Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials
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.