Case Series: Hepatic and Splenic Titanium Dioxide Deposition in Association With Intravenous Drug Use

Titanium dioxide is a versatile compound that is found in a variety of consumer products, medical hardware, and pharmaceuticals. Although oral and topical ingestion of this compound is common, intravenous introduction is much less common. We present three cases where significant titanium dioxide deposits were identified in liver and splenic tissue of three decedents, all of whom died of illicit drug overdose in the same geographic area and had fentanyl and its metabolites in blood on postmortem toxicologic testing. At autopsy, liver sections had a granular texture with fine white stippling grossly, and histologic examination of hepatic and splenic tissues showed scattered patches of black granular material with pink birefringence. Energy-dispersive x-ray spectroscopy performed on these tissues revealed the presences of clusters of titanium dioxide. Immunohistochemical staining of both the liver and spleen with CD68 confirmed the titanium dioxide clusters were within macrophages. Intravenous titanium dioxide nanoparticle elimination studies in rats suggest a time sensitive period for this elimination, with a transient period of pigment deposition between 1-58 days following injection. If a time-dependent link between titanium dioxide pigment deposition within tissues and intravenous drug use can be shown, this could be a valuable tool for Pathologists.