Ex vivo and in vivo evaluation of the potential toxicity of manufactured nanoparticles

Student thesis: Doc typesDoctor of Biomedical and Pharmaceutical Sciences

Abstract

During the last fifteen-years, nanotechnologies have been developed, and the presence of nanomaterials (NMs) in consumer products has increased. Due to their physicochemical properties, NMs are interesting in various domains as electronic, optic, chemistry, biology, medicine, etc. This highlights the importance of the multidisciplinary aspect and the complexity of the NM research field. Furthermore, NMs can enter into the organism after oral, dermal, pulmonary exposure or by direct contact with blood. It is thus of important interest to know their potential toxicity on human health. To date, only few studies report the toxicity of NMs and no guidelines are available. The potential toxicity of five NMs presenting diverse physicochemical properties (silicon carbide (SiC), titanium carbide (TiC), multi-walled carbon nanotubes (MWCNT), carbon black (CB) and silicon dioxide (SiO2)) was evaluated on three main exposure routes: the gastrointestinal and pulmonary tracts, and on blood. An acute and subacute evaluation of the potential toxicity of SiC, TiC and MWCNT was done as required in classical toxicological screening. To assess the pulmonary toxicity of NMs after inhalation, a nanoaerosol whole-body exposure model was designed, developed and validated. This was an important challenge due to the complexity of the model. In fact, it required the stable and reproducible generation of NM aerosol and the control of NM dispersion characteristics in real time during the experiment. Finally, clinically relevant specific tests were validated for studying the impact of NMs on red blood cells, platelet function and coagulation after evaluation of their suitability and feasibility. Indeed, due to their physicochemical properties, NMs are able to induce interference with many techniques. This work attempted to respond to a request of the scientific community for the proposal of guidelines for NMs.
Date of Award31 May 2012
Original languageEnglish
Awarding Institution
  • University of Namur
SupervisorBernard Masereel (Supervisor), Jean-Michel Dogne (President), Corinne Charlier (Jury), Michel Herin (Jury), Stephane Lucas (Jury) & Stéphanie Rolin (Supervisor)

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