Occupational Exposure to Carbon Nanotubes and Nanofibers

length, respectively) [Muller et al. 2009; Liang et al.2010] did not produce mesothelioma. These findingsare consistent with those reported by Yamashitaet al. [2010] and Nagai et al. [2011] who foundthat MWCNT injected into the peritoneal cavity ofmice or rats generated inflammation/genetic damageand mesothelioma that were related to the dimensionof the CNT. Results from these peritonealassay studies indicate that CNT of specific dimensionsand durability can cause inflammation, fibrosis,and mesothelial tumors in mice and in rats;however, additional experimental animal researchis needed to: (1) provide quantitative data on thebiopersistence of different types of CNT in the lungand, (2) address the key question as to the precisedimensions (and possibly other physical-chemicalcharacteristics) of CNT that pose a potential pathogenicrisk for cancer including mesothelioma.As synthesized, raw (unpurified) CNT, contain asmuch as 30% catalytic metals. Catalytic metals,such as iron-rich SWCNT, can generate hydroxylradicals in the presence of hydrogen peroxide andorganic (lipid) peroxides [Kagan et al. 2006], andwhen human epidermal keratinocytes cells are exposedto unpurified SWCNT (in vitro cellular studies),oxidant injury occurs [Shvedova et al. 2003].These catalytic metals can be removed from rawCNT by acid treatment or by high temperature toyield purified CNT with low metal content. Removalof catalytic metals abolishes the ability ofSWCNT or MWCNT to generate hydroxyl radicals.However, in laboratory animal studies the pulmonarybioactivity of SWCNT does not appear tobe affected by the presence or absence of catalyticmetals. Lam et al. [2004] compared the pulmonaryresponse of mice to intratracheal instillation of raw(containing 25% metal catalyst) with purified (~2%iron) SWCNT and found that the granulomatousreaction was not dependent on metal contamination.Likewise, the acute inflammatory reaction ofmice after aspiration of raw (30% iron) versus purified(< 1% iron) SWCNT was not affected by metalcontent [Shvedova et al. 2005, 2008].Pulmonary exposure to CNT have shown systemicresponses including an increase in inflammatorymediators in the blood, as well as oxidant stress inaortic tissue and increase plaque formation in anatherosclerotic mouse model [Li et al. 2007; Erdelyet al. 2009]. Pulmonary exposure to MWCNTalso depresses the ability of coronary arterioles torespond to dilators [Stapleton et al. 2011]. Thesecardiovascular effects may be due to neurogenicsignals from sensory irritant receptors in the lung.Mechanisms, such as inflammatory signals or neurogenicpathways causing these systemic responses,are under investigation.Results from in vitro cellular studies have shownthat SWCNT can cause genotoxicity and abnormalchromosome number, because of interference withmitosis (cell division), by disrupting the mitoticspindles in dividing cells and inducing the formationof anaphase bridges among the nuclei [Sargentet al. 2009]. In vitro studies also indicate that exposureto CNF can cause genotoxicity (micronuclei)as a result of reactive oxygen species (ROS) production,which in turn reacts with DNA, and byinterfering physically with the DNA/chromosomesand/or mitotic apparatus [Kisin et al. 2011]. Lowdose,long-term exposure of bronchial epithelialcells to MWCNT has been shown to induce celltransformation, and these transformed cells inducetumors after injection into nude mice [Stueckle etal. 2011; Wang et al. 2011].Currently, there are no studies reported in the literatureon the adverse health effects in workers producingor using CNT or CNF. However, becausehumans can also develop lung inflammation andfibrosis in response to inhaled particles and fibers,it is reasonable to assume that at equivalent exposures(e.g., lung burden/alveolar epithelial cell surface)to CNT and CNF, workers may also be at riskof developing these adverse lung effects.Although data on workplace exposures to CNT andCNF are limited, aerosolization of CNT and CNFhas been shown to occur at a number of operationsduring research, production, and use of CNT andCNF, including such work tasks as transferring,weighing, blending, and mixing. Worker exposureto airborne CNT and CNF has frequently been34 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers