Respiratory toxicity and immunotoxicity evaluations of microparticle and nanoparticle C60 fullerene aggregates in mice and rats following nose-only inhalation for 13 weeks.
C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 μm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2 mg/m3(0.033 and 0.112 m2/m3), while micro-C60 exposures were 2, 15 and 30 mg/m3(0.011, 0.084 and 0.167 m2/m3). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1α (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2 mg/m3and micro-C60 exposure at 30 mg/m3. Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles.
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Brian C
BC
Sayers
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Dori R
DR
Germolec
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Nigel J
NJ
Walker
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Kelly A
KA
Shipkowski
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Matthew D
MD
Stout
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Mark F
MF
Cesta
a Division of the National Toxicology Program , National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
Joseph H
JH
Roycroft
b Department of Pharmacology and Toxicology , Virginia Commonwealth University , Richmond , VA , USA.
Kimber L
KL
White
c Battelle Toxicology Northwest , Richland , WA , USA , and.
Gregory L
GL
Baker
c Battelle Toxicology Northwest , Richland , WA , USA , and.
Jeffrey A
JA
Dill
b Department of Pharmacology and Toxicology , Virginia Commonwealth University , Richmond , VA , USA.|d Richard Bland College of William & Mary , Petersburg , VA , USA.
Matthew J
MJ
Smith
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D037741:Fullerenes / Q000737:chemistry / Q000633:toxicity*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
D037741:Fullerenes; C069837:fullerene C60
Buckminsterfullerene; immunotoxicity; inhalation; nanoparticles; pulmonary inflammation