Toxicity of Soman after Repetitive Injection of Sublethal Doses in Guinea‐Pig and Mouse

Abstract

Injection of sublethal doses of soman in guinea-pig and mouse subcutaneously every 3.5,8, 12 or 24 hours led to cumulative LD50 doses which were markedly higher than the acute one. When animals were exposed every 24 hrs to half LD50 doses of soman, a majority of guinea-pigs but relatively few mice, survived a total exposure of 5-6 times the acute LD50 dose. Guinea-pig brain and diaphragm acetylcholinesterase activities declined steadily during the repeated soman exposure. Plasma cholinesterase activity was less than 10% 1 hr after soman injection, but was restored to 40-50% of control within 24 hrs. Liver aliesterase activity was not significantly inhibited by soman, whereas plasma aliesterase activity was 70% inhibited after 1 hr and restored to control level within 24 hrs. TOCP treatment of guinea-pig led to 3-fold increase in acute soman toxicity, and reduced their tolerance from more than 6LD50 to 2.5 LD50dose ofsoman. It is concluded that the recovery of plasma aliesterase and cholinesterase play an important part in the observed tolerance towards repeated soman treatment.

Reduction of Blood Cholinesterase Activities following Administration of Soman by Different Routes in Guinea‐pig

“…This is assumed to mean that soman is removed from the blood stream before it reaches its target organs, mainly by binding to plasma aliesterase (Sterri ef a/. 1981;Sterri 1981). The inhibition of erythrocyte acetylcholinesterase follows a biphasic curve, the second part of the curve is smaller (fig.…”

“…Rodents can tolerate repetitive exposure to the irreversible organophosphorus anticholinesterase soman, mainly because of rapid recovery of the enzyme aliesterase to which soman becomes bound (Sterri et a/. 1980(Sterri et a/. & 1981Sterri 1981).…”

“…1980(Sterri et a/. & 1981Sterri 1981). However, one could not exclude the possibility that other factors, such as storage of free soman in the organism and its subsequent detoxification by hydrolytic enzymes as originally proposed (Sterri et a/.…”