Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
Giovanni Sitia,
Fabio Fiordaliso,
Martina B. Violatto,
Jennifer Fernandez Alarcon,
Laura Talamini,
Alessandro Corbelli,
Lorena Maria Ferreira,
Ngoc Lan Tran,
Indranath Chakraborty,
Mario Salmona,
Wolfgang J. Parak,
Luisa Diomede,
Paolo Bigini
Affiliations
Giovanni Sitia
Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Fabio Fiordaliso
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Martina B. Violatto
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Jennifer Fernandez Alarcon
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Laura Talamini
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Alessandro Corbelli
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Lorena Maria Ferreira
Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Ngoc Lan Tran
Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
Indranath Chakraborty
Center for Hybrid Nanostructures (CHyN), Hamburg University, Luruper Chaussee 149, 22607 Hamburg, Germany
Mario Salmona
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Wolfgang J. Parak
Center for Hybrid Nanostructures (CHyN), Hamburg University, Luruper Chaussee 149, 22607 Hamburg, Germany
Luisa Diomede
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Paolo Bigini
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
Food-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO2) nanoparticles (NPs), posing concerns for its potential effects on human and animal health. Despite many studies, the actual relationship between the physicochemical properties of E171 NPs and their interaction with biological targets is still far from clear. We evaluated the impact of acute E171 administration on invertebrate and vertebrate animals. In the nematode, Caenorhabditis elegans, the administration of up to 1.0 mg/mL of E171 did not affect the worm’s viability and lifespan, but significantly impaired its pharyngeal function, reproduction, and development. We also investigated whether the intravenous administration of E171 in mice (at the dose of 6 mg/kg/body weight) could result in an acute over-absorption of filter organs. A significant increase of hepatic titanium concentration and the formation of microgranulomas were observed. Interstitial inflammation and parenchymal modification were found in the lungs, coupled with titanium accumulation. This was probably due to the propensity of TiO2 NPs to agglomerate, as demonstrated by transmission electron microscopy experiments showing that the incubation of E171 with serum promoted the formation of compact clusters. Overall, these data emphasize the actual risk for human and animal exposure to E171.