Occupational Exposure to Carbon Nanotubes and Nanofibers

and density. The following MMAD and GSD valueswere reported by airborne exposure concentrations:0.54 mg/m 3 (MMAD 1.9 µm; GSD 3.1);2.5 mg/m 3 (MMAD 3.2 µm; GSD 2.1); and 25 mg/m 3 (MMAD 3.3 µm; GSD 2.0). The density assumedfor this CNF is 0.08 g/ml. Density was not reportedin DeLorme et al. [2012] and was obtained fromthe manufacturer’s data analysis sheet, which indicatesit is the same material as that reported inDeLorme et al. [2012].The default breathing rates and parameters wereassumed, and inhalability adjustment was selected.In MPPD 2.90, nonspherical particle shape can betaken into account in the respiratory tract depositionestimates, but some of the required input parameters(GSD of structure diameter and lengthand correlation) were not reported in DeLormeet al. [2012]. So, the spherical particle assumption(aspect ratio of 1.0) was assumed, which maynot be unreasonable given that the fiber interceptionmechanism may be less for CNF structures oflength 5.8 µm than for longer fibers. The defaultbreathing parameters (including 0.21 ml tidal volumeand 102 breaths/min) may be reasonable forthe female Sprague Dawley rats in the DeLorme etal. [2012] study based on similar body weight (300g) associated with the default values [Kuempel andCastranova 2011], but may be too low for the maleSprague Dawley rats. The average body weights incontrol rats (air-only exposed) at the end of 13-wkexposure period and the 90-d post-exposure period,respectively, were: 252 and 329 g (females);520 and 684 g (males) [DeLorme et al. 2012]. Theretained lung burden at the end of the 13-wk exposurewas also estimated in MPPD 2.90 using theparticle size data for each exposure concentration(using MMAD and GSD values reported above).The lung dose estimates in rats and mice were normalizedby the lung weight or alveolar surface area toestimate the equivalent dose across species. The averagelung weights of rats were those reported in DeLormeet al. [2012] 1-d post-exposure in the control rats(1.9 g and 1.3 g in males and females, respectively).The average mouse lung weight was 0.15 g [personalcommunication, A. Shvedova to E. Kuempel, Aug.2012]. The average alveolar surface area assumed forthe rat lungs was 0.4 m 2 [Stone et al. 1992], and that ofmice was 0.055 m 2 [Mercer et al. 2010].The total deposited CNF dose in the alveolar regionwas estimated in rats in the DeLorme et al. [2012]study in the following equation:Deposited lung dose (mg) =Exposure Concentration (mg/m 3 ) × Duration (hr/d × d/wk × wk)× Minute Ventilation (L/min) × 0.001 m 3 /L × 60 min/hr× Alveolar Deposition Fractionwhere the exposure concentrations are 0.54, 2.5,or 25 mg/m 3 ; the duration of exposure is 6 hr/d, 5d/wk, 13 wk; the minute ventilation is 0.21 L/min;and the alveolar deposition fractions are reportedin Section A.7.5.A.7.6 Equivalent Lung DoseEstimation ResultsThe inhalable fraction estimates of CNF in rats were0.79, 0.73, and 0.72, respectively, in rats at the reportedparticles sizes for concentrations of 0.54 mg/m 3 (MMAD 1.9 µm; GSD 3.1); 2.5 mg/m 3 (MMAD3.2 µm; GSD 2.1); and 25 mg/m 3 (MMAD 3.3 µm;GSD 2.0) in DeLorme et al. [2012] (based on MPPDv. 2.90 [ARA 2009] as described in Section A.7.4).The alveolar deposition fraction estimates were0.0715, 0.0608, and 0.054, respectively, for the 0.54,2.5, and 25 mg/m 3 exposure concentrations.The normalized dose estimates in mice and rats(as CNF mass per alveolar surface area or mass oflungs) and associated lung responses are shown inTables A–15 and A–16. In mice, these lung dose estimatesare similar to or higher than the depositedlung dose estimate in the rat at the LOAEL (2.5 mg/m 3 ), but less than the deposited lung doses estimatedin rats at the highest concentration (25 mg/m 3 )(Tables A–15 and A–16). The mouse deposited lungburden estimates are higher than the rat retainedlung burden estimates at all doses, assuming spherical-particlemodel clearance in MPPD 2.90 [ARA2009]. If CNF is cleared in a similar manner as thatreported for MWCNT in Pauluhn [2010b], the actualretained lung dose in rats may be intermediateNIOSH CIB 65 • Carbon Nanotubes and Nanofibers141