Cresylbenzodioxaphosphorin oxide pretreatment alters soman-induced toxicity and inhibition of tissue cholinesterase activity of the rat

Abstract

The toxicity of soman was investigated in the rat with and without pretreatment with Cresylbenzodioxa-phosphorin oxide (CBDP). Without pretreatment, the 24-h LD 50 for soman was 118.2 μg/kg s.c., and soman inhibited Carboxylesterase (CaE) activity in plasma (ED 50 of 55 μg/kg) and cholinesterase (ChE) activity in brain regions (ED 50 values of 65–105 μg/kg) in a dose-related manner. With pretreatment, the 24-h LD 50 for soman was reduced by approximately 6-fold and 8-fold (by 1.0 mg/kg and 16.0 mg/kg of CBDP, respectively), and the ED 50 values for soman-induced inhibition of ChE activity in brain regions were reduced by approximately 10-fold (by 1.0 mg/kg of CBDP). The dose-dependent severity of soman intoxication varied widely in rats treated with soman alone but not in CBDP-pretreated rats, and the ED 50 for the occurrence of signs of soman intoxication was reduced approximately 7-fold following CBDP (1.0 mg/kg) pretreatment. These data support the hypothesis that CBDP pretreatment effectively blocks tissue CaE sites which serve to detoxify soman, thus potentiating both the soman-induced inhibition of ChE in the CNS and the lethality of soman.