Gastrointestinal Absorption and Toxicity of Nanoparticles and Microparticles: Myth, Reality and Pitfalls explored through Titanium Dioxide.

Daily oral exposure to vast numbers (>1013/adult/day) of micron or nano-sized persistent particles has become the norm for many populations. Significant airborne particle exposure is deleterious, so what about ingestion? Titanium dioxide in food grade form (fgTiO2) , which is an additive to some foods, capsules, tablets and toothpaste, may provide clues. Certainly, exposed human populations accumulate these particles in specialised intestinal cells at the base of large lymphoid follicles (Peyer's patches) and it's likely that a degree of absorption goes beyond this- i.e. lymphatics to blood circulation to tissues. We critically review the evidence and pathways. Regarding potential adverse effects, our primary message, for today's state-of-art, is that in vivo models have not been good enough and at times woeful. We provide a 'caveats list' to improve approaches and experimentation and illustrate why studies on biomarkers of particle uptake, and lower gut/mesenteric lymph nodes as targets, should be prioritized.