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Genotoxicity evaluation of nanosized titanium dioxide,synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes
Affiliation:1. Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal;2. Toxicology Laboratory of Institut Pasteur de Lille, EA 4483, 1 rue du Professeur Calmette, BP 245, 59019 Lille, France;3. Electron Microscopy-unit, Veterinary and Agrochemical Research Centre (CODA-CERVA), Groeselenberg 99, 1180 Brussels, Belgium;4. Danish Centre for Nanosafety National Research Centre for the Working Environment, Lerso Parkallé 105, Copenhagen DK-2100, Denmark;5. Nanosafety Research Center, Finnish Institute of Occupational Health, FI-00250 Helsinki, Finland;1. Department of Toxicology, Center for Pharmaceutical Research (CePhar), Vrije Universiteit Brussel (VUB), Belgium;2. Food and Nutrition Research Center, Agricultural Research Council, Rome, Italy;3. Novozymes A/S, Bagsvaerd, Denmark;4. Doerenkamp-Zbinden Chair, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
Abstract:Toxicological characterization of manufactured nanomaterials (NMs) is essential for safety assessment, while keeping pace with innovation from their development and application in consumer products. The specific physicochemical properties of NMs, including size and morphology, might influence their toxicity and have impact on human health. The present work aimed to evaluate the genotoxicity of nanosized titanium dioxide (TiO2), synthetic amorphous silica (SAS) and multiwalled carbon nanotubes (MWCNTs), in human lymphocytes. The morphology and size of those NMs were characterized by transmission electron microscopy, while the hydrodynamic particle size-distributions were determined by dynamic light scattering. Using a standardized procedure to ensure the dispersion of the NMs and the cytokinesis-block micronucleus assay (without metabolic activation), we observed significant increases in the frequencies of micronucleated binucleated cells (MNBCs) for some TiO2 NMs and for two MWCNTs, although no clear dose–response relationships could be disclosed. In contrast, all forms of SAS analyzed in this study were unable to induce micronuclei. The present findings increase the weight of evidence towards a genotoxic effect of some forms of TiO2 and some MWCNTs. Regarding safety assessment, the differential genotoxicity observed for closely related NMs highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs.
Keywords:Titanium dioxide nanomaterials  Synthetic amorphous silica nanomaterials  Multiwalled carbon nanotubes  Morphology and size  Primary human lymphocytes  Micronucleus assay
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