Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials.
The increasing use of multi-walled carbon nanotubes (MWCNTs) in consumer products and their potential to induce adverse lung effects following inhalation has lead to much interest in better understanding the hazard associated with these nanomaterials (NMs). While the current regulatory requirement for substances of concern, such as MWCNTs, in many jurisdictions is a 90-day rodent inhalation test, the monetary, ethical, and scientific concerns associated with this test led an international expert group to convene in Washington, DC, USA, to discuss alternative approaches to evaluate the inhalation toxicity of MWCNTs. Pulmonary fibrosis was identified as a key adverse outcome linked to MWCNT exposure, and recommendations were made on the design of an in vitro assay that is predictive of the fibrotic potential of MWCNTs. While fibrosis takes weeks or months to develop in vivo, an in vitro test system may more rapidly predict fibrogenic potential by monitoring pro-fibrotic mediators (e.g., cytokines and growth factors). Therefore, the workshop discussions focused on the necessary specifications related to the development and evaluation of such an in vitro 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 life cycle 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 alternative testing strategy to predict pulmonary toxicity and to generate data that will enable effective risk assessment of NMs.
PETA International Science Consortium Ltd., London, UK. AmyJC@PISCLtd.org.uk.
Amy J
AJ
Clippinger
University of Pisa, Pisa, Italy.
Arti
A
Ahluwalia
Contractor Supporting the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
David
D
Allen
North Carolina State University, Raleigh, NC, USA.
James C
JC
Bonner
NTP Interagency Center for the Evaluation of Alternative Toxicological Methods, Raleigh, NC, USA.
Warren
W
Casey
West Virginia University, Morgantown, WV, USA.
Vincent
V
Castranova
BASF Corporation, Florham Park, NJ, USA.
Raymond M
RM
David
Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON, Canada.
Sabina
S
Halappanavar
The Dow Chemical Company, Midland, MI, USA.
Jon A
JA
Hotchkiss
U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Annie M
AM
Jarabek
Evonik Industries AG, Hanau-Wolfgang, Germany.
Monika
M
Maier
Contractor Supporting the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Integrated Laboratory Systems, Inc., Research Triangle Park, NC, USA.
William
W
Polk
Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
Barbara
B
Rothen-Rutishauser
Department of Environmental Science, Baylor University, Waco, TX, USA.
Christie M
CM
Sayes
nanoRisk Analytics, LLC, Washington, MD, USA.
Phil
P
Sayre
PETA International Science Consortium Ltd., London, UK.
Monita
M
Sharma
Heriot-Watt University, Edinburgh, UK.
Vicki
V
Stone
D000336:Aerosols; D023401:Animal Use Alternatives; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004867:Equipment Design; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008954:Models, Biological; D049329:Nanostructures / Q000008:administration & dosage / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods*
D000336:Aerosols
In vitro testing strategies; Inhalation toxicity; MWCNTs; Multi-walled carbon nanotubes; Pulmonary fibrosis; Regulatory risk assessment