Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.
This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.
Analytical Toxicology Division, Medical Toxicology Branch, United States Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground, MD , USA.
Xinqi
X
Peng
Michael W
MW
Perkins
Jannitt
J
Simons
Alicia M
AM
Witriol
Ashley M
AM
Rodriguez
Brittany M
BM
Benjamin
Jennifer
J
Devorak
Alfred M
AM
Sciuto
D000110:Acetylcholinesterase / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D062025:Organophosphate Poisoning / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced; D011654:Pulmonary Edema / Q000139:chemically induced; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D066007:Toxicokinetics; D014132:Trachea / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014456:Ulcer / Q000209:etiology; D015431:Weight Loss / Q000187:drug effects
D000110:Acetylcholinesterase; D000336:Aerosols; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D009946:Organothiophosphorus Compounds; C009680:VX-agent
Chemical warfare nerve agents; VX; cholinesterases; inhalation exposure; respiratory toxicity