The effect of carboxylesterase inhibition on interspecies differences in soman toxicity.
Subcutaneous administration of 2 mg/kg cresylbenzodioxaphosphorin oxide (CBDP) produced complete inhibition of carboxylesterase activity in plasma and lung of mice, rats, guinea pigs and rabbits, without inhibition of acetylcholinesterase activity in either brain or diaphragm. This CBDP treatment also reduced the subcutaneous soman LD50 in these species by 48-90% in comparison to the soman LD50 in control animals. The interspecies differences in the soman LD50 values that were seen in control animals were absent in CBDP-treated animals. The soman LD50 values in control animals were 125 micrograms/kg (mouse), 116 micrograms/kg (rat), 32.3 micrograms/kg (guinea pig) and 22.8 micrograms/kg (rabbit), whereas the soman LD50 values in CBDP-treated animals from these species were clustered in a narrow dose range (11.8-15.6 micrograms/kg) and were not significantly different. This suggests that the amount of CBDP-sensitive carboxylesterase available for detoxification of soman in each species may be an important determinant of interspecies differences in soman toxicity.
Maxwell
D M
DM
United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Brecht
K M
KM
O'Neill
B L
BL
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*; D013045:Species Specificity
D009943:Organophosphorus Compounds; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D012999:Soman; D002265:Carboxylic Ester Hydrolases