Fluoroacetate toxicity

The mechanism of fluoroacetate toxicity in mammals has been extensively examined and was originally thought to involve simply initial synthesis of fluorocitrate that inhibits aconitase and thereby the functioning of the TCA cycle (Peters 1952). Walsh (1982) has... 

Mead, R.J., D.L. Moulden, and L.E. Twigg. 1985a. Significance of sulfhydryl compounds in the manifestation of fluoroacetate toxicity to the rat, brush-tailed possum, woylie and western grey kangaroo. Austral. Jour. Biol. Sci. 38 139-149. 

Gribble GW (1973) Fluoroacetate toxicity. Journal of Chemical Education 50 460—462. 

Fluoroacetic acid [144-49-OJ, FCH2COOH, is noted for its high, toxicity to animals, including humans. It is sold in the form of its sodium salt as a rodenticide and general mammalian pest control agent. The acid has mp, 33°C bp, 165°C heat of combustion, —715.8 kJ/mol( —171.08 kcal/mol) (1) enthalpy of vaporization, 83.89 kJ /mol (20.05 kcal/mol) (2). Some thermodynamic and transport properties of its aqueous solutions have been pubHshed (3), as has the molecular stmcture of the acid as deterrnined by microwave spectroscopy (4). Although first prepared in 1896 (5), its unusual toxicity was not pubhshed until 50 years later (6). The acid is the toxic constituent of a South African plant Dichapetalum i mosum better known as gifirlaar (7). At least 24 other poisonous plant species are known to contain it (8). 

Toxicity. Sodium fluoroacetate is one of the most effective all-purpose rodenticides known (18). It is highly toxic to all species of rats tested and can be used either in water solution or in bait preparations. Its absence of objectionable taste and odor and its delayed effects lead to its excellent acceptance by rodents. It is nonvolatile, chemically stable, and not toxic or irritating to the unbroken skin of workers. Rats do not appear to develop any significant tolerance to this compound from nonlethal doses. However, it is extremely dangerous to humans, to common household pets, and to farm animals, and should only be used by experienced personnel. The rodent carcasses should be collected and destroyed since they remain poisonous for a long period of time to any animal that eats them. 

Difluoroacetic acid is much less toxic than fluoroacetic acid (LD q = 180 mg/kg mouse iv) (41). It is available in research quantities for about 5/g... 

Health and Safety Factors. Unlike fluoroacetic acid, trifluoroacetic acid presents no unusual toxicity problems. However, owing to its strong acidity, its vapors can be irritating to tissue, and the Hquid acid can cause deep bums if allowed to contact the skin. The acid can be safely stored in containers made of glass or common corrosion-resistant alloys and metals such as stainless steel or alurninum. 

Sodium fluoroacetate (mono) [62-74-8] M 100.0, m 200-205 (dec). A free flowing white TOXIC powder which is purified by dissolving in ca 4 parts of H2O and the pH is checked. If it is alkaline, add a few drops of FCH2CO2H to make the solution just acidic. Evaporate (fumehood) on a steam bath until crystals start to separate, cool and filter the solid off. More solid can be obtained by adding EtOH to the filtrate. Dry at 100 in vacuum. [7 Chem Soc 1778 1948.]... 

There are several examples in which metabolites that toxify the organism responsible for their synthesis are produced. The classic example is fluoroacetate (Peters 1952), which enters the TCA cycle and is thereby converted into fluorocitrate. This effectively inhibits aconitase—the enzyme involved in the next metabolic step—so that cell metabolism itself is inhibited with the resulting death of the cell. Walsh (1982) has extensively reinvestigated the problan and revealed both the complexity of the mechanism of inhibition and the stereospecihcity of the formation of fluorocitrate from fluoroacetate (p. 239). It should be noted, however, that bacteria able to degrade fluoroacetate to fluoride exist so that some organisms have developed the capability for overcoming this toxicity (Meyer et al. 1990). 

Compared to conventional NMR isotopes (13C, 15N, 2H), 19F-labels cannot be readily placed into proteins in a versatile manner by any biosynthetic expression strategy. Certain auxotrophic bacterial strains can be used to incorporate iso-steric 19F-labelled amino acids (e.g. Fluoro-Phe, Fluoro-Trp, Fluoro-Leu, Fluoro-Ile see Fig. 3), but yields tend to be low. Many other fluoro-organics are toxic if they get converted into fluoroacetic acid, which blocks the enzyme aconitase in the citric... 

Other applications dealt with the development of a luciferin ester substrate to measure the luciferase activity in living cells [141], the detection of toxic compounds such as sodium azide, fluoroacetic acid, and antibiotics [142], the development of a biosensor for the determination of bioavailable mercury [143], the use of eukaryotic luciferases as bacterial markers with different colors of luminescence [144], the determination of complement-mediated killing of bacteria [145], and the development of a bioassay for the determination of HIV type 1 virus and HIV-1 Tat protein activity, valuable also for analysis of HlV-inhibi-tory agents [146],... 

Moran, S. 1991. Toxicity of sodium fluoroacetate and zinc phosphide wheat grain baits to Microtus guentheri and Meriones tristrami. Bull. OEPP/EPPO Bull. 21 73-80. 

Ethyl, n-propyl and isopropyl fluoroacetates were also readily prepared by heating the corresponding esters of chloroacetic acid with potassium fluoride in the rotating autoclave. Their toxicities were similar to that of methyl fluoroacetate. (It... 

These findings were in accordance with expectation, and it was now obvious that the toxicity was bound up with the FCHjCO group, whereas the FCO group was ineffective. Farther confirmation of this point was provided by the observation that ethyl fluoroformate, FCOOEt, was non-toxic. Fluoro-aoetic anhydride was slightly more toxic (by inhalation) than methyl fluoroacetate. 

Fluoroacetamide, FCHaCONHa, and many new substituted amides of the type FCHaCONHI2, were all convulsant poisons with delayed action. The magnitude of their toxicities suggested that they were hydrolysed in the animal body to fluoroacetic acid. In short, the effective part of the molecule was the FCHsCO grouping.3 Swarts4 was unable to obtain fluoroethyl... 

Ftuoropyruvic acid, FCH,COCOOH, is less toxic than expected and does not seem to be metabolized in vivo via fluoroacetic acid Avi-Dor and Mayer, Bioehem. J. 1966, 63, 613. 

In view of the fact that fluoroethyl alcohol produced a toxic effect comparable with that of fluoroacetic acid, it seemed worth... 

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