The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

Abstract

ABSTRACTThis study determines soman toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent studies. Male African green monkeys were surgically implanted with telemetry devices to monitor electroencephalographic (EEG) and electrocardiographic (ECG) activity. Blood was taken at various times to measure whole blood acetylcholinesterase (AChE) activity and cardiac troponin I (cTnI). Blood AChE activity relative to baseline was 0.0% to 2.5% 6 h after soman exposure and recovered to 31.9% to 72.0% by 30 days after exposure. The 6 h postexposure cTnI levels varied from 0.64 to 6.55 ng/mL, suggesting cardiac damage. Soman was prepared in saline to a concentration of 100 μg/mL. Using an up-down design for small samples, subjects were exposed to 5.01, 6.31, or 7.94 μg/kg soman IM. The first subject was given 5.01 μg/kg soman IM and survived. Three subjects received 6.31 μg/kg soman IM and survived. Three subjects received 7.94 μg/kg soman IM and died within 25 min, 26 min, or 6 h. In all subjects, toxic signs of muscle fasciculation, tremors, chewing, and profuse salivation developed within 2 to 7 min. Tonic-clonic motor convulsions and EEG seizure began between 2 and 18 min after tremor onset. The 48 h IM LD50 of soman in saline in the African green monkey was calculated to be 7.15 μg/kg. The signs and speed of soman intoxication in African green monkeys were consistent with those described in rhesus, cynomolguscynomolgus, and baboons.