Inhalation toxicity of soman vapor in non-anesthetized rats: A preliminary assessment of inhaled bronchodilator or steroid therapy

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• 作者：Michael W. Perkins ; Benjamin Wong ; Ashley Rodriguez ; Jennifer L. Devorak ; Derron A. Alves ; Gleeson Murphy ; Alfred M. Sciuto
• 关键词：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 conce
• 刊名：Chemico-Biological Interactions
• 出版年：5 December, 2013
• 年：2013
• 卷：206
• 期：3
• 页码：452-461
• 全文大小：1704 K

文摘

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 脳 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 脳 min/m³. All animals exposed to 825 and 1410 mg 脳 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 脳 min/m³ of soman revealed prominent morphological changes including alveolar histiocytosis, hemorrhage and inflammation consisting of neutrophilic exudate. Exposure of animals to 600 mg 脳 min/m³ of soman followed by treatment with two actuations for 10 s of Combivent (21 渭g of ipratropium bromide and 120 渭g of albuterol sulfate) and Symbicort (80 渭g budesonide and 4.5 渭g 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.