title: Lung deposition and clearance of microparticle and nanoparticle C60 fullerene aggregates in B6C3F1 mice and Wistar Han rats following nose-only inhalation for 13 weeks.
abstract: C60 fullerenes (C60) are spherical structures consisting of 60 carbon atoms that are generated via combustion from both natural and anthropogenic sources. C60 are also synthesized intentionally for industrial applications. Individual C60 structures have an approximate diameter of 1nm; however, C60 readily forms aggregates and typically exist as larger particles that range from nanometers to micrometers in diameter. In this report, lung and extrapulmonary tissue deposition and lung clearance of C60 nanoparticles (nano-C60, 50nm) and microparticles (micro-C60, 1μm) were examined in Wistar Han rats and B6C3F1/N mice after nose-only inhalation for 90 days. Exposure concentrations were 0.5 and 2mg/m(3) (nano-C60) and 2, 15, and 30mg/m(3) (micro-C60). For both C60 particle sizes, the C60 lung burden increased proportionally to exposure concentration. The C60 lung burden was greater in both species at all time points following exposure to nano-C60 particle exposure compared to micro-C60 exposure at the common exposure concentration 2mg/m(3). The calculated C60 particle lung retention half-times were similar for both nano-C60 and micro-C60 exposure at 2mg/m(3) in male mice (15-16 days). In contrast, in male rats, the half-time of C60 particles following nano-C60 exposure (61 days) was roughly twice as long as the half-time following micro-C60 exposure (27 days) at the same exposure concentration (2mg/m(3)) and was similar to the clearance following micro-C60 exposure at higher exposure concentrations (15 and 30mg/m(3)). C60 was detected in bronchial lymph nodes but the burden was not quantified due to the high variability in the data. C60 concentrations were below the experimental limit of quantitation (ELOQ) in liver, spleen, blood, brain and kidney tissues. These tissue burden data provide information for comparison between nanometer and micrometer sized C60 particle exposure and will aid in the interpretation of toxicity data.
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Sayers
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Walker
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Roycroft
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Baker
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Clark
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Barry K
authors.initials: BK
authors.lastname: Hayden
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: DeFord
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Dill
authors.affiliation: Battelle Toxicology Northwest, 900 Battelle Boulevard, Richland, WA 99354, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Electronic address: stoutm@niehs.nih.gov.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stout
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D005260:Female; D037741:Fullerenes / Q000378:metabolism*; D006207:Half-Life; D008168:Lung / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D053758:Nanoparticles / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D037741:Fullerenes; C069837:fullerene C60
keywords: C(60) fullerene; Inhalation; Lung clearance; Lung deposition; Nanoparticle