FP7Reintegration grant2013–2017

FISHTIO2 · TITANIUM DIOXIDE – THE SILENT KILLER: FINDING THE RELEVANT BIOLOGICAL TARGET FOR EXPOSURE CHARACTERIZATION AND RISK ASSESSMENT OF NANOPARTICLES TOXICITY IN FISH MODEL

FP7 — People (Marie Curie Actions)

Duration
2013-09-01 → 2017-08-31
EU contribution
€100,000
Participants
1
Scheme
MC-CIG

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Results in brief

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

The main objective of this study was to use multidisciplinary approach by combining immunology assays, bacterial challenge studies, and gross pathology of the kidney and liver, in order to determine toxicological effects and relevant biological targets upon acute exposure of fish to nano-TiO2. Our hypothesis was that exposure to nano-TiO2: will cause measurable changes in the function of the immune system; will cause significant changes in the transcriptomic response; ;and will cause significant pathology in the kidney, and liver of a fish model species.Under this primary objective, the project aimed to achieve the following sub-objectives: 1. Evaluate the neutrophil function, and innate immune response, of fish upon acute administration of nano-TiO2. 2. Evaluate the gross pathology of the organs (brain, kidney, and liver) upon acute administration of nano-TiO2. 3. Asses the biodistribution and bioconcentration of nano-TiO2 in the whole fish samples and fish organs upon acute administration of nano-TiO2.. 4. Determine effect of engineered nanoparticles to transcriptome responses upon acute oral administration of nano-TiO2. 5. Evaluate the synergistic/additive effect of nano-TiO2 acute administration on fish mortality upon challenge with the common environmental bacterial pathogens (Aeromanas hydrophilla and Edwardsiella ictaluri). The main results show that: 1) From 1916 to 2011, an estimated total of 165 050 000 metric tons of titanium dioxide (TiO2) pigment were produced worldwide. 2) TiO2 can pass and be absorbed by the mammalian gastrointestinal tract; can bioconcentrate and bioaccumulate in the tissues of mammals and other vertebrates; has a very limited elimination rate; and can cause histopathological and physiological changes in various organs of animals. 3) A phototoxicity ratio between the results of nano-TiO2 experiments conducted in the absence of sunlight and those conducted under solar or simulated solar radiation (SSR) for aquatic species was developed. 4. In fish exposure to TiO2 led to a significant: premature hatching and general decrease in time required for normal hatching in a dose-dependent manner. 5.Three tissue-specific inicroRNA-n1esengerRNA connecting networks and three biological response-specific microRNA-mnesengerRNA regulation networks were predicted based on computer modeling and simulations. Moreover, six microRNAs families were identified to potentially act as mediators. These six microRNAs are: dre-miR-124, -144, -148, -155, -19a, -217. Among them, dre-miR-144 and -148 regulation was predicted in 5 netvvorks targeting around 60 genes. 6. Nano-Ti02 is imunotoxic to fish and reduces the bactericidal function of fish neutrophils. By modulating fish immune responses and interfering with resistance to bacterial pathogens, manufactured nano-Ti02 has the potential to affect fish survival in a disease outbreak. As a final results we have enough data to conclude that the presence of nano-Ti02 in the environment may cause adverse effects in fish. We are confident that this project will provide European Union and the OECD with reliable and original data (the main goals of the OECD V/PMN program), and will provide solid ground for the future risk assessment of nanomaterials.

Data: CORDIS, © European Union

Project objective

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

Original text from CORDIS.

Participants

  • LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggCoordinatorGermany

Links

Data: CORDIS, © European Union