Final Report Summary - FISHTIO2 (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.
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.