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Food Additive Titanium Dioxide and Its Fate in Commercial Foods.

ABSTRACT: Titanium dioxide (TiO₂) is one of the most extensively utilized food additives (E171) in the food industry. Along with nanotechnology development, the concern about the presence of nanostructured particles in E171 TiO₂ and commercial food products is growing. In the present study, the physicochemical properties of commercially available E171 TiO₂ particles, including particle size distribution, were investigated, followed by their cytotoxicity and intestinal transport evaluation. The fate determination and quantification of E171 TiO₂ in commercial foods were carried out based on the analytical procedure developed using simulated foods. The results demonstrated that TiO₂ is a material mainly composed of particles larger than 100 nm, but present as an agglomerated or aggregated particle in commercial foods with amounts of less than 1% (wt/wt). Titanium dioxide particles generated reactive oxygen species and inhibited long-term colony formation, but the cytotoxicity was not related to particle size distribution or particle type (food- or general-grade). All TiO₂ particles were mainly transported by microfold (M) cells, but also by intestinal tight junction. These findings will be useful for TiO₂ application in the food industry and predicting its potential toxicity.

SUBMITTER: Hwang JS

PROVIDER: S-EPMC6724087 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Food Additive Titanium Dioxide and Its Fate in Commercial Foods.

Hwang Ji-Soo JS Yu Jin J Kim Hyoung-Mi HM Oh Jae-Min JM Choi Soo-Jin SJ

Nanomaterials (Basel, Switzerland) 20190816 8

Titanium dioxide (TiO2) is one of the most extensively utilized food additives (E171) in the food industry. Along with nanotechnology development, the concern about the presence of nanostructured particles in E171 TiO2 and commercial food products is growing. In the present study, the physicochemical properties of commercially available E171 TiO2 particles, including particle size distribution, were investigated, followed by their cytotoxicity and intestinal tran ...[more]

PMID: 31426388

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Project description:The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

Project description:ObjectiveUp to 44% of particulates of food-grade titanium dioxide (TiO2) are in nanoscale, while the effect and combined effect of which with other substances on intestinal barrier haven't been fully understood yet. This study is aimed to study the effect of two kinds of TiO2 nanoparticles (TiO2 NPs and TiO2 MPs) on intestinal barrier functions, to reveal the combined effect of TiO2 NPs and Lipopolysaccharide (LPS) on intestinal barrier.MethodsMale ICR mice were randomly divided into 18 groups (3 feed types * 3 exposure length * 2 LPS dosage) and were fed with normal or TiO2-mixed feed (containing 1% (mass fraction, w/w) TiO2 NPs or TiO2 MPs) for 1, 3, 6 months, followed by a single oral administration of 0 or 10 mg/(kg body weight) LPS. Four hours later, the transportation of TiO2, the intestinal barrier functions and the inflammatory response were evaluated.ResultsBoth TiO2 notably increased the intestinal villi height / crypt depth ratios after 1 and 3 months of exposure, and increased the expression of ileal tight junction proteins (ZO-1 and occludin) after 1 month of exposure. After 6 months of exposure, TiO2 NPs led to reduced feed consumption, TiO2 MPs caused spare microvilli in small intestine and elevated Ti content in the blood cells. The intestinal permeability didn't change in both TiO2 exposed groups. After LPS administration, we observed altered intestinal villi height / crypt depth ratios, lowered intestinal permeability (DAO) and upregulated expression of ileal ZO-1 in both (TiO2 +LPS) exposed groups. There are no significant changes of ileal or serum cytokines except for a higher serum TNF-α level in LPS treated group. The antagonistic effect was found between TiO2 NPs and LPS, but there are complicated interactions between TiO2 MPs and LPS.ConclusionLong-term intake of food additive TiO2 could alter the intestinal epithelial structure without influencing intestinal barrier function. Co-exposure of TiO2 and LPS would enhance intestinal barrier function without causing notable inflammatory responses, and there is antagonistic effect between TiO2 NPs and LPS. All the minor effects observed might associate with the gentle exposure method where TiO2 being ingested with feed.

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Food Additive Titanium Dioxide and Its Fate in Commercial Foods.

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Food Additive Titanium Dioxide and Its Fate in Commercial Foods.

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