Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

Abstract

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

A 104-week pulmonary toxicity assessment of long and short single-wall carbon nanotubes after a single intratracheal instillation in rats

“…We have also reported that a single intratracheal administration of SWCNTs with an average length of 0.69 lm did not induce lung tumors at 108 weeks after instillation (Fujita et al, 2015a). However, a substantial number of SWCNTs accompanied with chronic inflammation and fibrotic changes were observed in the lungs at 1-year post exposure to SWCNTs (Fujita et al, 2015a;Shvedova et al, 2014). We observed a continuous elevation in the levels of lactose dehydrogenase, total protein levels, and some cytokines in bronchoalveolar lavage fluid when SWCNTs were administrated by intratracheal instillation (Ema et al, 2017;Fujita et al, 2015aFujita et al, , 2015bFujita et al, , 2016.…”

“…Only a few studies on the longterm effects of airway exposure to SWCNTs have been published. Data from a 1-year observational study in mice on purified HiPco SWCNTs (1-3 lm in length) revealed no increase in the incidence of lung tumors after inhalation at 5 mg/m 3 (5 h/d for 4d) or a single pharyngeal aspiration at 40 lg/mouse (Shvedova et al, 2014). In rats, no pulmonary tumors were detected 754 d after a single intratracheal instillation of SWCNTs at 0.2 or 0.4 mg/rat (0.69 lm of average length) (Fujita et al, 2015a).…”

“…Many studies have been conducted to elucidate the pulmonary toxicity of multi-and single-walled CNTs (MWCNTs and SWCNTs, respectively) using in vivo rodent models (Fujita et al, 2015a(Fujita et al, , 2015b(Fujita et al, , 2016Lam et al, 2004;Ma-Hock et al, 2009;Morimoto et al, 2012aMorimoto et al, , 2012bMuller et al, 2009;Pauluhn, 2010;Shvedova et al, 2014;Warheit et al, 2004). Some reports have presented evidence that 1 type of MWCNT was carcinogenic to rodents (Sakamoto et al, 2009;Sargent et al, 2014;Takagi et al, 2008Takagi et al, , 2012, resulting in its classification as a Group 2B agent by the World Health Organization (WHO)/the International Agency for Research on Cancer (IARC) (Grosse et al, 2014).…”

Length effects of single-walled carbon nanotubes on pulmonary toxicity after intratracheal instillation in rats

“…In a one-year observational study on purified HiPco SWCNTs (0.1-1 μm in length) in mice, no increased incidence of lung tumor was reported after administration of the SWCNTs by inhalation or pharyngeal aspiration (Shvedova et al, 2014b). Furthermore, in a study conducted in rats, no pulmonary tumor was detected 754 days after intratracheal instillation of SWCNTs (average length, 0.69 μm) (Fujita et al, 2015b).…”

“…Furthermore, in a study conducted in rats, no pulmonary tumor was detected 754 days after intratracheal instillation of SWCNTs (average length, 0.69 μm) (Fujita et al, 2015b). However, a substantial number of SWCNTs as well as inflammation and fibrotic changes were observed in the lungs of the rats at 1-year post exposure to the SWCNTs (Shvedova et al, 2014b;Fujita et al, 2015b). In the present study, we showed that S-SWCNTs induced persistent pulmonary inflammation and L-SWCNTs caused increased levels of total protein in BALF during the later phase of the 6-month observational period.…”