Occupational Exposure to Carbon Nanotubes and Nanofibers

4 Conclusions—Hazard and Exposure AssessmentResults of laboratory animal studies with bothSWCNT and MWCNT report qualitatively similarpulmonary responses including acute lung inflammation,epithelioid granulomas (microscopic nodules),and rapidly developing fibrotic responses atrelatively low-mass doses (Section 3). Animal studieswith CNT and CNF have shown the following:1. Early onset and persistent pulmonary fibrosisin SWCNT-, MWCNT-, and CNF- exposedanimals in short-term and subchronic studies[Shvedova et al. 2005, 2008; Mercer et al. 2008;Ma-Hock et al. 2009; Porter et al. 2010; Pauluhn2010a; Mercer et al. 2011; Murray et al. 2012].2. Similar pulmonary responses in animals (e.g.,acute lung inflammation, interstitial fibrosis)when exposed to purified and unpurified SWCNT[Lam et al. 2004; Shvedova et al. 2005, 2008].3. Equal or greater potency of SWCNT, MWCNT,and CNF compared with other inhaled particles(ultrafine carbon black, crystalline silica,and asbestos) in causing adverse lung effectsincluding pulmonary inflammation and fibrosis[Shvedova et al. 2005; Muller et al. 2005;Murray et al. 2012].4. CNT agglomeration affects the site of lung depositionand response; large agglomerates tendto deposit at the terminal bronchioles andproximal alveoli and induce a granulomatousresponse, while more dispersed structures depositin the distal alveoli and cause interstitialfibrosis [Mercer et al. 2008; Porter et al. 2010].Agglomerated SWCNT tend to induce granulomas,while more dispersed CNF and asbestosdid not [Murray et al. 2012].5. Intraperitoneal injection of long (> 5 µm)MWCNT in mice causes fibrotic lesions andmesothelial cell proliferation [Takagi et al. 2008;Murphy et al. 2011].Although pulmonary responses to SWCNT andMWCNT are qualitatively similar, quantitativedifferences in pulmonary responses have been reported.In mice exposed to CNT by pharyngeal aspiration(10 µg/mouse), SWCNT caused a greaterinflammatory response than MWCNT at 1 daypost exposure [Shvedova et al. 2005, 2008; Porteret al. 2010]. Morphometric analyses indicate thatwell-dispersed purified SWCNT (< 0.23% iron) arenot well recognized by alveolar macrophages (only10% of the alveolar burden being within alveolarmacrophages) [Shvedova et al. 2005], and that 90%of the dispersed SWCNT structures have been observedto cross alveolar epithelial cells and enterthe interstitium [Mercer et al. 2008]. In contrast,approximately 70% of MWCNT in the respiratoryairways are taken up by alveolar macrophages, 8%migrate into the alveolar septa, and 22% are foundin granulomatous lesions [Mercer et al. 2010,2011]. These findings suggest that well-dispersedSWCNT may be more potent in causing interstitialfibrosis on an equal mass lung burden basis thanMWCNT [Mercer et al. 2008], possibly due to thegreater tube count per mass of SWCNT [Mercer2011; Wang et al. 2010a,b; Mercer et al. 2011]. Inaddition, although both SWCNT and MWCNThave been reported in the subpleural tissue of thelung [Mercer et al. 2008; Ryman-Rasmussen et al.2009], penetration of the visceral pleura and translocationto the intrapleural space has been reportedonly for MWCNT [Hubbs et al. 2009; Mercer et al.2010]. Despite these differences, CNTs of varioustypes, both purified and unpurified, dispersed oragglomerated, all cause adverse lung effects in ratsor mice at relatively low mass doses that are relevantto potential worker exposures.Animal studies have also shown asbestos-type pathologyassociated with the longer, straighter CNTstructures [Poland et al. 2008; Takagi et al. 2008;Murphy et al. 2011]. Mesothelial tumors have beenreported in mice receiving intraperitoneal injectionof long MWCNT (5–20 µm in length) [Takagi et al.2008; Murphy et al. 2011]; whereas chronic bioassaysof short MWCNT (avg. < 1 µm and < 2 µm inNIOSH CIB 65 • Carbon Nanotubes and Nanofibers33