Occupational Exposure to Carbon Nanotubes and Nanofibers

Table A–13. Human-equivalent retained lung burden and working lifetime 8-hr TWA concentrationsto rat subchronic NOAEL or LOAEL of 0.1 mg/m 3Subchronic rat study andnormalizing factorRat lung burden(µg) †Human-equivalentlung burden (mg) ‡Working lifetime8-hr TWA (µg/m 3 ) §Pauluhn [2010a]Alveolar macrophage volume 11.7 13.5 16Alveolar epithelial cell surface area 3.0 3.5Ma-Hock et al. [2009]Alveolar macrophage volume 16.0 18 18Alveolar epithelial cell surface area 4.1 4.0†Estimated retained lung burdens in rats from MPPD 2.0 [CIIT and RIVM 2006], assuming particle size (MMAD and GSD) inTable A–2 and unit density. MPPD adjusts for the rat ventilation rate, deposition fraction by respiratory tract region, and uses afirst-order clearance model (with rat overload at higher doses).‡Human-equivalent retained lung burden estimated by dividing the rat lung burden by a normalizing factor for interspecies differences—eitherthe total alveolar macrophage cell volume (3.03 x 10 10 µm 3 /3.49 × 10 13 µm 3 ) (rat/human) or the total alveolarepithelial cell surface area (0.4 m 2 /102 m 2 ) (rat/human).§Human-equivalent concentration and point of departure (HEC_POD) based on the rat NOAEL [Pauluhn 2010a] or LOAEL[Ma-Hock et al. 2009], as 8-hr TWA over a 45-year working lifetime, estimated using MPPD 2.0 [CIIT and RIVM 2006] (Yehand Schum human deposition model), reference worker ventilation rate and patterns [ICRP 1994], and the same particle size inTable A–2.A.6.4 Summary of SensitivityAnalyses FindingsMany of the areas of uncertainty in these risk estimatesfor CNT also occur in other standard riskassessments based on subchronic or short-termanimal study data. Potential chronic effects of CNTare an important area of uncertainty because nochronic study results were available. Uncertaintyexists about the estimated lung doses for the inhalationstudies because of lack of experimentalevaluation or validation of lung dosimetry modelsto predict deposition and retention of CNT. Informationis also limited on the relative potency of differenttypes of CNT to cause specific lung effects inanimals because of study differences. Despite thevariability in the risk estimates across the varioustypes of CNT, all of the risk estimates were associatedwith low-mass concentrations (below the upperand lower LOQ or 7 or 1 µg/m3, respectively).NIOSH CIB 65 • Carbon Nanotubes and NanofibersIn conclusion, these sensitivity analyses show thatthe estimates of a health-based OEL are not stronglydependent on the BMD-based risk assessmentmethods, and the use of an alternative (POD/UF)method provides supporting evidence indicatingthe need for a high level of exposure containmentand control for all types of CNT.A.7 Evaluation of CarbonNanofiber Studies inMice and RatsTwo in vivo studies of carbon nanofibers (CNF)have been recently published in mice and rats [Murrayet al. 2012 and DeLorme et al. 2012]. In orderto compare the lung responses to CNF observed inthese studies, estimates of the lung doses normalizedacross species are provided in this section.137