Non-Commercial Models for the Evaluation of Inhalable Materials In Vitro
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Inhaled chemical exposures are a ubiquitous aspect of daily life around the world. While there are thousands of inhalable chemicals and materials in use, there are few, or often no, data available to evaluate potential hazards posed by most of these agents. Traditional approaches to inhalation toxicity testing have relied on in vivo animal studies; however, the cost and duration of these studies makes their use to inform decision making for the large number of data poor chemicals, and an exponentially larger number of mixtures and repeated exposure scenarios, intractable. Further, the extrapolation from exposure effects in animals to human health outcomes is limited by concerns regarding the comparability of humans and surrogate animal species, especially in the context of inhalation exposures. As the portal of entry for inhaled toxicants, the respiratory tract is often subject to their adverse effects. Differentiated primary cell-based multi-cellular in vitro models of the human respiratory tract recapitulate key features of in vivo human biology and provide novel opportunities to increase throughput, decrease cost, and improve the human relevance of inhaled materials toxicity testing. While convenient, the cost and accessibility of commercially produced in vitro models can limit key aspects of study design including the range of chemicals tested, the range of doses and timepoints, and the endpoints evaluated. This presentation will discuss key aspects of primary human bronchial epithelial cell cultures and how these in vivo relevant in vitro models can be generated in-house and applied to broaden the scope and cost efficiency of inhaled materials testing in vitro. This abstract does not reflect EPA policy.