Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity.
Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Sarah S
SS
Poulsen
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Petra
P
Jackson
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Kirsten
K
Kling
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Kristina B
KB
Knudsen
b National Institute of Occupational Health , Oslo , Norway .
Vidar
V
Skaug
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Zdenka O
ZO
Kyjovska
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Birthe L
BL
Thomsen
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Per Axel
PA
Clausen
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Rambabu
R
Atluri
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Trine
T
Berthing
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Stefan
S
Bengtson
c Finnish Institute of Occupational Health , Helsinki , Finland .
Henrik
H
Wolff
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .
Keld A
KA
Jensen
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .|d Institute of Public Health, Copenhagen University , Copenhagen K , Denmark , and.
Håkan
H
Wallin
a National Research Centre for the Working Environment , Copenhagen Ø , Denmark .|e Department of Micro-and Nanotechnology , Technical University of Denmark , Kgs. Lyngby , Denmark.
Ulla
U
Vogel
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D020552:Comet Assay; D053960:DNA Breaks; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D012044:Regression Analysis; D013499:Surface Properties
D037742:Nanotubes, Carbon
BET surface area; CNT-diameter; CNT-length; functionalization; lymphocytic aggregates