In vitro, in the hemocytes of the marine mussel Mytilus hemocytes, suspension of TiO₂ NPs (Degussa P25, 10 μg/ml) stimulated immune and inflammatory responses, such as lysozyme release, oxidative burst and nitric oxide production. Vevers and Jha demonstrated the intrinsic genotoxic and cytotoxic potential of TiO₂ NPs on a fish-cell line derived from rainbow-trout gonadal tissue (RTG-2 cells) after 24 h of exposure to 50 μg/ml. Reeves et al. demonstrated a significant increase in the level of oxidative DNA damage in goldfish cells, and suggested that damage could not repaired by DNA repair mechanisms. Another suggestion from the mentioned study was that hydroxyl radicals are generated also in the absence of UV light. It has been shown that fish cells are generally more susceptible to toxic/oxidative injury than mammalian cells.

The FDA first approved the use of titanium dioxide in food in 1966, following its 1960 removal (along with the removal of other color additives) from the agency's original Generally Recognized as Safe list. In 1977, titanium dioxide joined the list of color additives that are exempt from certification, which means titanium dioxide doesn't have to be listed on the packaging of every product it's used in, Faber noted.