Journal Article

Clearance Kinetics of Fullerene C<sub>60</sub> Nanoparticles from Rat Lungs after Intratracheal C<sub>60</sub> Instillation and Inhalation C<sub>60</sub> Exposure

Naohide Shinohara, Tetsuya Nakazato, Moritaka Tamura, Shigehisa Endoh, Hiroko Fukui, Yasuo Morimoto, Toshihiko Myojo, Manabu Shimada, Kazuhiro Yamamoto, Hiroaki Tao, Yasukazu Yoshida and Junko Nakanishi

in Toxicological Sciences

Volume 118, issue 2, pages 564-573
Published in print December 2010 | ISSN: 1096-6080
Published online September 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq288
Clearance Kinetics of Fullerene C60 Nanoparticles from Rat Lungs after Intratracheal C60 Instillation and Inhalation C60 Exposure

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Fullerene (carbon sixty [C60]) has potential industrial and medical applications. In the future, people working in or residing near manufacturing facilities may be exposed to C60. Therefore, quantitative data on long-term C60 clearance from the lungs are required. To estimate the clearance rate and deposition fraction of C60 from inhalation exposure, the C60 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 C60 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 C60 aerosol prepared with nebulizer (GM of particle diameter based on number, 96 nm; GSD of particle diameter, 2.0; and exposure level, 120 μg/m3). C60 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 C60 from the organs. C60 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 C60 burden decreased with time and depended on the C60 concentration administered. The concentration of C60 in the liver and brain was below the detection limit: 8.9 ng/g tissue. The half-life of intratracheally instilled C60 was 15–28 days. The deposition mass fraction of inhaled C60 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.

Keywords: nano material; nanoparticle; fullerene; C60; inhalation exposure; intratracheal instillation; clearance; 2-compartment model

Journal Article.  6790 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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