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A Murine Oral-Exposure Model for Nano- and Micro-Particulates: Demonstrating Human Relevance with Food-Grade Titanium Dioxide.

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Riedle, Sebastian 
Miniter, Michelle 
Otter, Don E 
Singh, Harjinder 


Human exposure to persistent, nonbiological nanoparticles and microparticles via the oral route is continuous and large scale (1012 -1013 particles per day per adult in Europe). Whether this matters or not is unknown but confirmed health risks with airborne particle exposure warns against complacency. Murine models of oral exposure will help to identify risk but, to date, lack validation or relevance to humans. This work addresses that gap. It reports i) on a murine diet, modified with differing concentrations of the common dietary particle, food grade titanium dioxide (fgTiO2 ), an additive of polydisperse form that contains micro- and nano-particles, ii) that these diets deliver particles to basal cells of intestinal lymphoid follicles, exactly as is reported as a "normal occurrence" in humans, iii) that confocal reflectance microscopy is the method of analytical choice to determine this, and iv) that food intake, weight gain, and Peyer's patch immune cell profiles, up to 18 weeks of feeding, do not differ between fgTiO2 -fed groups or controls. These findings afford a human-relevant and validated oral dosing protocol for fgTiO2 risk assessment as well as provide a generalized platform for application to oral exposure studies with nano- and micro-particles.



Peyer's patches, diet, nanoparticles, titanium dioxide, validated exposure, Administration, Oral, Animals, Eating, Environmental Exposure, Humans, Metal Nanoparticles, Mice, Models, Animal, Peyer's Patches, Risk Assessment, Titanium, Weight Gain

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Medical Research Council (MR/R005699/1)
The research was mainly carried out at the Riddet Institute through its Centre of Research Excellence funding which has been awarded to the Riddet Institute by the New Zealand government. Additional funding was provided by AgResearch, MRC Elsie Widdowson Laboratory (formerly MRC Human Nutrition Research, Grant number U105960399) and Nutrigenomics New Zealand, a collaboration between AgResearch, Plant and Food Research, and The University of Auckland (primarily supported by funding from the Ministry for Science and Innovation contract C11X1009). SR was supported by doctoral scholarships from Massey University and AgResearch.