Biotransformation of Food-Grade and Nanometric TiO2 in the Oral-Gastro-Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells.

Arianna Marucco,Enrico Bergamaschi,Marie Carriere,Marion Prono,Enrica Alasonati,Ivana Fenoglio,Paola Fisicaro,David Beal

doi:10.3390/nano10112132

Abstract

Background: Oral exposure to titanium dioxide (TiO2) is common since it is widely used in food and pharmaceutical products. Concern on the safety of this substance has been recently raised, due to the presence of an ultrafine fraction in food-grade TiO2. Discrepancy exists among data reported in in vitro and in vivo studies on intestinal acute/chronic toxicity of TiO2. This might be due to the different biological identity of TiO2 in traditional in vitro test by respect in vivo conditions. Methods: One food-grade TiO2 and two nanometric TiO2 samples were treated with a simulated human digestive dystem (SHDS) in order to investigate the bio-transformation occurring to the particles once ingested in term of size distribution (Dynamic Light Scattering—DLS-, Flow Particle Imaging, Asymmetric Flow Field Flow Fractionation-AF4-) and surface modification (Electrophoretic Light Scattering—ELS-, Electron Paramagnetic Resonance Spectroscopy—EPR-). The effect of SHDS on the cyto-, genotoxicity and potential to induce oxidative stress towards human colorectal carcinoma HCT116 cells was also assessed. Results: Aggregation as a consequence of the high ionic strength of the gastric and intestinal simulated fluids was observed, together with the formation of a partially irreversible bio-corona containing phosphate ions and proteins. Such bio-corona led to a partial masking of the TiO2 particles surface and reactivity. Pristine and treated TiO2 nanoparticles showed comparable acute toxicity and genotoxicity toward HCT116 cells, whereas a small decrease of the induction of oxidative stress after treatment was observed. Conclusions: Overall the results underline the importance of SHDS as a tool to improve the predictive power of in vitro tests towards intestinal nanomaterial toxicity.

Highlights

Titanium dioxide is a white metal oxide commonly used as whitening and brightening agent in many consumer products such as cosmetic and food goods
As food additive TiO2 is referred as E171 and INS171 respectively in EU and US
We previously reported that phosphate ions strongly adsorb on the surface of TiO2 by decreasing theWζe-pporteevnitoiaulssly[3r5e]p.oInrteodrdtherattophaossspeshsattheeiornoslestorof npghloysapdhsaotrebioonnsthoensTuirOfa2caegogfrTegiOat2iobny,dtheceresaasminpgles thwe ζe-rpeostuesnptieanlsde[3d5]i.nIna o1r0dmerMto saaslsienses pthheosrpolheaotef pbhuoffseprh(aPtBeSio) nasndonthTeiOh2yadgrgordeygnaatimonic, tdhieamsaemteprlewsas wemreeassuusrpeedn(dFeigduirne 6a).10 mM saline phosphate buffer (PBS) and the hydrodynamic diameter was measured (Figure 6)

Summary

Introduction

Titanium dioxide is a white metal oxide commonly used as whitening and brightening agent in many consumer products such as cosmetic and food goods. Discrepancy exists among data reported in in vitro and in vivo studies on intestinal acute/chronic toxicity of TiO2. This might be due to the different biological identity of TiO2 in traditional in vitro test by respect in vivo conditions. Results: Aggregation as a consequence of the high ionic strength of the gastric and intestinal simulated fluids was observed, together with the formation of a partially irreversible bio-corona containing phosphate ions and proteins. Such bio-corona led to a partial masking of the TiO2 particles surface and reactivity. Conclusions: Overall the results underline the importance of SHDS as a tool to improve the predictive power of in vitro tests towards intestinal nanomaterial toxicity

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Conclusion