title: Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats.
abstract: Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, were substituted into the lattice of the CeO2 nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd-doped CeO2 nanoparticles were compared to pure CeO2 nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1-, 7-, or 84-day post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1-day post-exposure and was sustained 7-day post-exposure, but subsided to control levels 84-day post-exposure. Furthermore, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO2 nanoparticle toxicity in vivo.
authors.affiliation: a HELD , National Institute for Occupational Safety and Health , Morgantown , WV , USA .|b Pharmaceutical and Pharmacological Sciences , West Virginia University , Morgantown , WV , USA .
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Dunnick
authors.affiliation: a HELD , National Institute for Occupational Safety and Health , Morgantown , WV , USA .
authors.forename: Anna M
authors.initials: AM
authors.lastname: Morris
authors.affiliation: a HELD , National Institute for Occupational Safety and Health , Morgantown , WV , USA .
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Badding
authors.affiliation: a HELD , National Institute for Occupational Safety and Health , Morgantown , WV , USA .
authors.forename: Mark
authors.initials: M
authors.lastname: Barger
authors.affiliation: c RHD , National Institute for Occupational Safety and Health , Morgantown , WV , USA , and.
authors.forename: Aleksandr B
authors.initials: AB
authors.lastname: Stefaniak
authors.affiliation: d WVU Benjamin M. Statler College of Engineering and Mineral Resources , Morgantown , WV , USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sabolsky
authors.affiliation: a HELD , National Institute for Occupational Safety and Health , Morgantown , WV , USA .|b Pharmaceutical and Pharmacological Sciences , West Virginia University , Morgantown , WV , USA .
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Leonard
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002563:Cerium / Q000737:chemistry* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000737:chemistry; D007322:Instillation, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D002563:Cerium; C030583:ceric oxide; D005682:Gadolinium; D010100:Oxygen
keywords: Cerium oxide; intratracheal instillation; nanoparticles; nanotoxicity; valence state