Sodium monofluoroacetate (SMFA) occurs naturally in plants native to Brazil, Australia, and South and West Africa, in the gifblaar (Dichapetalum cymosum).11 The highest concentration (8.0 mg/g) is found in the seeds of a South African plant, Dichapetalum braunii.11 In the 1940s, SMFA was released as a rodenticide (CAS No. 62-74-8) and assigned the compound number 1080, which was registered as its trade name. Fluoroacetamide, a similar pesticide, is known as Compound 1081. These compounds are used as poisons against most mammals and some amphibians.23 Both products were banned in the United States in 1972, except in the form of collars intended to protect sheep and cattle from coyotes. Collars embedded with SMFA are placed around the neck of livestock, the typical point of attack for coyotes.
Sodium monofluoroacetate is used extensively in New Zealand and Australia to control the possum population and other animal species considered pests that have no natural predators. Its continued use is extremely controversial, but, following a recent review of the ramifications of the use of the compound, the government of New Zealand has retained both the aerosolized and collar applications.
Sodium monofluoroacetate is an odorless and tasteless white powder with the consistency of flour. When it is dissolved in water, it is said to have a vinegar-like taste. Sodium monofluoroacetate and fluoroacetamide (CAS No. 640-19-7) are well absorbed by the oral and inhalational routes.10,11,12,24 Detailed toxicokinetic data are lacking in humans, but in sheep, up to 33% can be excreted unchanged in the urine over 48 hours. Glucuronide and glutathione conjugates have also been isolated.11 Substantial defluorination is not thought to occur in vivo. The serum half-life is estimated to be 6.6 to 13.3 hours in sheep.10 Sodium monofluoroacetate has an LD50 of 0.07 mg/kg in dogs.17 The oral dose thought to be lethal to humans is 2 to 10 mg/kg.3
Sodium monofluoroacetate, a structural analog of acetic acid (Fig. 110–1), is an irreversible inhibitor of the tricarboxylic acid cycle (Fig. 12-3). Monofluoroacetic acid enters the mitochondria, where it is converted to monofluoroacetyl-coenzyme A (CoA) by acetate thiokinase. Once inside the mitochondria, citrate synthase joins the monofluoroacetyl-CoA complex with oxaloacetate to form fluorocitrate. Fluorocitrate then covalently binds aconitase, preventing the enzyme from any further interaction in the tricarboxylic acid cycle.15 Thus, fluorocitrate acts as a "suicide inhibitor" of aconitase, producing a biochemical dead end. The presence of fluorocitrate and the subsequent increase in citrate, which chelates divalent cations, causes hypocalcemia. The toxicity caused by fluorocitrate results from the increase in substrate prior to inhibition of aconitase and the depletion of substrate after the step catalyzed by aconitase.
Structural similarities among acetyl-CoA, sodium monofluoroacetate, and fluoroacetamide.
This inhibition of aconitase impairs energy production, leading ...