NIOSHTIC-2 Publications Search

Nanoparticles - toxicological approaches.

Simeonova-P; Shvedova-A; Luster-MI; Li-Z
First Annual Meeting of the American Academy of Nanomedicine, August 15-16, 2005, Baltimore, Maryland. Washington DC: American Academy of Nanomedicine, 2005 Aug; :26
Nanotechnologies will revolutionize our life including medicine, but they also pose important toxicological questions that are related to the unique nature of materials and processes at the nanometer scale. Human contact with nanomaterials can be related to targeted exposure through therapeutics and cosmetics or untargeted exposure through occupational and environmental contamination. The accumulation of toxicological data on engineered nanomaterials will allow for development of adequate risk assessment and regulations. One direction of the nanomaterial industries is production of new carbon nanomaterials. Graphite sheets are rolled-up, usually in the presence of metal catalyst, to form long single wall carbon nanotubes which are about 1 nm in diameter. Since the discovery of their one-dimensional electronic band structure, the carbon nanotubes (CNT) have emerged as leading candidates for nanodevice applications. Recently, it has been demonstrated that respiratory exposure to CNT, in contrast to the exposure to ultrafine carbon black, is associated with increased oxidative stress, inflammation, and fibrosis in the lung. The unique physical characteristics of CNT raise concerns that they may have not only more pulmonary toxicity but might be associated with systemic effects. We hypothesized that CNT respiratory exposure is related to oxidative and inflammatory responses in the vascular system, which might be a prerequisite of atherogenesis. C57BL/6 mice were exposed to CNT in doses (0.5; 1; 2 mg/kg) by single intra-pharyngeal installation and the mice were sacrificed at different time points (1; 7; 28; 56; and 180 days) after the exposure (the experimental settings have been related to pulmonary toxicity including development of granulomas). By extra long quantitative PCR of mitochondrial (mt) DNA, we found that CNT exposure induced a dosedependent aortic mtDNA damage, an oxidative stress dependable parameter, at day 7, 28, 56, and 180 days after exposure. These responses were accompanied by increase production of reactive oxygen species in the aortic tissue, measured by an electron spin resonance assay. Similar oxidative modifications were observed in the aortic tissue of ApoE-/- mice, a model of human atherosclerosis. Consistent with these results, we demonstrated that the acute pharyngeal aspiration of CNT exposure induces activation of the oxidative sensitive gene, heme-oxygenase (HO-1) in the lung, heart, and aorta in transgenic mice which carries a mouse HO-1-luc construct. Overall, these initial studies demonstrated that the respiratory exposure to CNT provokes dose-dependent severe lung toxicity and vascular effects related to oxidative stress. The role of these effects in atheroma formation or acceleration will be evaluated in the next sets of experiments.
Occupational-exposure; Environmental-exposure; Environmental-contamination; Risk-analysis; Pulmonary-system-disorders; Lung-disorders; Lung-fibrosis; Fibrosis; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment; Nanotechnology
Publication Date
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
NIOSH Division
Source Name
First Annual Meeting of the American Academy of Nanomedicine, August 15-16, 2005, Baltimore, Maryland
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division