Fluoroacetate lethal dose

All the available evidence indicates that fluoroacetate is probably excreted in the urine as such. Tolerance to increasing doses (below the lethal dose) has been detected in the mouse and rat.1 The resistance appears to be of a temporary nature. 

Buffa and Peters3 then demonstrated the accumulation of citrate in vivo. The rat was injected with a lethal dose of sodium fluoroacetate and the following results obtained ... 

These materials, as well as more recent poisons like zinc phosphide and fluoroacetic acid, work as acute rodenticides and can be effective when a rodent consumes a lethal quantity of poison in a single dose in its food or drink. Unfortunately, animals often consume less than a lethal dose, which produces side effects which the animals associate with the bait. The result is that they become "bait shy" and are likely to be wary of the same poison bait a second time. 

Toxicity. Fluoroacetic acid and sodium fluoroacetate are extremely toxic to animals and man the minimum lethal dose is about 5 mg/kg. Toxic effects are delayed for several hours following ingestion or absorption through the skin. The maximum permissible atmospheric concentration is 50 pg/m. ... 

CAUTION Monofluoroacetates are intermediates for some literature syntheses of fluorinated heterocycles. Fluoroacetic acid and its derivatives, such as fluoroacetamide and ethyl fluoroacetate, and compounds which could be metabolically converted into fluoroacetate, such as 2-fluoroethanol, are extremely toxic and have no antidote. A lethal dose of the acid in humans may be as low as 100 mg. They should be avoided if at all possible, but if their use is essential, they must only be used under rigorous control. 

The quantitative and qualitative response among different species to fluoro-acetic acid is unique [115]. Lethal doses range from 50 [xg/kg in dogs to 50 mg/kg in some monkeys, while some data indicate that man is intermediate. The mouse responds like the monkey, while the cat and rabbit are nearly as sensitive as the dog. Fluoroacetate is biochemically converted into fluorocitrate, a lethal synthesis, which results in the inhibition of a step in the tricarboxylic acid cycle. Various species may die from central nervous system stimulation, others from cardiac irregularities, and others from a combination of central and cardiac effects. A simple explanation for these variations is not available. 

Methyl fluoroacetate, a mobile liquid, has an extremely faint odour. Animals did not usually exhibit any symptoms while being exposed to lethal concentrations of this vapour, and no obvious effects were noted until some 30-60 min. (depending upon the concentration) after exposure. Violent convulsions then took place and death usually followed within a few hours. For rabbits and guinea-pigs the lethal concentration (l.c. 50) for a 10 min. exposure was of the order of 0-1 mg./l. Mice were rather more resistant. Intravenous injection produced symptoms similar to those displayed after exposure to the vapour. Even with large doses a delayed action was observed. The l.d. 50 for rabbits (intravenously) was found to be about 0-25 mg./kg. 

Among the most deadly of simple compounds is sodium fluoroacetate. The LD50 (the dose lethal for 50% of animals receiving it) is only 0.2 mg/kg for rats, over tenfold less than that of the nerve poison diisopropylphosphofluoridate (Chapter 12).a b Popular, but controversial, as the rodent poison "1080," fluoroacetate is also found in the leaves of several poisonous plants in Africa, Australia, and South America. Surprisingly, difluoroacetate HCF2-COO is nontoxic and biochemical studies reveal that monofluoroacetate has no toxic effect on cells until it is converted metabolically in a "lethal synthesis" to 2R,3R-2-fluorocitrate, which is a competitive inhibitor of aconitase (aconitate hydratase, Eq. 13-17).b This fact was difficult to understand since citrate formed by the reaction of fluorooxalo-acetate and acetyl-CoA has only weak inhibitory activity toward the same enzyme. Yet, it is the fluorocitrate formed from fluorooxaloacetate that contains a fluorine atom at a site that is attacked by aconitase in the citric acid cycle. 

As with all chemicals, the dose makes the poison. The chlorine-containing insecticide dichlorodiphenyltrichloroethane (DDT) is highly effective in killing disease-ridden mosquitoes, ticks, and fleas, but it is virtually nontoxic to mammals. The fluorine-containing pesticide 1080, or fluoroacetic add (FCH2CO2H), is highly toxic and often lethal to all mammals. The industrial and combustion by-product dioxin is highly toxic to some animals but not to others in humans, dioxin causes the skin disease chloracne. 

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