The effect of carboxylesterase inhibition on interspecies differences in soman toxicity

Abstract

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 μg/kg (mouse), 116 μg/kg (rat), 32.3 μg/kg (guinea pig) and 22.8 μg/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 μg/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.