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- Systematic Literature Reviews as a tool to develop Adverse Outcome Pathway landscapes in Nanotoxicology: case study of ingested Titanium dioxide nanomaterialsPublication . Rolo, Dora; Assunção, Ricardo; Silva, Maria João; Louro, HenriquetaWorldwide, 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.
- Study on cellulose nanofibrils biological effects in different cellular modelsPublication . Pinto, Fátima; Ventura, Célia; Teixeira, Sara; Vilar, Madalena; Lourenço, Ana Filipa; Ferreira, Paulo J.T.; Louro, Henriqueta; Silva, Maria JoãoCellulose nanofibrils (CNFs), is an innovative environmental friendly material that has been incorporated into several types of materials, in both pure and composite forms and holds great promise in different fields of application. This leads to a rising level of human exposure and draws considerable concerns regarding its potential toxicity in humans, which are specially motivated by the physicochemical resemblance of cellulose nanofibrils with multi-walled carbon nanotubes and asbestos that have shown deleterious health effects. Currently, several in vitro toxicological studies have been performed with the aim of predicting health effects caused by exposure to CNFs. A literature review was performed to gather and analyse recent data regarding the potential cytotoxic, genotoxic, immunotoxic and epigenetic effects, in different in vitro cell models, triggered by the exposure to CNFs produced from vegetal biomass and consequently differing in critical physicochemical characteristics. The main findings of this review work demonstrate that different functionalization affects CNFs hydrophobicity, surface charge and chemistry, which may either facilitate or difficult the uptake and interaction of its functional groups with the cell membrane, affecting the biological responses. Generally, CNFs are not phagocytized and do not cause inflammatory response, but revealed in vitro genotoxicity. In fact, our data have shown that CNFs may induce chromosome damage in some cell models, e.g., a co-culture of epithelial lung alveolar cells and macrophages. However, more studies are required to assess CNFs toxicity and to understand the relationship between their physicochemical properties, their behaviour in biological media and mechanism of action, which are of outmost importance to predict their nanosafety.