Occupational nanosafety considerations for carbon nanotubes and carbon nanofibers.

Carbon nanotubes (CNTs) are carbon atoms arranged in a crystalline graphene lattice with a tubular morphology. CNTs exhibit high tensile strength, possess unique electrical properties, are durable, and can be functionalized. These properties allow applications as structural materials, in electronics, as heating elements, in batteries, in the production of stain-resistant fabric, for bone grafting and dental implants, and for targeted drug delivery. Carbon nanofibers (CNFs) are strong, flexible fibers that are currently used to produce composite materials. Agitation can lead to aerosolized CNTs and CNFs, and peak airborne particulate concentrations are associated with workplace activities such as weighing, transferring, mixing, blending, or sonication. Most airborne CNTs or CNFs found in workplaces are loose agglomerates of micrometer diameter. However, due to their low density, they linger in workplace air for a considerable time, and a large fraction of these structures are respirable. In rat and mouse models, pulmonary exposure to single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), or CNFs causes the following pulmonary reactions: acute pulmonary inflammation and injury, rapid and persistent formation of granulomatous lesions at deposition sites of large CNT agglomerates, and rapid and progressive alveolar interstitial fibrosis at deposition sites of more dispersed CNT or CNF structures. Pulmonary exposure to SWCNTs can induce oxidant stress in aortic tissue and increases plaque formation in an atherosclerotic mouse model. Pulmonary exposure to MWCNTs depresses the ability of coronary arterioles to respond to dilators. These cardiovascular effects may result from neurogenic signals from sensory irritant receptors in the lung. Pulmonary exposure to MWCNTs also upregulates mRNA for inflammatory mediators in selected brain regions, and pulmonary exposure to SWCNTs upregulates the baroreceptor reflex. In addition, pulmonary exposure to MWCNTs may induce levels of inflammatory mediators in the blood, which may affect the cardiovascular system. Intraperitoneal instillation of MWCNTs in mice has been associated with abdominal mesothelioma. MWCNTs deposited in the distal alveoli can migrate to the intrapleural space, and MWCNTs injected in the intrapleural space can cause lesions at the parietal pleura. However, further studies are required to determine whether pulmonary exposure to MWCNTs can induce pleural lesions or mesothelioma. In light of the anticipated growth in the production and use of CNTs and CNFs, worker exposure is possible. Because pulmonary exposure to CNTs and CNFs causes inflammatory and fibrotic reactions in the rodent lung, adverse health effects in workers represent a concern. NIOSH has conducted a risk assessment using available animal exposure-response data and is developing a recommended exposure limit for CNTs and CNFs. Evidence indicates that engineering controls and personal protective equipment can significantly decrease workplace exposure to CNTs and CNFs. Considering the available data on health risks, it appears prudent to develop prevention strategies to minimize workplace exposure. These strategies would include engineering controls (enclosure, exhaust ventilation), worker training, administrative controls, implementation of good handling practices, and the use of personal protective equipment (such as respirators) when necessary. NIOSH has published a document containing recommendations for the safe handling of nanomaterials.

[1]  Jeffery A. Steevens,et al.  Potential for Occupational Exposure to Engineered Carbon-Based Nanomaterials in Environmental Laboratory Studies , 2009, Environmental health perspectives.

[2]  Vincent Castranova,et al.  Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular responses that correlate with fibrogenesis biomarkers and fibrosis in the murine lung. , 2011, ACS nano.

[3]  A. Hart,et al.  Exposure to nanoscale particles and fibers during machining of hybrid advanced composites containing carbon nanotubes , 2009 .

[4]  Vincent Castranova,et al.  Single-walled Carbon Nanotubes: Geno- and Cytotoxic Effects in Lung Fibroblast V79 Cells , 2007, Journal of toxicology and environmental health. Part A.

[5]  B. van Ravenzwaay,et al.  Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[6]  A. Rao,et al.  Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice , 2011, Particle and Fibre Toxicology.

[7]  Samy Rengasamy,et al.  Filtration Performance of NIOSH-Approved N95 and P100 Filtering Facepiece Respirators Against 4 to 30 Nanometer-Size Nanoparticles , 2008, Journal of occupational and environmental hygiene.

[8]  Vincent Castranova,et al.  Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies , 2010, Particle and Fibre Toxicology.

[9]  Antonio Nunes,et al.  Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura. , 2011, The American journal of pathology.

[10]  Li Wang,et al.  Distribution And Persistence Of Pleural Penetrations By Multi-Walled Carbon Nanotubes , 2010, ATS 2010.

[11]  V. Castranova,et al.  Potential pulmonary effects of engineered carbon nanotubes: in vitro genotoxic effects , 2010, Nanotoxicology.

[12]  Yongjun Li,et al.  Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation , 2007, Environmental toxicology.

[13]  Craig A. Poland,et al.  Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma , 2010, Particle and Fibre Toxicology.

[14]  G. Palleschi,et al.  Cardiac autonomic regulation after lung exposure to carbon nanotubes , 2009, Human & experimental toxicology.

[15]  C. Santeufemio,et al.  Characterization of Exposures To Nanoscale Particles and Fibers During Solid Core Drilling of Hybrid Carbon Nanotube Advanced Composites , 2010, International journal of occupational and environmental health.

[16]  P. Baron,et al.  Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[17]  Gwi-Nam Bae,et al.  Monitoring Multiwalled Carbon Nanotube Exposure in Carbon Nanotube Research Facility , 2008 .

[18]  P. Baron,et al.  Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[19]  K. D. de Jong,et al.  Carbon Nanofibers: Catalytic Synthesis and Applications , 2000 .

[20]  P. Baron,et al.  Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity using Human Keratinocyte Cells , 2003, Journal of toxicology and environmental health. Part A.

[21]  Nianqiang Wu,et al.  Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. , 2010, Toxicology.

[22]  V. Castranova,et al.  Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[23]  J. Nagy,et al.  Respiratory toxicity of multi-wall carbon nanotubes. , 2005, Toxicology and applied pharmacology.

[24]  Anna Shvedova,et al.  Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes , 2006, Environmental health perspectives.

[25]  D. Frazer,et al.  Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways , 2012, Nanotoxicology.

[26]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[27]  V. Castranova,et al.  Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos? , 2011, Toxicology and applied pharmacology.

[28]  Craig A. Poland,et al.  Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. , 2008, Nature nanotechnology.

[29]  J. Kanno,et al.  Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. , 2008, The Journal of toxicological sciences.

[30]  Laura Hodson,et al.  Approaches to safe nanotechnology; managing the health and safety concerns associated with engineered nanomaterials , 2009 .

[31]  Mark M. Methner,et al.  Engineering Case Reports , 2008, Journal of occupational and environmental hygiene.

[32]  G. Bae,et al.  Exposure assessment of carbon nanotube manufacturing workplaces , 2010, Inhalation toxicology.

[33]  François Huaux,et al.  Absence of carcinogenic response to multiwall carbon nanotubes in a 2-year bioassay in the peritoneal cavity of the rat. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[34]  Anna A Shvedova,et al.  Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity. Materials and Methods , 2022 .

[35]  V. Castranova,et al.  Cross-talk between lung and systemic circulation during carbon nanotube respiratory exposure. Potential biomarkers. , 2009, Nano letters.

[36]  Vincent Castranova,et al.  Pulmonary fibrotic response to aspiration of multi-walled carbon nanotubes , 2011, Particle and Fibre Toxicology.

[37]  P. Baron,et al.  Exposure to Carbon Nanotube Material: Aerosol Release During the Handling of Unrefined Single-Walled Carbon Nanotube Material , 2004, Journal of toxicology and environmental health. Part A.

[38]  Douglas E. Evans,et al.  Exposure and emissions monitoring during carbon nanofiber production--Part I: elemental carbon and iron-soot aerosols. , 2011, The Annals of occupational hygiene.

[39]  Liying Wang,et al.  Direct Fibrogenic Effects of Dispersed Single-Walled Carbon Nanotubes on Human Lung Fibroblasts , 2010, Journal of toxicology and environmental health. Part A.

[40]  V. Castranova,et al.  Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia , 2012, Nanotoxicology.

[41]  M. Andersen,et al.  Inhaled Carbon Nanotubes Reach the Sub-Pleural Tissue in Mice , 2009, Nature nanotechnology.

[42]  Mark D. Hoover,et al.  Identification and Characterization of Potential Sources of Worker Exposure to Carbon Nanofibers During Polymer Composite Laboratory Operations , 2007, Journal of occupational and environmental hygiene.

[43]  J. Crapo,et al.  Allometric relationships of cell numbers and size in the mammalian lung. , 1992, American journal of respiratory cell and molecular biology.

[44]  V. Castranova,et al.  Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: Two faces of Janus? , 2009, Pharmacology & therapeutics.

[45]  V. Castranova,et al.  Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. , 2006, Toxicology letters.

[46]  Jürgen Pauluhn,et al.  Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[47]  Bengt Fadeel,et al.  Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos , 2012, Particle and Fibre Toxicology.

[48]  Vincent Castranova,et al.  Quantitative techniques for assessing and controlling the dispersion and biological effects of multiwalled carbon nanotubes in mammalian tissue culture cells. , 2010, ACS nano.