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      Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia

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          Abstract

          Background

          TiO 2 particles are commonly used as dietary supplements and may contain up to 36% of nano-sized particles (TiO 2-NPs). Still impact and translocation of NPs through the gut epithelium is poorly documented.

          Results

          We show that, in vivo and ex vivo, agglomerates of TiO 2-NPs cross both the regular ileum epithelium and the follicle-associated epithelium (FAE) and alter the paracellular permeability of the ileum and colon epithelia. In vitro, they accumulate in M-cells and mucus-secreting cells, much less in enterocytes. They do not cause overt cytotoxicity or apoptosis. They translocate through a model of FAE only, but induce tight junctions remodeling in the regular ileum epithelium, which is a sign of integrity alteration and suggests paracellular passage of NPs. Finally we prove that TiO 2-NPs do not dissolve when sequestered up to 24 h in gut cells.

          Conclusions

          Taken together these data prove that TiO 2-NPs would possibly translocate through both the regular epithelium lining the ileum and through Peyer’s patches, would induce epithelium impairment, and would persist in gut cells where they would possibly induce chronic damage.

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          Most cited references52

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          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            Titanium dioxide nanoparticles in food and personal care products.

            Titanium dioxide is a common additive in many food, personal care, and other consumer products used by people, which after use can enter the sewage system and, subsequently, enter the environment as treated effluent discharged to surface waters or biosolids applied to agricultural land, incinerated wastes, or landfill solids. This study quantifies the amount of titanium in common food products, derives estimates of human exposure to dietary (nano-) TiO(2), and discusses the impact of the nanoscale fraction of TiO(2) entering the environment. The foods with the highest content of TiO(2) included candies, sweets, and chewing gums. Among personal care products, toothpastes and select sunscreens contained 1% to >10% titanium by weight. While some other crèmes contained titanium, despite being colored white, most shampoos, deodorants, and shaving creams contained the lowest levels of titanium (<0.01 μg/mg). For several high-consumption pharmaceuticals, the titanium content ranged from below the instrument detection limit (0.0001 μg Ti/mg) to a high of 0.014 μg Ti/mg. Electron microscopy and stability testing of food-grade TiO(2) (E171) suggests that approximately 36% of the particles are less than 100 nm in at least one dimension and that it readily disperses in water as fairly stable colloids. However, filtration of water solubilized consumer products and personal care products indicated that less than 5% of the titanium was able to pass through 0.45 or 0.7 μm pores. Two white paints contained 110 μg Ti/mg while three sealants (i.e., prime coat paint) contained less titanium (25 to 40 μg Ti/mg). This research showed that, while many white-colored products contained titanium, it was not a prerequisite. Although several of these product classes contained low amounts of titanium, their widespread use and disposal down the drain and eventually to wastewater treatment plants (WWTPs) deserves attention. A Monte Carlo human exposure analysis to TiO(2) through foods identified children as having the highest exposures because TiO(2) content of sweets is higher than other food products and that a typical exposure for a US adult may be on the order of 1 mg Ti per kilogram body weight per day. Thus, because of the millions of tons of titanium-based white pigment used annually, testing should focus on food-grade TiO(2) (E171) rather than that adopted in many environmental health and safety tests (i.e., P25), which is used in much lower amounts in products less likely to enter the environment (e.g., catalyst supports, photocatalytic coatings).
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              Fityk: a general-purpose peak fitting program

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                Author and article information

                Contributors
                Journal
                Part Fibre Toxicol
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2014
                25 March 2014
                : 11
                : 13
                Affiliations
                [1 ]UMR3299 CEA-CNRS, Service Interdisciplinaire des Systèmes Moléculaires et Matériaux, Laboratoire Structure et Dynamique par Résonance Magnétique (LSDRM), CEA Saclay, 91191 Gif sur Yvette, France
                [2 ]Université Paris-Diderot, UMR 843, F75019 Paris, France
                [3 ]INSERM, U843, F75019 Paris, France
                [4 ]European Synchrotron Radiation Facility (ESRF), ID21 beamline, B.P. 220, 38043 Grenoble, France
                [5 ]UMR8502 CNRS-Université Paris Sud, Laboratoire de Physique des solides (LPS), Université Paris-Sud, 91405 Orsay, France
                [6 ]CENBG, Université Bordeaux 1, IN2P3, UMR5797, 33175 Gradignan Cedex, France
                [7 ]UPMC, Univ Paris 06, CNRS, UMR 7574, Chimie de la Matière Condensée de Paris, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France
                [8 ]Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Université de Strasbourg, IPHC, CNRS UMR7178, Strasbourg, France
                [9 ]Pro-MD team, UMR CNRS 5249, Laboratoire de Chimie et Biologie des Métaux, UMR CNRS-CEA-UJF, Grenoble, France
                [10 ]CEA, Direction des Sciences du Vivant, iBiTec-S, Service de Pharmacologie et d’Immunoanalyse, 91191 Gif sur Yvette, France
                [11 ]URA2453 CEA-CNRS, Service des Photons, Atomes et Molécules, Laboratoire Francis Perrin (LFP), CEA Saclay, 91191 Gif sur Yvette, France
                [12 ]Université Grenoble Alpes, INAC, SCIB, F-38000, Grenoble, France 14 CEA, INAC, SCIB, F-38054 Grenoble, France
                [13 ]INSERM U1043, Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Toulouse, France
                Article
                1743-8977-11-13
                10.1186/1743-8977-11-13
                3987106
                24666995
                f7adcfd7-b4d9-4e02-9ceb-3d63473a477a
                Copyright © 2014 Brun et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 October 2013
                : 6 March 2014
                Categories
                Research

                Toxicology
                titanium dioxide,nanoparticle,ingestion,translocation,dissolution,accumulation,gut,toxicity,m-cells,paracellular

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