Survivors of soman poisoning: recovery of the soman LD50 to control value in the presence of extensive acetylcholinesterase inhibition

Abstract

Initially, mice were pretreated with atropine (17.4 mg/kg; IP) and the oxime reactivator HI-6 (50 mg/kg; IP) 5 min prior to an injection of soman (287 μg/kg, SC); approximately 2.1 × LD₅₀ dose). More than 95% of the mice survived this dose of soman with atropine and HI-6 pretreatment. In these survivors of soman poisoning the return of the soman LD₅₀ value to control value (124 μg/kg, SC) was determined at various times after the initial soman exposure. Mice which survived exposure to a lethal dose of soman by pretreatment with atropine and HI-6 were sensitized to the lethal effects of soman upon re-exposure. The SC soman LD₅₀ at 4 h, after surviving the initial soman exposure, was 20 μg/kg. The normal soman LD₅₀ (as evidenced by a LD₅₀ value which was not significantly different from the control value) returned within 4 days, at which time there was still extensive acetylcholinesterase inhibition in all brain regions (striatum, pons-medulla, cerebellum, hypothalamus, hippocampus), diaphragm and erythrocytes. Serum carboxylesterase recovered to control levels within 48 h, whereas liver carboxylesterase activity was not inhibited following the initial soman exposure. The results demonstrate that there is an excess of acetylcholinesterase which is required for normal response in the toxicological sense.