Increasing Scientific Confidence in Reliable and Relevant Approaches for Regulatory Testing – A Respiratory Toxicity Case Study

June 2, 2022

Please join Dr. Amy Clippinger and Dr. Andreas Stucki as they share their experience with New Approach Methods and regulatory testing; walking us through their case study on Respiratory Toxicity. 

What you’ll learn: 

  • To gain confidence in new approach methodologies (NAMs) for predicting human health effects, it is essential to focus on the relevance of the test system to human biology. Direct comparison of NAM results to animal test results should be avoided in light of critical differences in respiratory physiology, anatomy, and biochemistry of rats when compared to humans that limit the ability of the rat to predict human responses.
  • We present the results of the INSPiRE project, which provide insights on how in vitro systems can be used to predict portal of entry effects on the human respiratory tract and inform regulatory decision-making.
  • The results help us to better understand the impact of the cell system used and the exposure scenario, as well as which biological endpoints are most informative.

Watch the Recording!


About our Speakers:

Dr. Amy Clippinger: Dr. Amy Clippinger is the President of PETA Science Consortium International e.V. She received her doctorate in Cellular and Molecular Biology and Genetics in 2009 from Drexel University College of Medicine and was a postdoctoral fellow in the Cancer Biology Department at the University of Pennsylvania from 2009 to 2012. In 2012, Dr. Clippinger joined the Science Consortium where she collaborates with regulatory agencies, industry, academia, and method developers to advance robust non-animal toxicity testing approaches. She is a member of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) that advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). She is a member of the Society of Toxicology (SOT), recipient of the SOT 2022 Enhancement of Animal Welfare Award, and Past President of the SOT In Vitro and Alternative Methods Specialty Section.

Dr. Andreas Stucki: 

Dr. Andreas Stucki is an adviser to PETA Science Consortium International e.V. He received his doctorate in biomedical sciences from the University of Bern, Switzerland. His doctoral research focused on the development and biological evaluation of a lung-on-a-chip – an advanced in vitro model of the human air-blood barrier. After his PhD, he worked on in vitro respiratory toxicology testing before returning to the University of Bern for his postdoctoral research. With several years of experience in organ-on-a-chip and pulmonary research, he advises the Science Consortium on inhalation toxicity testing. Dr Stucki is a full member of the Society of Toxicology (SOT) and the European Society of Toxicology In Vitro (ESTIV).

Abstract: As new approach methodologies (NAMs) are developed, there is a need for robust and efficient processes to establish scientific confidence in these approaches. To gain scientific confidence in NAMs, we can apply a framework that focuses on fitness for purpose, human biological relevance, and technical characterization. Using this framework, several critical differences in physiology, anatomy, and biochemistry between the rat and human respiratory tract become apparent and highlight the value of using human-relevant in vitro models to predict human responses. Because of these differences and the way they limit the ability of the rat to predict human effects, there has been a shift to develop and use human cell-based approaches to characterize potential portal-of-entry effects of inhaled substances. We describe the INSPiRE project, which assessed the value of in vitro models to predict the ability of chemicals to cause portal-of-entry effects on the human respiratory tract. To better understand the impact of experimental design, we assessed four chemicals from two distinct chemical classes in two different cell systems (BEAS-2B cells and MucilAirTM) using various exposure scenarios and biological endpoints. The results give important insights in how in vitro systems can be used to predict effects on the human respiratory tract and inform regulatory decision-making.

About ScitoVation: ScitoVation helps clients assess chemical compound safety using innovative science, next-generation technology, and professional expertise. ScitoVation is known for partnership, flexibility, and proven success in its work to develop safer and more effective pharmaceuticals, food ingredients, agricultural chemicals, commodity chemicals and consumer products. A spin-off of the former The CIIT and The Hammer Institutes for Chemical & Drug Safety Sciences, ScitoVation is an industry leader of New Approach Methods (NAMS) for chemical/drug discovery & development in the rapidly evolving global regulatory landscape.