Development of a Guinea Pig Model for Low-Dose Chronic Exposure to Organophosphorus Nerve Agents
Abstract
An animal dosing model and related maximum tolerated dose (MTD) were developed for repeated exposures in guinea pigs to three organophosphorus chemical warfare nerve agents (CWNA). Male animals were injected subcutaneously with sarin (GB), soman (GD) or VX once a day (Monday through Friday) for 2-, 4-, or 13-weeks. An initial 13-week study for each CWNA employed doses of vehicle (normal saline), 0.2, 0.4, 0.6, and 0.8 x the previously established acute LD50. A 2-week and 4-week exposure were also performed for each agent at doses less than the 13-week MTD to verify lack of toxicity. Animals dosed daily for 13 weeks with 0.4 x LD50 of GB or GD or with 0.2 x LD50 of VX did not display signs of acute cholinergic toxicity. In animals dosed daily for either 2- or 4-weeks, the MTDs were 0.4 x the acute LD50 for all 3 CWNA. There were no differences among these groups and their respective vehicle controls for weight gains, body temperature, complete blood cell counts, blood chemistries, nor by histopathology. At the MTD in all groups, red blood cell cholinesterase activity one hour alter the last exposure was inhibited up to 90% compared with controls.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA418295
Entities
People
- Chessley R. Atchison
- Robert E. Sheridan
- Steven M. Duniho
- Tsung-ming A. Shih
Organizations
- United States Army Medical Research Institute of Chemical Defense