1. Inhalation toxicity of soman vapor in non-anesthetized rats: a preliminary assessment of inhaled bronchodilator or steroid therapy.
- Author
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Perkins MW, Wong B, Rodriguez A, Devorak JL, Alves DA, Murphy G, and Sciuto AM
- Subjects
- Acetylcholinesterase blood, Acetylcholinesterase metabolism, Acute Lung Injury pathology, Acute Lung Injury physiopathology, Administration, Inhalation, Albuterol administration & dosage, Albuterol, Ipratropium Drug Combination, Animals, Brain drug effects, Brain enzymology, Budesonide administration & dosage, Budesonide, Formoterol Fumarate Drug Combination, Disease Models, Animal, Drug Combinations, Ethanolamines administration & dosage, Inhalation Exposure, Ipratropium administration & dosage, Lung drug effects, Lung enzymology, Lung pathology, Male, Rats, Rats, Sprague-Dawley, Soman administration & dosage, Acute Lung Injury drug therapy, Adrenal Cortex Hormones administration & dosage, Bronchodilator Agents administration & dosage, Chemical Warfare Agents toxicity, Soman toxicity
- Abstract
Respiratory toxicity, injury and treatment following vapor inhalational exposure to the chemical warfare nerve agent (CWNA) soman (GD) were examined in non-anesthetized rats. This study exposed male Sprague-Dawley rats (250-300g) to 520, 560, 600, 825 or 1410mg×min/m(3) of soman in a customized head-out inhalation system. Signs of CWNA-induced cholinergic crises were observed in all soman-exposed animals. The LCt50 of vaporized soman as determined by probit analysis was 593.1mg×min/m(3). All animals exposed to 825 and 1410mg×min/m(3) developed severe convulsions and died within 4-8min post-exposure. Edema measured by wet/dry weight ratio of the left lung lobe increased in a dose-dependent manner in all soman-exposed animals. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase (AChE) activities were inhibited dose-dependently in soman-exposed groups at 24h. A significant increase in total BAL protein was observed in soman-exposed animals at all doses. AChE activity was inhibited in lung and whole brain tissues in all soman-exposed animals. Histopathological analysis of the lungs of animals exposed to 600mg×min/m(3) of soman revealed prominent morphological changes including alveolar histiocytosis, hemorrhage and inflammation consisting of neutrophilic exudate. Exposure of animals to 600mg×min/m(3) of soman followed by treatment with two actuations for 10s of Combivent (21μg of ipratropium bromide and 120μg of albuterol sulfate) and Symbicort (80μg budesonide and 4.5μg formoterol) by inhalation into a modified metered dose inhaler (MDI) 10min post-exposure resulted in increased minute volume, but did not decrease mortality. These results indicate that inhalation exposure to soman vapor causes acute respiratory toxicity and injury in untreated, un-anesthetized rats and that inhalation treatment with Combivent or Symbicort did improve the respiratory outcomes, but did not influence lethality., (Published by Elsevier Ireland Ltd.)
- Published
- 2013
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