Occupational Exposure to Carbon Nanotubes and Nanofibers

Table A–11. Comparison of MPPD model and cobalt-tracer based estimates of MWCNT lungburden—single day (6-hr) inhalation exposure in rats [Ellinger-Ziegelbauer and Pauluhn 2009]Exposureconcentration(mg/m 3 )Depositedlung dose(µg)Retainedlung dose(µg)Depositedlung dose(µg)Retainedlung dose(µg)MPPD 2.0 * MPPD 2.11 † MWCNT retainedlung dose (µg)estimated fromcobalt-tracer ‡11 50 12 18 3.4 ≤26241 933 568 557 285 339*MMAD (GSD)—2.9 (1.8) and 2.2 (2.6), respectively, for 11 and 241 mg/m 3 , from Ellinger-Ziegelbauer and Pauluhn [2009]; alveolardeposition fraction—0.050 and 0.043, respectively, for 11 and 241 mg/m 3 ; assumed density of 1 g/ml; tidal volume—2.45 ml.†Assumed density of 0.2 g/ml; tidal volume—2.45 ml; alveolar deposition fraction—0.019 and 0.026, respectively for 11 and241 mg/m 3 .‡Mass of cobalt at 91 d post-exposure was estimated from Figure 2 in Ellinger-Ziegelbauer and Pauluhn [2009] to be approximately0.03 µg (11 mg/m 3 ) and 0.39 µg (241 mg/m 3 ). The CNT amount in the lungs was estimated from the reported 0.115% Co thatwas matrix-bound to the CNT [Pauluhn 2010a]; the remaining mass (99.885% was assumed to be CNT). The CNT mass wasthus calculated as CNT (µg) = [0.99885 × Co mass (µg)] / 0.00115.model to those from the cobalt tracer measurementsreported in two studies [Pauluhn 2010a;Ellinger-Ziegelbauer and Pauluhn 2009].Table A–10 shows that the cobalt-based estimateof CNT in the rat lungs is numerically between thedeposited and retained dose estimated by MPPD2.0 (density of 1). The MPPD 2.11 model (densityof 0.2) [Pauluhn 2010b] underestimated theCo-based lung burden, even the deposited doseestimate (assuming no clearance). These findingssuggest that the model-based estimates of the depositedand retained rat lung doses in the mainanalyses (MPPD 2.0, density 1) provided reasonableestimates of the bounds on the estimatedlung burden. Moreover, these findings are consistentwith the animal toxicokinetic data that showCNT overloads alveolar clearance at lower massdoses than for particles with lower total surfacearea or volume lung dose, resulting in increasedretention of CNT in the lungs of rats and micethan expected for other poorly soluble respirableparticles [Pauluhn 2010a; Mercer et al. 2009]. Thefinding that the cobalt-tracer estimates were betweenthe deposited and retained lung doses isconsistent with CNT reduced clearance comparedwith spherical particles.Similar comparisons were made of the cobalt-traceror lung model estimated lung dose of MWCNT in astudy of rats exposed for 1 day (Table A–11). Resultsshow that the MPPD 2.0 model overestimated theretained lung dose of CNT by nearly a factor of two(at the higher dose) compared with the estimatesbased on the cobalt tracer in the Ellinger-Ziegelbauerand Pauluhn [2009] study (Table A–11). Thissuggests greater clearance than would be predictedat this high dose (241 mg/m3) based on overloadingof lung clearance in the rat model (MPPD2.0). If the retained lung dose estimated by cobalttracer is the best estimate (closest to actual), thissuggests that the BMD estimates using the modelestimatedlung burdens may be overestimates (i.e.,they underestimate potency because the responseproportion is constant while the actual lung burdencausing the effect may be lower). Some errormay also exist in the cobalt-tracer measurementsof the MWCNT mass (estimated from Figure 2 inEllinger-Ziegelbauer and Pauluhn [2009]).128 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers