each the subpleural tissue in mice. Nat Nanotechnol4(11):747–751. [http://dx.doi.org/10.1038/NNANO.2009.305].Sager TM, Wolfarth M, Porter D, Castranova V, WuN, Holian A [2011]. Effect of surface modificationon the bioavailability <strong>and</strong> inflamma<strong>to</strong>ry potentialof multi-walled carbon nanotubes. The Toxicologist120:A1178.Sanchez VC, Pietruska JR, Miselis NR, Hurt RH,Kane AB [2009]. Biopersistence <strong>and</strong> potential adversehealth impacts of fibrous nanomaterials: whathave we learned from asbes<strong>to</strong>s? Nanomed Nanobiotechnol5(1):511–529.Sargent LM, Shvedova AA, Hubbs AF, SalisburyJL, Benkovic SA, Kashon ML, Lowry DT, MurrayAR, Kisin ER, Friend S, McKinstry KT, Battelli L,Reynolds SH [2009]. Induction of aneuploidy bysingle-walled carbon nanotubes. Environ Mol Mutagen50(8):708–717.Sargent LM, Hubbs AF, Young SH, Kashon ML,Dinu CZ, Salisbury JL, Benkovic SA, Lowry DT,Murray AR, Kisin ER, Siegrist KJ, Battelli L, Mas<strong>to</strong>vichJ, Sturgeon JL, Bunker KL, Shvedova AA, ReynoldsSH [2011]. Single-walled carbon nanotube-inducedmi<strong>to</strong>tic disruption. Mutat Res: Genetic Toxicology<strong>and</strong> Environment, Dec 8. [Epub ahead of print].Sayes CM, Fortner J, Guo W, Lyon D, Boyd AM,Ausman KD, Tao YJ, Sitharaman B, Wilson LJ,Hughes JB, West JL, Colvin VL [2004]. The differentialcy<strong>to</strong><strong>to</strong>xicity of water soluble fullerenes. NanoLett 4(10):1881–1887.Sayes CM, Liang F, Hudson JL, Mendez J, Guo W,Beach JM, Moore VC, Doyle CD, West JL, BillupsWE, Ausman KD, Colvin VL [2006]. Functionalizationdensity dependence of single-walled carbonnanotubes cy<strong>to</strong><strong>to</strong>xicity in vitro. Toxicol Lett161(2):135–142.Schauer JJ, Kleeman MJ, Cass GR, Simoneit BR[1999]. Measurement of emissions from air pollutionsources. 2. C-1 through C-30 organic compoundsfrom medium duty diesel trucks. EnvironSci Technol 33(10):1578–1587.Schauer JJ, Mader BT, DeMinter JT, Heidemann G,Bae MS, Seinfeld JH, Flagan RC, Cary RA, Smith D,Huebert BF, Bertram T, Howell S, Kline JT, QuinnP, Bates T, Turpin B, Lim HJ, Yu JZ, Yang H, KeywoodMD [2003]. ACE-Asia intercomparison of athermal-optical method for the determination ofparticle-phase organic <strong>and</strong> elemental carbon. EnvironSci Technol 37(5):993–1001.Schubauer-Berigan MK, Dahm MM, YenchenMS [2011]. Engineered carbonaceous nanomaterialsmanufacturers in the United States: workforcesize, characteristics, <strong>and</strong> feasibility of epidemiologicstudies. J Occup Environ Med 53(Suppl6):S62–S67.Schulte PA, Salamanca-Buentello [2007]. Ethical<strong>and</strong> scientific issues of nanotechnology in theworkplace. Environ Health Perspect 115(1):5–12.Schulte P, Geraci C, Zumwalde R, Hoover M, KuempelE [2008]. <strong>Occupational</strong> risk management ofengineered nanoparticles. J Occup Environ Hyg5:239–249.Schulte PA, Murashov V, Zumwalde R, KuempelED, Geraci CL [2010]. <strong>Occupational</strong> exposurelimits for nanomaterials: state of the art. J NanopartRes 12:1971–1987.Schulte PA, Kuempel ED, Zumwalde RD, GeraciCL, Schubauer-Berigan MK, Castranova V, HodsonL, Murashov V, Dahm MM, Ellenbecker M[2012]. Focused actions <strong>to</strong> protect carbon nanotubeworkers. Am J Ind Med 55(5):395–411. [Epub2012 Mar 5].Shaffer RE, Rengasamy S [2009]. Respira<strong>to</strong>ry protectionagainst airborne nanoparticles: a review.J Nanopart Res 11(7):1661–1672 [http://dx.doi.org/10.1007/s11051-009-9649-3].Sheesley RJ, Schauer JJ, Smith TJ, Garshick E,Laden F, Marr LC, Molina LT [2008]. Assessmen<strong>to</strong>f diesel particulate matter exposure in the workplace:freight terminals. J Environ Monit [http://dx.doi.org/10.1039/b715429a].Shvedova AA, Castranova V, Kisin ER, Schwegler-Berry D, Murray AR, G<strong>and</strong>elsman VZ, Maynard86 NIOSH CIB 65 • <strong>Carbon</strong> <strong>Nanotubes</strong> <strong>and</strong> <strong>Nanofibers</strong>
AD, Baron PA [2003]. <strong>Exposure</strong> <strong>to</strong> carbon nanotubematerial: assessment of the biological effectsof nanotube materials using human keratinocytecells. J Toxicol Environ Health A 66(20):1901–1918.Shvedova AA, Kisin ER, Mercer R, Murray AR,Johnson VJ, Potapovich AI, Tyurina YY, GorelikO, Arepalli S, Schwegler-Berry D, Hubbs AF, An<strong>to</strong>niniJ, Evans DE, Ku B-K, Ramsey D, Maynard A,Kagan VE, Castranova V, Baron P [2005]. Unusualinflamma<strong>to</strong>ry <strong>and</strong> fibrogenic pulmonary responses<strong>to</strong> single-walled carbon nanotubes in mice. Am JPhysiol Lung Cell Mol Physiol 289(5):L698–L708.Shvedova AA, Sager T, Murray A, Kisin E, PorterDW, Leonard SS, Schwegler-Berry D, Robinson V,Castranova V [2007]. Critical issues in the evaluationof possible effects resulting from airbornenanoparticles. In: Monteiro-Riviere N, Tran L, eds.Nanotechnology: characterization, dosing, <strong>and</strong>health effects. Chapter 14. Philadelphia: InformaHealthcare, pp. 221–232.Shvedova AA, Kisin E, Murray AR, Johnson VJ,Gorelik O, Arepalli S, Hubbs AF, Mercer RR, KeohavongP, Sussman N, Jin J, S<strong>to</strong>ne S, Chen B, DeyeG, Maynard A, Castranova V, Baron PA, Kagan V[2008]. Inhalation versus aspiration of single walledcarbon nanotubes in C57BL/6 mice: inflammation,fibrosis, oxidative stress <strong>and</strong> mutagenesis. Am JPhysiol Lung Cell Mol Physiol 295(4):L552−L565.Snipes MB [1989]. Long-term retention <strong>and</strong> clearanceof particles inhaled by mammalian species.Crit Rev Toxicol 20(3):175–211.Sriram K, Porter D, Tsuruoka S, Endo M, JeffersonA, Wolfarth W, Rogers GM, Castranova V, LusterMI [2007]. Neuroinflamma<strong>to</strong>ry responses followingexposure <strong>to</strong> engineered nanomaterials. TheToxicologist 96(1):A1390.Sriram K, Porter DW, Jefferson AM, Lin GX,Wolfarth MG, Chen BT, McKinney W, Frazer DG,Castranova V [2009]. Neuroinflammation <strong>and</strong>blood-brain barrier changes following exposure<strong>to</strong> engineered nanomaterials. The Toxicologist108(1):A2197.Staple<strong>to</strong>n PA, Minarchick V, Cumps<strong>to</strong>n A, McKinneyW, Chen BT, Frazer D, Castranova V, NurkiewiczTR [2011]. Time-course of improved coronaryarteriolar endothelium-dependent dilationafter multi-walled carbon nanotube inhalation. TheToxicologist (120):A194.S<strong>to</strong>ckstill BL, Chang LY, Ménache MG, MellickPW, Mercer RR, Crapo JD [1995]. Bronchiolarizedmetaplasia <strong>and</strong> interstitial fibrosis in rat lungschronically exposed <strong>to</strong> high ambient levels ofozone. Toxicol Appl Pharmacol 134(2):251–263.S<strong>to</strong>ne KC, Mercer RR, Freeman BA, Chang LY,Crapo JD [1992]. Distribution of lung cell numbers<strong>and</strong> volumes between alveolar <strong>and</strong> nonalveolar tissue.Am Rev Respir Dis 146(2):454–456.Stueckle TA, Mirshra A, Derk R, Rojanasakul Y,Castranova V, Wang L [2011]. In vitro assessmen<strong>to</strong>f potential tumorigenicity of chronic SWCNT <strong>and</strong>MWCNT exposure <strong>to</strong> lung epithelium. The Toxicologist120:A1182.Sturm R, Hofmann W [2009]. A theoretical approach<strong>to</strong> the deposition <strong>and</strong> clearance of fiberswith variable size in the human respira<strong>to</strong>ry tract. JHazard Mater 170(1):210–218.Subramanian R, Khlys<strong>to</strong>v AY, Cabada JC, RobinsonAL [2004]. Positive <strong>and</strong> negative artifacts inparticulate organic carbon measurements with denuded<strong>and</strong> undenuded sampling configurations.Aerosol Sci Technol 38:27–48.Tabet L, Bussy C, Setyan A, Simon-Deckers A,Rossi MJ, Boczkowski J, Lanone S [2011]. Coatingcarbon nanotubes with a polystyrene-based polymerprotects against pulmonary <strong>to</strong>xicity. Part FibreToxicol 8:3.Takagi A, Hirose A, Nishimura T, Fukumori N,Ogata A, Ohashi N, Kitajima S, Kanno J [2008].Induction of mesothelioma in p53+/− mouse byintraperi<strong>to</strong>neal application of multi-wall carbonnanotube. J Toxicol Sci 33(1):105–116.Thostenson ET, Ren ZF, Chou TW [2001]. Advancein the science <strong>and</strong> technology of carbon nanotubesNIOSH CIB 65 • <strong>Carbon</strong> <strong>Nanotubes</strong> <strong>and</strong> <strong>Nanofibers</strong>87
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CURRENT INTELLIGENCE BULLETIN 65Occ
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Current Intelligence Bulletin 65Occ
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ForewordThe Occupational Safety and
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Executive SummaryOverviewCarbon nan
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2009; Pauluhn 2010a; Porter et al.
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neurogenic sig nals from sensory ir
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possible. Until the results from an
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••Follow exposure and hazard as
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Periodic Evaluations••Evaluatio
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ContentsForeword ..................
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A.3.2 Comparison of Short-term and
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ESPFeFMPSFPSSgGMGSDHCLHECHEPAhrISOI
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AcknowledgementsThis Current Intell
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1 IntroductionMany nanomaterial-bas
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2 Potential for ExposureThe novel a
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CNMs, with MWCNT agglomerates obser
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composite materials with local exha
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information on air contaminants. Sa
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3 Evidence for Potential Adverse He
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decreasing agglomerate size increas
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examined up to 60 days post-exposur
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3.3 SWCNT and MWCNTIntraperitoneal
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The same potency sequence was obser
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Table 3-3. Findings from published
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Table 3-5. Findings from published
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Table 3-6. Findings from published
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Table 3-7 (Continued). Findings fro
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Table 3-8. Findings from published
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length, respectively) [Muller et al
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- Page 97 and 98: 7 Research NeedsAdditional data and
- Page 99 and 100: ReferencesACGIH [1984]. Particle si
- Page 101 and 102: Bolton RE, Vincent HJ, Jones AD, Ad
- Page 103 and 104: eport issued on July 22, 2011. NEDO
- Page 105 and 106: Kobayashi N, Naya M, Mizuno K, Yama
- Page 107 and 108: Methner M, Hodson L, Geraci C [2010
- Page 109 and 110: Human Services, Centers for Disease
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Table A-13. Human-equivalent retain
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A.7.1 Particle CharacteristicsBoth
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and density. The following MMAD and
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Table A-15. CNT lung dose normalize
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B.1 Key Terms Related toMedical Sur
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APPENDIX CNIOSH Method 5040
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filter. In the method evaluation, d
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Most of the studies on sampling art
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e analyzed to determine the onset o
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Delivering on the Nation’s promis