Occupational Exposure to Carbon Nanotubes and Nanofibers

SWCNT on a mass basis is likely due to its greatersurface area available to react with lung tissue.Comparison of other CNT types and metal contentis generally impeded by differences in study design.In one of the few studies to investigate CNT withdifferent metal content, Lam et al. [2004] reportedlung granuloma and inflammation responses inmice administered IT doses of SWCNT containingeither 2% Fe, 27% Fe, or 26% Ni. The number ofmice developing granulomas by group (each containing5 mice) were the following:••0.1 mg dose: 2 (2% Fe); 5 (27% Fe); and 0(26% Ni)••0.5 mg dose: 5 (2% Fe); 5 (27% Fe); and 5(26% Ni)In addition, three mice died in the first week in the0.5 mg dose of the 26% Ni group.Because of the sparse data and the steep doseresponserelationship, only the SWCNT containing2% Fe were adequately fit by the BMDS model. Thehigh mortality rate in mice exposed to the SWCNTcontaining Ni suggests this material is highly toxic.The greater response proportion in the mice exposedto 0.1 mg SWCNT with 27% Fe (5/5) compared withrats exposed to the same dose of SWCNT with 2%Fe (2/5) suggests that the CNT with higher Fe contentare more toxic than CNT with lower Fe content.In Shvedova et al. [2005, 2008], higher iron contentwas also associated with greater lung responseand thus lower BMD(L) estimates. The BMD(L) estimatesfor SWCNT with 18% Fe were lower thanthose for SWCNT with 0.2% Fe (Table A–3), eventhough the post-exposure time was longer (60 vs.28 days) for the 0.2% Fe SWCNT [Shvedova et al.2005, 2008]. All types of CNT (including SWCNTand MWCNT, purified or unpurified, and with varioustypes and percentages of metals) were of similaror greater potency (i.e., similar or greater lungresponses at the same mass dose) in these animalstudies compared to the other types of particlesor fibers tested (asbestos, silica, ultrafine carbonblack) [Lam et al. 2004; Muller et al. 2005; Shvedovaet al. 2005, 2008].A.4.3 Lung Dose EstimationIn any CNT risk assessment, there may be greateruncertainty in the estimated lung dose of respirableCNT than there is for spherical airborne particlesfor which lung dosimetry models have been developedand validated. Evaluations have not beenmade on the influence of particle characteristics(e.g., shape and density) on the inhalability anddeposition of CNT in the human respiratory tract,and on the clearance or biopersistence of CNT.However, the available data on the aerodynamicsize of CNT provides an initial estimate (basedon validated models for spherical particles) of thedeposited mass fraction of airborne CNT in thehuman respiratory tract, and specifically in the alveolar(gas exchange) region. The clearance rate ofCNT from the lungs may be more uncertain thanthe deposition efficiency, as animal studies indicatethat CNT clearance becomes impaired in rat lungsat lower mass doses than for larger particles ofgreater density [Pauluhn 2010a, b]. The NIOSH riskassessment helps to characterize this uncertaintyby providing bounds on the range of possible lungdose estimates, from assuming normal clearance toassuming no clearance of the deposited CNT. Thisapproach also provides a framework for introducingimproved dose estimates when validated lungdosimetry models for CNT become available.The assumptions used in the lung dose estimationhave a large influence on the animal andhuman-equivalent BMD(L) or BMC(L) estimates(Tables A–5 and A–6), as well as on the estimatedhuman-equivalent NOAEL (Section A.6.3). The ratBMD(L) estimates based on the estimated retainedlung dose after subchronic inhalation exposure inrats are lower than those based on the estimateddeposited lung dose (Table A–5). This is becausethe retained dose estimates allow for some lungclearance to occur during the 13-week exposure inrats, and a lower dose estimate is therefore associatedwith a given fixed response proportion. Thehuman-equivalent BMD(L) estimates based onretained dose are also lower because they are proportionalto the rat BMD(L)s (i.e., calculated basedon the ratio of the human to rat alveolar epithelial122 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers