Grantee Research Project Results
2009 Progress Report: Safety/Toxicity Assessment of Ceria (A Model Engineered NP) to the Brain
EPA Grant Number: R833772Title: Safety/Toxicity Assessment of Ceria (A Model Engineered NP) to the Brain
Investigators: Yokel, Robert A. , Graham, Ursula M. , Tseng, Michael T. , Butterfield, Allan , Grulke, Eric
Institution: University of Kentucky , University of Louisville
EPA Project Officer: Hahn, Intaek
Project Period: April 1, 2008 through March 31, 2012
Project Period Covered by this Report: April 1, 2009 through March 31,2010
Project Amount: $2,000,000
RFA: Manufactured Nanomaterials: Physico-chemical Principles of Biocompatibility and Toxicity (R01) (2007) RFA Text | Recipients Lists
Research Category: Nanotechnology , Safer Chemicals
Objective:
The overall objectives are to determine the physico-chemical properties of engineered nanomaterials (ENMs) that influence their distribution into the blood-brain barrier (BBB) and brain cells and to assess their beneficial and/or hazardous effects on the brain.Progress Summary:
A study was completed to assess the distribution of a commercial ~ 30 nm crystalline ceria into the brain, compared to peripheral organs, 1 and 20 hours after its intravenous administration to rats. Much less cerium was seen in the brain than in the liver, spleen and kidney. Light and electron microscopic assessment of ceria also showed little ceria in the brain, but massive agglomerations in the liver, and spleen, with small agglomerations in the kidney. Reticuloendothelial organs which appear to clear ceria ENM from circulation. A significant increase of 4-hydroxy-2-nonenal was seen in the hippocampus 20 hours after completion of the ceria administration, indicating induction of oxidative stress by the ceria ENM. Some blood-brain barrier disruption was seen, particularly 20 hours after completion of the ceria administration. The report of this study has been accepted for publication. Subsequent work has investigated ~ 5 and 45 nm ceria that we have manufactured and characterized. Ongoing work with a citrate-stabilized 5 nm ceria shows it to be considerably more toxic than the ~ 30 nm commercial material, and to enter the brain to a greater extent.Future Activities:
Investigate the effects of smaller and larger ceria ENM using similar procedures to those we used to study the Aldrich ~ 30 nm ceria, as described in the Nanotoxicology manuscript.Journal Articles on this Report : 20 Displayed | Download in RIS Format
| Other project views: | All 29 publications | 20 publications in selected types | All 20 journal articles |
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Boyes W, Chen R, Chen C, Yokel R. The neurotoxic potential of engineered nanomaterials. NEUROTOXICOLOGY 2012;33(4):902-910 |
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Carlander U, Moto T, Desalegn A, Yokel R, Johanson G. Physiologically based pharmacokinetic modeling of nanoceria systemic distribution in rats suggests dose- and route-dependent biokinetics. INTERNATIONAL JOURNAL OF NANOMEDICINE 2018;13:2631-2646 |
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Dan M, Wu P, Grulke E, Graham U, Unrine J, Yokel R. Ceria-engineered nanomaterial distribution in, and clearance from, blood: size matters. NANOMEDICINE 2011;7(1):95-110 |
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Graham U, Tseng M, Jasinski J, Yokel R, Unrine J, Davis B, Dozier A, Hardas S, Sultana R, Grulke E, Allan D. Inâ Vivo Processing of Ceria Nanoparticles inside Liver: Impact on Free-Radical Scavenging Activity and Oxidative Stress. CHEMPLUSCHEM 2014;79(8):1083-1088 |
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Graham U, Yokel R, Fernback J, Dozier A, Drummy L, Mahalingam K, Tseng M, Birtch E. Analytical High-resolution Electron Microscopy Reveals Organ-specific Nanoceria Bioprocessing. TOXILOGIC PATHOLOGY 2017;46(1):47-61 |
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Graham U, Dozier A, Oberdorster G, Yokel R, Molina R, Brain J, Pinto J. Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review. CHEMICAL RESEARCH IN TOXICOLOGY 2020;33(5):1145-1162 |
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Hardas S, Butterfield D, Sultana R, Tseng M, Dan M, Florence R, Unrine J, Graham U, Wu P, Grulke E, Yokel R. Brain Distribution and Toxicological Evaluation of a Systemically Delivered Engineered Nanoscale Ceria. TOXICOLOGICAL SCIENCES 2010;116(2):562-576 |
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Hardas S, Sultana R, Warrier G, Dan M, Florence R, Wu P, Grulke E, Tseng M, Unrine J, Graham U, Yokel R, Butterfield D. Rat brain pro-oxidant effects of peripherally administered 5 nm ceria 30 days after exposure. NEUROTOXICITY 2012;33(5):1147-1155 |
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Hardas S, Sultana R, Warrier G, Dan M, Wu P, Grulke E, Tsang M, Unrine J, Graham U, Yokel R, Butterfield D. Rat hippocampal responses up to 90 days after a single nanoceria dose extends a hierarchical oxidative stress model for nanoparticle toxicity. NANOTOXICOLOGY 2014;8(1):155-166 |
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Harris S, Wegner S, Hong SW, Faustman EM. Phthalate metabolism and kinetics in an in vitro model of testis development. Toxicology in Vitro 2016;32:123-131. |
R833772 (2009) R834514 (Final) R834514C003 (Final) R835738 (2016) R835738 (2017) R835738C004 (2015) R835738C004 (2016) R835738C004 (2017) |
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Kanniah V, Wu P, Mandzy N, Grulke E. Fractal analysis as a complimentary technique for characterizing nanoparticle size distributions. POWDER TECHNOLOGY 2012;226:189-198 |
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Laux P, Riebeling C, Booth A, Brain J, Brunner J, Cerrillo C, Creutzenberg O, Estrela-Lopis I, Gebel T, Johanson G, Jungnickel H, Kock H, Tentscert J, Tlili A, Schaffer A, Sips A, Yokel R, Luch A. Biokinetics of nanomaterials: The role of biopersistence. NANOLMPACT 2017;6:69-80 |
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Tseng M, Lu X, Duan X, Hardas S, Sultana R, Wu P, Unrine J, Graham U, Butterfield A, Grulke E, Yokel R. Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria. TOXICOLOGY AND APPLIED PHARMACOLOGY 2012;260(2):173-182 |
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Wang B, Wu P, Yokel R, Grulke E. Influence of surface charge on lysozyme adsorption to ceria nanoparticles. APPLIED SURFACE SCIENCE 2012;258(14):5332-5341 |
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Yokel RA, Florence RL, Unrine JM, Tseng MT, Graham UM, Wu P, Grulke EA, Sultana R, Hardas SS, Butterfield DA. Biodistribution and oxidative stress effects of a systemically-introduced commercial ceria engineered nanomaterial. Nanotoxicology 2009;3(3):234-248. |
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Yokel R, MacPhail R. Engineered nanomaterials: exposures, hazards, and risk prevention. JOURNAL OF OCCUPATIONAL MEDICINE AND TOXICOLOGY 2011;6(7) |
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Yokel R, Au T, MacPhail R, Hardas S, Butterfield D, Sultana R, Goodman M, Tseng M, Dan M, Haghnazar H, Unrine J, Graham U, Wu P, Grulke E. Distribution, Elimination, and Biopersistence to 90 Days of a Systemically Introduced 30 nm Ceria-Engineered Nanomaterial in Rats. TOXILOGICAL SCIENCES 2012;127(1):256-268 |
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Yokel R, Tseng M, Dan M, Unrine J, Graham U, Wu P, Grulke E. Biodistribution and biopersistence of ceria engineered nanomaterials: size dependence. NANOMEDICINE: NANOTECHNOLOGY, BIOLOGY AND MEDICINE 2013;9(3):398-407 |
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Yokel R, Unrine J, Wu P, Wang B, Grulke E. Nanoceria biodistribution and retention in the rat after its intravenous administration are not greatly influenced by dosing schedule, dose, or particle shape. ENVIRONMENTAL SCIENCE: NANO 2014;1:549-560 |
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Yokel R, Hussain S, Garantziotis S, Demokritou P, Castranova V, Cassee F. The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity. ENVIRONMENTAL SCIENCE: NANO 2014;1(5):406-428 |
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Supplemental Keywords:
ceria, oxidative stress, rat, systemic administrationRelevant Websites:
Butterfield:http://www.as.uky.edu/academics/departments_programs/Chemistry/Chemistry/FacultyResearch/Faculty/DAllanButterfield/Pages/default.aspx Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.