Sodium fluoroacetate
Sodium fluoroacetate is the organofluorine chemical compound with the formula FCH2CO2Na. This colourless salt has a taste similar to that of sodium chloride and is used as a metabolic poison. Sodium fluoroacetate does not occur naturally, and can only be produced synthetically. A similar compound, potassium fluoroacetate, occurs naturally as an anti-herbivore metabolite in various plants, and can also be produced synthetically. Both are derivatives of fluoroacetic acid, a carboxylic acid. The more common fluorinated acetic acid and its derivatives are far less toxic.
History and production
The effectiveness of sodium fluoroacetate as a rodenticide was reported in 1942. The name "1080" refers to the catalogue number of the poison, which became its brand name.The salt is synthesized by treating sodium chloroacetate with potassium fluoride.
Occurrence
The related compound potassium fluoroacetate occurs naturally 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.Potassium fluoroacetate occurrence in ''Gastrolobium'' species
Gastrolobium is a genus of flowering plants in the family Fabaceae. There are over 100 species in this genus, and all but two are native to the south west region of Western Australia, where they are known as "poison peas". Gastrolobium growing in south western Australia are unique in their ability to concentrate fluoroacetate from low fluorine soils. Brush-tailed 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 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.Following bushfires in north-western Queensland cattlemen have to move livestock before the poisonous Gastrolobium grandiflorum emerges from the ashes.
Toxicology
Sodium fluoroacetate is toxic to all 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 similar to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate disrupts the citric acid cycle by combining with coenzyme A to form fluoroacetyl CoA, which reacts with citrate synthase to produce fluorocitrate which 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.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 secondary lung infections.Symptoms in domestic animals vary: dogs tend to show nervous system signs such as convulsions, vocalization, and uncontrollable running, whilst 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 — in particular, the brain, gonads, heart, lungs, and fetus. 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 Dr. Goncharov and co-workers resulted in development of a successful therapeutic complex, containing a phenothiazine compound, a dioic acid compound, and a pharmaceutically acceptable carrier. In another aspect the pharmaceutical composition can include a phenothiazine compound, a nitroester compound, ethanol, and a pharmaceutically acceptable carrier.
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.
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.
Pesticide use
Sodium fluoroacetate is used as a pesticide, especially for mammalian pest species. Farmers and graziers use the poison to protect pastures and crops from various herbivorous mammals. In New Zealand and Australia it is also used to control 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 and safety". 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, compared to the predatory and competitive effects of those introduced species being managed using 1080.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 48,000 hectares 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 a more humane alternative to 1080, due in part to its ability to kill faster, as well as having an antidote, which 1080 does not. However, as of 2018, 1080 was still being used in attempts to reduce feral cat populations.
New Zealand
Worldwide, New Zealand is the largest user of sodium fluoroacetate. This high usage is attributable to the fact that, apart from two species of bat, New Zealand has no native land mammals, and some of those that have been introduced have had devastating effects on vegetation and native species.1080 is used to control possums, rats, stoats, deer, and rabbits. The largest users, despite some vehement opposition, are OSPRI New Zealand and the Department of Conservation.
United States
Sodium fluoroacetate is used in the United States to kill coyotes. Prior to 1972 when the EPA cancelled all uses, sodium fluoroacetate was used much more widely as a cheap predacide and rodenticide; in 1985, the restricted-use "toxic collar" approval was finalized.Other countries
1080 is used as a rodenticide in Mexico, Japan, Korea, and Israel.Environmental impacts
Water
Because 1080 is highly water-soluble, it will be dispersed and diluted in the environment by rain, stream water and ground water. Sodium fluoroacetate at the concentrations found in the environment after standard baiting operations will break down in natural water containing living organisms, such as aquatic plants or micro-organisms. Water-monitoring surveys, conducted during the 1990s, have confirmed that significant contamination of waterways following aerial application of 1080 bait is possible, but unlikely. Research by NIWA showed that 1080 deliberately placed in small streams for testing was undetectable after 8 hours, as it washed downstream.In New Zealand, surface water is routinely monitored after aerial application of 1080, and water samples are collected immediately after application, when there is the highest possibility of detecting contamination. Of 2442 water samples tested in New Zealand between 1990 and 2010, following aerial 1080 operations: 96.5% had no detectable 1080 at all and, of all the samples, only six were equal to, or above the Ministry of Health level for drinking water, and none of these came from drinking water supplies. Of 592 samples taken from human or stock drinking supplies, only four contained detectable 1080 residues at 0.1ppb and 0.2 ppb – all well below the Ministry of Health level of 2 ppb.
In an experiment funded by the Animal Health Board and conducted by NIWA simulating the effects of rainfall on 1080 on a steep soil-covered hillside a few meters from a stream, it was found that 99.9% of the water containing 1080 leached straight into the soil and did not flow over the ground to the stream as had been expected. The experiment also measured contamination of soil water, which was described as the water carried through the soil underground at short horizontal distances, downhill towards the stream. The experiment did not measure contamination of deeper soil and ground water immediately beneath the site of application.