade TiO2 as of 2025, though USRTK and other organizations are calling for a US ban.

Caramel Color IV: The primary concern with Caramel Color IV is 4-methylimidazole (4-MEI), a byproduct of the ammonia-sulfite caramel production process. The National Toxicology Program (NTP) found that 4-MEI caused lung cancer in male and female mice at high doses in 2-year bioassay studies, leading to California listing 4-MEI as a known carcinogen under Proposition 65 in 2011. The Prop 65 safe harbor level is 29 micrograms 4-MEI per day (the level that would cause 1 additional cancer per 100,000 people over a 70-year lifetime). CSPI testing in 2011-2012 found Coca-Cola and Pepsi sold in California contained 4-MEI levels that, at typical consumption rates, would exceed this threshold — triggering voluntary reformulation by both companies to reduce 4-MEI in their US products. The FDA reviewed 4-MEI and concluded that typical exposure levels 'are not a safety concern.' EFSA's evaluation found the NTP findings concerning but noted the margin of safety at typical European exposure levels. The cancer mechanism in mice involves high doses that may not extrapolate to typical human cola consumption.