Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats

Abstract

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.

The Respiratory Toxicity of Chemical Warfare Agents

“…Airway resistance was significantly increased at 20 min and 6 h post-exposure at all VX concentrations tested and at the two highest doses, 343 and 514 mg × min/m 3 , 24 h post-exposure (Peng et al, 2014). In this work, VX aerosol was administered at 514 mg/min/m 3 and produced significant increases in BALF protein concentrations at 6 and 24 h after exposure, suggesting the prevalence of pulmonary edema.…”

“…This delay could be due to the time it takes for extravasation of inflammatory cells, such as neutrophils and macrophages (Peng et al, 2014). Lung and tracheal lesions were generally less severe in the 3-and 6-h VX post-exposure groups than in the 24-h VX post-exposure groups consistent with its delayed effects.…”

“…Lung and tracheal lesions were generally less severe in the 3-and 6-h VX post-exposure groups than in the 24-h VX post-exposure groups consistent with its delayed effects. Peng et al (2014) also showed that at high levels of inhaled aerosolized VX, exposure produced prominent alterations in airway and lung pathology at 24 h in the rat. The tracheal lesions in these animals showed evidence of ulceration accompanied by neutrophilic inflammation and necrotic epithelial lining (necrotic membrane).…”

“…In the aerosolized VX rat exposure model of Peng et al (2014), blood AChE activity was decreased 41% at 343 and 52% at 514 mg × min/m 3 24 h post-exposure. Similar to G agents, V agents likewise inhibit blood and lung tissue AChE activity.…”

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

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