INFLUENCE OF 2--O-CRESYL--4 H-1-3-2-BENZODIOXA-PHOSPHORIN-2-OXIDE (CBDP) ON ORGANOPHOSPHATE POISONING AND ITS THERAPY

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 42  (3) , 207-216
Abstract
The aim of the experiments was to obtain more information on the toxicity of organophopshates and protection against them. Pretreatment of mice with CBDP [2-/o-cresyl/-4H-1:3:2-benzodioxa-phosphorin-2-oxide] increased the s.c. toxicity of soman 19.1-fold, and its i.p. toxicity 17.8-fold. The protective effect of atropine and the oximes HS-3 [N,N''-oxydimethylene-bis/pyridinium-2,4-aldoxime-dichloride], HS-6 [N,N''-oxydimethylene-bis/pyridinium-2-aldoxime-3-carboxamido/-dichloride] and HI-6 [N,N''-oxydimethylene-bis/pyridinium-2-aldoxime-4-carboxamido/-dichloride] in soman poisoning was much greater in CBDP-pretreated than in control animals. Atropine + HI-6 raised the s.c. LD50 of soman in the CBDP pretreated animals from 6.8 .mu.g/kg to 166 .mu.g/kg ([protective index] PI = 24.3), but in control animals the i.p. LD50 was only raised from 370 .mu.g/kg to 608 .mu.g/kg (PI = 0.6). CBDP inhibited blood and brain acetylcholinesterase [AChE] activity, but had no effect on aliesterase (AE) activity in plasma, liver and brain of mice in vivo. CBDP increased s.c. toxicities of sarin 11-fold, of tabun 5-fold and of VX 0.24-fold. The protective index of atropine + HS-3 in sarin poisoning, as in the case of soman poisoning, was much higher in CBDP pretreated than in control animals (20.1 : 13.6), only slightly higher in tabun poisoning (4.3 : 3.4) and in the case of VX poisoning lower in CBDP pretreated than in control animals (32 : 47). CBDP potentiates soman, sarin and tabun toxicities evidently by blocking their binding to non-specific sites in body.