- Exposure to in vitro/ex vivo pulmonary models used to evaluation complex human pulmonary adverse events
How 3D test systems differ and can offer unique functional endpoints of the respiratory tract
- Different methodologies and the benefits of standardization
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About our Speaker:
Dr. Holger Behrsing:
Dr. Behrsing is the Director of Respiratory Toxicology at the Institute for In Vitro Sciences, Inc. in Gaithersburg, Maryland. He obtained his Ph.D. in Pharmacology and Toxicology at UC Davis, and has worked with various in vitro models for over 25 years. In addition to directing toxicology testing for the Respiratory Toxicology program at IIVS, his efforts are focused on optimizing human relevant pulmonary models and developing non-animal methodology to detect key events associated with lung disease progression. He has presented as an invited speaker at numerous venues including the National Academy of Sciences, and recently served as Councilor for the Inhalation and Respiratory Specialty Section of the Society of Toxicology.
With the increase in chemicals and materials that may cause pulmonary toxicity through inhalation, a need for cost-effective toxicity testing of new chemicals continues to grow. The 2007 report, “Toxicity Testing in the 21st Century – a Vision and a Strategy”, The National Academies Press, Washington D.C., describes a path forward for toxicology and envisions the use of more predictive human-relevant in vitro models for estimating human health risks. The ethical considerations, poor predictive value of animal testing, and vast numbers of chemicals/materials requiring evaluation further drives this argument for the application of in vitro models to assess pulmonary toxicity.
In vitro models utilizing human-derived cell lines and primary cells provide endpoints that reflect cytotoxic, genotoxic, and other relevant adverse events following exposure to toxicants. The emergence of multicellular three-dimensional (3D) tissue culture systems of the respiratory tract provide toxicologists with test platforms that more accurately model the complex processes observed in native tissues. Human donor-tissue derived reconstructed human airways and precision-cut lung slices provide conventional toxicity endpoints as well as complex, relevant events following chemical exposure. The varied cell types, physiological structure, relevant toxicokinetics, and other properties of these models allow additional evaluations ranging from chronic-exposure related events (e.g. persistent inflammation, goblet cell hyperplasia, etc.) to functional outcomes (e.g. ciliary beating assays) that can reflect serious health complications that may lead to chronic obstructive pulmonary disease. This presentation will provide an overview of in vitro/ex vivo pulmonary models used to evaluate complex human pulmonary adverse events, and how standardization of methodologies will help promote their acceptance for use in a regulatory setting.
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.