Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology.
Erdely-A; Dahm-M; Chen-BT; Zeidler-Erdely-PC; Fernback-JE; Birch-ME; Evans-DE; Kashon-ML; Deddens-JA; Hulderman-T; Bilgesu-SA; Battelli-L; Schwegler-Berry-D; Leonard-HD; McKinney-W; Frazer-DG; Antonini-JM; Porter-DW; Castranova-V; Schubauer-Berigan-MK
Part Fibre Toxicol 2013 Oct; 10:53
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.
Nanotechnology; Environmental-exposure; Exposure-levels; Physiological-function; Physiological-effects; Physiology; Aerosols; Risk-factors; Laboratory-animals; Animals; Neurological-system; Neurological-reactions; Molecular-biology; Molecular-structure; Workers; Dosimetry; Analytical-processes; Risk-analysis; Exposure-assessment;
Author Keywords: Workplace exposure assessment; Inhalation exposure; Mouse model; MWCNT Dose response and time dependence; Protein; Gene expression
Aaron Erdely, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505-2888, USA
HELD; DSHEFS; DART
Manufacturing; Public Safety
Particle and Fibre Toxicology