An In Vitro System to Predict the Development of Pulmonary Fibrosis

In 2015, PETA Science Consortium International held a workshop that resulted in expert recommendations on the design of an in vitro system to predict the development of pulmonary fibrosis. The Consortium subsequently funded MatTek Life Sciences to optimize a 3-dimensional reconstructed human tissue model of the lower respiratory tract (EpiAlveolarTM) and funded Professor Dr Barbara Rothen-Rutishauser of the Adolphe Merkle Institute at the University of Fribourg, Switzerland and Professor Dr Vicki Stone of Heriot-Watt University, Edinburgh, U.K. to use the tissue model to test various nanomaterials (here).

This work is part of the Consortium’s larger effort to replace inhalation toxicity testing in animals. In addition to the above, in 2015 and 2016, the Consortium co-sponsored webinars and workshops on acute systemic toxicity testing (here) and acute inhalation toxicity testing (here), and in 2017, held a contest to award researchers with VITROCELL® in vitro inhalation exposure devices. One of these devices was awarded to Professor Dr Vicki Stone so that her research team can expand upon Dr Rothen-Rutishauser’s work as part of the EU Horizon 2020-funded project, PATROLS.

To complement the in vitro system, Consortium scientists are also working on the development of an adverse outcome pathway on lung fibrosis (see the AOP-wiki entry here).

The long-term goal of this work is to develop in silico and in vitro approaches that can be used to assess toxicity following inhalation exposure.


Barosova H, Maione AG, Septiadi D, Sharma M, Haeni L, Balog S, O’Connell O, Jackson GR, Brown D, Clippinger AJ, Hayden P, Petri-Fink A, Stone V, Rothen-Rutishauser B. Use of EpiAlveolar lung model to predict fibrotic potential of multi-walled carbon nanotubesACS Nano. March 2020:  [Epub ahead of print]

Clippinger, A.J., Ahluwalia A., Allen D., Bonner J.C., Casey W., Castranova V., David R.M., Halappanavar S., Hotchkiss J.A., Jarabek A.M., Maier M., Polk W., Rothen-Rutishauser B., Sayes C.M., Sayre P., Sharma M., Stone V. (2016). Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterialsArchives of Toxicology. 90(7):1769-83.

Polk W., Sharma M., Sayes C.M., Hotchkiss J.A., Clippinger A.J. (2016). Aerosol generation and characterization of multi-walled carbon nanotubes exposed to cells cultured at the air-liquid interfaceParticle and Fibre Toxicology. 13(1):20.

Sharma M., Nikota J., Halappanavar S., Castranova V., Rothen-Rutishauser B., Clippinger, A.J. (2016). Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs)Archives of Toxicology. 90(7):1605-22.

2018 Society of Toxicology poster: Development of a cell-based approach to assess pulmonary fibrosis following exposure to nanomaterials
2017 Society of Toxicology poster: An integrated approach to assessing the inhalation toxicity of nanomaterials
2016 Society of Toxicology poster: Development of an in vitro test to assess the inhalation toxicity of nanomaterials

2015 Workshop Presentations
James Bonner: In vitro approaches for predicting pulmonary fibrosis in rodents and humans after exposure to carbon nanotubes.
Iris Camacho: Challenges of evaluating the human health risks of nanomaterials
Maria Doa: Improving information used in decision-making
Sabina Halappanavar: Adverse outcome pathways: a conceptual framework to support the evaluation and extrapolation of toxicological hazards of nanomaterials
Annie Jarabek: “Mind the gap”: Dosimetry modelling to aid experimental design, evidence integration and inferences
William Polk: Nanomaterial- and air-liquid interface (NanoALI)-enabled in vitro exposure systems
Barbara Rothen-Rutishauser: Advanced in vitro lung models in nanotoxicology research – advantages and limitations
Christie Sayes: State-of-the-science aerosol generation and characterization
Vicki Stone: Longer term ideas for developing in vitro models for pulmonary toxicology

Nano workshop 2015 collage pic2