Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice

Food-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO<sub>2</sub>) 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 N...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Nanomaterials
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Online Access:https://www.mdpi.com/2079-4991/12/10/1669
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author 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
author_facet 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
author_sort Giovanni Sitia
collection DOAJ
description Food-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO<sub>2</sub>) 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, <i>Caenorhabditis elegans</i>, 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 TiO<sub>2</sub> 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.
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spelling doaj.art-b1715a2c301c4d43a1ab9673107d16e62023-11-23T12:26:20ZengMDPI AGNanomaterials2079-49912022-05-011210166910.3390/nano12101669Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in MiceGiovanni Sitia0Fabio Fiordaliso1Martina B. Violatto2Jennifer Fernandez Alarcon3Laura Talamini4Alessandro Corbelli5Lorena Maria Ferreira6Ngoc Lan Tran7Indranath Chakraborty8Mario Salmona9Wolfgang J. Parak10Luisa Diomede11Paolo Bigini12Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyExperimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, ItalyExperimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, ItalyCenter for Hybrid Nanostructures (CHyN), Hamburg University, Luruper Chaussee 149, 22607 Hamburg, GermanyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyCenter for Hybrid Nanostructures (CHyN), Hamburg University, Luruper Chaussee 149, 22607 Hamburg, GermanyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyDepartment of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, ItalyFood-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO<sub>2</sub>) 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, <i>Caenorhabditis elegans</i>, 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 TiO<sub>2</sub> 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.https://www.mdpi.com/2079-4991/12/10/1669titanium dioxideE171nanoparticles<i>C. elegans</i>micetoxicity
spellingShingle 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
Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
Nanomaterials
titanium dioxide
E171
nanoparticles
<i>C. elegans</i>
mice
toxicity
title Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
title_full Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
title_fullStr Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
title_full_unstemmed Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
title_short Food-Grade Titanium Dioxide Induces Toxicity in the Nematode <i>Caenorhabditis elegans</i> and Acute Hepatic and Pulmonary Responses in Mice
title_sort food grade titanium dioxide induces toxicity in the nematode i caenorhabditis elegans i and acute hepatic and pulmonary responses in mice
topic titanium dioxide
E171
nanoparticles
<i>C. elegans</i>
mice
toxicity
url https://www.mdpi.com/2079-4991/12/10/1669
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