Repurposing thiosulfate for chlorine gas exposure

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Chlorine gas is a chemical warfare agent and toxic industrial chemical (TIC) that produces respiratory failure and edema due to chemical burns of the airway and alveolar epithelium. Chemical warfare agents are an important threat to military personnel and civilians. The broad long-term goal of this project is to develop medical countermeasures against chemical agents that produce a lung toxidrome. Chlorine gas and other TICs can elevate oxidative damage leading to cellular injury and inflammation. Cellular injury from chlorine gas exposure is believed to result from its rapid hydration that generates hypochlorous acid (bleach) and hydrochloric acid. Sodium thiosulfate is an FDA approved treatment for cyanide poisoning, but also is used as an effective dechlorinating agent. We hypothesize that the dechlorinating and antioxidant actions of sodium thiosulfate will target hypochlorous acid and hypochloric acid generated during chlorine exposure along with other oxidants that are produced during oxidative stress and inflammation associated with a chlorine gas exposure. We will test our hypothesis with two specific aims. The first aim will develop a swine model of chlorine gas-induced acute lung injury model. The second aim will optimize dose, dose regimen, and rescue window of sodium thiosulfate in this swine model. These data will be used as proof of principle studies to support regulatory approval for the use of sodium thiosulfate as a medical countermeasure for chlorine gas lung injury under the FDA animal rule. If successful this FDA approved product could be rapidly developed as a medical countermeasure against chlorine gas injury.