Determination of LCt50s in Anesthetized Rats Exposed to Aerosolized Nerve Agents
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
Pagination or Media Count:
Nerve agents pose a threat to the respiratory tract with exposure that could result in acute compromised lung performance and death. The determination of toxicity by inhalation is important for the rational development of timely therapeutic countermeasures. This study was designed to deliver aerosolized dilute nerve agents in a dose-response manner to investigate the extent of lethality of nerve agents soman, sarin, VX and VR. Male rats 240-270 g were anesthetized intramuscularly with 10 mgkg xylazine and 90 mgkg ketamine. Following anesthesia, rats were intubated with a glass endotracheal tube ET and placed in a glove box. The ET was connected to a closed circuit nebulizer system Aeroneb, Aerogen, Inc. that delivered a particle size of 2.0 micro m and was in series between the ventilator and the ET. Nerve agents were delivered by a small animal ventilator set for a volume of 2.5 ml x 60-80 breathsmin. VX or VR were nebulized and delivered in concentrations ranging from 6.25-800 micro gkg over a 10-min exposure time period. Sarin GB or soman GD, 6.5-1250 micro gkg, were delivered in a similar manner. Lethality by inhalation occurred either during the 1 0-min exposure period or less than 15 min after the cessation of exposure. Survivors were euthanized at 24 h postexposure. LCt50 estimates 95 confidence intervals Cis were obtained from the sequential stage-wise experiments using the probit analysis. Probit analysis revealed that the LD50 for VX was 110.7 micro gkg CI 73.5-166.7, VR 64.2 micro gkg CI 42.1-97.8 soman GD, 1 67 micro gkg CI 90-31 0, and sarin GB, 154 micro g kg CI 98-242, respectively. Although VR is a structural isomer of VX, the compounds appear to be markedly different in terms of toxicity when delivered by aerosol.
- Weapons Effects (Biological)
- Physical Chemistry
- Chemical, Biological and Radiological Warfare