Cellular and Molecular Mechanisms of Toxicity of Ingested Titanium Dioxide Nanomaterials

Abstract

An exponential increase in products containing titanium dioxide nanomaterials (TiO2), in agriculture, food and feed industry, lead to increased oral exposure to these nanomaterials (NMs). Thus, the gastrointestinal tract (GIT) emerges as a possible route of exposure that may drive systemic exposure, if the intestinal barrier is surpassed. NMs have been suggested to produce adverse outcomes, such as genotoxic effects, that are associated with increased risk of cancer, leading to a concern for public health. However, to date, the differences in the physicochemical characteristics of the NMs studied and other variables in the test systems have generated contradictory results in the literature. Processes like human digestion may change the NMs characteristics, inducing unexpected toxic effects in the intestine. Using TiO2 as case-study, this chapter provides a review of the works addressing the interactions of NMs with biological systems in the context of intestinal tract and digestion processes, at cellular and molecular level. The knowledge gaps identified suggest that the incorporation of a simulated digestion process for in vitro studies has the potential to improve the model for elucidating key events elicited by these NMs, advancing the nanosafety studies towards the development of an adverse outcome pathway for intestinal effects.

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles—A Systematic Review

“…The technology based on manufactured nanoparticles (NPs) has been pointed as a key enabling technology, due to its potential to improve many products and processes, namely in agriculture, food, and feed industry [1]. Several commercialized products have NPs in its constitution, such as silver, titanium dioxide NPs (TiO 2 -NPs), or synthetic amorphous silica and many others are being developed, such as cellulose nanomaterials.…”

“…TiO 2 is one of the NPs most frequently applied in food additives, and in pharmaceuticals and personal hygiene products, such as toothpaste [1], and its consumption (as E171 food additive) is estimated to be 5-9 mg per person per day or even reach up to 32.4 mg/kg per day in children [4]. The exposure by ingestion due to other NPs applied in agriculture, food and feed industry, food packaging, or even food supplements and oral contact products, remains unknown.…”

Long Non-Coding RNA Expression Profile Alteration Induced by Titanium Dioxide Nanoparticles in HepG2 Cells

“…Moreover, there is a growing interest in the in vitro epigenetic changes induced by TiO 2 NPs [12,13]. TiO 2 NPs are one of the most commonly used nanomaterials in food additives, pharmaceuticals, and personal hygiene products, such as toothpaste [14], so oral exposure is more likely to happen. The liver is a multicellular organ that plays an important role in activating and eliminating many metabolites; therefore, the liver is the primary target organ of oral exposure to TiO 2 NPs [15][16][17][18].…”