Occupational Exposure to Carbon Nanotubes and Nanofibers

and reference worker conditions, including 9.6 m3of air inhaled per 8-hr day (corresponding to 17.5breaths/min and tidal volume of 1143 ml), andwork for 8 hr/d, 5 d/wk, 50 wk/yr, for 45 years.In the two subchronic inhalation studies for MW-CNT, excess risk estimates were derived based oneither the estimated deposited lung dose or the estimatedretained lung dose [Ma-Hock et al. 2009;Pauluhn 2010a].A.3 ResultsA.3.1 Benchmark Dose andWorking LifetimeExposure EstimatesThe estimates of the rodent BMD(L)s, the humanequivalentBMD(L)s, and the associated workinglifetime 8-hr TWA exposure concentrations (MLEand 95% LCL)—called the benchmark concentration(BMC) and the BMCL (95% LCL of theBMC)—are shown in Tables A–3 through A–5.All dose-response models used in this risk assessmentprovided adequate fit (P > 0.05) to the rodentdata for BMD(L) estimation (P values for thePearson X2 goodness of fit test shown in TablesA–3 through A–5).In Table A–3, the BMD(L) and BMC(L) * estimatesare based on the IT, PA, or short-term inhalationexposure studies of SWCNT or MWCNT withcontinuous response measures. Lung responses inrodents were evaluated at 32 to 60 days after firstexposure. Rodent dose is the administered (IT orPA) or estimated deposited dose (inhalation). TheBMR is the specified adverse lung response at 1.1standard deviations above the estimated rodentcontrol mean response (i.e., alveolar connectivetissue thickness or amount of hydroxyproline) (asexplained in Section A.2.3.2). Considerably higher8-hr TWA concentrations are estimated basedon the endpoint of lung hydroyxproline amount[Muller et al. 2005] compared with those based on*Abbreviation for both BMC and BMCL estimates.the alveolar connective tissue thickness endpoint,which is a more sensitive (earlier) indicator of fibrosis[Mercer et al. 2008].In Table A–4, the BMD(L) and BMC(L) estimatesare based on the IT exposure study of SWCNT withdichotomous response measures. Lung responseswere evaluated 90 days after the first exposure. TheBMR is the 10% excess risk of the specified adverselung response (proportion of rats with lung granulomas).Although Lam et al. [2005] report doseresponsedata for three different preparations ofSWCNT (containing either 2% Fe, 27% Fe, or 26%Ni), the BMD(L) and BMC(L) estimates are providedonly for the SWCNT with 2% Fe, which wasthe only dataset of the three reported by Lam et al.[2005] that was adequately fit by the BMD model(Table A–4).Table A–5 provides the BMD(L) and BMC(L) estimatesbased on the two subchronic inhalation studiesof MWCNTs, which also report dichotomousresponse measures. Lung responses were evaluatedat the end of the 13-week (91 d) exposure period.Rodent dose is either the total deposited lung doseor the retained lung dose at the end of exposure.The BMR is estimated as the 10% excess risk of thespecified adverse lung response (granulomatousinflammation or alveolar septal thickening of histopathologygrade 1 or higher). As expected, the estimatesbased on deposited lung dose are lower thanthose based on the retained lung dose, because theassumption of no clearance in the deposited lungdose results in a lower estimated 8-hr TWA concentrationto attain the human-equivalent BMD(L)lung burdens. The estimates for MWCNT (with9.6% Al 2O 3) based on the rat granulomatous inflammationresponse are lower than those for MW-CNT (Baytubes) (with 0.53% Co) based on the ratalveolar septal thickening response.Table A–6 shows the animal and human BMD(L)estimates and equivalent working lifetime 8-hrTWA concentration estimates, BMC(L), associatedwith grade 2 (slight/mild) or higher lung responsesin the subchronic inhalation studies, based on theestimated deposited lung dose. As expected, higherBMD(L)s and BMC(L)s are estimated from the110 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers