With the expected increase in novel chemicals, a greater demand for cost-effective toxicity testing of new chemicals follows suit. 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. Aside from the ethical considerations and often poor predictive value of animal testing, the vast numbers of chemicals requiring evaluation will require a new strategy that many researchers believe depends upon the use of competent human-relevant, in vitro/ex vivo test systems applied in a pragmatic manner. 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. More recently, the emergence of modern 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 that involve multiple cells types. Human donor-tissue derived spheroids/organoids, reconstructed human airways, and precision-cut lung slices provide conventional toxicity endpoints as well as more complex, relevant events that follow chemical exposure. The complement of multiple cell types, physiological structure, relevant toxicokinetics, and other properties of these models allow additional evaluations, including chronic-exposure related (e.g. inflammation), functional (e.g. ciliary beating assays), and other endpoints (e.g. Goblet cell hyperplasia) that can reflect more serious health complications that may lead to chronic obstructive pulmonary disease. This presentation will provide an overview of in vitro/ex vivo pulmonary models and how they can be incorporated into a screening/testing strategy for chemicals that can include more complex human pulmonary adverse events that are evaluable in modern 3D systems.

Advanced in vitro test systems provide human-relevant results to support regulatory decision-making

254th National Meeting (2017)

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