A method for generating toxic vapors of soman: toxicity of soman by inhalation in rats.
A method for administration of highly toxic chemicals by inhalation was developed. The model has three features of special interest: (1) a diffusion cell for producing a constant gas concentration, if necessary for several hours and days, (2) a small rapidly equilibrated inhalation chamber (1100 ml), and (3) complete isolation of the toxic chemicals from the atmosphere. The LCt50 of the anticholinesterase soman [o-(1,2,2 trimethylpropyl)-methyl-phosphonofluoridate] was 400 mg min/m3, registered 24 hr after the end of exposure. The lethal concentration X time of soman was 520 +/- 60 mg min/m3 when exposing the animals until death in the inhalation chamber. The exposure was less than 30 min and the concentration of soman was 21 mg/m3. The inhibition of acetylcholinesterase, cholinesterase, and carboxylesterase activities in different tissues was analyzed to study the possible barrier mechanisms that might exist in the body to soman. There was a large inhibition of the carboxylesterase and cholinesterase activities in bronchi and lungs as well as in blood. Carboxylesterases were important as detoxifying enzymes, as shown by 70% enhancement in toxicity of soman following sc pretreatment with TOCP (tri-ortho-cresyl-phosphate), a carboxylesterase inhibitor.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001273:Atmosphere Exposure Chambers; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000633:toxicity; D002802:Cholinesterases / Q000378:metabolism; D004347:Drug Interactions; D007279:Injections, Subcutaneous; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000008:administration & dosage* / Q000633:toxicity; D014317:Tritolyl Phosphates / Q000008:administration & dosage / Q000633:toxicity; D014835:Volatilization
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; D012999:Soman; D002265:Carboxylic Ester Hydrolases; D000110:Acetylcholinesterase; D002802:Cholinesterases; C025541:tri-o-cresyl phosphate