<strong>and</strong> their composites: a review. Compos Sci Tech61(13):1899–1912.Tran CL, Buchanan D [2000]. Development of abiomathematical lung model <strong>to</strong> describe the exposure-doserelationship for inhaled dust among U.K.coal miners. Institute of <strong>Occupational</strong> Medicine,Edinburgh, U.K. IOM Research Report TM/00/02.Tran CL, Jones AD, Cullen RT, Donaldson K[1999]. Mathematical modeling of the retention<strong>and</strong> clearance of low-<strong>to</strong>xicity particles in the lung.Inhal Toxicol 11(12):1059–1076.Tran CL, Buchanan D, Cullen RT, Searl A, JonesAD, Donaldson K [2000]. Inhalation of poorlysoluble particles. II. Influence of particle surfacearea on inflammation <strong>and</strong> clearance. Inhal Toxicol12:1113–1126.Trout DB, Schulte PA [2009]. Medical surveillance,exposure registries, <strong>and</strong> epidemiologic researchfor workers exposed <strong>to</strong> nanomaterials. Toxicology,269(2–3):128–135.Tsai S, Hofmann M, Hallock M, Ada E, Kong J, EllenbeckerM [2009]. Characterization <strong>and</strong> evaluationof nanoparticle release during the synthesis ofsingle-walled <strong>and</strong> multiwalled carbon nanotubesby chemical vapor deposition. Environ Sci Technol43(15):6017–6023.Tsai S, Huang RF, Ellenbecker MJ [2010]. Airbornenanoparticle exposures while using constant-flow,constant-velocity, <strong>and</strong> air-curtain isolated fumehoods. Ann Occup Hyg 54(1):78–87.Turpin BJ, Huntzicker JJ, Hering SV [1994]. Investigationof organic aerosol sampling artifacts in theLos Angeles basin. Atmos Environ 28(19):3061–3071.Turpin BJ, Saxena P, Andrews E [2000]. Measuring<strong>and</strong> simulation particulate organics in the atmosphere:problems <strong>and</strong> prospects. Atmos Environ34(18):2983–3013.US EPA [1988]. Reference physiological parametersin pharmacokinetic modeling. Washing<strong>to</strong>n, DC: Officeof Health <strong>and</strong> Environment Assessment, <strong>Exposure</strong>Assessment Group, U.S. Environmental ProtectionAgency. EPA report no. EPA/600/6-88/004.US EPA [1994]. Methods for derivation of inhalationreference concentrations <strong>and</strong> application ofinhalation dosimetry. Research Triangle Park, NC:U.S. Environmental Protection Agency. EPA reportno. EPA/600/8-90/066F.US EPA [1996]. Air quality criteria for ozone <strong>and</strong>related pho<strong>to</strong>chemical oxidants. Washing<strong>to</strong>n, DC:Office of Research <strong>and</strong> Development, NationalCenter for Environmental Assessment, U.S.Environmental Protection Agency. EPA report no.EPA/600/P-93/004aF. Vol. III, p. 8–78.US EPA [2006]. Approaches for the applicationof physiologically based pharmacokinetic(PBPK) models <strong>and</strong> supporting data in risk assessment.Washing<strong>to</strong>n, DC: National Center forEnvironmental Assessment, Office of Research<strong>and</strong> Development, U.S. Environmental ProtectionAgency. [http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=157668].US EPA [2010]. Benchmark dose software, Version2.1.2. Washing<strong>to</strong>n, DC: U.S. Environmental ProtectionAgency, National Center for EnvironmentalAssessment.US EPA [2012]. Benchmark dose technical guidance.Washing<strong>to</strong>n, DC: U.S. Environmental ProtectionAgency. EPA/100/R-12/001.US DOE [2008]. Approach <strong>to</strong> nanomaterial ES & H.Washing<strong>to</strong>n, DC: U.S. Department of Energy, U.S.Department of Energy’s Nanoscale Science ResearchCenters. [http://science.energy.gov/~/media/bes/pdf/doe_nsrc_approach_<strong>to</strong>_nanomaterial_esh.pdf]Vankoningsloo S, Piret JP, Saout C, Noel F, MejiaJ, Zouboulis CC, Delhalle J, Lucas S, Toussaint O[2010]. Cy<strong>to</strong><strong>to</strong>xicity of multi-walled carbon nanotubesin three skin cellular models: effects of sonication,dispersive agents <strong>and</strong> corneous layer of reconstructedepidermis. Nano<strong>to</strong>xicol 4(1):84–97.88 NIOSH CIB 65 • <strong>Carbon</strong> <strong>Nanotubes</strong> <strong>and</strong> <strong>Nanofibers</strong>
Varga C, Szendi K [2010]. <strong>Carbon</strong> nanotubes inducegranulomas but not mesotheliomas. In Vivo24(2):153–156.Wagner GR, Fine LJ [2008]. Surveillance <strong>and</strong> healthscreening in occupational health. In: Wallace RB,ed. Maxcy-Rosenau-Last Public Health <strong>and</strong> PreventiveMedicine. 15th ed. New York: McGraw-HillMedical Publishing, pp. 759–793.Walters A, Ericson LM, Casavant MJ, Liu J, ColbertDT, Smith KA, Smalley RE [1999]. Elasticstrain of freely suspended single-walled carbonnanotube ropes. Appl Phys Lett 74:3803. [http://dx.doi.org/10.1063/1.124185].Wang L, Castranova V, Mishra A, Chen B, MercerRR, Schwegler-Berry D, Rojanasakul Y [2010a].Dispersion of single-walled carbon nanotubes by anatural lung surfactant for pulmonary in vitro <strong>and</strong>in vivo <strong>to</strong>xicity studies. Part Fibre Toxicol 7:31.Wang L, Mercer RR, Rojanasakul YA, Qiu A, LuY, Scabilloni JF, Wu N, Castranova V [2010b]. Directfibrogenic effects of dispersed single-walledcarbon nanotubes on human lung fibroblasts. JToxicol Environ Health Part A, 73(5):410–422.Wang L, Luanpitpong S, Castranova V, Tse W,Lu Y, Pongrakhananon V, Rojanasakul Y [2011].<strong>Carbon</strong> nanotubes induce malignant transformation<strong>and</strong> tumorigenesis of human lung epithelialcells. Nano Lett 11(7):2796–2803. [Epub ahead ofprint] [http://dx.doi.org/10.1021/nl2011214]Wang /x, Xia T, Ntim SA, Ji Z, Lim S, Meng H,Chung CM, George S, Zhang H, Wang M, Li N,Yang Y, Castranova V, Mitra S, Bonner JC, Nel AE[2012]. The dispersal state of multi-walled carbonnanotubes elicits pro-fibrogenic cellular responsethat correlate with fibrogenesis biomarkers <strong>and</strong> fibrosisin the murine lung. ACS Nano.Warheit DB, Laurence BR, Reed KL, Roach DH,Reynolds GAM, Webb TR [2004]. Comparativepulmonary <strong>to</strong>xicity assessment of single-wall carbonnanotubes in rats. Toxicol Sci 77(1):117–25.WHO [2005]. Chemical-specific adjustment fac<strong>to</strong>rsfor interspecies differences <strong>and</strong> human variability:Guidance document for use of data indose/concentration-response assessment. HarmonizationProject Document No. 2. Geneva: WorldHealth Organization.Wirnitzer U, Herbold B, Voetz M, Ragot J [2009].Studies on the in vitro geno<strong>to</strong>xicity of baytubes,agglomerates of engineered multi-walled carbonnanotubes(MWCNT). Toxicol Lett 186(3):160–165.Wolfarth MG, Porter DW, Hubbs AF, LeonardS, Battelli L, Andrews M, Castranova V [2009].Pulmonary <strong>to</strong>xicity of multi-walled carbon nanotubes.The Toxicologist 108:A2196Wolfarth MG, Chen BT, Castranova V, Porter DW[2011]. Acute pulmonary responses <strong>to</strong> MWCNTinhalation. The Toxicologist 120:A53.Xu J, Futakuchi M, Shimizu H, Alex<strong>and</strong>er DB,Yanagihara K, Fukamachi K, Suzui M, Kanno J,Hirose A, Ogata A, Sakamo<strong>to</strong> Y, Nakae D, OmonT, Tsuda H [2012]. Multi-walled carbon nanotubestranslocate in<strong>to</strong> the pleural <strong>and</strong> induce visceralmesothelial proliferation in rats. Cancer Science103(12):2045–2050.Yamashita K, Yoshioka Y, Higashisaka K, MorishitaY, Yoshida T, Fujimura M, Kayamuro H, Nabeshi H,Yamashita T, Nagano K, Abe Y, Kamada H, KawaiY, Mayumi T, Yoshikawa T, I<strong>to</strong>h N, Tsunoda S, TsutsumiY. [2010]. <strong>Carbon</strong> nanotubes elicit DNA damage<strong>and</strong> inflamma<strong>to</strong>ry response relative <strong>to</strong> their size<strong>and</strong> shape. Inflammation 33(4):276–280.Yan L, Zhao F, Li S, Hu Z, Zhao Y [2011]. Low-<strong>to</strong>xic<strong>and</strong> safe nanomaterials by surface-chemical design,carbon nanotubes, fullerenes, metallofullerenes,<strong>and</strong> graphenes. Nanoscale 3:362–382.Yu M-F, Louire O, Dyer MJ, Moloni K, Kelly TF,Ruoff RS [2000]. The strength <strong>and</strong> breaking mechanismof multiwalled carbon nanotubes under tensileload. Science 287(5453):637–640.NIOSH CIB 65 • <strong>Carbon</strong> <strong>Nanotubes</strong> <strong>and</strong> <strong>Nanofibers</strong>89
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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
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- 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
- Page 111 and 112: Piegorsch WW, Bailer AF [2005]. Qua
- Page 113: AD, Baron PA [2003]. Exposure to ca
- Page 119 and 120: ContentsA.1 Introduction ..........
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- Page 149 and 150: cell surface area). However, the wo
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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