Design of an In Vitro System to Assess the Inhalation Toxicity of Nanomaterials

PHASE I (completed)

The PETA International Science Consortium Ltd. convened an expert workshop that was held at the US EPA headquarters in Washington, DC on February 24-25, 2015. The invitation-only workshop included experts from government, industry, academia and NGOs to discuss the development of an in vitro system to predict the development of pulmonary fibrosis in cells co-cultured at the air-liquid interface following exposure to aerosolized multi-walled carbon nanotubes (MWCNTs). During the workshop, experts made recommendations on cell types, exposure systems, endpoints and dosimetry considerations required to develop the in vitro model for hazard identification of MWCNTs.

Phase I Outputs

Publications

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.

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.

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.

PHASE II (in progress)

The Science Consortium is funding Professor Dr. Barbara Rothen-Rutishauser of the Adolphe Merkle Institute at the University of Fribourg, Switzerland and Professor Dr. Vicki Stone of the School of Life Sciences at Heriot-Watt University, Edinburgh, U.K. to jointly develop the system. The Consortium is also funding MatTek Corporation for the development of a three-dimensional reconstructed primary human lung tissue model to be used in Professors Rothen-Rutishauser and Stone’s work.

Phase II Outputs

2016 Society of Toxicology poster: Development of an In Vitro Test to Assess the Inhalation Toxicity of Nanomaterials.
2016 Nanotox Congress poster: Development of an In Vitro System to Assess the Inhalation Toxicity of Nanomaterials.

PHASE III

The system developed in Phase II will be tested in additional laboratories and using different nanomaterials (NMs). The method is intended to be included in a nonanimal test battery to reduce and eventually replace the use of animals in studies to assess the inhalation toxicity of engineered NMs. The long-term vision is to develop a battery of in silico and in vitro assays that can be used in an integrated testing strategy, providing comprehensive information on biological endpoints relevant to inhalation exposure to NMs which could be used in the hazard ranking of substances in the risk assessment process.

Please direct any questions, to:
Monita Sharma, Ph.D.
Nanotoxicology Specialist
PETA International Science Consortium Ltd.
Email: MonitaS@piscltd.org.uk
Nano workshop 2015 collage pic2