Comparative Pulmonary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats

Abstract

The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mg/kg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mg/kg) SWCNT produced mortality in ~15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent pulmonary toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in pulmonary inflammation, cytotoxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that pulmonary exposures to quartz particles (5 mg/kg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung toxicity by assessing lavage parameters, (2) lack of lung toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation toxicity study.

Nanoparticulate materials and regulatory policy in Europe: An analysis of stakeholder perspectives

“…The research covering the new types of NPM is limited and the number of studies of the environmental impacts of NPM are few. Carbon nanotubes have been shown to cause granulomas in the lungs of animals, an immunological response to foreign objects (Lam et al, 2004;Warheit et al, 2004;Muller et al, 2005;Shvedova et al, 2005), and was found in one study to be more toxic than carbon black and quartz (Lam et al, 2004). Fullerenes have been shown in studies to be bioavailable when released in aqueous environments, cause lipid peroxidation in fishbrain (Oberdorster, 2004a) and inhibit bacterial growth (Fortner et al, 2005).…”

In vitro tagging of embryos with nanoparticles

“…The mechanisms for the lack of continued embryo development remained unknown. Studies in other cell types have shown that internalized nanoparticles [7] derived from materials other than that tested here disrupted fibroblast and cancer cells after adhering to the cell membranes, impaling and/or releasing toxic ions [27][28][29][30][31][32]. Moreover, nanoparticles internalized into cells increased the reactive oxygen species (ROS), elevated intracellular calcium, activated transcription factors [10] and initiated apoptosis or cell death [14].…”

Approaches to safe nanotechnology: managing the health and safety concerns associated with engineered nanomaterials (withdrawn).

“…In a study of SWCNTs instilled into the lungs of rats, multi-focal granulomas (without transient inflammation or persistent lesions) were observed at doses of 1 or 5 mg / kg body weight [Warheit et al 2004]. In a study of mice instilled with one of several types of SWCNTs (i.e., raw, purified, iron-containing, and nickel-containing) at doses of 0.1 or 0.5 mg/mouse (approximately 3 or 16 mg/kg body weight), dose-dependent epithelioid granulomas were observed at 7 days, which persisted at 90 days [Lam et al 2004[Lam et al , 2006.…”