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ToxSci Advance Access originally published online on July 7, 2009
Toxicological Sciences 2009 112(2):468-481; doi:10.1093/toxsci/kfp146
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Inhalation Toxicity of Multiwall Carbon Nanotubes in Rats Exposed for 3 Months

Lan Ma-Hock*, Silke Treumann*, Volker Strauss*, Sandra Brill*, Frederic Luizi{dagger}, Michael Mertler{ddagger}, Karin Wiench*, Armin O. Gamer*, Bennard van Ravenzwaay*,1 and Robert Landsiedel*

* Product Safety, BASF SE, 67056 Ludwigshafen, Germany {dagger} Nanocyl S. A., 5060 Sambreville, Belgium {ddagger} Process Engineering, BASF SE, 67056 Ludwigshafen, Germany

1 To whom correspondence should be addressed at GV/T-Z470, BASF SE, 67056 Ludwigshafen, Germany. Fax: +49 620 60 51734. E-mail: bennard.ravenzwaay{at}basf.com.

Received April 28, 2009; accepted June 27, 2009


   Abstract

Carbon nanotubes (CNT) are of great commercial interest. Theoretically, during processing and handling of CNT and in abrasion processes on composites containing CNT, inhalable CNT particles might be set free. For hazard assessment, we performed a 90-day inhalation toxicity study with a multiwall CNT (MWCNT) material (Nanocyl NC 7000) according to Organisation for Economic Co-operation and Development test guideline 413. Wistar rats were head-nose exposed for 6 h/day, 5 days/week, 13 weeks, total 65 exposures, to MWCNT concentrations of 0 (control), 0.1, 0.5, or 2.5 mg/m3. Highly respirable dust aerosols were produced with a proprietary brush generator which neither damaged the tube structure nor increased reactive oxygen species on the surface. Inhalation exposure to MWCNT produced no systemic toxicity. However, increased lung weights, pronounced multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic inflammation, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5 mg/m3. These effects were accompanied by slight blood neutrophilia at 2.5 mg/m3. Incidence and severity of the effects were concentration related. At 0.1 mg/m3, there was still minimal granulomatous inflammation in the lung and in lung-associated lymph nodes; a no observed effect concentration was therefore not established in this study. The test substance has low dust-forming potential, as demonstrated by dustiness measurements, but nonetheless strict industrial hygiene measures must be taken during handling and processing. Toxicity and dustiness data such as these can be used to compare different MWCNT materials and to select the material with the lowest risk potential for a given application.

Key Words: carbon nanotubes; MWCNT; pulmonary toxicity; 90-day inhalation study; granulomatous inflammation; lung; lymph nodes.


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