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Published on: September 24, 2020
Acute respiratory toxicity following inhalation exposure to soman in guinea pigs
Michael W Perkins1, Zdenka Pierre, Peter Rezk
1Medical/Analytical Toxicology, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, USA.
Abstract:
Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m(3) concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m(3) soman survived, while animals exposed to 841, and 1121 mg/m(3) resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt(50) for soman determined by probit analysis was 827.2mg/m(3). A majority of the animals that died at 1121 mg/m(3) developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.
Insights
Exposure to the nerve agent soman caused significant lung injury and respiratory toxicity in guinea pigs. Higher concentrations led to decreased survival, seizures, and physiological damage, highlighting soman
Area of Science:
- Toxicology
- Pulmonary Medicine
- Chemical Warfare Agents
Background:
- Soman is a potent chemical warfare nerve agent.
- Inhalation exposure poses a significant risk for respiratory toxicity and lung injury.
- Understanding the toxicological effects of soman is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the respiratory toxicity and lung injury induced by soman inhalation in guinea pigs.
- To determine the lethal concentration (LCt50) of soman via microinstillation inhalation exposure.
- To characterize the physiological and biochemical changes associated with soman exposure.
Main Methods:
- Guinea pigs were exposed to varying concentrations of soman (280–1121 mg/m³) using a microinstillation inhalation technique.
- Survival rates, physiological parameters (pulse rate, oxygen saturation), and body weight were monitored.
- Bronchoalveolar lavage (BAL) fluid and blood were analyzed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, protein content, and cell counts.
- Lung and trachea tissue were assessed for edema using wet/dry weight ratios.
Main Results:
- Soman exposure resulted in a dose-dependent decrease in survival, with LCt50 determined to be 827.2 mg/m³.
- Higher soman concentrations induced seizures and rapid mortality.
- Significant dose-dependent inhibition of AChE and BChE activity was observed in BAL fluid and blood.
- Increased BAL fluid protein, cell death, edema, and alterations in lymphocyte and neutrophil counts indicated acute lung injury.
Conclusions:
- Microinstillation inhalation exposure to soman causes significant respiratory toxicity and acute lung injury in guinea pigs.
- The study quantifies the dose-dependent effects of soman on survival and physiological parameters.
- Findings underscore the severe pulmonary consequences of soman exposure and the need for rapid therapeutic interventions.
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