Inhalation toxicity of soman vapor in non-anesthetized rats: A preliminary assessment of inhaled bronchodilator or steroid therapy |
| |
| Authors: | Michael W Perkins Benjamin WongAshley Rodriguez Jennifer L DevorakDerron A Alves Gleeson MurphyAlfred M Sciuto |
| |
| Institution: | Analytical Toxicology Division, Medical Toxicology Branch, United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, United States |
| |
| 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 (250–300 g) to 520, 560, 600, 825 or 1410 mg × min/m3 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 593.1 mg × min/m3. All animals exposed to 825 and 1410 mg × min/m3 developed severe convulsions and died within 4–8 min 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 24 h. 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 600 mg × min/m3 of soman revealed prominent morphological changes including alveolar histiocytosis, hemorrhage and inflammation consisting of neutrophilic exudate. Exposure of animals to 600 mg × min/m3 of soman followed by treatment with two actuations for 10 s of Combivent (21 μg of ipratropium bromide and 120 μg of albuterol sulfate) and Symbicort (80 μg budesonide and 4.5 μg formoterol) by inhalation into a modified metered dose inhaler (MDI) 10 min 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. |
| |
| Keywords: | AChE acetylcholinesterase CWNA chemical warfare nerve agent BAL bronchoalveolar lavage BALC bronchoalveolar lavage cells BALF bronchoalveolar lavage fluid ATC acetylthiocholine iodide DFP diisopropyl fluorophosphate DTP 4 4&prime -dithidiopyridine 2-PAM 2-pralidoxime i m intramuscular i p intraperitoneal SLPM standard liters per minute s c subcutaneous GD soman PFH perfluorohexane ATCH acetylthiocholine iodide PBS phosphate buffered saline LCt50 lethal concentration measured in mg × min/m3 of a vapor exposure to cause death in 50% of the exposed population multiplied by the time the individual is exposed MDI metered dose inhaler MV minute volume |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
