Advanced in vitro exposure systems.

Comparing the Toxicological Responses of Pulmonary Air–Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers

18. Jan. 2023

https://doi.org/10.3390/ijms24031927

Alexandra Friesen 1, Susanne Fritsch-Decker 2, Sonja Mülhopt 3 , Caroline Quarz 1, Jonathan Mahl 3, Werner Baumann 3, Manuela Hauser 3, Manuela Wexler 3, Christoph Schlager 4, Bastian Gutmann 4, Tobias Krebs 4, Ann-Kathrin Goßmann 5 , Frederik Weis 5 , Matthias Hufnagel 1, Dieter Stapf 3 , Andrea Hartwig 1, and Carsten Weiss 2,
1 Karlsruhe Institute of Technology (KIT), Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, 76131 Karlsruhe, Germany
2 Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems, Biological Information Processing, 76344 Eggenstein-Leopoldshafen, Germany
3 Karlsruhe Institute of Technology (KIT), Institute for Technical Chemistry, 76344 Eggenstein-Leopoldshafen, Germany
4 Vitrocell Systems GmbH, 79183 Waldkirch, Germany
5 Palas GmbH, 76229 Karlsruhe, Germany

 

In this study, we assessed the toxicological responses to mechanically (mCF) and thermo-mechanically treated PAN-based carbon fibers (tmCF), applied to BEAS-2B mono-, BEAS-2B/dTHP-1 co-, and BEAS-2B/dTHP-1/CCD-33Lu triple-cultures at an air–liquid interface. The results emphasize the need to further characterize the hazard of CF and the importance of determining exposure levels at workplaces as well as safety measures during the use of CF-containing materials. Moreover, the development and application of more complex in vitro models of the human lung help to establish new approach methodologies in the general field of particle and fiber toxicology and contribute to a reduction in in vivo investigations in the context of the 3R initiative.

 

Abstract
In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air–liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triplecultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials.

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