Phosgene oxime: a highly toxic urticant and emerging chemical threat

Abstract

Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as potential chemical weapons. In addition, their accidental release can lead to chemical emergencies and mass casualties. CX, an urticant, or nettle agent, grouped with vesicating agents, causes instant pain, injury and systemic effects, which can lead to mortality. With faster cutaneous penetration, corrosive properties, and more potent toxicity compared to other vesicating agents, CX causes instantaneous and severe tissue damage. CX, a potential chemical terrorism threat agent, could therefore be weaponized with other chemical warfare agents to enhance their harmful effects. CX is the least studied vesicant and its acute and long-term toxic effects as well as its mechanism of action are largely unknown. This has hampered the identification of therapeutic targets and the development of effective medical countermeasures. There are only protective measures, decontamination, and supportive treatments available for reducing the toxic effects from CX exposure. This review summarizes CX toxicity, its known mechanism of action, and our current studies exploring the role of mast cell activation and associated signaling pathways in CX cutaneous exposure under the National Institutes of Health Countermeasures Against Chemical Threats program. Potential treatment options and the development of effective targeted countermeasures against CX-induced morbidity and mortality is also discussed.

Keywords:

• Phosgene oxime
• urticant
• vesicating agent
• toxicity
• molecular mechanisms
• inflammation
• mast cells
• medical countermeasures

Acknowledgements

The authors would like to thank Advaita Singh for help in editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Countermeasures Against Chemical Threats (CounterACT) Program, Office of the Director National Institutes of Health (OD) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [Grant Numbers R21AR073544 and U01AR075470].