TOXICITY OF THE COMBINED NERVE AGENTS GB/GF IN MICE - EFFICACY OF ATROPINE AND VARIOUS OXIMES AS ANTIDOTES

The toxicity of a combination of isopropyl methylphosphonofluoridate (sarin; GB) and cyclohexyl methylphosphonofluoridate (GF) and the efficacy of various oxime reactivators in combination with atropine against the combined GB/GF challenge were evaluated in mice. The 24-h s.c. LD(50) of the GB/GF combination was 1.15 mu mol/ kg (1.10-1.21; 95% confidence limits). Mice administered GB/GF displayed typical signs of nerve agent poisoning such as tremors and convulsions, with death most likely due to anoxia subsequent to respiratory arrest. The GB/GF LD(50) value was comparable to the s.c. LD(50) of 1.35 and 1.21 mu mol/kg for GF and GB in mice, respectively. Combining the two nerve agents did not result in potentiation of the toxicity. In combination with atropine sulfate (17.4 mg/kg, i.p.), which alone did not reduce mortality, the oximes tested, 2-PAM, obidoxime and HI-6, were all effective when administered 5 min before 3xLD(50) dose of GB/GF with 24-h ED(50) values of 102.5, 18.22 and 1.96 mu mol/kg, respectively. Use of the GB/GF combination does not appear to confer any unique toxicity profile and appears to be easily treated with the standard therapy of a cholinolytic and oxime.