title: Acute respiratory toxicity following inhalation exposure to soman in guinea pigs.
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.
authors.affiliation: Medical/Analytical Toxicology, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pierre
authors.forename: Peter
authors.initials: P
authors.lastname: Rezk
authors.forename: Praveena
authors.initials: P
authors.lastname: Sabnekar
authors.forename: Kareem
authors.initials: K
authors.lastname: Kabra
authors.forename: Soma
authors.initials: S
authors.lastname: Chanda
authors.forename: Samuel
authors.initials: S
authors.lastname: Oguntayo
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D055371:Acute Lung Injury / Q000139:chemically induced*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000097:blood; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D010100:Oxygen / Q000097:blood; D012999:Soman / Q000633:toxicity*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002619:Chemical Warfare Agents; D012999:Soman; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D010100:Oxygen