Occupational Exposure to Carbon Nanotubes and Nanofibers

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the BMDL, NOAEL, or LOAEL is the estimatedpoint of departure (POD) for extrapolation belowthe range of the data. This low dose extrapolationmay be risk-based (e.g., from the 10% BMDL) bylinear or nonlinear modeling (depending on themode of action information); or in noncancer riskassessment, the POD may be adjusted downwardto account for uncertainty in the extrapolationfrom animals to humans and other factors (SectionA.6.3.3).The risk estimates based on the subchronic andshort-term animal studies (Section A.3) generallyindicate that risks less than 10% would be associatedwith working lifetime exposures below1 µg/m 3 (8-hr TWA). This is estimated by eitherlinear or model-based low-dose extrapolation ofthe rat BMDL estimates (Section A.3.3). Althoughan acceptably low level of risk for early-stage pulmonaryeffects has not been established, some ofthe working lifetime excess risk estimates at 1 µg/m 3(8-hr TWA) are less than 10% (e.g., approximately0.5% to 16% for the slight/mild, grade 2) lung effectsin the rat subchronic inhalation studies; 95%UCL estimates) (Table A–8). Given the uncertaintyabout the early-stage lung effects and the shapeof the dose-response relationship, the actual riskcould be much lower, even zero (if exposures arebelow an effect threshold). Alternatively, adjustingthe POD downward using standard uncertaintyfactors, also generally results in estimates of
(3) Rat lung dose estimationIn the absence of CNT-specific lung models, standardrat and human lung dosimetry models wereused to estimate either the deposited or the retainedlung dose. These two estimates are considered torepresent the upper or lower bounds on the possiblelung burden estimates. The effect of assumingdeposited dose (no clearance) versus retaineddose (normal clearance) resulted in a difference ofapproximately five-fold. However, the actual estimatesare expected to lie within this range. Theworking lifetime exposure estimates (associatedwith 10% excess risk of early stage lung effects)were lower based on deposited dose estimates thanthose based on retained dose estimates (AppendixA, Table A–5).NIOSH CIB 65 • Carbon Nanotubes and Nanofibers49
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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
Page 23 and 24: ESPFeFMPSFPSSgGMGSDHCLHECHEPAhrISOI
Page 25 and 26: AcknowledgementsThis Current Intell
Page 27 and 28: 1 IntroductionMany nanomaterial-bas
Page 29: 2 Potential for ExposureThe novel a
Page 32 and 33: CNMs, with MWCNT agglomerates obser
Page 34 and 35: composite materials with local exha
Page 36 and 37: information on air contaminants. Sa
Page 39 and 40: 3 Evidence for Potential Adverse He
Page 41 and 42: decreasing agglomerate size increas
Page 43 and 44: examined up to 60 days post-exposur
Page 45 and 46: 3.3 SWCNT and MWCNTIntraperitoneal
Page 47 and 48: The same potency sequence was obser
Page 49 and 50: Table 3-3. Findings from published
Page 55 and 56: Table 3-7 (Continued). Findings fro
Page 57: Table 3-8. Findings from published
Page 60 and 61: length, respectively) [Muller et al
Page 63 and 64: 5 CNT Risk Assessment and Recommend
Page 65 and 66: A-6). Risk estimates derived from o
Page 67 and 68: Table 5-4. Factors, assumptions, an
Page 69 and 70: and analytical methods. NIOSH is re
Page 71 and 72: Table 5-5. Recommended occupational
Page 73: deficits in animals or clinically s
Page 78 and 79: tasks where worker exposures exceed
Page 80 and 81: As part of the evaluation of worker
Page 82 and 83: Table 6-1. EC LODs and LOQs for 25-
Page 84 and 85: 6.2 Engineering ControlsOne of the
Page 86 and 87: Table 6-6 (Continued). Examples of
Page 88 and 89: Table 6-7 (Continued). Engineering
Page 90 and 91: exposure estimates for SWCNT on ind
Page 92 and 93: Table 6-8. Respiratory protection f
Page 94 and 95: ••Workers in areas or in jobs w
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
Page 111 and 112: Piegorsch WW, Bailer AF [2005]. Qua
Page 113 and 114: AD, Baron PA [2003]. Exposure to ca
Page 115: Varga C, Szendi K [2010]. Carbon na
Page 119 and 120: ContentsA.1 Introduction ..........
Page 121 and 122: A.1 IntroductionThe increasing prod
Page 123 and 124: provide an informal check on the es
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these same dose groups; this effect
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Table A-1. Rodent study information
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the deposited (no clearance) and th
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The other BMDS models failed to con
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Figure A-2. Benchmark dose model (m
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Figure A-3 (continued). Benchmark d
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Table A-3. Benchmark dose estimates
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Table A-5. Benchmark dose estimates
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histopathology grade 2 or higher lu
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Table A-8. Working lifetime percent
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developing early-stage adverse lung
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Figure A-4. Dose-response relations
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cell surface area). However, the wo
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purified or unpurified (with differ
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Table A-9. Comparison of rat or hum
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A.6.1.3 Pulmonary Ventilation RateT
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used as the effect levels in evalua
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the DF estimate, although a larger
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or overloading, of particle clearan
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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
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Occupational Exposure to Carbon Nanotubes and Nanofibers

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