The increasing use of multi-walled carbon nanotubes (MWCNTs) in consumer goods such as paints, building materials, and electronics has greatly increased the likelihood of human exposure.

Inhalation is one of the most prevalent routes by which exposure can occur, and because inhalation of MWCNTs may be linked to lung problems such as pulmonary fibrosis, hazard testing is conducted to assess the safety of these materials.

In many jurisdictions, the current regulatory requirement for substances of concern, such as MWCNTs, is a 90-day rodent inhalation test, but there are financial, ethical, and scientific concerns associated with testing on animals.

For this reason, thePETA International Science Consortium Ltd.initiated aprojectto devise a non-animal approach to assessing pulmonary effects of nanomaterials. Thereview by William Polk and coauthorsrecently published inParticle and Fibre Toxicologyis a part of this initiative.

First phase: workshop

The first phase of the project involved the organization of an internationalworkshopheld at the headquarters of the Environmental Protection Agency in Washington, D.C.

At the workshop, experts in the field of inhalation toxicology discussed the state-of-the-science of inhalation toxicity testing and the design of anin vitrosystem

At the workshop, experts in the field of inhalation toxicology discussed the state-of-the-science of inhalation toxicity testing and the design of anin vitrosystem predictive of the fibrotic potential of aerosolized MWCNTs.

The experts stressed that human-relevant dosimetry and lifecycle transformations of nanomaterials should be considered when exposing lung-relevant cells co-cultured at the air-liquid interface (ALI) to these materials.

The workshop proceedings, including recommendations on aerosol generation and exposure systems, characterization parameters, dose and dosimetry considerations, and relevant cell models and biomarkers, were published in three separate reports in peer-reviewed journals (here;hereandhere).

The publications from the workshop assess the state-of-the-science and provide specific details on what should be included in anin vitrosystem to assess the pulmonary toxicity of nanomaterials.

For instance, while Sharmaet al. describe the relevant cell types and biomarkers, Polket al. commingle the interdisciplinary concepts on the engineering side of the aerosol science with the complex biological aspects of the lung physiology, making it easier for researchers to choose the appropriate system based on their own needs.

Second phase: funding research groups

In the second ongoing phase of the project, the PETA International Science Consortium is funding three research groups to develop the aforementionedin vitrosystem.

In the second ongoing phase of the project, the PETA International Science Consortium is funding three research groups to develop the aforementionedin vitrosystem.

Dr. Barbara Rothen-Rutishauser of the Adolphe Merkle Institute at the University of Fribourg in Switzerland and Dr. Vicki Stone of the School of Life Sciences at Heriot-Watt University in Edinburgh, U.K., are jointly developing the system.

The consortium is also funding the design of a human lung-tissue model byMatTek Corporationthat will complement the work being done by Drs. Rothen-Rutishauser and Stone.

Third phase: further testing

In the third phase of the project, the system developed in the second phase will be tested in additional laboratories and using different nanomaterials. In the longer term, the system is intended to make up one part of a non-animal test battery, includingin silicoandin vitroassays that can be used in an integrated testing strategy.

It will provide comprehensive information on biological endpoints relevant to inhalation exposure to nanomaterials, which could be used in the hazard ranking of substances during the risk assessment process.

The PETA International Science Consortium Ltd.works to accelerate the development, validation, and global implementation of robust, human-relevant animal-free test methods. It was established in 2012 to coordinate the scientific and regulatory expertise of its international members.

For more information, please visitPISCLtd.org.ukandwww.PISCLtd.org.uk/nanoworkshop, or follow us on twitter@PISCLtd.