Carbon nanotube dosimetry: From workplace exposure assessment to inhalation toxicology

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. © 2013 erdely et al.; licensee biomed central ltd.