Occupational Exposure to Carbon Nanotubes and Nanofibers

A.6.1.3 Pulmonary Ventilation RateThe pulmonary ventilation rate influences the depositedand retained lung dose estimates. Rat inhalationrate estimates vary slightly among differentsources [US EPA 1994; Pauluhn 2010a, citingSnipes 1989]. Species-specific ventilation rates canbe calculated based on the following allometricscaling equation [US EPA 1994]:Equation A.6:ln(V E) = b0 + b1 ln(BW)where V Eis the minute ventilation (L/min); BW isbody weight; and b0 + b1 are species-specific parameters.For the rat, b0 + b1 are -0.578 and 0.821, respectively(Table 4–6 of US EPA [1994]). For a 300 grat, the ventilation rate can be calculated as follows:Equation A–7:0.21 L/min = Exp [-0.578 + 0.821 × Ln(0.3)]This is also the default minute ventilation in MPPD[CIIT and RIVM 2007; ARA 2011].Rat mean body weights in Pauluhn [2010a] werereported as 369 g (male) and 245 g (female) in thecontrol (unexposed) group at 13 weeks. Becausethe alveolar septal thickening response data in Pauluhn[2010a] were based on male rats only, a malerat minute ventilation of 0.25 L/min (calculatedfrom equation A–6) was used to estimate lung dosein that study.Ma-Hock et al. [2009] did not report the rat bodyweight, although the rat strain (Wistar) and studyduration (13 weeks) were the same as in Pauluhn[2010a]. Because the granulomatous inflammationresponse data in Ma-Hock et al. [2009] were combinedfor the 10 male and 10 female rats in eachdose group (since response proportions were statisticallyconsistent), an average rat body weight inmale and female rats of 300 g was assumed, whichis similar to the male and female average bodyweight of 307 g reported in Pauluhn [2010a] andthe default value of 300 g in MPPD. Subsequently,body weights were obtained for the Ma-HockNIOSH CIB 65 • Carbon Nanotubes and Nanofiberset al. [2009] study [personal communication, L.Ma-Hock and E. Kuempel, 10/14/10]. The averagemale and female rat body weight at 13 weeks wasnearly identical (305 g) to that reported in Pauluhn[2010a]. Other rat minute ventilation rates of0.8–1 L/min per kg [Pauluhn 2010a, citing Snipes1989] would result in somewhat higher lung doseestimates.Based on equation A–6, a minute ventilation of0.21 L/min is calculated for female and male rats inMa-Hock et al. [2009], and 0.25 L/min for male ratsin Pauluhn [2010a]. Minute ventilation is the productof tidal volume and breathing frequency. Assumingthe same breathing frequency (102 min -1 ), atidal volume of 2.45 ml is calculated (equation A–6)and used instead of the default value in MPPD 2.0[CIIT and RIVM 2006] in estimating the rat lungdose in the Pauluhn [2010a] data.In humans, based on the MPPD 2.0 model [CIITand RIVM 2006], the default pulmonary ventilationrate is 7.5 L/min, based on default values of 12min -1 breathing frequency and 625 ml tidal volume.The “reference worker” ventilation rate is 20 L/min[ICRP 1994] or 9.6 m3/8 hr (given 0.001m3/L, and480 min/8-hr). In these estimates, 17.5 min -1 breathingfrequency and 1143 ml tidal volume [NIOSH2011a] were used in MPPD 2.0 to correspond to a20 L/min reference-worker ventilation rate.A.6.2 Critical EffectLevel SelectionA key step in the dose-response analyses of any riskassessment is estimating the critical effect level.A critical effect level from an animal study is extrapolatedto humans to derive a POD for low doseextrapolation (Section A.2.3). A critical effect istypically the most sensitive effect associated withexposure to the toxicant (i.e., the effect observedat the lowest dose) which is adverse or is causallylinked to an adverse effect. The early-stage lungeffects discussed in Section A.2.1.3 are the criticaleffects used in both the main risk assessmentand in these sensitivity analyses. The primary129