Pulmonary-toxicity-screening studies with single-wall carbon nanotubes

IEC 24

David B Warheit, Brett R Laurence, Kenneth L Reed, and Thomas R. Webb. Pulmonary Toxicology, DuPont Haskell Laboratory, 1090 Elkton Road, Newark, DE 19714-0050
The potential hazards of inhaled carbon nanotubes (CNT) are unknown. Recent experimental studies in rats indicate that inhaled nano/ultrafine particles may produce significant lung toxicity and the hazard potential increases with decreasing particle size. The aim of this study was to assess in rats, using a well-developed, short-term bioassay the acute pulmonary toxicity effects of intratracheally instilled CNT samples compared to other particulate reference materials; and to bridge these results with data from earlier inhalation studies with quartz and carbonyl iron particles as the inhalation/instillation bridge materials. Groups of rats were instilled with PBS-Tween, or 1 or 5 mg/kg of carbon nanotubes (CNT), quartz (Q), or carbonyl iron (CI) particles. The lungs of PBS and particle-exposed rats were evaluated by bronchoalveolar lavage (BAL) and tissue analysis at 24 hr, 1 week, 1 month and 3 months postexposure (pe). Exposure to 5 mg/kg produced mortality in ~15% of the CNT-instilled rats within 24 hrs, however, this was due to mechanical blockage of the upper airways by the instillate, and not due to lung toxicity. The results of BAL fluid and pulmonary cellular toxicity studies at 24 hrs, 1 week and 1 month pe demonstrated that Q exposure produced the greatest levels of lung toxicity and pulmonary inflammation. CNT-related toxicity was transient and intermediate between Q and CI. Our interim results indicate that CNT exposure did not produce any sustained lung inflammatory effects, unlike Q particles. Studies are ongoing to assess airway/alveolar cell proliferation patterns and lung histopathology following CNT exposures in rats. In addition, the results of exposure assessment studies at the workplace will be presented.