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Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

Aaron Erdely14*, Matthew Dahm2, Bean T Chen1, Patti C Zeidler-Erdely1, Joseph E Fernback3, M Eileen Birch3, Douglas E Evans3, Michael L Kashon1, James A Deddens2, Tracy Hulderman1, Suzan A Bilgesu1, Lori Battelli1, Diane Schwegler-Berry1, Howard D Leonard1, Walter McKinney1, David G Frazer1, James M Antonini1, Dale W Porter1, Vincent Castranova1 and Mary K Schubauer-Berigan2

Author Affiliations

1 Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA

2 Division of Surveillance, Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, OH, USA

3 Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Cincinnati, OH, USA

4 NIOSH/HELD/PPRB, 1095 Willowdale Rd, MS-2015, Morgantown, WV 26505-2888, USA

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Particle and Fibre Toxicology 2013, 10:53  doi:10.1186/1743-8977-10-53

Published: 21 October 2013

Abstract

Background

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.

Results

Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m3 (geometric mean 4.21 μg/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/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.

Conclusion

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.

Keywords:
Workplace exposure assessment; Inhalation exposure; Mouse model; MWCNT Dose response and time dependence; Protein; Gene expression