The biochemical toxicology of 1,3-difluoro-2-propanol, the major ingredient of the pesticide Gliftor: The potential of 4-methylpyrazole as an antidote
Feldwick, M.G., Noakes, P.S., Prause, U., Mead, R.J. and Kostyniak, P.J. (1998) The biochemical toxicology of 1,3-difluoro-2-propanol, the major ingredient of the pesticide Gliftor: The potential of 4-methylpyrazole as an antidote. Journal of Biochemical and Molecular Toxicology, 12 (1). pp. 41-52.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Biological Sciences and Biotechnology|
|Publisher:||John Wiley and Sons Inc.|
|Copyright:||© 1997 John Wiley & Sons, Inc.|
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