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The biochemical toxicology of 1,3-difluoro-2-propanol, the major ingredient of the pesticide Gliftor: The potential of 4-methylpyrazole as an antidote
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The biochemical toxicology of 1,3-difluoro-2-propanol, the major ingredient of the pesticide Gliftor: The potential of 4-methylpyrazole as an antidote

M.G. Feldwick, P.S. Noakes, U. Prause, R.J. Mead and P.J. Kostyniak
Journal of Biochemical and Molecular Toxicology, Vol.12(1), pp.41-52
1998
DOI: https://doi.org/10.1002/(SICI)1099-0461(1998)12:1<41::AID-JBT6>3.0.CO;2-P
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Abstract

Administration to rats of 1,3-difluoro-2-propanol (100 mg kg−1 body weight), the major ingredient of the pesticide gliftor, resulted in accumulation of citrate in the kidney after a 3 hour lag phase. 1,3-Difluro-2-propanol was found to be metabolized to 1,3-difluoroacetone and ultimately to the aconitate hydratase inhibitor (-) erythrofluorocitrate and free fluoride. The conversion of 1,3-difluoro-2-propanol to 1,3-difluoroacetone was found to be catalyzed by an NAD+-dependent alcohol dehydrogenase, while the defluorination was attributed to microsomal monooxygenase activity induced by phenobarbitone and inhibited by piperonyl butoxide. 4-Methylpyrazole was found to inhibit both of these processes in vitro and when administered (90 mg kg−1 body weight) to rats, 2 hours prior to 1,3-difluoro-2-propanol, eliminated signs of poisoning, prevented (-) erythrofluorocitrate synthesis, and markedly decreased citrate and fluoride accumulation in vivo. 4-Methylpyrazole also appeared to diminish (-) erythrofluorocitrate synthesis from fluoroacetate in vivo, and this was attributed to its capacity to inhibit malate dehydrogenase activity. The antidotal potential of 4-methylpyrazole and the potential for 1,3-difluoro-2-propanol to replace fluoroacetate (compound 1080) as a vertebrate pesticide is discussed.

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