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Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials
Citation:
Clippinger, A., A. Ahluwalia, D. Allen, J. Bonner, W. Casey, V. Castranova, R. David, S. Halappanavar, J. Hotchkiss, A. Jarabek, M. Maier, W. Polk, B. Rothen-Rutishauser, C. Sayes, P. Sayre, M. Sharma, AND V. Stone. Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials. Archives of Toxicology. Springer, New York, NY, , 1-15, (2016).
Impact/Purpose:
Inhalation is considered an important route of entry into the human body for aerosolized nanomaterials (NMs) released into the environment (during production, processing, intended usage, or disposal of products). Research into the potential hazards of these materials has therefore often focused on effects on the respiratory tract as a target tissue. Traditional in vivo inhalation toxicity tests require large numbers of animals, specialized facilities and expertise, and are resource intensive with respect to both time and cost. Concerns related to the use of animals, cost, and time as well as the technical difficulty and predictive ability of the 90-day rodent inhalation test for humans have motivated interest in developing in vitro lung cell-based methods. As the prevalence and diversity (different functionalizations, or physical chemical properties) of NMs in commerce continues to grow, so does the need for efficient and accurate, human-relevant test methods to assess the potential hazards associated with NMs in a timely manner. With this in mind, in February 2015, the PETA International Science Consortium Ltd. co-organized with the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods an international workshop that was attended by representatives from industry, government, academia, and non-governmental organizations with expertise in in vivo and in vitro lung systems, respiratory toxicology, inhalation particle dosimetry, nanotoxicology, and hazard and human health risk analysis. The goal of the workshop was to review the state-of-the-science and determine the technical needs to develop an in vitro system that will reduce and eventually replace the use of animals for evaluating the potential inhalation toxicity of NMs in a regulatory setting. The workshop discussion focused specifically on the development and preliminary assessment of the relevance and reliability of an in vitro test system to predict the development of pulmonary fibrosis by assessing pro-fibrogenic markers in lung cells cultured at the air-liquid interface (ALI) following exposure to aerosolized NMs, such as multi-walled carbon nanotubes (MWCNTs). This report provides an overview of the presentations, discussions, and recommendations of the participants on the design of an in vitro system for the prediction of pulmonary fibrosis.
Description:
Report from an international workshop with the goal of reviewing the state-of-the-science and determine the technical needs to develop an in vitro system that will reduce and eventually replace the use of animals for evaluating the potential inhalation toxicity of nanomaterials (NMs) in a regulatory setting. Workshop was co-organized in February 2015 by the PETA International Science Consortium Ltd. with the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods an international workshop that was attended by representatives from industry, government, academia, and non-governmental organizations with expertise in in vivo and in vitro lung systems, respiratory toxicology, inhalation particle dosimetry, nanotoxicology, and hazard and human health risk analysis. This report provides an overview of the presentations, discussions, and recommendations of the participants on the design of an in vitro system for the prediction of pulmonary fibrosis. The workshop participants identified multi-walled carbon nanotubes (MWCNTs), which have been shown to induce fibrosis in animal experiments and represent an important commercial nanomaterial class, as representative pro-fibrogenic NMs to use for the development of an in vitro test system. Recommendations were made for designing a system using lung relevant cells co-cultured at the air-liquid interface to assess the pro-fibrogenic potential of aerosolized MWCNTs, while considering human-relevant dosimetry and NM lifecycle transformations. The workshop discussions provided the fundamental design components of an air-liquid interface in vitro test system that will be subsequently expanded to the development of an in vitro testing strategy to predict the pulmonary toxicity of NMs and to the generation of data that will enable effective risk assessment of such NMs.
URLs/Downloads:
CLIPPINGER ET AL (2016)_IN VITRO MWCNT.PDF (PDF, NA pp, 678.813 KB, about PDF)http://link.springer.com/article/10.1007/s00204-016-1717-8
