Toxicity of soman after repetitive injection of sublethal doses in guinea-pig and mouse.

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 6 lD50 to 2.5 LD50 dose of soman. It is included that the recovery of plasma aliesterase and cholinesterase play an important part in the observed tolerance towards repeated soman treatment.

Reference values for erythrocyte acetylcholinesterase and plasma cholinesterase activities in children, implications for organophosphate intoxication.

Acetylcholinesterase and cholinesterase activity was measured in the blood of both healthy children 0-12 years of age and adults by a recently developed radiochemical method. Children less than 4 months of age were found to have lower levels for these enzymes than adults. Above this age, however, similar values were obtained for children and adults. A case report of an organophosphate intoxication is presented and is discussed in the light of our results.

Toxicity of soman after repetitive injection of sublethal doses in rat.

Injection of sublethal doses of soman in rat intraperitoneally or subcutaneously every 4, 8, 12 or 24 hours led to chronic LD50 doses which were markedly higher than the acute one. When rats were exposed every 24 hrs to half LD50 doses of soman, several of the animals did not show symptoms of soman poisoning and survived a total exposure of 4-7 times the acute LD50 dose. Brain and diaphragm acetylcholinesterase activities declined steadily during the chronic soman exposure. The so-called external acetylcholinesterase activity of the diaphragm was inhibited to a slightly less degree than the total acetylcholinesterase of the same tissue. The ability of the liver to hydrolyze soman was similar in rats which survived several 24 hr doses and untreated rats.

Effect of toxogonin and P2S on the toxicity of carbamates and organophosphorus compounds.

Toxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos-methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5-3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals.