Development of a Guinea pig model for low-dose, long-term exposure to organophosphorus nerve agents.

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.

Control of nerve agent-induced seizures is critical for neuroprotection and survival.

This study evaluated the potency and rapidity of some anticholinergics (atropine, biperiden, and trihexyphenidyl) and benzodiazepines (diazepam and midazolam) as an anticonvulsant treatment against seizures induced by six nerve agents (tabun, sarin, soman, cyclosarin, VR, and VX) and summarized the relationship between anticonvulsant activity and nerve agent-induced lethality and neuropathology. Guinea pigs, previously implanted with cortical electrodes for EEG recording, were pretreated with pyridostigmine bromide (0.026 mg/kg im) 30 min prior to challenge with 2x LD50 dose (sc) of a given nerve agent; in a separate experiment, animals were challenged with 5x LD50 sc of soman.

Acute changes in lung histopathology and bronchoalveolar lavage parameters in mice exposed to the choking agent gas phosgene.

Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonary edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveolar lavage fluid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to filtered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes.