Emerging chemical threats of interest to the chemical biological defense (CBD) program have the potential to cause systemic and/or localized target organ toxicities in response to acute exposure. While traditional in vivo models have been useful to characterize these threats in the past, new methodologies that utilize human tissue and replicate mechanistic functionality of organ systems have the potential to substantially reduce the animal testing burden of the CBD program, reduce costs, streamline testing needs and deliver more rapid characterizations of new threats with human relevant detail. This research opportunity will develop and/or optimize existing organoid systems to characterize human toxicity. Of primary concern is respiratory toxicity, where replication of lung physiology can be difficult in vitro and exposure to aerosolized compounds can be cumbersome. However, development and/or optimization of other organoid models that replicate cardiac, hepatic, vascular and central nervous system acute toxicity will also be considered.