Occupational Exposure to Carbon Nanotubes and Nanofibers

A.1 IntroductionThe increasing production and use of CNT and thepreliminary significant toxicology findings necessitatean assessment of the potential adverse healtheffects in workers who produce or use these materials.Risk assessment is a process that uses standardizedtools and procedures to characterize thehealth risk of exposure to a hazardous substance, aswell as the uncertainties associated with those riskestimates. Research studies in toxicology, epidemiology,exposure measurement, and other areasprovide the data needed to perform the risk assessment.The standard risk assessment paradigm inthe United States includes four basic steps: hazardassessment, exposure assessment, dose-responseanalysis, and risk characterization [NRC 1983,2009]. Risk assessment also involves the initialsteps in problem formulation and evaluation of thevarious risk management options [NRC 2009]. Themost recent guidance [NRC 2009] recommendsasking these questions: ”What are the options availableto reduce the hazards or exposures that havebeen identified, and how can risk assessment beused to evaluate the merits of the various options?”Risk assessment is intended to provide informationneeded to determine risk management options.Risk assessment practice seeks to use the best availabledata and scientific methods as the basis forpublic and occupational health decision-making[NRC 2009]. When sufficient dose-response dataare available (e.g., from animal studies), quantitativerisk assessment can be performed. Quantitativerisk assessment provides estimates of the severityand likelihood of an adverse response associatedwith exposure to a hazardous agent [Piegorsch andBailer 2005; NRC 2009]. Risk assessments are usedin developing occupational exposure limits and inselecting and evaluating the effectiveness of exposurecontrols and other risk management strategiesto protect workers’ health.The best data available for risk assessment, in theabsence of epidemiological studies of workers producingor using CNT, are from animal studieswith CNT. These studies include two subchronicinhalation studies of MWCNT in rats and severalNIOSH CIB 65 • Carbon Nanotubes and Nanofibersshort-term studies of SWCNT, MWCNT, or CNFin rats or mice. These studies provide the data andinformation on the dose-response relationshipsand the biological mechanisms of early-stage inflammatoryand fibrotic lung effects from exposureto CNT. No chronic animal studies of CNTwere available for this risk assessment.The biological mode of action for CNT and CNF, asfor inhaled particles and fibers, generally relates totheir physical and chemical properties. These propertiesinclude: (1) nano-structure which increasesthe surface area and associated inflammogenic andfibrogenic response; (2) fiber shape which maydecrease clearance of long structures, resulting intranslocation to the interstitial and pleural tissuesof the lungs; and (3) the graphitic structure of CNTand CNF which influences their durability andbiopersistence [Donaldson et al. 2006; Shvedova etal. 2009; Castranova 2011]. CNT and CNF are heterogeneousstructures, and differences can includesize (length and diameter), metal contaminants(type and amount), surface chemistry, and tendencyto aggregate/agglomerate. CNT and CNF typicallyform agglomerates in air but may also exist asindividual structures Johnson et al. 2010, Methneret al. 2010, Dahm et al. 2011]. Evidence from shorttermand subchronic studies in animals indicatesthat CNT may be biopersistent in the lungs [Mulleret al. 2005; Deng et al. 2007; Elgrabli et al. 2008b;Mercer et al. 2009; Pauluhn 2010a,b] However,some evidence suggests that functionalization mayincrease biodegradation of CNT [Kagan et al. 2010;Osmond-McLeod et al. 2011].Dose metrics that have been associated with lungresponses to CNT or CNF in animal studies includemass, volume, number, and surface area. The CNTvolume dose was associated with the overloading ofCNT clearance from rat lungs and to the lung responses[Pauluhn 2010a]. The specific surface area(m2/g) dose of various types of CNTs was associatedwith the pulmonary inflammation response inrats [Nakanishi 2011a]. Mercer et al. [2011] showedthat on a mass basis, SWCNT is more fibrogenicthan MWCNT, but this difference disappeared afteraccounting for the greater specific surface area ofthe SWCNT than MWCNT. Murray et al. [2012]95