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

Abstract

Recent studies indicate the presence of nano-scale titanium dioxide (TiO2) as an additive in human foodstuffs, but a practical protocol to isolate and separate nano-fractions from soluble foodstuffs as a source of material remains elusive. As such, we developed a method for separating the nano and submicron fractions found in commercial-grade TiO2 (E171) and E171 extracted from soluble foodstuffs and pharmaceutical products (e.g., chewing gum, pain reliever, and allergy medicine). Primary particle analysis of commercial-grade E171 indicated that 54% of particles were nano-sized (i.e., < 100 nm). Isolation and primary particle analysis of five consumer goods intended to be ingested revealed differences in the percent of nano-sized particles from 32%‒58%. Separation and enrichment of nano- and submicron-sized particles from commercial-grade E171 and E171 isolated from foodstuffs and pharmaceuticals was accomplished using rate-zonal centrifugation. Commercial-grade E171 was separated into nano- and submicron-enriched fractions consisting of a nano:submicron fraction of approximately 0.45:1 and 3.2:1, respectively. E171 extracted from gum had nano:submicron fractions of 1.4:1 and 0.19:1 for nano- and submicron-enriched, respectively. We show a difference in particle adhesion to the cell surface, which was found to be dependent on particle size and epithelial orientation. Finally, we provide evidence that E171 particles are not immediately cytotoxic to the Caco-2 human intestinal epithelium model. These data suggest that this separation method is appropriate for studies interested in isolating the nano-sized particle fraction taken directly from consumer products, in order to study separately the effects of nano and submicron particles.

Physicochemical Characterization of the Pristine E171 Food Additive by Standardized and Validated Methods

“…The application of E171 in food was subjected to a (re-)evaluation by the European Food Safety Authority (EFSA) in 2016 [4] and was re-approved for use in food. It is commonly applied in confectionery (including candies, chewing gum, glazings) but was demonstrated also in pastries, low-fat dairy products, and sauces [5][6][7][8][9].…”

“…In addition to the EFSA opinion, several studies characterized commercially available pristine E171 materials and food products containing E171 [6,7,9,42,43,52,[56][57][58]. In general, mean particle sizes between 106 and 145 nm and size distributions ranging from 30 nm to 400 nm were reported for electron microscopy (EM) analyses [6,9,42,43,[56][57][58]. One study showed a size distribution ranging from 30 to 600 nm for scanning electron microscopy (SEM) and 20 to 400 nm for asymmetric flow field-flow fractionation coupled with inductively coupled plasma mass spectrometry (AF4-ICP-MS) [7].…”

“…One study showed a size distribution ranging from 30 to 600 nm for scanning electron microscopy (SEM) and 20 to 400 nm for asymmetric flow field-flow fractionation coupled with inductively coupled plasma mass spectrometry (AF4-ICP-MS) [7]. In these studies, the fraction of nanoparticles (<100 nm) ranged from 10% to 54% [6,7,9,42,43,56,57]. Geiss et al were able to characterize E171 contained in finished and semi-finished confectionery products, along with exactly those pristine E171 samples used in each of the products, allowing a direct comparison of the particle size distribution in the pristine and extracted materials.…”

Impact of an Artificial Digestion Procedure on Aluminum-Containing Nanomaterials

“…The use of aluminum-containing packaging, consumer products and kitchenware has increased 10 , as well as the use of chemical solvents, leaches and acids. Several metal species are present in a significant amount in food as nano-scaled particles [11][12] and migrate into food from packaging material [13][14][15] . Like other orally ingested metals, aluminum nanoparticles overcome the different compartments of the human digestion tract.…”

Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice

“…Food-grade titanium dioxide (TiO 2 ) labeled as E171 in the European Union has been consumed by humans for more than 50 years (Joint Food and Agriculture Organization of the United Nations and the World Health Organization in 2013) but the TiO 2 toxicity caused by inhalation has highlighted the attention regarding possible adverse effects by other routes of exposure, including oral intake. E171 is a food additive used for whitening and brightening in foodstuffs, dried vegetables, soups, vitamins, chocolates, snacks, chewing gums and solid candies (Kim et al, 2018;Peters et al, 2014;Rompelberg et al, 2016;Weir, Westerhoff, Fabricius, Hristovski, & von Goetz, 2012), generic and name-brand medicines (Faust, Doudrick, Yang, Capco, & Westerhoff, 2016), among others. E171 can be used at quantum satis in the European Union, which means that there is no established limit of E171 added to achieve the quality of the food product, while in the USA, the Food and Drug Administration (FDA) permits 1% E171 as maximum in the food (Lehto et al, 2017).…”