Food grade titanium dioxide disrupts intestinal brush border microvilli in vitro independent of sedimentation

Abstract

Bulk- and nano-scale titanium dioxide (TiO2) has found use in human food products for controlling color, texture, and moisture. Once ingested, and because of their small size, nano-scale TiO2 can interact with a number of epithelia that line the human gastrointestinal tract. One such epithelium responsible for nutrient absorption is the small intestine, whose constituent cells contain microvilli to increase the total surface area of the gut. Using a combination of scanning and transmission electron microscopy it was found that food grade TiO2 (E171 food additive coded) included ∼25% of the TiO2 as nanoparticles (NPs; <100 nm), and disrupted the normal organization of the microvilli as a consequence of TiO2 sedimentation. It was found that TiO2 isolated from the candy coating of chewing gum and a commercially available TiO2 food grade additive samples were of the anatase crystal structure. Exposure to food grade TiO2 additives, containing nanoparticles, at the lowest concentration tested within this experimental paradigm to date at 350 ng/mL (i.e., 100 ng/cm(2) cell surface area) resulted in disruption of the brush border. Through the use of two independent techniques to remove the effects of gravity, and subsequent TiO2 sedimentation, it was found that disruption of the microvilli was independent of sedimentation. These data indicate that food grade TiO2 exposure resulted in the loss of microvilli from the Caco-2BBe1 cell system due to a biological response, and not simply a physical artifact of in vitro exposure.

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…As detailed above, the resulting changes to surface chemistry, agglomeration state, and biocorona of iENMs can have profound effects on their absorption, accumulation, biodistribution, and toxicity (Bouwmeester et al , 2009; Ensign et al , 2012; Frohlich and Roblegg, 2012; Powell et al , 2010). Most in vitro studies of iENM fate and toxicity have ignored these interactions, employing pristine ENMs suspended in culture media (Esch et al , 2014; Faust et al , 2014; Natarajan et al , 2015), often leading to erroneous conclusions (Gerloff et al , 2013). As discussed above, what is needed is development of in vitro and in vivo methods for studying transformations of iENMs in the GIT, and identifying structure activity relationships that influence absorption and accumulation.…”

A Facile Method for Separating and Enriching Nano and Submicron Particles from Titanium Dioxide Found in Food and Pharmaceutical Products

“…These studies have shown that TiO 2 additives have a variety of nano- and submicron-sized particles as determined by passing the extracted material through 0.45 μm filters [1]. Although the intended use of the additive is benign, the fact that portions of these additives are nano-scale raises concern that this subset of nanomaterial in the additive could interact with the human gastrointestinal tract in fundamentally different ways compared to its submicron counterpart [12]. Most recently, TiO 2 found in pharmaceuticals was found in the bloodstream of human volunteers [13].…”

Understanding toxicology: mechanisms and applications

“…TiO 2 , however, also causes a dosedependent disruption of the brush border on the epithelial surface of absorptive cells of the intestine (Koeneman et al 2010). A paper by Faust et al (2014) reports the effect of titanium dioxide (TiO 2 ) on the microvilli of the human, brush border expressing cell line, Caco-2 BBe1 . Once ingested, nano-scale TiO 2 can interact with epithelia that line the human gastrointestinal tract.…”