Biodistribution and oxidative stress effects of a systemically-introduced commercial ceria engineered nanomaterial

Abstract

The objective was to characterize the biodistribution of nanoscale ceria from blood and its effects on oxidative stress endpoints. A commercial 5% crystalline ceria dispersion in water (average particle size Â3194 nm) was infused intravenously into rats (0, 50, 250 and 750 mg/kg), which were terminated 1 or 20 h later. Biodistribution in rat tissues was assessed by microscopy and ICP-AES/MS. Oxidative stress effects were assessed by protein-bound 4-hydroxy 2-transnonenal (HNE), protein-bound 3-nitrotyrosine (3-NT), and protein carbonyls. Evans blue (EB)-albumin and Na fluorescein (Na 2 F) were given intravenously as blood-brain barrier (BBB) integrity markers. The initial ceria t ½ in blood was Â7 min. Brain EB and Na 2 F increased some at 20 h. Microscopy revealed peripheral organ ceria agglomerations but little in the brain. Spleen Ce concentration was !liver !blood !brain. Reticuloendothelial tissues cleared ceria. HNE was significantly increased in the hippocampus at 20 h. Protein carbonyl and 3-NT changes were small. The nanoparticle characterizations before and after biodistribution, linked with the physiological responses, provide a foundation for evaluating the effects of engineered nanomaterial physico-chemical properties on peripheral organ distribution, brain entry and resultant toxicity.

Frameworks and tools for risk assessment of manufactured nanomaterials

“…Advanced REACH Tool (ART) (Fransman et al, 2009) Occupational exposure assessment (Gorman et al, 2012) Occupational/consumer exposure assessment (Gottschalk et al, 2010a, 2010b, Sun et al, 2014, Gottschalk et al, 2009, Gottschalk et al, 2011 (Yokel et al, 2009, Yokel et al, 2012, Hardas et al, 2010, Dan et al, 2011 In vivoIkinetic tools for human exposure and hazard assessment (Lammel et al, 2013, Lammel andNavas, 2014) In vitro and in vivo tools for human hazard assessment…”

“…In order to fill this gap, several projects have developed and/or applied in vivo kinetic protocols. For instance, the U.S. STAR project developed methods to determine the distribution, persistence, translocation on and biotransformation of metal oxide MNs, their tolerability, and effects, focusing on oxidative stress endpoints (Yokel et al, 2009, Yokel et al, 2012, Hardas et al, 2010. This tool is an in vivo protocol including comprehensive physicochemical characterization for properties such as size, shape, zeta potential, extent of surface coating, and solubility.…”

“…This tool is an in vivo protocol including comprehensive physicochemical characterization for properties such as size, shape, zeta potential, extent of surface coating, and solubility. It includes investigation of multiple oxidative stress and inflammatory markers (Yokel et al, 2009, Yokel et al, 2012, Dan et al, 2011. Moreover, the EU-funded SUN project adapted and applied the Short-term Inhalation Studies (STIS) protocol developed in the NANOSAFE2 and NANOCARE projects (Klein et al, 2012).…”

Analysis of engineered nanomaterials in complex matrices (environment and biota): General considerations and conceptual case studies

“…Transmission electronic microscopy instruments with energy-dispersive spectrometry (EDS), and electron diffraction can further determine the elemental composition and crystal phase, respectively. Scanning transmission electron microscopy may be particularly useful at identifying ENM in specimens at low concentrations [37], especially when used in conjunction with a high-angle annular dark field detector, which has greater sensitivity with increasing Z number for elements [39]. Electron energy loss spectroscopy can be used to obtain information about the electronic configuration of elements and is also good for quantitative analyses of low Z elements such as oxygen.…”

“…1, pp. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]2012 # 2011 SETAC Printed in the USA DOI: 10.1002/etc.723 This paper evolved from discussions held at a SETAC-endorsed Technical Workshop held at Clemson University in August, 2010. The workshop was sponsored by the United States Environmental Protection Agency (U.S. EPA), Arcadis-US, and the Clemson University Institute of Environmental Toxicology.…”