Development of a Model for Nerve Agent Inhalation in Conscious Rats
Abstract
This study characterizes the development of a head-out inhalation exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl fluorophosphate (DFP) induces classical cholinergic toxicity following inhalation exposure and was utilized to validate the effectiveness of this newly designed inhalation exposure system. A saturator cell apparatus was used to generate DFP vapor at 9750, 10950, 12200, 14625 and 19500mg min/m(expn 3) which was carried by filtered nitrogen into a glass mixing tube, where it combined with ambient air before being introduced to the custom-made glass exposure chamber. Male Sprague-Dawley rats (250 300 g) were restrained in individual head-out plethysmography chambers, which acquired respiratory parameters before, during and after agent exposure. All animals were acclimated to the exposure system prior to exposure to reduce novel environment-induced stress. The LCt50, as determined by probit analysis, was 12 014mg min/m3. Weight loss in exposed animals was dose-dependent and ranged from 8 to 28% of their body weight 24 h after exposure. Increased salivation, lacrimation, urination, defecation (SLUD) and mild muscular fasciculation were observed in all DFP-exposed animals during and immediately following exposure. In all exposed animals, DFP vapor produced significant inhibition of acetylcholinesterase (AChE) activity in cardiac blood, bronchoalveolar lavage fluid (BALF), whole brain and lung tissue as well as alterations in tidal volume and minute volume. These studies have provided valuable information leading to the initiation of studies evaluating inhalational toxicity and treatments following exposure to the more lethal and potent chemical warfare nerve agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 23, 2013
- Accession Number
- ADA589575
Entities
People
- Alfred M. Sciuto
- Ashley M. Rodriguez
- Benjamin Wong
- Gleeson Murphy
- Mariton D. Santos
- Michael W. Perkins
Organizations
- United States Army Medical Research Institute of Chemical Defense