Sodium fluoroacetate
Sodium fluoroacetate, also known by its trade name as a mammal poison compound 1080, is an organofluorine chemical compound with the chemical formula. It is the sodium salt of fluoroacetic acid, and contains sodium cations and fluoroacetate anions . A colourless salt with a taste similar to table salt, it is used under the name "1080" to kill small and medium mammals, including rodents. New Zealand has no endemic ground-based mammals and is the world's biggest user of 1080, particularly to kill introduced brushtail possums, often with aerial distribution of bait pellets.
Natural occurrence
Fluoroacetate occurs naturally in at least 40 plants in Australia, Brazil, and Africa. It is one of only five known organofluorine-containing natural products.Fluoroacetate occurrence in ''Gastrolobium'' species
Gastrolobium is a genus of flowering plants in the family Fabaceae. This genus consists of over 100 species, and all but two are native to the southwest region of Western Australia, where they are known as "poison peas". Gastrolobium growing in southwestern Australia concentrate fluoroacetate from low-fluoride soils. The brushtail possums, bush rats, and western grey kangaroos native to this region are capable of safely eating plants containing fluoroacetate, but livestock and introduced species from elsewhere in Australia, and even the eastern populations of the brushtail possum and bush rat, are highly susceptible to the poison, as are species introduced from outside Australia, such as the red fox. The fact that many Gastrolobium species also have high secondary toxicity to non-native carnivores is thought to have limited the ability of cats to establish populations in locations where the plants form a major part of the understorey vegetation.The presence of Gastrolobium species in Western Australia has often forced farmers to 'scalp' their land, that is, remove the top soil and any poison pea seed which it may contain, and replace it with a new poison pea-free top soil sourced from elsewhere in which to sow crops. Similarly, after bushfires in north-western Queensland, cattlemen have to move livestock before the poisonous Gastrolobium grandiflorum emerges from the ashes.
The related compound occurs naturally as a defensive compound in at least 40 plant species in Australia, New Zealand, Brazil, and Africa. It was first identified in Dichapetalum cymosum, commonly known as gifblaar or poison leaf, by Marais in 1944. As early as 1904, colonists in Sierra Leone used extracts of Chailletia toxicaria, which also contains fluoroacetic acid or its salts, to poison rats. Several native Australian plant genera contain the toxin, including Gastrolobium, Gompholobium, Oxylobium, Nemcia, and Acacia. New Zealand's native Puha contains 1080 in very low concentrations.
Structure and synthesis
confirms that solid sodium fluoroacetate is a salt with intact fluoroacetate anions interacting with Na+ via a network of Na-O bonds.Sodium fluoroacetate can be produced by the reaction of fluoroacetic acid and a basic sodium salt, such as sodium carbonate and sodium hydroxide. However, it is industrially produced by treating sodium chloroacetate with potassium fluoride.
Toxicology
Sodium fluoroacetate is toxic to most obligate aerobic organisms, and highly toxic to mammals and insects. The oral dose of sodium fluoroacetate sufficient to be lethal in humans is 2–10 mg/kg.The toxicity varies with species. The New Zealand Food Safety Authority established lethal doses for a number of species. Dogs, cats, and pigs appear to be most susceptible to poisoning.
The enzyme fluoroacetate dehalogenase has been discovered in a soil bacterium, which can detoxify fluoroacetate in the surrounding medium.
Mechanism of action
Fluoroacetate is structurally similar to acetate, which has a pivotal role in cellular metabolism. This similarity is the basis of the toxicity of fluoroacetate. Two related mechanisms for its toxicity have been discussed, with both beginning with the conversion of fluoroacetate to 2-fluorocitrate. 2-Fluorocitrate arises by condensation with oxaloacetate with fluoroacetyl coenzyme A, catalyzed by citrate synthase. Fluorocitrate binds very tightly to aconitase, thereby halting the citric acid cycle. This inhibition results in an accumulation of citrate in the blood. Citrate and fluorocitrate are allosteric inhibitors of phosphofructokinase-1, a key enzyme in glycolysis. When PFK-1 is inhibited, cells are no longer able to metabolize carbohydrates, depriving them of energy. Alternatively, fluorocitrate interferes with citrate transport in the mitochondria.Symptoms
In humans, the symptoms of poisoning normally appear between 30 minutes and three hours after exposure. Initial symptoms typically include nausea, vomiting, and abdominal pain; sweating, confusion, and agitation follow. In significant poisoning, cardiac abnormalities including tachycardia or bradycardia, hypotension, and ECG changes develop. Neurological effects include muscle twitching and seizures; consciousness becomes progressively impaired after a few hours leading to coma. Death is normally due to ventricular arrhythmias, progressive hypotension unresponsive to treatment, and aspiration pneumonia.Symptoms in domestic animals vary: dogs tend to show nervous system signs such as convulsions, vocalization, and uncontrollable running, while large herbivores such as cattle and sheep more predominantly show cardiac signs.
Sub-lethal doses of sodium fluoroacetate may cause damage to tissues with high energy needs, especially the brain, gonads, heart, lungs. Fetuses are also highly susceptible. Sub-lethal doses are typically completely metabolised and excreted within four days.
Treatment
Effective antidotes are unknown. Research in monkeys has shown that the use of glyceryl monoacetate can prevent problems if given after ingestion of sodium fluoroacetate, and this therapy has been tested in domestic animals with some positive results. In theory, glyceryl monoacetate supplies acetate ions to allow continuation of cellular respiration which the sodium fluoroacetate had disrupted.Experiments of N. V. Goncharov and co-workers resulted in development of two varieties of potentially successful treatments. One combines a phenothiazine compound and a dioic acid compound. The other includes a phenothiazine compound, a nitroester compound, and ethanol.
In clinical cases, use of muscle relaxants, anti-convulsants, mechanical ventilation, and other supportive measures may all be required. Few animals or people have been treated successfully after significant sodium fluoroacetate ingestions.
Tolerance
Animals can tolerate varying amounts of fluoroacetate. Mammalian carnivores and rodents tend to be the least tolerant, followed by mammalian herbivores, reptiles and amphibians, and finally fish. A lower metabolic rate seems to help with poison tolerance in general.Many animals native to Australia seem to have developed additional tolerance to fluoroacetate beyond what general trends predict. Herbivore, seed-eating birds are exposed to very high amounts of natural fluoroacetate with no ill effect. Emus living in areas where fluoroacetate-producing plants grow can tolerate 150 times the concentration compared to emus living outside. Some native insects tolerate fluoroacetate and repurpose it as a defense chemical against carnivores.
Fluoacetate tolerance can be acquired in animals, though it is not fully clear how. In one study, sheep gut bacteria were genetically engineered to contain the fluoroacetate dehalogenase enzyme that inactivates sodium fluoroacetate. The bacteria were administered to sheep, who then showed reduced signs of toxicity after sodium fluoroacetate ingestion. A strain of natural bacterium that does the same was isolated from cattle rumen in 2012.
Pesticide use
History and production
The effectiveness of sodium fluoroacetate as a rodenticide was reported in 1942. The salt is synthesized by treating sodium chloroacetate with potassium fluoride. Both sodium and potassium salts are derivatives of fluoroacetic acid. The name "1080" refers to the catalogue number of the poison, which became its brand name.Sodium fluoroacetate is used as a pesticide, especially for mammalian pest species. The agricultural industry uses 1080 to kill herbivorous mammals to stop them from eating pasture plants and crops. In New Zealand and Australia it is also used to control introduced, invasive non-native mammals that prey on or compete with native wildlife and vegetation.
Australia
In Australia, sodium fluoroacetate was first used in rabbit control programmes in the early 1950s, where it is regarded as having "a long history of proven effectiveness". It is seen as a critical component of the integrated pest-control programmes for rabbits, foxes, wild dogs, and feral pigs. Since 1994, broad-scale fox control using 1080 meat baits in Western Australia has significantly improved the population numbers of several native species and led, for the first time, to three species of mammals being taken off the state's endangered species list. In Australia, minor direct mortality of native animal populations from 1080 baits is regarded as acceptable by the regulatory bodies, compared to the predatory and competitive effects of those introduced species being managed using 1080. 1080 is also used by the agricultural industry to destroy populations of Dingos, Australia's only pre-colonial mammalian apex predator, a practice condemned by numerous conservation groups and wildlife experts around the continent due to its far-reaching destabilisation of the natural balance of the ecosystem.Western Shield is a project to boost populations of endangered mammals in south-west Australia conducted by the Department of Environment and Conservation of Western Australia. The project entails distributing fluoroacetate-baited meat from the air to kill predators. Wild dogs and foxes will readily eat the baited meat. Cats pose a greater difficulty as they are generally not interested in scavenging. However, an Australian RSPCA-commissioned study criticized 1080, calling it an inhumane killer. Some Western Australian herbivores have, by natural selection, developed partial immunity to the effects of fluoroacetate, so that its use as a poison may reduce collateral damage to some native herbivores specific to that area.
In 2011, over 3,750 toxic baits containing 3 ml of 1080 were laid across 520 properties over between the Tasmanian settlements of Southport and Hobart as part of an ongoing attempt at the world's biggest invasive animal eradication operation – the eradication of red foxes from the island state. The baits were spread at the rate of one per 10 hectares and were buried, to mitigate the risk to non-target wildlife species like Tasmanian devils. Native animals are also targeted with 1080. During May 2005 up to 200,000 Bennett's wallabies on King Island were intentionally killed in one of the largest coordinated 1080 poisonings seen in Tasmania.
In 2016, PAPP became available for use, which the RSPCA has endorsed as an alternative to 1080, due in part to its ability to kill faster and cause less suffering, as well as having an antidote, which 1080 does not. However, as of 2023, 1080 was still being used in attempts to reduce feral cat populations.