title: 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.
abstract: 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%).
authors.affiliation: Institute of Toxicology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Ellinger-Ziegelbauer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pauluhn
mesh_terms: D000336:Aerosols; D056151:Airway Remodeling / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011791:Quartz / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D004785:Environmental Pollutants; D037742:Nanotubes, Carbon; D011791:Quartz