From 1916 to 2011, an estimated total of 165 050 000 metric tons of titanium dioxide (TiO₂) pigment were produced worldwide. Current safety regulations on the usage of the TiO₂ pigment as an inactive ingredient additive in human food are based on legislation from 1969 and are arguably outdated. This article compiles new research results to provide fresh data for potential risk reassessment. However, even after 45 years, few scientific research reports have provided truly reliable data. For example, administration of very high doses of TiO₂ is not relevant to daily human uptake. Nevertheless, because dose makes the poison, the literature provides a valuable source for understanding potential TiO₂ toxicity after oral ingestion. Numerous scientific articles have observed that TiO₂ can pass and be absorbed by the mammalian gastrointestinal tract; can bioconcentrate, bioaccumulate, and biomagnify in the tissues of mammals and other vertebrates; has a very limited elimination rate; and can cause histopathological and physiological changes in various organs of animals. Such action is contrary to the 1969 decision to approve the use of TiO₂ as an inactive ingredient in human food without an established acceptable daily intake, stating that neither significant absorption nor tissue storage following ingestion of TiO₂ was possible. Thus, relevant governmental agencies should reassess the safety of TiO₂ as an additive in human food and consider establishing an acceptable maximum daily intake as a precautionary measure. Integr Environ Assess Manag 2015;11:10–20. © 2014 The Author. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.