Occupational Exposure to Carbon Nanotubes and Nanofibers

Ma-Hock et al. [2009] subchronic rat inhalationstudy of MWCNT. Aschberger et al. [2010] proposedOELs of 1 µg/m 3 for MWCNT studied byMa-Hock et al. [2009] and 2 µg/m 3 for MWCNTfrom Pauluhn [2010a], by adjusting 0.1 mg/m 3 (theLOAEL in Ma-Hock et al. [2009] and the NOAELin Pauluhn [2010a]) for rat-to-human daily exposureand respiratory volume, and applying an overallassessment factor of 50 and 25, respectively.Pauluhn [2010b] derived an OEL using subchronicdata in rats inhaling MWCNTs (Baytubes®) [Pauluhn2010a]. This approach was based on the biologicalmechanism of volumetric overloading of alveolarmacrophage-mediated clearance of particlesfrom the lungs of rats [Morrow 1988]. Increasedparticle retention half-time (an indication of lungclearance overload) was reported in rats exposedby subchronic inhalation to MWCNT (Baytubes®)at 0.1, 0.4, 2.5, or 6 mg/m 3 The overloading of ratlung clearance was observed at lower-mass doses ofMWCNT (Baytubes®) compared with other poorlysoluble particles; and the particle volume dose wasbetter correlated with retention half-time amongpoorly soluble particles including CNT [Pauluhn2010a, b]. Pauluhn [2010b] reported benchmarkconcentration (BMC) estimates of 0.16 to 0.78 mg/m 3 for rat lung responses of pulmonary inflammationand increased collagen, but selected the lowerNOAEL of 0.1 mg/m 3 to derive a human-equivalentconcentration. The NOAEL was adjusted for humanand rat differences in factors affecting theestimated particle lung dose (i.e., ventilation rate,alveolar deposition fraction, retention kinetics, andtotal alveolar macrophage cell volume in each species).The product of these ratios resulted in a finalfactor of 2, by which the rat NOAEL was divided,to arrive at a human-equivalent concentration of0.05 mg/m 3 (8-hr TWA) as the OEL for MWCNT(Baytubes®). No uncertainty factors were used inderiving that estimate.The Japanese National Institute of Advance IndustrialScience and Technology (AIST) derived anOEL for CNT of 30 µg/m 3 [Nakanishi 2011a,b],based on studies supported by the New Energy andIndustrial Technology Development Organization(NEDO) of Japan. Rat NOAELs for pulmonaryinflammation were identified in 4-week inhalationstudies of SWCNT and MWCNT [Morimotoet al. 2011a,b]. Human-equivalent NOAELs wereestimated by accounting for rat and human differencesin exposure duration, ventilation rate, particledeposition fraction, and body weight [Nakanishi2011b]. The rat NOAELs of 0.13 and 0.37 mg/m 3 forSWCNT and MWCNT, respectively, were estimatedto be equivalent to 0.03 and 0.08 mg/m 3 in humansincluding adjustment by an uncertainty factorof 6. This total uncertainty factor included a factorof 2 for uncertainty in subchronic-to-chronicextrapolation and a factor of 3 for uncertainty inrat to human toxicokinetic differences (factors of 1were assumed for toxicodynamic differences in ratsand humans and for worker inter-individual variability).A relationship was reported between theBET specific surface area of various types of CNTand pulmonary inflammation (percent neutrophilsin bronchoalveolar lavage fluid) (Figure V.2 in Nakanishi[2011b]). Thus, the OEL of 0.03 mg/m 3 wasproposed for all types of CNT, based on the data forthe SWCNT with the relatively high specific surfacearea of ~1,000 m 2 /g (which was noted wouldbe more protective for other CNTs with lower specificsurface area). A period-limited (15-yr) OELwas proposed due to uncertainty in chronic effectsand based on the premise that the results will be reviewedagain within that timeframe with furtherdata [Nakanishi 2011a].In summary, these currently proposed OELs forCNT range from 1 to 50 µg/m 3 (8-hr TWA concentration)[Aschberger et al. 2010; Nanocyl 2009;Pauluhn 2010b; Nakanishi (ed) 2009a], includingthe NIOSH REL of 1 µg/m 3 . Despite the differencesin risk assessment methods and assumptions, all ofthe derived OELs for CNT are low airborne massconcentrations relative to OELs for larger respirablecarbon-based particles. For example, the currentU.S. OELs for graphite or carbon black are approximately2.5 to 5 mg/m 3 . Each of these CNT riskassessments supports the need to control exposuresto CNT in the workplace to low airborne mass concentrations(µg/m 3 ) to protect workers’ health.44 NIOSH CIB 65 • Carbon Nanotubes and Nanofibers