Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies

Abstract

BackgroundWe used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies.ResultsIn the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group.ConclusionThese data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

“…10 However, some studies have shown that NiONP exposure induces only mild and reversible inflammation. 33,34 Zhang et al 35 found that NiO (20 µg suspended in 50 µL of PBS) exposure induced less neutrophil cell counts, monocyte chemotactic protein-1, and IL-6 levels in BALF compared with the same amount of CuO and Cr 2 O 3 exposure in C57 BL/6 mice. We suppose that the discrepancy in these results may be due to the different properties and the ability to induce oxidative stress of NPs.…”

Hazard Assessments of Manufactured Nanomaterials

“…Inhalation exposure studies of C 60 on mice and rats have also taken place by Yokoyama et al 51) and Morimoto et al 50) . Using the same dispersed fullerene suspension as used in the intratracheal instillation study, Shimada et al 52) succeeded in stabilizing the particle concentration and nanoscale sizes of airborne fullerenes with a pressurized nebulizer.…”

“…The second step involves the estimation of the acceptable exposures of TiO 2 nanomaterials for humans by extrapolating the NOAEL for experimental animals to humans taking into consideration the uncertainty factor (UF), which will be described later (2 a positive control, but not that of C 60 51) . Furthermore, Morimoto et al 50) exposed Wistar rats to 0.12 mg/m 3 C 60 aerosol (mean geometric diameter, 96 nm; particle concentration, 4.1 × 10 4 /cm 3 ) for 6 h/day, 5 days/wk for 4 wk, followed by 3 mo observation. In the lungs there was only slight transient inflammation.…”

“…Their size and concentration were confirmed to be stable for 3 wk. Morimoto et al 50) performed single intratracheal instillations of fullerenes at 0.1, 0.2 or 1.0 mg (0.33, 0.66 or 3.3 mg/kg) to Wistar rats followed by observation for 6 mo using the C 60 suspension. At the high dose (3.3 mg/kg), pulmonary inflammation mainly by neutrophils was observed in BALF and lung, and the expression of heme-oxygenase-1 (HO-1) was also increased, but both findings were transient and mild in severity.…”

“…The exposure time, t, was the daily exposure period of Morimoto's experiment 50) ; f r and f h are values calculated utilizing a multi-path particle dosimetry (MPPD) model; q r , S r and S h were taken and calculated from United States Environmental Protection Agency data (1994); and q h is the respiration rate for light work of 36 m 3 /day. Since the significant adverse effects of C 60 were not observed even in intratracheal instillation studies when the intrapulmonary amounts found were more than 40 times those seen in inhalation studies, and applying this as a correction factor, as well as an uncertainty factor of 6 for estimation of a long-term index from short-or medium-term indices, the provisional Threshold Level (TL) was estimated as implying an acceptable exposure concentration of 0.8 mg/m 3 in working environments for C 60 fullerene nanoparticles having a geometric mean diameter of 96 nm.…”