Cellular and Molecular Mechanisms of Toxicity of Ingested Titanium Dioxide Nanomaterials

Adriana Vieira, Ana Gramacho, Dora Rolo, Nádia Vital, Maria João Silva, Henriqueta Louro

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


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.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
Number of pages33
Publication statusE-pub ahead of print - 19 May 2022

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Ingestion
  • Intestinal cells
  • Nanomaterials
  • Nanotoxicology
  • Titanium dioxide


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