International Programme on Chemical Safety
Poisons Information Monograph 494
Chemical
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8.4 Other biomedical (diagnostic) investigations and their interpretation |
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10.2 Life supportive procedures and symptomatic/specific treatment |
Sodium fluoroacetate
Fluoroacetic acid derivative
2-Fluoroacetic acid
Acide-monofluoracetique
Acido monofluoroacetico
Compound 1080
Cymonic acid
FAA
Fluoroacetate
Fluoracetato de sodium
Fluoroacetic acid sodium salt
Fluoroacetic acid (DOT)
Fluoroethanoic acid
Gifblaar poison
MFA
Monofluorazijnzuur
Monofluoressigsaure
Monofluoroacetate
Monofluoroacetic acid
Sodium fluoroacetate
Sodium monofluoroacetate
Sodium perfluoroacetate
UN2642 (DOT)
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Fluoroacetate : |
144-49-0 |
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Sodium fluoroacetate : |
62-74-8 |
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Fluoroacetate : |
RTECS |
AH5950000 |
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Sodium fluoroacetate: |
RTECS |
AH9100000 |
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UN |
2629 |
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EU EINECS/ELINCS |
200-548-2 |
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EC |
607-082-00-2 |
1080 gel
1080 paste
1080 solution
Nissol
Tenate
Tenate 1080
Sodium fluoroacetate acts by inhibiting energy production in most cells of the body. An indirect effect of the energy blockade is a depletion of available calcium, which also plays a role in clinical manifestations of fluoroacetate toxicity.
The main target organs affected are the central nervous, respiratory and cardiovascular system. This normally induces metabolic derangement that includes alteration in transaminase, calcium and glucose levels apart from acidosis and renal failure.
There may be a latent period of up to 6 hours or more during which minor symptoms are exhibited, including vomiting, tingling of nose and numbness of face. Serious symptoms may be broadly divided into neurological and cardiac effects. CNS effects include tremulousness, hallucinations, convulsions, and respiratory depression. Cardiac effects comprise arrhythmias, ventricular fibrillation, and cardiac arrest.
Clinical outcome seems to be either death or complete recovery, although some evidence points to long-term cardiac damage.
The occurrence of serious symptoms depends mainly on the dose, however symptomology varies markedly between species. Carnivores such as dogs appear to be more susceptible to CNS effects, while herbivores show predominantly cardiac effects which evoke less prominent symptoms. Omnivores such as humans show mixed symptomology.
Diagnosis is usually made on the basis of verified exposure, clinical signs, necropsy findings and chemical analysis. Samples for analysis should include suspected baits, vomitus, stomach contents, liver and kidney.
Elevated citric acid levels in kidney and serum is indicative of fluoroacetate (or fluorocitrate) poisoning when correlated with clinical history. Differential diagnosis must be made amongst compounds such as strychnine, chlorinated hydrocarbons, plant alkaloids and lead. Fluoroacetate convulsions cannot be induced by noise or touch, and the time of onset for symptoms is longer than with strychnine. Certain fluorinated ethanes are known to form fluoroacetate upon inhalation, and such cases should be treated as fluoroacetate intoxications.
Induction of emesis is contraindicated (due to potential arrhythmias and convulsions). Refer promptly for medical attention. Treatment is symptomatic and supportive.
Wash skin with copious amounts of water for 10-15 minutes. Skin contact can contribute to overall exposure.
Rinse eyes with copious amounts of water for 10-15 min, and seek specialist attention.
If inhalation is suspected, provide rest and fresh air, artificial respiration if indicated. Seek medical attention.
Synthetic
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Structural formula |
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Molecular structure: |
C2H2FO2.Na |
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Relative molecular mass of sodium salt : |
100.02 |
White powder
Fine white hygroscopic powder.
The commercial product is often dyed black with 0.5% nigrosine.
Odourless, virtually tasteless, although dilute solutions taste like vinegar. (Hayes 1991)
Saturation vapor concentration: nearly 0 mg/m3
Solubility (at 25 C) in
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water |
111 g/dL at 25C |
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methanol |
5 g/dL |
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ethanol |
1.4 g/dL |
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acetone |
0.04 g/dL |
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Stability |
Chemically stable due to the strong C-F bond. Stable up to 100C under normal storage conditions. The aqueous solution is expected to be stable at any pH. (WHO 1975) |
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Decomposition |
Decomposes below the 200C melting point. (IPCS 1996) |
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Vapour pressure |
Non-volatile |
Sodium fluoroacetate is not combustible. In a fire, it gives off irritating or toxic fumes including CO2, CO, and hydroflouric acid (20% by weight).
Control of rodents and vertebrate pests. Sodium fluoroacetate is used in the USA and UK to control rodents in areas of restricted access, such as ships, sewers and warehouses. Coyotes are controlled by the use of fluoroacetate-impregnated carcasses or collars on livestock. In Australia and New Zealand vertebrate pests such as rabbits, wallabies, goats, wild pigs, deer and opossums are controlled with the use of baits based on apple, carrot or grain. Aerial sowing is used to control large or remote areas. (ACGIH 1991), (WHO 1975)
Concentrated 20% w/v stock solution is available for incorporation into apple paste, carrot or cereal-based baits. 0.08% w/v is commonly used in New Zealand. (Livingstone 1994)
In the United Kingdom fluoroacetate is formulated as a 5% solid concentrate and a 0.375% bait for dilution to 0.25% with water.
Exposure to stock solution during formulation and dermal/respiratory exposure during paste/paste application are the main health concerns.
Ingestion of cooked meat from 1080-poisoned animals is not thought to constitute a human health hazard due to the low concentration of toxicant present in muscle tissue, and degradation of fluoroacetate at cooking temperatures. (Temple & Edwards 1984) Poisoned carcasses are a significant risk to dogs due to their susceptibility and feeding habits. (Gooneratne et al. 1995)
Formulators and pest control workers are the largest risk group.
Sodium fluoroacetate is rapidly absorbed from the gastrointestinal tract.
Dust formulations are easily absorbed by inhalation.
Dermal absorption is normally low, but may be increased in the presence of cuts or dermatitis. (Brockmann et al 1955)
Blurred vision may occur.
Animal toxicity studies have been conducted via intravenous, intramuscular and intraperitoneal routes.
No data available
The bioavailability of sodium fluoroacetate appears to be similar for oral, injected and inhaled doses. Dermal absorption is lower since a subcutaneous LD50 is 10 to 15 fold higher than the oral dose. (NIOSH 1996)
Oral :
Distribution was consistent with the water soluble nature of fluoroacetate. Plasma levels of sodium fluoroacetate were roughly double that of other organs. In sheep, 2.5 hours after 0.1 mg/kg was administered, levels in plasma, kidney, heart, muscle, spleen and liver were 0.098, 0.057, 0.052, 0.042, 0.026 and 0.021. (Eason et al. 1994)
Oral :
The plasma t1/2 of 0.1 mg/kg sodium fluoroacetate given via gastric cannula was found to be 3.6 - 6.9 hours in goats and 6.6 - 13.3 hours in sheep, (Eason et al. 1994). The same dose given to rabbits showed an initial plasma t1/2 of 1.1 hours. (Gooneratne et al. 1995)
Studies on mice show elimination t1/2’s in plasma, muscle and liver to be 1.6 - 1.7 hours.
Defluorination has been demonstrated in several species, with most metabolism occurring in the liver. One study found levels of fluorocitrate produced to be below the detection limits of 3%, but fluorinated amino acids were resolvable (Schaefer & Machleidt 1971). Fluoride has been detected in the bones of rats fed on low levels of fluoroacetate (Lopez & Hall 1977). GSH and o-glucuronide conjugates can be found in bile. (Tecle & Casida 1989)
The development of tolerance to increasing doses of fluoroacetate has been reported in rats and mice, whereby a dose of 0.5 mg/kg protects rats against a dose of 5 mg/kg for a period of 48 hours. (Chenoweth et al, 1949)
The mechanism of fluoroacetate resistance in certain species is not well understood, but rate of defluorination does not appear to play a significant role. (Mead et al. 1985)
In sheep there was found to be a total excretion of unchanged sodium fluoroacetate ranging from 7.5% to 33.9%, most of which occurred in the urine within the first 48 hours. (Eason et al. 1994)
Rats dosed with 0.25 mg/kg 14C-labelled fluoroacetate excreted the following cumulative percentages of radiolabel in the urine : 6% at 4 hours, 32% at 24 hours, and 45% at 72 hours. After 72 hours various organs each contained between 0.5-1% of the total amount labelled. (Tecle & Casida 1989)
Fluoroacetate is converted to fluoroacetyl-CoA, thereby gaining entry to the citric acid cycle. Citrate synthase then condenses fluoroacetate with oxaloacetate to form fluorocitrate, a process dubbed as "lethal synthesis". (Buffa & Peters, 1950)
The time taken for lethal synthesis is on the order of 30 - 150 minutes, and symptoms will be exhibited at some point after this latent period, depending on the species and dose. (Egekeze & Oehme 1979)
The toxic isomer (-)-erythro-2-fluorocitrate exerts its action mainly on the citric acid cycle enzyme aconitase, where it is thought to act as a suicide substrate at the sulphydryl-bearing active site of the enzyme, causing a blockade at this point of the cycle (Clarke 1991). ATP is rapidly depleted, disrupting energy-dependent processes. The capacity of cells to restore inactivated aconitase and combat oxidative damage is probably also hindered.
Other enzymes affected include mitochondrial citrate carriers (Kun et al. 1978), pyruvate dehydrogenase kinase, (Taylor et al. 1977), succinate dehydrogenase, (Mehlman MA 1967), glutamine synthetase, (Paulsen & Fonnum 1990), phosphofructokinase, (Godoy & del Carmen Villarruel 1974), and possibly ATP-citrate lyase (Rokita & Walsh 1983).
As a result of the blockade at aconitase, citrate levels rise dramatically, causing chelation of divalent metal ions, espcially Ca2+. Depletion of these ions at a CNS site may be responsible for seizures in certain species. (Hornfeldt & Larson 1990)
Serum citrate levels generally provide a reliable biochemical marker of fluoroacetate intoxication. (Bosakowski & Levin 1986)
It is estimated that the human LD50 is approximately 2-10 mg/kg. (Egekeze & Oehme 1979)
There is no data suggesting differential toxicity between adults and children.
Toxicity of sodium fluoroacetate varies markedly with species. Cold-blooded species (eg. Reptiles) are generally more resistant than warm-blooded (mammals). Sites of action also vary between species : notably, herbivores experience cardiovascular complications, carnivores exhibit CNS effects such as seizures and respiratory arrest, while omnivores show mixed symptomology. Dogs are among the most susceptible of animals tested.
Species have been categorized into 4 groups according to symptomology (Chenoweth et al, 1949) :
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1. |
Rabbit, goat, horse, sheep, spider monkey : CNS action is not observed, and death is due to cardiac effects with ventricular fibrillation. |
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2. |
Cat, pig, rhesus monkey, human : Heart and CNS are affected, death usually resulting from respiratory failure during convulsions, but occasionally due to ventricular fibrillation. |
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3. |
Dog, guinea pig : Epileptiform convulsions predominate, with death being due to cessation of respiratory activity following running movements like those of strychnine poisoning. |
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4. |
Rat, hamster : Respiratory depression and delayed bradycardia is the main feature. |
Selected animal data (Chenoweth et al, 1949) :
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Dog |
0.05 mg/kg (IV) |
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Cat |
0.2 mg/kg (IV) |
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Rabbit |
~0.5 mg/kg (IV) |
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Goat |
0.6 mg/kg (IM) |
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Pig |
0.4-1 mg/kg (IP) |
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Sheep |
2 mg/kg (oral) |
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Rat |
0.1-5 mg/kg (various strains/species and routes) |
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Mouse |
0.5-19.3 mg/kg (various strains/species and routes) |
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Monkey |
4-15 mg/kg (IV) |
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Bird |
~10-20 mg/kg (various species orally) |
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Frog |
150 mg/kg |
Four months of chronic dietary sodium monofluoroacetate at 26 ppm caused temporary growth retardation in rats. There was damage to the testes and loss of sperm. (Smith et al. 1977)
Chronic intoxication of sheep at doses as low as 0.11 mg/kg/day causes myocardial damage in the form of microscopic lesions. Sheep at rest appear relatively normal, but fatalies may occur after 3-7 such doses.
Studies of systems without intact mitochondria suggest that the inhibition of aconitase by fluorocitrate is competitive and reversible with an average constant of inhibition (Ki) of 22-45 micromolar, (Eanes & Kun 1974) however, intact mitochondrial systems imply that mitochondrially-bound aconitase is far more sensitive to inhibition. (Guarriera-Bobyleva & Buffa, 1969). These results might be explained by the inhibition of mitochondrial citrate transporter enzymes at picomolar fluorocitrate concentrations, and concomitant citrate/fluorocitrate accumulation within the mitochondria. (Kirsten et al., 1978)
Fluorocitrate causes an unequal inhibition of the two reactions catalyzed by aconitase. The first step involving conversion of citrate into cis-aconitate is inhibited more than the second step transforming cis-aconitate into isocitrate. (Guarriera-Bobyleva & Buffa 1969)
The tricarboxylic acid cycle of astrocytes is inhibited by fluoroacetate, and the resultant ATP depletion decreases the activity of glutamine synthetase. (Hassel et al. 1994) Reuptake of glutamate into glia is also inhibited, probably due to inhibition of the ATP-dependent Na+/ K+ pump. (Szerb & O’Regan 1988)
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TLV-STEL |
0.15 mg/m3, deletion has been proposed. |
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TLV-ACGIH |
0.05 mg/m3 (skin) |
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STEL |
0.15 mg/m3 |
Fluoroacetate has no acceptable daily intake.
No data available
Teratogenic effects in rats are only manifested at overtly toxic doses. No teratogenic malformations (including skeletal abnormalities) were detected when pregnant rats were dosed with 1 mg/kg fluoroacetate in a single dose on days ranging from 9 to 11 of the organogenesis phase. (Spielmann et al. 1972)
Injection of 2-3 mg/kg fluoroacetate into pregnant rats and mice caused necroses of fetal neuroblasts, or irregular neuroblast growth, after 24 hours. (Hicks & Cooney)
No mutagenicity studies have been conducted, however DNA synthesis rates decrease by 40-60% in rats intraperitoneally dosed with 5 mg/kg fluoroacetate. (ACGIH 1991)
Ethylene fluorohydrin forms fluoroacetate in the body and should be treated as fluoroacetate.
A series of 1-(di)halo-2-fluoroethanes reported in the literature to be non toxic or of low toxicity were found to be highly toxic by the inhalation route. The compounds, 1,2-difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane were highly toxic to rats upon inhalation for 4 hours. All indications point to the formation of fluoroacetate. (Keller et al. 1996)
Nausea, vomiting, and abdominal pain initially occur, followed by anxiety, agitation, muscle spasm, stupor, seizure, and coma. Reversible acute renal failure has been reported. Sinus tachycardia and hypotension are the common cardiovascular signs. (Chi et al 1996)
A case involving the inhalation of sodium fluoroacetate after a wind gust blew powder into a man’s face has been described. Following inhalation there was an almost immediate tingling sensation around the corners of the subject’s mouth and nasal passages and soon his entire face became numb. This was accompanied by salivation and loss of speech. His vision was blurred from onset with an inability to focus on objects. Although paraethesias spread to his arms and legs, and violent convulsions and coma followed, the patient ultimately recovered. (Grant 1986)
No data available.
Blurred vision, pain, and nystagmus may occur. (Grant 1986)
No data available.
No data available
No data available.
Neurologic dysfunction, mild hepatic dysfunction and renal tubular lesions were reported in farmer workers who were exposed to sodium fluoroacetate for 10 years. (Hayes & Laws, 1991)
Neurologic dysfunction, mild hepatic dysfunction and renal tubular lesions were reported in farmer workers who were exposed to sodium fluoroacetate for 10 years. (Hayes & Laws, 1991)
No data available
No data available
No data available
Initially, nausea and mental apprehension appear, followed by grand mal convulsions, depressed consciousness and eventually coma. Cardiovascular effects, which often result in death, include ventricular tachycardia and fibrillation. (Chi et al 1996) Neurological and behavioural deficits are rare in patients surviving the ictal period, (Trabes et al. 1983) although severe mental deficiencies were found in a patient who had prolonged cardiac arrest. (McTaggart 1970)
Sinus tachycardia and hypotension are the common cardiovascular signs and the cardiac rhythm may deteriorate into ventricular tachycardia/fibrillation or sudden cardiac arrest. (McTaggart 1970) The ECG normally shows prolonged QTc interval especially in the presence of hypocalcemia (Hayes & Laws, 1991). Other ECG abnormalities that have been reported include ventricular premature beats, non-specific T wave abnormalities and ST-T changes, and atrial fibrillation with rapid ventricular response. (Chi et al 1996)
Respiratory distress and pulmonary oedema may occur (Hayes & Laws, 1991).
Hyperactivity has been noted initially following ingestion, gradually leading to tonic clonic convulsions, coma and neurologic impairment. Between convulsions, pupils were miotic but responsive to light, but not during spasm. Cerebellar dysfunction and loss of speech have been observed in patients. Auditory hallucinations may occur (Hayes & Laws, 1991).
Paresthesias of the arms and legs have occurred following ingestion of sodium fluoroacetate (Grant 1986).
No data available.
No data available
Nausea, vomiting and diarrhoea may occur. (Chi et al 1996)
Mild hepatic dysfunction has been reported. (Hayes & Laws, 1991)
Degeneration of renal tubules has been reported, and renal failure occurred in a rabbiter with 10 years chronic exposure to sodium fluoroacetate. (Hayes & Laws, 1991)
No data available
Testicular damage has been reported in rats at chronic dietary doses of fluoroacetate, (Smith et al. 1977) and is associated with depletion and deformation of spermatids. (ACGIH 1991)
Hypothyroidism has been reported. (Hayes & Laws, 1991)
No data available
Numbness of the face and facial twitching , blurred vision (Grant 1986) and nystagmus (Proctor et al 1988) may occur.
No data available
No data available
Metabolic acidosis results from a build up of citric acid, lactic acid and ammonium in blood and organs, (Stewart et al. 1969) and has been observed in humans. (Hayes and Laws 1991)
Metabolic acidosis is associated with elevated serum creatinine and transaminase levels.
Hypocalcaemia and hypokalaemia are the most common electrolyte disturbances (Chi et al 1996)
Hyperglycaemia occurs due to blockade of glucose metabolism by citrate. (Egekeze and Oehme 1979)
No data available
When thermoregulation is affected, animals become vulnerable to changes in external temperature. Keeping animals at either high or low temperature increases their sensitivity to fluoroacetate. (Novak et al. 1969) Mouse LD50’s have been measured at 12.1 mg/kg at 23 degrees, and 5.16 mg/kg at 17 degrees centrigrade, under otherwise identical conditions. (Hayes and Laws 1991)
Treatment is essentially symptomatic and supportive following decontamination procedures to prevent further absorption. Special attention should be paid to stabilise cardiac and CNS function.
Make a proper assessment of airway, breathing, circulation and neurological status of the patient.
Maintain a clear airway.
Aspirate secretions from airway.
Administer oxygen.
Perform endotracheal intubation.
Support ventilation using appropriate mechanical device.
Control convulsions with appropriate drug regimen.
Open and maintain at least one intravenous route.
Administer intravenous fluids.
Perform cardio-respiratory resuscitation.
Perform gastric decontamination measures, thereafter keep the patient as quiet as possible.
Monitor vital signs.
Correct hypotension/hypertension as required.
Monitor blood pressure and ECG.
Monitor fluid and electrolyte balance.
Monitor acid-base balance.
Control body temperature by appropriate drugs or physical means.
Control cardiac dysrhythmias with proper drug regimen (proper means).
Hypocalcemia should be parenterally treated with calcium gluconate or calcium chloride.
Remove and discard contaminated clothing.
Irrigate exposed eyes with copious amounts of water or saline.
Wash skin with (soap and) copious amounts of water.
The optimum early decontamination treatment for 1080 is not clear.
Sodium monofluoroacetate does not (apparently) adsorb well to activated charcoal (Norris et al 2000), whole bowel irrigation is recommended for ingestions of potentially severe toxicity.
There is no specific antidote which has been adequately evaluated in humans. The following compounds have been partially successful in some animal species :
Acetamide appears to enhance survival, and has been administered to patients as a 10% solution in 5% glucose.
A limited degree of therapeutic success has been reported for acetate donors such as acetate, ethanol, and glycerol monoacetate. Acetate and ethanol are partially effective in mice, guinea pigs and rabbits but not in dogs, (Tourtellote and Coon 1950).
A combination of calcium gluconate and sodium succinate in the ratio of 130 mg/kg to 240 mg/kg has proven effective in mice. (Omara and Sisodia 1990) Calcium gluconate has been successfully used to treat tetanic symptoms of human fluoroacetate intoxications. (Gajdusek and Luther 1950) Laboratory experiments have shown no reduction in mortality in mice, (Omara and Sisodia 1990) however calcium chloride has antidotal effect in cats. (Roy et al. 1980)
No data available.
Hypotension and the early onset of metabolic acidosis and increased serum creatinine are associated with poor short-term survival. All such patients should be observed intensively for at least 48 hours (Chi et al 1996)
The use of cardiac glycosides has been rejected by some studies, (Chenoweth et al. 1951) but lanatoside C appears to have been remarkably successful and without noticeable side-effects in one human case. (Hayes and Laws 1991)
Identification of research needs
The efficacy of N-acetyl cysteine and bioavailable forms of sulphydryl as a potential antidote for fluoroacetate needs further attention.
A 40 year old man died after suicidal ingestion of an unknown amount of sodium fluoroacetate. At the time of admission he was unconscious, had nystagmus, slight muscular spasms, irregular heart beat and soft abdomen. He was lavaged, given cathartic and an enema, after which time he had an epileptiform convulsion and was sedated. Throughout the 17 hour time course he continued to experience muscle spasms and restlessness, frothed at the mouth, and secreted excess mucous. Death was due to respiratory and cardiac failure. Pathological examination revealed a relatively uniform distribution of fluoroacetate throughout the organs tested. A total of 465 mg recovered, suggesting a minimum dose of 6 mg/kg. (Harrisson et al. 1952)
An 8 year old boy was left with severe neurological impairment after ingesting 1080-impregnated wheat. Before admission he vomited twice, and was unconscious after having had repeated convulsions. An endotracheal tube was inserted, he was given oxygen, and convulsions were controlled with intravenous thiopentone sodium and diazepam. ECG was monitored, and heart rate was 160 per minute. He underwent ventricular asystole after 14 hours and resuscitation took 10 minutes (with massage, ventilation and sodium bicarbonate infusion). Once bradycardic contraction resumed, isoprenaline was administered intravenously to produce sinus tachycardia. On the 10th day he kept his eyes open and could appreciate movement, but had marked hypertonicity of all limbs. Subsequent improvement was gradual, with paresis of the legs and a severe degree of mental defect which is likely to remain. (McTaggart 1970)
No antidote available.
Terrestrial fate :
Fluoroacetate is degraded by halidohydrolase action possessed by many microbial and fungal species (Walker and Lien 1981). Persistence of fluoroacetate in carcasses is dependent on a number of factors such as temperature, weather conditions and the size and amount of disintegration of the animal.
The ion exchange properties of forest soils greatly exceeds the levels of toxin used in vertebrate control operations, therefore it is thought that in normal (New Zealand) use there is little likelihood of fluoroacetate moving in the soil. (Peters 1975)
Plants can take up fluoroacetate from soil or water. Some species are vulnerable, (Lien et al. 1978), while others, particularly some Australian and African varieties, produce the toxin and possess natural resistance. (Meyer et al. 1992)
Aquatic fate :
In most cases analysis of fluoroacetate levels in surface and groundwater following aerial bait drops has found no evidence of the toxin above detection limits. Aquaria simulating New Zealand aquatic conditions degraded 0.1 ppm sodium fluoroacetate by 70% within 24 hours, and below detectable limits after 100 hours. (Eason et al. 1993)
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Mr William R. Norris
New Zealand National Poisons Centre
Box 913
Dunedin
New Zealand
Peer Review Update: Awang R; Besbelli N, Caldas, LQA;
17th. September 2001, Edinburgh
Section 9 updated November 1, 2001 Dr W A Temple, Dunedin
Final review November 2001 Penang
See Also:
Toxicological Abbreviations
Sodium fluoroacetate (ICSC)