Lung burdens and kinetics of multi-walled carbon nanotubes (Baytubes) are highly dependent on the disaggregation of aerosolized MWCNT.
Previous repeated inhalation exposure studies on rats with multi-walled carbon nanotubes (MWCNT, Baytubes®) suggested that their pulmonary toxicity was predominated by the morphology and density of the aggregated structure. Evidence of any disintegration of these structures in the lung did not exist. The objective of this study was to study as to which extent the formulation of pristine MWCNT as wet-dispersion changes the morphology of assemblage structures in the presence of disintegrated sub-structures. The focus was on the comparative inhalation dosimetry and kinetics of dry- and wet-dispersed Baytubes to better understand the cause of putative differences in pulmonary toxicity originating from pristine and rigorously formulated MWCNT. Rats were nose-only exposed to dry-dispersed and wet-dispersed Baytubes for 6-h at 25-30 mg/m(3). Aerodynamic particle size measurements demonstrate substantial differences in the particle size of dry- (MMAD 2.6 µm) and wet-dispersed (MMAD 0.8 µm) MWCNT. Time-course changes of MWCNT retained in the lung were examined during a post-exposure period of 3 months. Lung burdens were analytically determined in digested lungs using the EC/OC total carbon method. Dosimetry was complemented by light and transmission electron microscopy (TEM) of MWCNT retained in alveolar macrophages (AM). As a result, the initially deposited pulmonary dose of MWCNT was three times higher following wet-dispersed MWCNT at essentially similar inhalation chamber concentrations. The elimination half-time of dry- and wet-dispersed MWCNT was 87 and 46 d, respectively. TEM provided evidence that wet-dispersed MWCNT were inhaled as disintegrated structures with distribution-patterns within the cytoplasm of AMs that differed appreciably from those of dry-dust exposed animals. In summary, this study shows that specialized technical processes to formulate MWCNT may have dramatic consequences on their pulmonary fate and associated toxicity. Such properties can only be revealed by the comparison of pulmonary toxicity with pulmonary (micro-)dosimetry and kinetics.
Department of Experimental Toxicology , Bayer Pharma AG, Wuppertal , Germany.
Jürgen
J
Pauluhn
Martin
M
Rosenbruch
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis; D007700:Kinetics; D008168:Lung / Q000737:chemistry*; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage / Q000648:ultrastructure; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure*; D009928:Organ Specificity; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000336:Aerosols; D037742:Nanotubes, Carbon
Dosimetry; MWCNT; particle disaggregation and clearance; read-across