Though the regulated use of titanium dioxide in food products is legal in the U.S. and Canada, it's banned in some other countries, notably throughout Europe. In May 2021, the European Food Safety Authority announced that titanium dioxide can no longer be considered safe as a food additive.

Nano-sized TiO₂ generally shows low or no acute toxicity in both invertebrates and vertebrates. However, exposure of Daphnia magna to 20 ppm TiO₂ for 8 consecutive days was found to cause 40 % mortality. Zhu et al. showed minimal toxicity to D. magna after 48 h exposure, while upon chronic exposure for 21 days, D. magna suffered severe growth retardation and mortality. A significant amount of nano-sized TiO₂ was found also accumulated in the body of the animals. Similar findings with coated nano-sized TiO₂ (T-Lite™ SF, T-Lite™ SF-S and T-Lite™ MAX; BASF SE) were reported by Wiench et al. Biochemical measurements showed that exposure to TiO₂ NPs induces significant concentration-dependent antioxidant enzyme activities in D. magna. Lee et al. showed that 7 and 20 nm-sized TiO₂ induced no genotoxic effect in D. magna and in the larva of the aquatic midge Chironomus riparius.

In the same year (2019), the Netherlands Food and Consumer Product Safety Authority (NVWA) also delivered an opinion on possible health effects of food additive titanium dioxide, which highlighted the importance of examining immunotoxicological effects in addition to potential reprotoxicological effects.

Introduction