Carcinogenicity Assessment of Titanium Dioxide

Introduction Titanium dioxide is a white mineral that is used to color paints, plastics, paper and other materials and is approved by the FDA as both a direct (with restricted uses) and indirect food additive. It is a non-genotoxic poorly soluble particulate. As such it has been found to not cause cancer by various routes in a number of animal models except for the rat. Titanium dioxide, as with other poorly soluble particulates, will cause lung tumors in rats when exposures are sufficient to cause particle overload, a condition associated with impaired particle clearance and macrophage function and chronic inflammation. The rat is particularly sensitive to developing this condition. This treatise discusses carcinogenic testing of titanium dioxide, mechanisms the development of lung tumors with particle overload, the uniqueness of the rat model and assessments of whether or not findings in the rat model indicate risk to man. Because there is a different potency in the rat model between pigmentary and ultrafine titanium dioxide, these are discussed separately.