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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| 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-Difluoro-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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| Authors | M G Feldwick, P S Noakes, U Prause, R J Mead, P J Kostyniak |
| Journal | Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 12 Issue 1 Pg. 41-52 ( 1998) ISSN: 1095-6670 [Print] United States |
| PMID | 9414486 (Publication Type: Journal Article) |
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