TiO₂ comes in many different forms. However, only a few of these forms are considered food-grade (acceptable to be added to food). Many studies that raised concern about the safety of TiO₂, including the concern for genotoxicity, used forms of TiO₂ that are not considered acceptable for use in food and have different properties than food-grade TiO₂. Other studies did use food-grade TiO₂, but took steps to break the material down into smaller particles than what would normally be found in food.

The major restraint to the global Lithopone market is the availability of numerous white pigment substitutes. It can be replaced by other inorganic white pigments such as Titanium Dioxide (TiO2) and Sachtolith. Among these substitutes, the introduction of TiO2 has reduced the commercial importance of Lithopone white pigment. Compared to other white pigments, TiO2 has high brightness and refractive index, which results in lower pigment loading. 

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.