title: Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats.
abstract: Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Academic Medical Center, University of Kentucky, Lexington, Kentucky 40536-0596, USA. ryokel@email.uky.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yokel
authors.forename: Tu C
authors.initials: TC
authors.lastname: Au
authors.forename: Robert
authors.initials: R
authors.lastname: MacPhail
authors.forename: Sarita S
authors.initials: SS
authors.lastname: Hardas
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tseng
authors.forename: Mo
authors.initials: M
authors.lastname: Dan
authors.forename: Hamed
authors.initials: H
authors.lastname: Haghnazar
authors.forename: Jason M
authors.initials: JM
authors.lastname: Unrine
authors.forename: Uschi M
authors.initials: UM
authors.lastname: Graham
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Grulke
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002563:Cerium / Q000493:pharmacokinetics* / Q000633:toxicity*; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000633:toxicity* / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002563:Cerium; C030583:ceric oxide