Ellinger-Ziegelbauer Heidrun, Pauluhn Jürgen
Institute of Toxicology, Bayer Schering Pharma AG, 42096 Wuppertal, Germany.
Toxicology. 2009 Dec 21;266(1-3):16-29. doi: 10.1016/j.tox.2009.10.007. Epub 2009 Oct 28.
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%).
人造多壁碳纳米管（MWCNT）因其独特的结构、化学和物理特性而备受关注。本研究采用了1次6小时吸入暴露方案，随后是3个月的暴露后观察期。将Wistar大鼠通过仅鼻吸入的方式暴露于可吸入的固态气溶胶形式的11和241 mg/m³的MWCNT（Baytubes）中。对残留金属含量降低（钴含量从0.53%降至0.12%）的MWCNT在11 mg/m³剂量下进行了比较。同样暴露于空气和α-石英（248 mg/m³）的大鼠分别作为阴性和阳性对照。通过支气管肺泡灌洗（BAL）、肺组织病理学、器官负荷测定以及对肺匀浆进行基因表达分析（重点关注细胞外基质成分）来表征肺部反应。这种急性吸入暴露方案适合于区分急性沉积相关效应与MWCNT留存的长期后遗症。该方案能够揭示由于金属污染差异导致的急性肺毒性效力的细微差别。与难溶性颗粒较长的留存半衰期一致，即使是短期吸入研究也可能需要至少3个月的暴露后观察期，以揭示MWCNT相对于α-石英的特定处置和毒理学特征。MWCNT和α-石英在肺部炎症时间进程上存在明显差异。转录组学被证明是分析BAL和组织病理学检测到的胶原蛋白病因病理的有用工具。总之，暴露于MWCNT后的肺部炎症发生具有浓度依赖性，且有随时间消退的迹象。相反，α-石英随时间导致渐进性变化。与留存的MWCNT相关的肺部炎症时间进程与残留钴的浓度无关。这支持了以下结论：对吸入MWCNT的主要反应主要与组装结构有关，而非催化剂杂质（如果在≤0.5%的范围内）。
