Despite its many advantages, the production of lithopone is not without its challenges. The raw materials used to make lithopone, particularly zinc sulfide, can be expensive and difficult to source. In addition, the production process itself can be complex and energy-intensive, requiring specialized equipment and skilled workers to operate. As a result, lithopone manufacturers must carefully manage their operations to ensure they remain competitive in the market.

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.