Pulmonary toxicity of multi-walled carbon nanotubes (Baytubes) relative to alpha-quartz following a single 6h inhalation exposure of rats and a 3 months post-exposure period. 2009

Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
Institute of Toxicology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany.

Manufactured multi-walled carbon nanotubes (MWCNT) have attracted a great deal of attention due to their unique structural, chemical, and physical characteristics. This study utilized a 1x 6h inhalation exposure protocol followed by a 3 months post-exposure period. Wistar rats were nose-only exposed to 11 and 241 mg/m(3) MWCNT (Baytubes) of respirable, solid aerosol. MWCNT depleted of residual metals (depletion from 0.53% to 0.12% Co) were compared at 11 mg/m(3). Rats similarly exposed to air and alpha-quartz (248 mg/m(3)) served as negative and positive controls, respectively. Pulmonary response was characterized by bronchoalveolar lavage (BAL), lung histopathology, organ burden determinations, and gene expression analyses of lung homogenates with emphasis on extracellular matrix components. This acute inhalation exposure protocol was suitable to characterize and distinguish acute deposition-related effects from the long-term sequelae of retained MWCNT. Subtle differences in acute pulmonary toxic potency due to differences in metal contaminations could be revealed by this protocol. Consistent with the long retention halftime of poorly soluble particles, even short-term inhalation studies may require post-exposure periods of at least 3 months to reveal MWCNT-specific dispositional and toxicological characteristics relative to alpha-quartz. Distinct differences in the time course of pulmonary inflammation of MWCNT and alpha-quartz could be demonstrated. Transcriptomics proved to be a useful tool to analyze the etiopathology of collagen detected by BAL and histopathology. In summary, the pulmonary inflammogenicity following exposure to MWCNT was concentration-dependent with evidence of regression over time. Conversely, alpha-quartz resulted in progressive changes over time. The time course of pulmonary inflammation associated with retained MWCNT was independent on the concentration of residual cobalt. This supports the conclusion that the predominant response to inhaled MWCNT is principally related to the assemblage structure and not catalyst impurities (if in the range of < or = 0.5%).

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011014 Pneumonia Infection of the lung often accompanied by inflammation. Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D011791 Quartz Quartz (SiO2). A glassy or crystalline form of silicon dioxide. Many colored varieties are semiprecious stones. (From Grant & Hackh's Chemical Dictionary, 5th ed)
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004785 Environmental Pollutants Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS. Environmental Pollutant,Pollutant,Pollutants,Pollutants, Environmental,Pollutant, Environmental
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression

Related Publications

Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
July 2013, Particle and fibre toxicology,
Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
January 2014, Particle and fibre toxicology,
Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
June 2013, Journal of toxicologic pathology,
Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
December 2009, Toxicological sciences : an official journal of the Society of Toxicology,
Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
January 2016, Archives of toxicology,
Heidrun Ellinger-Ziegelbauer, and Jürgen Pauluhn
September 2012, Nanotoxicology,
Copied contents to your clipboard!