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Titanium Dioxide

Role of Nano-Titanium Dioxide Immunotoxicity in Infectious Disease pathology

Project link: (CIG) project CIG PCIG13-GA-2013-618152 "TiTOXPATH"

The rise in use of nanotechnology has significantly increased risks of human exposure and interaction of nanoparticles with the immune system, potentially jeopardizing host responses to infection. There is a critical need to define the functional immunological consequences of chronic nanoparticle exposure. Lack of this knowledge could potentially confound efforts to prevent, diagnose, and treat infectious diseases in people whose immune system responses may have been affected by exposure to nanomaterials. The objective of the proposed studies is to define genetic and innate immune responses of zebrafish neutrophils to exposure to nano-TiO2 as well as functional consequences in host responses to disease causing pathogens. The hypothesis is that exposure to nano-TiO2 will 1) cause measurable changes in leukocyte transcriptome response and neutrophil function; and 2) increase morbidity and mortality in disease challenged zebrafish. The rationale for the proposed research is that insights into nano-TiO2 dependent changes in host immune response to pathogens will allow better assessment of risks associated with chronic exposures to metallic oxide nanoparticles.

The public health relevance of the proposed research is reflected in the fact that nano products are rapidly accumulating in the environment and their potential for causing adverse health effects is growing proportionately, but the contribution of environmentally-relevant nanoparticle doses to modulation of infectious disease pathology remains unclear. The proposed research is significant because it is expected to increase our mechanistic understanding of the biological activity of nano-metallic oxides and assess their potential for chronic toxicity, and to allow us to evaluate the safety of metallic oxide nanoparticles. Integration of Dr Palic to EU scientific community network will be greatly enhanced with this opportunity to retain and expand collaborations with knowledge transfer from the U.S. to Germany.

 


TITANIUM DIOXIDE – THE SILENT KILLER: FINDING THE RELEVANT BIOLOGICAL TARGET FOR EXPOSURE CHARACTERIZATION AND RISK ASSESSMENT OF NANOPARTICLES TOXICITY IN FISH MODEL

Project link: (CIG) project CIG PCIG13-GA-2013-618006 "FishTiO2"

The nano-ecotoxicological research is supported and promoted by European Commission. In 2005, the Action Plan “Nanosciences and nanotechnologies: An Action Plan for Europe 2005–2009” was adopted (European Commission, 2004). The European Commission clearly states the need for the new scientific experiments that will provide quantitative data on toxicology and ecotoxicology and allow for the risk assessments to be carried out on nanomaterials. In year 2006 the Chemicals Committee of the OECD has formed special Working Party on Manufactured Nanomaterials [WPMN]. One of the nanomaterials included in the OECD WPMN priority list is titanium dioxide (TiO2). Titanium dioxide nanoparticles (nano-TiO2) present the biggest ecotoxicological concern due to the rapid increase of anthropogenic input into the environment. Estimated environmental concentrations of nano-TiO2 in water range from 0.7 to 24.5 ng/mL.

CURRENT AQUATIC EXOTOXICOLOGY TESTING OF NANO-TIO2 ARE NOT SUFFICIENT FOR THE RISK ASSESSMENT, as the testing is done by exposing the aquatic organisms to water suspension of nano-TiO2. Although the nano-TiO2 can be absorbed by the gills and skin of aquatic animals, the absorbed amount is insignificant compared to the potential of uptake through diet. Based on our previous research (Jovanovic et al., 2011, Jovanovic & Palic , 2012) we have classified nano-TiO2 as a potent immunotoxin, and there have been no previous studies that have investigated synergistic effects of nano-TiO2 during co-exposure to pathogenic bacteria. Therefore, we propose to use multidisciplinary approach by combining immunology assays, bacterial challenge studies, gross pathology of the brain, kidney and liver, and next generation deep gene sequencing - in order to determine toxicological effects and relevant biological targets upon acute exposure to nano-TiO2 through diet. Such study will provide regulatory agencies with long-time sought relevant ecotoxicological data for performing the risk assessment.