Occupational Exposure to Carbon Nanotubes and Nanofibers

egion of the lung 1 day post exposure, with subpleuralfibrosis occurring at 2 weeks post exposurethat progressed through 6 weeks of follow-up. Nofibrosis was observed in mice exposed to 1 mg/m 3 ofMWCNT or in mice exposed to 30 mg/m 3 of nanoscalecarbon black.Subchronic inhalation studies with MWCNT havealso been conducted in laboratory studies withrats to assess the potential dose-response and timecourse for developing pulmonary effects [Arkema2008; Ma-Hock et al. 2009; Pauluhn 2010a]. Ma-Hock et al. [2009] reported on the results of a 90-day inhalation (head-nose) study with rats exposedat concentrations of 0.1, 0.5, or 2.5 mg/m 3 MWCNT(BASF Nanocyl NC 7000) for 6 hr/day, 5 days/weekfor 13 weeks with a resultant lung burden of 47–1170 µg/rat. No systemic toxicity was observed,but the exposure caused hyperplastic responsesin the nasal cavity and upper airways (larynx andtrachea), and granulomatous inflammation in thelung and in lung-associated lymph nodes at all exposureconcentrations. The incidence and severityof the effects were concentration-related. No lungfibrosis was observed but pronounced alveolar lipoproteinosisdid occur.Ellinger-Ziegelbauer and Pauluhn [2009] conducteda short-term inhalation bioassay (beforethe Pauluhn 2010a subchronic study) to investigatethe dependence of pulmonary inflammationresulting from exposure to one type of MWCNT(Bayer Baytubes®), which was highly agglomeratedand contained a small amount of cobalt (residualcatalyst). Groups of rats were exposed to 11 mg/m 3MWCNT containing either 0.53% or 0.12% cobaltto assess differences in pulmonary toxicity becauseof metal contamination. Another group of rats wasexposed to 241 mg/m 3 MWCNT (0.53% cobalt)to serve the purpose of hazard identification. Allanimals were exposed to a single nose-only inhalationexposure of 6 hr followed by a post-exposureperiod of 3 months. Time course of MWCNTrelatedpulmonary toxicity was compared with ratsexposed to quartz in post-exposure weeks 1, 4, and13 to distinguish early, possibly surface area/activityrelatedeffects from retention-related poorly solubleparticle effects. Rats exposed to either quartz orMWCNT resulted in somewhat similar patternsof concentration-dependent pulmonary inflammationduring the early phase of the study. Thepulmonary inflammation induced by quartz increasedduring the 3 months post-exposure period,whereas that induced by MWCNT regressed ina concentration-dependent manner. The time courseof pulmonary inflammation associated with retainedMWCNT was independent on the concentrationof residual cobalt. Pauluhn [2010a], using the sameMWCNT (0.53% cobalt) used in the study byEllinger-Ziegelbauer and Pauluhn [2009] exposedrats (nose-only) at concentrations 0.1, 0.4, 1.5, and6 mg/m 3 for 6 hr/day, 5 days/week for 13 weeks. Theaerosolized MWCNT were described as being highlyagglomerated (mean diameter of 3 µm). Lungclearance of MWCNT at the low doses was slow,with a marked inhibition of clearance at 1.5 and6 mg/m 3 . Histopathology analysis at 6 months postexposure revealed exposure-related lesions in theupper respiratory (e.g., goblet cell hypermetaplasiaand/or metaplasia) and lower respiratory (e.g., inflammationin the bronchiole-alveolar region) tractin animals exposed at concentrations of 0.4, 1.5, and6 mg/m 3 , as well as inflammatory changes in thedistal nasal cavities that were similar to those foundby Ma-Hock et al. [2009]. In rats exposed at 6 mg/m 3 , a time-dependent increase of bronchioloalveolarhyperplasia was observed, as well as changes ingranulomas and an increase in collagen depositionthat persisted through the 39-week post-exposureobservation period. No treatment-related effectswere reported for rats exposed at 0.1 mg/m 3 .In a report submitted by Arkema [2008] to EPA, ratsexposed (nose only) to agglomerates of MWCNT(Arkema) at concentrations of 0.1, 0.5, and 2.5 mg/m 3 for 6 hr/day for 5 days exhibited histopathologicaleffects that were consistent with those reportedby Ma-Hock et al. [2009], Ellinger-Ziegelbauer andPauluhn [2009] and Pauluhn [2010a]. An increase ofvarious cytokines and chemokines in the lung, alongwith the development of granulomas were found inthe 0.5 and 2.5 mg/m 3 exposure groups, while notreatment-related effects were reported at 0.1 mg/m 3 .18 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers