title: Clearance kinetics of fullerene C₆₀ nanoparticles from rat lungs after intratracheal C₆₀ instillation and inhalation C₆₀ exposure.
abstract: Fullerene (carbon sixty [C(60)]) has potential industrial and medical applications. In the future, people working in or residing near manufacturing facilities may be exposed to C(60). Therefore, quantitative data on long-term C(60) clearance from the lungs are required. To estimate the clearance rate and deposition fraction of C(60) from inhalation exposure, the C(60) burden in the lungs, liver, and brain of rats was determined after intratracheal instillation and inhalation. Male Wistar rats were intratracheally instilled with different concentrations of a C(60) suspension prepared with Tween 80 (geometric mean [GM] of particle diameter based on number, 18-29 nm; geometric standard deviation [GSD] of particle diameter, 1.5; and doses, 100, 200, and 1000 micrograms per body) or exposed to a C(60) aerosol prepared with nebulizer (GM of particle diameter based on number, 96 nm; GSD of particle diameter, 2.0; and exposure level, 120 μg/m(3)). C(60) burden in the lungs, liver, and brain was determined at various time points (1 h to 6 months) by a newly developed sensitive high-performance liquid chromatography-ultraviolet absorptiometry combined with extraction and concentration of C(60) from the organs. C(60) clearance was evaluated using a 2-compartment model: fast clearance after deposition on lung surface and slow clearance after retention in the epithelium. The detection limit of our analysis method was 8.9 ng/g tissue. Pulmonary C(60) burden decreased with time and depended on the C(60) concentration administered. The concentration of C(60) in the liver and brain was below the detection limit: 8.9 ng/g tissue. The half-life of intratracheally instilled C(60) was 15-28 days. The deposition mass fraction of inhaled C(60) was 0.14. Mode evaluation revealed that most instilled particles could be eliminated by the fast clearance pathway. This finding is consistent with the transmission electron microscopy finding that many particles were present in alveolar macrophages.
authors.affiliation: Research Institute of Science for Safety and Sustainability (RISS), National Institute of Advanced Industrial Science and Technology, Onogawa 16-1, Tsukuba, Ibaraki 305-8569, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Shinohara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakazato
authors.forename: Moritaka
authors.initials: M
authors.lastname: Tamura
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Endoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukui
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tao
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Junko
authors.initials: J
authors.lastname: Nakanishi
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001822:Body Burden; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide; D002851:Chromatography, High Pressure Liquid; D037741:Fullerenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D007442:Intubation, Intratracheal; D057230:Limit of Detection; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D053758:Nanoparticles / Q000648:ultrastructure; D010316:Particle Size; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000393:Air Pollutants; D037741:Fullerenes; D002245:Carbon Dioxide; C069837:fullerene C60