Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis

Abstract

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.

Aerosolization System for Experimental Inhalation Studies of Carbon-Based Nanomaterials

“…There are few studies that have developed aerosolization systems and delivered carbon-based nanomaterials via inhalation (Li et al 2007;Mitchell et al 2007;Ryman-Rasmussen et al 2008;Shvedova et al 2008). In the Mitchell et al (2007) study, MW-CNTs were aerosolized with a jet mill coupled to a dry chemical screw feeder and a 2-µm cut-point cyclone.…”

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

“…14 On an equal mass lung burden basis, the fibrotic response following inhalation was 4-fold greater than after aspiration of SWCNTs. 13,14 This was because SWCNTs were more dispersed in the dry aerosol (inhalation exposure) than in an aqueous suspension (pharyngeal aspiration). Aspiration of a well-dispersed suspension of SWCNTs resulted in a less severe granulomatous response and a 4-fold greater interstitial fibrotic response than a poorly dispersed SWCNT suspension.…”

“…Similarly, the inflammatory response to aspiration of raw (17.7% iron) vs purified (0.23% iron) SWCNTs was not significantly different. 13,14 …”

“…Shvedova et al 14 compared pulmonary responses of mice to pharyngeal aspiration vs a short-term inhalation (4 days) of SWCNTs. In this investigation, the SWCNT dry aerosol preparation for inhalation was more dispersed than the CNT suspension used for aspiration exposure.…”

Nanotechnology, Society, and Environment

“…An important element for characterising nanoparticles and their toxicology is studying states of agglomeration (particles coagulation after turbulence in liquids or gases) and aggregation (particle attraction through van der Waals forces) (Oberdorster et al, 2007) These days, researchers look at how nanoparticles represent hazards to human and other mammalian tissue. For example, Shvedova et al (2008) have found that single walled carbon nanotubes can impact adversely on mice lungs when inhaled. Many scientific studies show that nanoparticles have the propensity to cross cell barriers and interact with cellular structures.…”