Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

Particle and Fibre Toxicology (Impact Factor: 6.99). 10/2013; 10(1):53. DOI: 10.1186/1743-8977-10-53
Source: PubMed

ABSTRACT Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice.
Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 mug/m3 (geometric mean 4.21 mug/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 mug/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose.
These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level.

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Available from: Douglas E Evans, Aug 26, 2015
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    • "The dose of 56 μg corresponds to 3 times the life-long dose and 162 μg/mouse corresponds to 9 times the proposed life dose. Work place exposure to CNT are reported in the range of 10–300 μg/m 3 (Birch et al., 2011; Dahm et al., 2013; Erdely et al., 2013; Han et al., 2008; Lee et al., 2010; Maynard et al., 2004; Methner et al., 2010b, 2012), thus 10–300 times above the proposed exposure limit. At an air concentration of 10 μg/m 3 , 162 μg/mouse would correspond to the total dose during a 40-year working life, whereas 162 μg/mouse corresponds to pulmonary deposition during 1.5 work years at 300 μg/m 3 . "
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