Toxicity and Treatment of Russian V-Agent (VR) Intoxication in Guinea Pigs

摘要

VR (O-isobutyl-S-2- (DIETHYLAMINO)ETHYLmethyl phosphonothioate) is a structural isomer of VX and is thought to be the principal V-agent found in Russian chemical weapons. We evaluated the toxicity (24 hr LD50) of VR and determined the effectiveness of oxime and atropine (ATR) treatment and pyridostigmine (PB) pretreatment in guinea pigs. Lethality dose-response curves for VR were generated in untreated animals and in animals treated with atropine (ATR) and oxime with or without PB pretreatment. PB was injected i.m. 30 min prior to s.c. VR challenge. One min after VR the animals were treated i.m. with ATR (16 mg/kg) plus an equimolar dose of either 2-PAM (25 mg/kg) or HI-6 (55 mg/kg). Mortality was assessed at 24 hours. The LD50 of VR was 11.3 g/kg. Treatment with ATR plus 2-PAM or HI-6 resulted in protective ratios (PR) of 6.5 and 43.9, respectively. In PB-pretreated animals, the PRs were 7.1 and 28.7, respectively. The results indicate that 1) VR is a highly toxic organophosphorus agent, 2) it can be effectively treated with oximes and atropine, 3) HI-6 is significantly more effective than 2-PAM, and 4) PB pretreatment affords no further enhancement to the efficacy of atropine and oximes. When compared with previous findings in guinea pigs, ATR + 2-PAM is significantly less effective against VR than against VX. This observation may necessitate a careful examination of the best oxime to use as an antidote against V-agents, particularly.