A Murine Oral‐Exposure Model for Nano‐ and Micro‐Particulates: Demonstrating Human Relevance with Food‐Grade Titanium Dioxide. Issue 21 (4th May 2020)

• Record Type: Journal Article
• Authors: Riedle, Sebastian; Wills, John W.; Miniter, Michelle; Otter, Don E.; Singh, Harjinder; Brown, Andy P.; Micklethwaite, Stuart; Rees, Paul; Jugdaohsingh, Ravin; Roy, Nicole C.; Hewitt, Rachel E.; Powell, Jonathan J.
• Is Part Of: Small. Volume 16:Issue 21(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-04
• Subjects: diet -- nanoparticles -- Peyer's patches -- titanium dioxide -- validated exposure; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202000486
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Human exposure to persistent, nonbiological nanoparticles and microparticles via the oral route is continuous and large scale (10 12 –10 13 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. Abstract : Gastrointestinal exposure to persistent particles is continuous for humans but the risks unknown. Rodents are often used to assess human safety but existing techniques poorly reflect real‐world oral exposures to particles. Here, a generalizable approach is presented, for delivery of dietary particles to intestinal rodent cells in the exact same manner as in humans, and exemplified with food‐additive titanium dioxide.