Worldwide, Titanium dioxide nanomaterials are one of the most frequently applied nanomaterial as food additive, pharmaceuticals and toothpastes. Many studies addressed their potential adverse effects considering the nanomaterials primary physicochemical characteristics. However, surrounding matrix can affect their properties and consequently the secondary features may be more relevant for determining the toxicological outcome. In this regard, further research is needed. In fact, the potential of Ingested TiO2 nanomaterials (Ing-TiO2) to cause undesirable effects on human life is still unknown. Of major concern is their potential to lead to genotoxicity that may contribute to cancer. A valuable tool in predictive nanotoxicology is the establishment of Adverse Outcome Pathways (AOPs) landscapes. However, there is a lack of systematic approaches to assess this issue. A systematic literature review (SLR), that integrates information produced on this topic and provides data for a standardized assessment of the evidence, is necessary.

The goal of this study was to conduct a SLR evaluating the genotoxicity of Ing-TiO2, for identifying key cellular and molecular events leading to adverse health outcomes in order to guide future research needs on the assessment of potential AOPs.

It is expected that a framework of AOPs for Ing-TiO2, that describes a sequence of causally linked events at different levels of biological organization leading to adverse health effects, may contribute to support risk assessment based on mechanistic reasoning. Strengths and limitations of this strategy are discussed in view of their usefulness as a tool for risk assessment.

Funded by FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 and co-funded by ToxOmics (UIDB/00009/2020) and CESAM (UIDP/50017/2020+UIDB/50017/2020).