Occupational Exposure to Carbon Nanotubes and Nanofibers

purified or unpurified (with different types andamounts of metals), i.e., 0.08–12 µg/m3 (Tables A–3and A–4). Lower risks are estimated at the lowerLOQ of 1 µg/m3, which are approximately 0.5% to16% based on the rat subchronic dose-responsedata for the slight/mild lung effects and differentlung dose estimation (95% UCL estimates) (TableA–8). Higher risks are estimated for the more sensitiveendpoint of minimal grade 1 lung effects(Table A–7). Additional analyses and risk estimatesbased on other methods and assumptions are providedin Section A.6.A.6 Sensitivity AnalysesSpecific areas of uncertainty in this CNT risk assessmentare evaluated in this section, including: (1) therat lung dose estimation; (2) the critical effect levelselection in animals and relevance to humans; and(3) alternative assumptions used in the OEL estimationmethods. Sensitivity analyses in these areaswere performed to qualitatively and quantitativelyevaluate the influence of the different options andassumptions on the draft REL [NIOSH 2010].A.6.1 Lung Dose EstimationKey factors that influence the estimates of CNTlung burden in rats and humans include: (a) thelung geometry and airway dimensions; (b) lung andbreathing parameters (including, functional residualcapacity, total lung capacity, breathing frequency,and tidal volumes; (c) lung retention kinetics; and(d) interspecies dose normalization. The depositionfraction is based on the airborne particle size (andto some extent shape for nonspherical particles), onthe breathing pattern (nasal, oral, or combination)and minute ventilation, and on the lung airway geometry.The ventilation rate depends on the speciesand on the activity level. Reference values are availablefor the average ventilation rates in rats and humans[EPA 1988, 1994; ICRP 1994]. The airborneparticle size data (as reported in the animal studies)(Table A–2) were used to estimate the depositedlung dose of CNT in rats and humans, using sphericalparticle based models. The long-term clearancekinetics have been well studied and validated forinhaled poorly soluble spherical particles in rats[Anjilvel and Asgharian 1995; Asgharian et al. 2001,2003] and in humans [ICRP 1994; Kuempel et al.2001a, b; Gregoratto 2010, 2011], but models specificallyfor CNT are not yet available.This section examines some of the key parametervalues used in the lung dose estimation, andalso characterizes the quantitative influence ofalternative models and assumptions. Two studieswere available to evaluate the lung dose estimatesin rats. Pauluhn [2010a] and Ellinger-Ziegelbauer and Pauluhn [2009] provided cobalttracer-based measurements of the CNT lungburden based on cobalt-tracer measurements.These data were used to compare MPPD modelbasedestimates. Because of prediction equationchanges in the MPPD model from version 2.0 to2.1, which affect the model-predicted rat alveolardeposition fraction predictions (discussedfurther in Section A.2.2), the cobalt tracer-basedestimates are compared to each model version(Section A.6.1.2). The influence of assumeddensity on the CNT lung deposition fraction isquantified in addition to the evaluation of theMPPD model version 2.0 vs. 2.1 predictions(Section A.6.1.1). The derivation of allometricbased(body weight scaled) lung ventilation rateestimates is also discussed (Section A.6.1.3).A.6.1.1 Lung Dosimetry ModelbasedDeposition Fractionand Dose EstimatesThe fraction of inhaled CNT that is deposited inthe respiratory tract is predicted from the aerosolcharacteristics. The deposition mechanisms includeimpaction, sedimentation, interception, and diffusion.The aerodynamic diameter, by definition,represents the gravitational settling (sedimentation)behavior of particles [Hinds 1999]. The definitionof aerodynamic diameter standardizes the shape(to spherical) and density (to that of water, 1 g/ml).The aerodynamic diameter of a particle, regardlessof its shape and density, is the diameter of a spherewith the same gravitational settling velocity as theNIOSH CIB 65 • Carbon Nanotubes and Nanofibers125