Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos

Abstract

BackgroundCarbon nanotubes (CNT) and carbon nanofibers (CNF) are allotropes of carbon featuring fibrous morphology. The dimensions and high aspect ratio of CNT and CNF have prompted the comparison with naturally occurring asbestos fibers which are known to be extremely pathogenic. While the toxicity and hazardous outcomes elicited by airborne exposure to single-walled CNT or asbestos have been widely reported, very limited data are currently available describing adverse effects of respirable CNF.ResultsHere, we assessed pulmonary inflammation, fibrosis, oxidative stress markers and systemic immune responses to respirable CNF in comparison to single-walled CNT (SWCNT) and asbestos. Pulmonary inflammatory and fibrogenic responses to CNF, SWCNT and asbestos varied depending upon the agglomeration state of the particles/fibers. Foci of granulomatous lesions and collagen deposition were associated with dense particle-like SWCNT agglomerates, while no granuloma formation was found following exposure to fiber-like CNF or asbestos. The average thickness of the alveolar connective tissue - a marker of interstitial fibrosis - was increased 28 days post SWCNT, CNF or asbestos exposure. Exposure to SWCNT, CNF or asbestos resulted in oxidative stress evidenced by accumulations of 4-HNE and carbonylated proteins in the lung tissues. Additionally, local inflammatory and fibrogenic responses were accompanied by modified systemic immunity, as documented by decreased proliferation of splenic T cells ex vivo on day 28 post exposure. The accuracies of assessments of effective surface area for asbestos, SWCNT and CNF (based on geometrical analysis of their agglomeration) versus estimates of mass dose and number of particles were compared as predictors of toxicological outcomes.ConclusionsWe provide evidence that effective surface area along with mass dose rather than specific surface area or particle number are significantly correlated with toxicological responses to carbonaceous fibrous nanoparticles. Therefore, they could be useful dose metrics for risk assessment and management.

Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

“…A possible explanation is that increasing the diameter increases the bioactivity and induces significant immune response, which is consistent with previous studies showing that longer MWCNT are more bioactive. 43 Studies have also shown that degree of agglomeration, 26,44,45 charge, 46 surface chemical modification, 47 and metal contaminants 48 could affect CNT toxicity in vivo or in vitro. Comparing with f-MWCNT, more inflammation occurred in the p-MWCNTs.…”

Development of risk-based nanomaterial groups for occupational exposure control

“…range (<100 nm), the fraction of inhaled particles that deposit in the alveolar (gas-exchange) region of the lungs generally increases (up to ~50 %) (ICRP 1994;Maynard and Kuempel 2005). The dose metrics of mass, volume, number, or surface area of particles or fibers retained in the lungs have been associated with lung responses to inhaled particles or fibers in rats and mice (Morrow 1988;Oberdörster and Yu 1990;Muhle et al 1991;Oberdörster et al 1994;Tran et al 2000;Elder et al 2005;Nakanishi 2011;Pauluhn 2011;Murray et al 2012). Working lifetime exposures to respirable particle mass and fiber number concentrations have been associated with nonmalignant and malignant lung diseases in workers (reviewed in: Kuempel and Maynard 2005;Oberdörster et al 2005b;Rom and Markowitz 2006).…”

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

“…18 This results in a greater fibrotic reaction to an equal lung burden of SWCNTs compared with MWCNTs. 18 Recently, Murray et al 19 reported that aspiration of CNFs in a mouse model also resulted in transient inflammation and damage and persistent fibrosis. The fibrotic potency (on a mass lung burden basis) was SWCNTs > CNFs = asbestos.…”

“…Murray et al 19 compared the potencies on an equal mass basis of SWCNTs, CNFs, and asbestos to induce pulmonary inflammation, lung injury, and fibrosis from 1 to 28 days after pharyngeal aspiration in mice. At 1 day postexposure, potency for acute inflammation and damage was SWCNTs > CNFs > asbestos, while at 7 days postexposure the potency sequence was SWCNTs > CNFs = asbestos.…”