The Toxicity of Inhaled Sulphur Mustard
Final rept. 18 Feb 2009-29 Sep 2012
MINISTRY OF DEFENCE LONDON (UNITED KINGDOM)
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The overall objectives of the study were to understand the mechanism of action of sulfur mustard HD on the lung, and ultimately design therapeutic interventions to preserve pulmonary function and life. Under the previous contract HDTRA 1-07-C-0027 a small proof of principle study investigated the toxicity of inhaled HD. Injury development was monitored in an anesthetized large white pig for 6 hours post exposure and identified dose dependent changes in injury development. The first year of this contract W81XWH-09-C-0083 was a continuation of the study and extended the model to 12 hours. A reproducible model, representative of human exposure, has been established. Exposure to 100 g.kg-1 inhaled HD resulted in a significant decrease in oxygenation from 6 to 12 hours post exposure. Pathological examination revealed mucus plugs, areas of edema, inflammatory cell infiltration and necrosis of the tracheal epithelium. The data are consistent with clinical descriptions reported following human exposure to HD Pechura and Rall., 1993 Hefazi et al., 2005 Balali-Mood Hefazi 2006. The final phase of the programme was to investigate an appropriate treatment strategy against inhaled HD-induced lung injury in the established model. The thiol compound, N-acetyl-L-cysteine NAC - Mucomyst was chosen due to its anti-oxidant and mucolytic effects, administered via the inhaled route. NAC had been shown to present potential therapeutic benefit against HD-induced lung injury in a small animal model Anderson D et al 2000. In our model results indicate physiological benefit following inhaled NAC therapy further studies are warranted to look at NAC in combination with other beneficial therapies.
- Inorganic Chemistry
- Chemical, Biological and Radiological Warfare