In vitro intestinal epithelium responses to titanium dioxide nanoparticles

Titanium dioxide (TiO₂) is enclosed in many consumer products including pharmaceuticals, cosmetics, and foods. TiO₂ (E171) is daily ingested as mixed nano- and submicron-sized particles since it is approved as a white colorant in Europe in a wide variety of food products, Noteworthy, the relevant risk assessment has never been satisfactorily concluded and growing alarms for human hazards deriving from TiO₂ exposure are incrementally reported. The objective of the present study was to establish conceivable mechanisms by which nano-sized TiO₂ particles affect physiological function of the intestinal epithelium layer. The well-established Caco-2 cell line differentiated for 21 days on permeable supports was used as a predictive model of the human intestinal mucosa to identify the biological response triggered by TiO₂ particles. Exposure to 42 μg/mL TiO₂ nanoparticles disrupted the tight junctions-permeability barrier with a prompt effect detectable after 4 h incubation time and wide effects on barrier integrity at 24 h. Transport and ultrastructural localization of TiO₂ nanoparticles were determined by ICP-OES, TEM and ESI/EELS analysis, respectively. Nano-sized particles were efficiently internalized and preferentially entrapped by Caco-2 monolayers. Storage of TiO₂ nanoparticles inside the cells affected enterocytes viability and triggered the production of pro-inflammatory cytokines, including TNF-α and IL-8. Taken together these data indicate that nano-sized TiO₂ particles exert detrimental effects on the intestinal epithelium layer.