Vertebrate Pesticide Toxicology Manual (Poisons)

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1.1.4 Toxicology and pathology

Onset of symptoms

The latent period between the time monofluoroacetate is ingested and the appearance of clinical signs in mammals is between 0.5 and 3 hours. Peak plasma concentrations of monofluoroacetate occurred in possums and rabbits 0.5 hours after ingestion, 0.75 hours in goats, and 2.5 hours in sheep. This correlates with the latent period between ingestion and clinical signs and reflects the time taken for absorption and distribution of monofluoroacetate, and the conversion of monofluoroacetate to fluorocitrate. Animals receiving small sub-lethal doses of 1080 show mild clinical signs of poisoning, metabolise and excrete 1080 within 1–4 days, and then recover. Animals receiving a lethal dose usually show more severe signs of poisoning in addition to non-specific clinical signs such as nausea and vomiting. Specific signs include cyanosis, drowsiness, tremors, staggering, and death from ventricular fibrillation or respiratory failure. In general, herbivores experience cardiac failure, whereas carnivores experience central nervous system disturbances and convulsions then die of respiratory failure (Egekeze & Oehme 1979). Possums usually die within 6–18 hours (Eason et al. 1997). The clinical signs of 1080 poisoning in birds will vary according to the species. Common signs may be lack of balance, slowness, ruffled feathers, and salivation. Vomiting will occur in some species such as raptors. In the terminal phase of poisoning, birds and mammals may exhibit convulsions and coma.

Mode of action

Monofluoroacetate is converted within the animal to fluorocitrate, which inhibits the tricarboxylic acid cycle. This results in accumulation of citrate in the tissues and plasma, energy deprivation, and death. Synthesis of fluorocitrate occurs in the mitochondria, and the fluorocitrate formed inhibits mitochondrial aconitate hydratase. There is also evidence to suggest that fluorocitrate inhibits citrate transport into and out of mitochondria, and that fluorocitrate has an inhibitory effect on succinate dehydrogenase. The high levels of citrate concentration that occur during monofluoroacetate intoxication can also have an inhibitory effect on the glycolytic enzyme, phosphofructokinase.


Death from monofluoroacetate poisoning is caused by the inhibition of energy production which, in turn, results in either cardiac or respiratory failure. Fluorocitrate is commonly described as a specific metabolic inhibitor of glial cells in the brain. Glial cells are thought to be important for extracellular fluid ion and pH regulation, and the control of breathing (Erlichman et al. 1998).

Pathology and regulatory toxicology

Known target organs in animals following 1080 exposure include the heart, lungs, liver, kidney, testes, and foetus (Annison et al. 1960; McTaggart 1970; Buffa et al. 1977; Sullivan et al. 1979; Schultz et al. 1982; Trabes et al. 1983; Chung 1984; Savarie 1984; Chi et al. 1996; Gregg et al. 1998; Twigg et al. 1988; Eason et al. 1999b). The pathological changes observed at post-mortem appear to be largely the result of progressive cardiac failure with congestion of the abdominal viscera and lungs. Examination of monofluoroacetate-poisoned mammals usually reveals cyanosis of mucous membranes and other tissues. Diffuse visceral haemorrhage has been described in some animals, particularly cattle. Subepicardial haemorrhages on the epicardium and endocardium as well as on the epiglottis and trachea have been observed in sheep and possums poisoned with monofluoroacetate. The presence or absence of tissue damage is likely to be dose-related, and subepicardial haemorrhages have been observed in rabbits receiving a lethal dose of monofluoroacetate but not in those receiving a sub-lethal dose. It is apparent that the target organs vary to some extent in different species, which may relate to the citrate response in different species, or the metabolic activity in different tissue. In birds a target organ appears to be wing muscle (Ataria et al. 2000) as well as the heart, which is a more common target in other species.


Repeated exposure of rats to small doses of monofluoroacetate appears to afford some protection to subsequent challenge (Atzert 1971). However, at a histopathological level, this is not the case in sheep, probably because even small doses of monofluoroacetate result in myocardial damage in this species, and this damage will be cumulative with subsequent exposure (Annison et al. 1960). In sheep that had received multiple sub-lethal doses of 1080, myocardial degeneration has been reported as well as necrosis of individual or small groups of myocardial fibres (Schultz et al. 1982). Researchers in Australia noted macroscopic lesions in the heart of sheep, described as acute multifocal injury to the myocardium, after doses as low as 0.11 mg/kg/day for 3–7 days. A dose of 0.1 mg/kg is approximately equivalent to a 30-kg sheep eating one 4-g 1080 possum bait containing 0.08% 1080 w/w. Mild cardiac histopathology at doses of 0.055 mg/kg/day has been reported, but the duration of treatment was not specified (Whitten & Murray 1963). Although 1080 itself is not cumulative (Rammell 1993; Eason et al. 1994c), these reports in sheep clearly demonstrate that cumulative damage to the heart or other organs from repeated exposure to large sub-lethal doses of 1080 can occur.

A recent study demonstrated that ewes surviving a single exposure to 1080 did not experience any adverse long-term effects (Wickstrom et al. 1997b). Nevertheless, pathological abnormalities related to 1080 exposure were found in the heart and brain. Glial cells in the brain are particularly sensitive to fluorocitrate (Erlichman et al. 1998; Hulsmann et al. 2000). Obviously livestock must not be allowed access to toxic baits, and even partially degraded baits should be regarded as hazardous. Pregnant ewes are more susceptible to the acute toxic effects of 1080 than non-pregnant animals (O’Connor et al. 1999).


Many regulatory toxicology studies were completed in the USA before 1995, as 1080 is still used there in livestock protection collars. They included 17 studies on product chemistry, six studies on wildlife hazards, and four studies relevant to human health. The results from these studies were summarised in the Science Workshop Proceedings on 1080 (Fagerstone et al. 1994) (Table 2).

The most important of these studies to the health of those involved in pest control in New Zealand was on acute dermal toxicity of 1080 in rabbits. In this test, five male and five female rabbits for each of four dose levels were treated dermally with 1080 paste. The estimated LD50 was 324 mg/kg for females and 277 mg/kg for males. It had long been known that 1080 can be absorbed through the gastrointestinal and respiratory tracts, open wounds, and mucous membranes, but is less readily absorbed through intact skin (Atzert 1971). However, the results of this study demonstrated that poor dermal absorption of 1080 (Atzert 1971) does not imply no absorption, and there are obviously implications with regard to enforcing strict codes of practice and appropriate protective clothing for those involved in the manufacture or handling of 1080 baits.

Regulatory (laboratory-based) toxicology studies of this type are usually conducted before the launch of new drugs or pesticides, and are used to proactively assess the risk of these compounds to humans, pets, livestock, and wildlife. Alternatively, they may be conducted on older products, such as 1080, to provide an update to the toxicology data generated to meet new standards and data requirements that are now commonplace internationally.

The new regulatory toxicology studies (targeting human health concerns) listed in Table 2 were conducted following internationally recognised protocols. The methods are routine (Wilson 1965; Ames et al. 1975; Hoddle et al. 1983; Blazak et al. 1989). These data provide answers to the following general questions: does 1080 alter genetic material (mutagenic) and therefore have the potential to cause cancer; and does it cause birth defects (developmental toxicant)?


Results from a series of in vitro (cell culture) and laboratory animal studies (in rats and mice) to update the regulatory toxicology database for 1080 provided information on mutagenicity and teratogenicity. Results of three different, complementary tests indicate that 1080 is not mutagenic, and therefore unlikely to cause cancer. Results of a developmental toxicity study in rats indicate that 1080 causes developmental defects in rats when pregnant females are exposed to relatively high doses (0.33 and 0.75 mg/kg) on a daily basis during the period of organogenesis (from days 6 through to 17 of gestation). The developmental abnormalities observed were mild skeletal effects: slightly curved forelimbs, and bent or ‘wavy’ ribs. These results highlight the highly toxic nature of 1080 and the need for extreme care when handling this pesticide during the manufacture and distribution of bait, but do not preclude its proper use (Eason et al. 1999b). Spielman et al. (1973) reported that 1080 at a dose just below the maternal LD50 was not teratogenic to rats. The embryos in this study showed no macroscopic or skeletal abnormalities. Spielman et al.’s work involved only a single dose and the results contrast with our investigation following current international guidelines that require dosing rats from day 6–17 of gestation at three dose levels.

Comparison of the study by Spielman et al. (1973) and Eason et al. (1999b) is relevant to human risk assessment in New Zealand. It is noteworthy that the NOEL derived from the present multi-dose study (0.1 mg/kg/day) was 10-fold less than the single dose NOEL (1 mg/kg) reported by Spielman et al. (1973). In the most recent 90-day exposure study in rats, the NOEL for effects on testes was 0.075 mg/kg/day. In the high-dose group (0.75 mg/kg) gross examination revealed small testes and microscopic examination at necropsy revealed damaged sperm. Effects occurred in only one out of three dose groups and they were partially reversible on cessation of dosing. At the time of completing this edition of the manual (March 2000) the histopathology is incomplete. Possible heart defects are being reported in the males of the top-dose group, but this requires confirmation. The effects on these target organs are consistent with earlier work. The difference between these current regulatory toxicology studies and earlier animal studies are that no effect levels have been defined.


Table 2. Toxicology studies on 1080 relevant to human health: current status (* = new studies)

Study types

Status

Acute toxicity

Skin and eye irritation

Skin sensitisation

Ames assay

Mouse lymphoma assay

Mouse micronucleus test

Developmental toxicity in rats (including pilot study)

3-month feeding study in rats* (including pilot study)

Metabolism/pharmacology studies

Extensive database in the literature (see Rammell & Fleming 1978; Seawright & Eason 1994; Eisler 1995)

Completed (see Fagerstone et al. 1994)

Completed (see Fagerstone et al. 1994)

Completed January 1998

Completed January 1998

Completed January 1998

Completed January 1998

Scheduled for completion (report in 2000)

Extensive published database (see Eason et al. 1994c)

* This core component of the study was completed in December 1999. Histopathological assessment and a full report will be prepared prior to July 2000.

Fate in animals
Absorption, metabolism, and excretion

Sodium monofluoroacetate (1080) is absorbed through the gastrointestinal tract or via the lungs if inhaled. (While it is not volatile, the inhalation of 1080 powder must be avoided). Monofluoroacetate is not readily absorbed through intact skin, but it can be absorbed more readily through cuts and abrasions.

Studies of laboratory animals since the 1950s have shown that sub-lethal amounts of 1080 are excreted both unchanged and as a range of non-toxic metabolites. After oral or intravenous dosing of laboratory rodents, 1080 is rapidly absorbed and distributed through the soft tissues and organs (Hagan et al. 1950; Egeheze & Oehme 1979; Sykes et al. 1987). This contrasts with the action of commonly used anticoagulant rodenticides, such as brodifacoum, which preferentially bind to liver cells (Bachman & Sullivan 1983). Sodium monofluoroacetate is excreted as unchanged fluoroacetate and a range of metabolites (Gal et al. 1961; Schaefer & Machleidt 1971). Approximately 30% of a dose of 1080 administered to rats was excreted unchanged in the urine over 4 days (Gal et al. 1961). At least seven unidentified metabolites other than fluoroacetate and fluorocitrate, the toxic metabolite of 1080, were also detected in rat urine (Gal et al. 1961).

Administration of 14C-labelled fluoroacetate to rats showed that fluorocitrate, the toxic metabolite of 1080, accounted for only 3% of the radioactivity (Gal et al. 1961), and this was confirmed by Schafer & Machleidt (1971). The major metabolite, unlike fluorocitrate, does not inhibit the activity of aconitase (Gal et al. 1961). Phillips & Langdon (1955) suggested that the unidentified metabolites include non-saponifiable lipids that probably serve as intermediates for cholesterol, and some radioactivity was found in fatty acids and cholesterol in the liver. Up to 3% of the radioactivity appeared as respiratory CO2, which implied cleavage of the C-F bond (Gal et al. 1961).


Defluorination of 1080 or its metabolites, including fluorocitrate, has been demonstrated in animals and other living organisms (Kirk & Goldman 1970; Smith et al. 1977; Egekeze & Oehme 1979; Soifer & Kostyniak 1983, 1984; Twigg et al. 1986; Tecle & Casida 1989). Although fluoride is extensively excreted, primarily in urine, some deposition occurs in bone (Sykes et al. 1987; Eason et al. 1993a,b; Rammell 1993; Eason et al. 1994b).

The earliest reports on rats suggested that some 1080 is retained for 1–4 days. In a study using mice, 1080 concentrations in plasma, muscle, and liver decreased by half in less than 2 hours. Prolonged persistence of 1080 in animals after sub-lethal exposure therefore seems unlikely, and this has been confirmed for larger animals such as rabbits, goats, possums, and sheep (Gooneratne et al. 1994; Eason et al. 1994c). Sodium monofluoroacetate was readily absorbed and excreted. The highest concentrations occurred in the blood, with moderate levels in the muscle and kidneys, and the lowest concentration in the liver. In sheep, the highest concentrations in blood occurred 2.5 hours after dosing and there were negligible amounts in tissue and plasma 4 days after dosing. All traces of the toxin are, therefore, likely to be eliminated within 1 week.

If recommended practices are followed in possum control operations, 1080 is unlikely to be present in meat for human consumption. Where any contact of livestock (farm animals or animals intended for slaughter) with 1080 is suspected, an adequate margin of safety should be achieved by imposing a minimum withholding period of 5 days. Should a death in a flock or herd be attributed to 1080, the withholding period should be doubled to 10 days for the surviving stock, which should be removed to a 1080-free pasture (Rammell 1993; Eason et al. 1994c).


Whilst 1080 is comparatively rapidly eliminated from living animals it can persist in carcasses for many months where it will break down more slowly and will pose a risk to dogs (Meenken & Booth 1997).

Limited research has been conducted on the pharmacokinetics of monofluoroacetate in invertebrates. In a laboratory study weta were dosed with 1080 and the persistence of 1080 residues at specified times after dosing was determined. In this experiment 1080 was eliminated from weta 6–10 days after exposure, and all weta survived dose levels of 15 mg/kg (Eason et al. 1993a,b). Similar results were obtained from a native ant (Booth & Wickstrom 1999). Insects have been monitored in forests for 1080 residues after toxic baits were aerially sown for possum control. No 1080 was found in living earthworms, spiders, beetles, millipedes, or centipedes. Although 1080 was found in some cockroaches, bush weta, and cave weta during the period the baits were on the ground, after 3–4 weeks all invertebrate samples were free from 1080 residues. Field and laboratory results for invertebrates do show that 1080 is taken up by some of the terrestrial invertebrate species. Its persistence in invertebrates is short-lived and the risk to insectivorous birds or other predators is therefore also confined to a short period after sowing baits for possum or rabbit control. However, large invertebrates frequently eat bait (Spurr & Drew 1999) and, since species like weta can contain large amounts of bait, the concerns regarding secondary poisoning via this route remain unresolved.

Species variation in response to monofluoroacetate

Whilst monofluoroacetate is a broad-spectrum toxin, there are some marked differences in susceptibility (Table 3). There is an extensive database on the acute toxicity of 1080 in a diverse spectrum of species, including birds, mammals, and reptiles (Atzert 1971; Harrison 1978; Rammell & Fleming 1978; Eisler 1995). Unlike most other vertebrate pesticides, 1080 also has insecticidal properties (Negherbon 1959; Notman 1989; Booth & Wickstrom 1999). As with other poisons, the relative susceptibility and LD50 values can be influenced by the vehicle used to deliver the poison, and environmental conditions (Henderson et al. 1999). Dogs are extremely susceptible, and most other carnivores are highly sensitive to poisoning. Herbivores are less sensitive, and birds and reptiles are increasingly resistant (Atzert 1971; Rammell & Fleming 1978; Eisler 1995). Several studies have revealed that animals that forage in areas where fluoroacetate-producing plants are common have evolved an increasing resistance to fluoroacetate compared to animals from areas where plants containing the toxin are not indigenous. This phenomenon is well-documented in Australia where the effect is most dramatic in herbivores and seed eaters, which are more directly exposed to the toxin than carnivores. The emu (Dromaius novaehollandiae) is the oldest seed-eating bird species in Australia, and has a very high level of resistance with an LD50 of 100–200 mg/kg. In contrast, seed-eating birds from regions outside the range of fluoroacetate-producing plant species have an LD50 in the range of 0.2 to 20 mg/kg. Similarly the brushtail possum of south-western Australia is 150 times less susceptible to fluoroacetate poisoning than the same species in eastern Australia where plant species containing the toxin are not present. The biochemical basis for tolerance and species variation is not clear. This species variation in mammals in response to monofluoroacetate poisoning may in part be due to differences in the biochemical response of different organs to the toxin, which may be linked to difference in glutathione level and a glutathione-requiring defluorinating enzyme. For example, 1080-induced changes in citrate content of the heart are more pronounced than in any other organs in sheep, and for this reason citrate concentrations in sheep hearts may have diagnostic value (Annison et al. 1960; Schultz et al. 1982). Guinea pigs and rabbits, like sheep, are sensitive to myocardial damage. In rats there is some short-lived elevation of citrate in the heart and, by contrast, in dogs elevation of citrate concentrations in heart tissue is reported to be minimal (Bowsakowski & Levin 1986). Furthermore, dogs do not show the ECG changes seen in sheep that are suggestive of cardiac ischaemia (Matsubara et al. 1986). In comparison with dogs the clinical signs in cats are less severe (Eason & Frampton 1991). In birds, damage to wing muscle is a unique feature that occurs at sub-lethal dose levels (Ataria et al. 2000). Most deaths in mammals generally occur 8–48 hours after ingestion of a lethal dose.


Table 3. Acute oral toxicity (LD50 mg/kg) for sodium monofluoroacetate. N.B. These results represent a very small proportion of the LD50 data available in the literature. (Rammell & Fleming 1978; Hone & Mulligan 1982; Eisler 1995)

Species LD50mg/kg

Dog 0.07

Cat 0.3

Pig 0.3

Rabbit 0.4

Sheep 0.4

Cow 0.4

Deer 0.5

Goat 0.6

Wallaby <1.0

Rat 1.2

Possum 1.2

Human 2.5

Duck 9.0

Weka 8.0

Clawed toad (South Africa) 500

A recent review paper has highlighted the effects of ambient temperature on possum mortality, specifically how the acute toxicity of 1080 is reduced at low temperatures, and the importance of conducted aerial control in months with coldest average temperatures (Veltman & Pinder in press).

Aquatic toxicology:

Historical data indicate that fish are relatively resistant to 1080. Fingerling bream and bass (species unidentified) survived indefinitely, without any signs of toxicity, in water containing 370 mg 1080/L (King & Penfound 1946). In New Zealand, fingerling trout were subjected to 1080 concentrations of 500 mg/L and 1000 mg/L without any visible effect on the fish. Force-feeding pellets containing a total of about 4 mg of 1080 (two fingerling trout and five adult trout) or about 8 mg of 1080 (two adult trout) also had no visible effect (Rammell & Fleming 1978). Fluoroacetamide (a compound related to 1080) at a concentration of 3500 mg/L killed only 50% of a harlequin fish (Rasbara heteromorpha) population in 48 hours. The LD50 of 1080 after intraperitoneal injection was approximately 500 mg/kg (Bauermeister et al. 1977). No explanation of the high resistance of fish to 1080 has been published but it is presumably associated with differences in the pathways or relative importance of the Krebs cycle in fish metabolism (Rammell & Fleming 1978).


During 1993, three aquatic toxicity tests were completed in the USA. The first estimated the acute toxicity of 1080 to bluegill sunfish (Lepomis macrochirus). No mortality or sub-lethal effects were observed at any concentration tested, with a highest NOEC (the no-observed-effect concentration) of 970 mg/L. Based on the results of this study and criteria established by the US Environmental Protection Agency (EPA), 1080 would be classified as practically non-toxic to bluegill sunfish. The second test, on rainbow trout (Oncorhynchus mykiss), used the same test conditions as the bluegill sunfish studies. Mortality ranged from 50% to 90% in four treatment levels ranging from 39 to 170 mg/L. In addition, mortality was 10% at the 23 mg/L treatment level, and sub-lethal effects were observed at levels over 23 mg/L. No mortality or sub-lethal effects were observed at the 13 mg/L level. The NOEC was 13 mg/L, which the US EPA classifies as slightly toxic to rainbow trout.

The third test estimated the acute toxicity (EC50) of 1080 to the small fresh water invertebrate Daphnia magna. The EC50 is defined as the concentration in water that immobilises 50% of the exposed daphnids. Of daphnids exposed to levels of 350 to 980 mg/L (ppm), 70 to 100% respectively were immobilised. Immobilisation of 5% was observed among daphnids exposed to 220 mg/L. Sub-lethal effects were observed among all the mobile daphnids exposed to 220–590 mg/L, but not among those exposed to 130 mg/L. The 48-hour EC50 value for daphnids exposed to 1080 was 350 mg/L and the NOEC was 130 mg/L, making 1080 practically non-toxic to Daphnia magna by US EPA classification standards (Fagerstone et al. 1994). An early experiment reported that mosquito larvae (Anopheles quadrimaculatus) were comparatively sensitive to 1080 (Deonier et al. 1946). In 48 hours, 1080 concentrations of 0.025 mg/L were fatal to 15%, 0.5 mg/L to 40%, and 0.1 mg/L to 65% of fourth-instar larvae. Since the concentrations of 1080 described above are many times higher than the residue concentrations rarely associated with 1080 use (<0.001 mg/L or ppm), adverse effect on aquatic animals is unlikely (see Table 1). In practice this data would only be of value in risk assessment relating to a large amount of 1080 bait or stock solutions being deliberately or accidently tipped into a waterway.


1.1.5 Diagnosis and treatment of 1080 poisoning

Diagnosis of non-target poisoning in domestic animals

Diagnosis of 1080 toxicosis is based on exposure history, clinical signs, laboratory analyses, and in lethal cases, lesions. Differential diagnoses (varies with species) include hypomagnesemia, hypocalcaemia, acute lead poisoning, cardiac glycoside toxicosis, strychnine, organochlorine insecticide or methyxanthine toxicosis, traumatic brain injury, epilepsy, and infectious central nervous system diseases such as distemper and rabies.


Clinical signs

Clinical signs of 1080 toxicosis vary with the species involved. In general, neurotoxic signs predominate in carnivores, while herbivores manifest signs of cardiotoxicity. However, there are exceptions and overlapping effects in some cases. The onset of clinical signs usually ranges from 30 minutes to 2–3 hours after oral exposure. Humans may experience nausea, vomiting, and abdominal pain initially, followed by respiratory distress, anxiety, agitation, muscle spasms, stupor, seizures, and coma. Hypertension is thought to be one of the more important predictors of mortality in 1080 intoxication (Chi et al. 1996, 1999).

Primary poisoning in sheep and cattle exposed to 1080 cereal bait is characterised initially by anorexia and depression, followed by staggering, muscle tremors, cardiovascular and pulmonary abnormalities (e.g. arrhythmias, ventricular fibrillation, tachypnoea, dyspnoea), terminal tonic convulsions, coma, and death from cardiac and/or respiratory failure. Severe trembling and sweating have been reported in horses (Beasley et al. 1997c). Death may occur within 12–24 hours. Animals alive 4 days after acute oral exposure are expected to make a complete recovery (Wickstrom et al. 1997b; O’Connor et al. 1999).

Secondary (or primary) poisoning in domestic dogs is characterised by rapid onset of anxiety, nausea, and vomiting (usually too late to prevent absorption of a lethal dose, given the extreme sensitivity of this species to 1080). These signs are followed by fits of wild barking and frenzied running (in a straight line or around the perimeter of an enclosure), with repeated urination, defecation, convulsions and paddling. Affected dogs appear to be oblivious to their surroundings. Seizures increase in frequency and severity with time until animals become exhausted. Death may occur during an extended tonic seizure, or from subsequent respiratory paralysis, usually 2–12 hours after ingestion (Lloyd 1983; Beasley et al. 1997c).
Neurological signs associated with 1080 exposure are generally less severe in domestic or feral cats than in dogs. Signs reported include depression or excitation, vocalisation, salivation, diarrhoea, and cardiac arrhythmias (Lloyd 1983; Eason & Frampton 1991; Beasley et al. 1997c).
Laboratory diagnosis

The most reliable diagnostic indicators of 1080 exposure are measurement of 1080 residues in blood, skeletal or cardiac muscle tissue, or stomach/rumen contents or vomitus. Analytical laboratories require at least 1 mL of serum or plasma, or 10 g of tissue, for residue determination. Samples should be stored at <4C and analysed promptly2 (Wickstrom & Eason 1997).

Ante-mortem clinical pathology changes consistent with 1080 toxicosis include increased serum citrate concentration (the most specific and reliable biomarker), hyperglycaemia, azotemia (increased serum urea nitrogen), lactic acidosis (secondary to seizure activity), and hypocalcaemia. In animals that survive, clinical pathology parameters return to baseline levels by day 3–4 after exposure (Beasley et al. 1997c; Wickstrom et al. 1997b; O’Connor et al. 1999; Ataria et al. 2000).

Lesions

Rigor mortis occurs rapidly in animals poisoned with 1080, but distinctive, specific post-mortem lesions have not been described. Grossly, there is generalised cyanosis. The heart is usually observed in diastole with petechial subepicardial haemorrhages. Petechial haemorrhages are also often observed on the epiglottis, trachea, and abdominal viscera, and the lungs, liver, and kidney may be congested secondary to progressive cardiac failure. The stomach, colon, and urinary bladder of dogs and cats will invariably be empty (Lloyd 1983; Beasley et al. 1997c).

Histopathological lesions observed in sheep that died from acute 1080 exposure included multifocal or diffuse, severe, pulmonary oedema, and scattered foci of myocardial degeneration and necrosis (Wickstrom et al. 1997b; O’Connor et al. 1999). Cerebral oedema and lymphocytic infiltration of the Virchow-Robin space have also been described.
Treatment of 1080 toxicosis in domestic animals

Sodium monofluoroacetate poisoning is an urgent medical emergency, and veterinary treatment should be initiated rapidly in order to maximise the probability of survival. Although research continues, no specific antidote for 1080 poisoning has been identified, and treatment is largely symptomatic and supportive. Most animals that present with severe signs will die in spite of treatment, but veterinary intervention will increase the chance of survival in individuals that receive less than an LD50 dose.

Therapeutic goals for veterinarians are (1) to decrease 1080 absorption and facilitate toxin excretion; (2) to control seizures; and (3) to support respiration and cardiac function. Recommendations for the treatment of 1080 toxicosis in companion animals are as follows (Tourtellotte & Coon 1950; Chenoweth et al. 1951; Lloyd 1983; Beasley et al. 1997c):


  • Where an owner sees the dog scavenging 1080-poisoned carcasses, giving a simple emetic like supersaturated household salt solution or washing soda within approximately an hour can help save dogs.

  • Rapid onset of severe neurological signs precludes the induction of emesis as a means of decontamination in some cases.

  • Induce anaesthesia and perform enterogastric lavage (after endotracheal intubation) if there is any likelihood of continued toxin absorption.

  • Administer activated charcoal (1–2 g/kg) with a saline cathartic (magnesium sulphate at 250 mg/kg in 5–10 times as much water). (However, data from rodent studies indicate that activated charcoal is ineffective at reducing 1080 uptake from the gastrointestinal tract.)

  • Control seizures with barbiturates (phenobarbitone or pentobarbitone as needed).

  • Intravenous fluid therapy to enhance renal excretion of 1080 (proposed), treat hypotension/shock, lactic acidosis, and electrolyte imbalances (e.g. hypocalcaemia).

  • Calcium gluconate at 0.2–0.5 mL/kg IV (5% solution, slowly, in fluids) to control tetany.

  • Glycerol monoacetate (monacetin) at 0.55 g/kg IM has been recommended as a source of acetate (competitive inhibitor of fluoroacetate). However, it is difficult to obtain, and ineffective except when administered early to dogs with relatively low dose exposures.
  • Ethanol at 1.5–8.0 mL/kg (50% solution) orally has also been recommended as an acetate donor. However, combined therapy with ethanol and barbiturates produces profound depression of the central nervous system and prolonged (days) anaesthesia, with high risk of pneumonia and other complications. Use of acetate donors does not appear to be more effective than supportive treatment alone.

  • Antiarrhythmics for treatment of cardiac arrhythmias.

  • Maintain normal core body temperature.


  • Other symptomatic treatment, such as respiratory support, as needed.

1.1.6 Non-target effects

Non-target effects of 1080 used for possum control have been studied extensively during the last 20 years in New Zealand (Spurr 1991, 1994a,b; Eason et al. 1998a; Innes & Barker 1999; Powlesland et al. 1999). Dead birds may be found after aerial application of 1080 baits (Caithness & Williams 1970). However, cold-blooded animals such as reptiles are less susceptible than birds (Atzert 1971). Spurr has noted that fewer and fewer species of birds have been reported dead after 1080 poisoning operations since 1978. Most dead birds were found after large-scale control operations and trials using undyed, raspberry-lured, unscreened carrot bait that had a high percentage of small fragments or ‘chaff’. Reductions in bird deaths can be attributed to the screening of carrot baits to remove small fragments, the banning of raspberry lure, the use of cinnamon oil as a deterrent, the reduced rates of bait application, and the increased use of cereal-based baits. Bait specifications now minimise the amount of fragments and chaff (likely to be eaten by birds and insects) in bait consignments, which in turn minimises the effects on non-target species. It is imperative that only high-quality baits (carrot or cereal baits) are used in control operations. Carrot or cereal baits containing substantial amounts of fragments or chaff will result in substantial bird deaths. For carrot and cereal-pellet bait specifications see Appendices 2 and 3. However, improvements in quality will not reduce the secondary poisoning risk for forest insectivores, such as tomtit, hedge sparrow, and short-tailed bats, which may be exposed to concentrations of 130 mg/kg in some invertebrates (Lloyd & McQueen 2000).

Regardless of the route of exposure, extensive monitoring indicates that populations of common birds are not adversely affected (Spurr 1994a). The impacts on non-target species of 70 aerial 1080 operations or trials carried out between 1978 and 1993 were reviewed by Spurr. Dead birds were reported from six of the 11 operations where systematic searches were made and from nine of the 59 operations where only incidental observations were made. Most birds found dead were introduced species (blackbirds and chaffinches), but some native birds were also killed. These losses were insignificant in population terms as no population reductions were detected for any of the more common bird species in the 35 operations where bird populations were monitored both before and after poisoning (Spurr 1994a). However, less common bird species (e.g. kiwi and kokako) have been less frequently monitored, at least for some bait types. And the sub-lethal effects of 1080 in birds have received limited attention (Ataria et al. 2000). In contrast, Powlesland et al. (1999) have produced recent data to show that there can be very significant mortality of robins (43–55%) after aerial operations, even when quality control standards of bait are met. However, their data indicate that robin populations benefit in the longer term. They argue that the results suggest that as long as carrot protocols are strictly adhered to, and baits are distributed over large blocks of forest so that mammalian predator populations remain low during the next robin nesting season, robin populations will benefit from aerial 1080-carrot possum control operations (Powlesland et al. 1999).


Since 1993, radio transmitters have been increasingly used to monitor less common bird species. For example, in the Hauhungaroa 1080 poisoning operation in 1994, radio transmitters were fitted to 21 kaka and 19 blue ducks. All the radio-tagged birds survived for at least 4 weeks after the poison operation. Radio transmitters were also fitted to nine great spotted kiwi, five weka, and six moreporks on the Gouland Downs; 16 weka and one morepork in Tennyson Inlet; seven great spotted kiwi at Karamea; and eight weka at Rotomanu. One radio-tagged weka died from 1080 poisoning, but all other birds survived for at least 4 weeks after the operations. In 1995, radio transmitters were fitted to 24 North Island brown kiwi in Aponga Scenic Reserve, Northland, and all birds survived at least 6 weeks after 1080 baits were distributed in their territories (Fraser et al. 1995).

Lizards and frogs were not monitored in any 1080 poisoning operations prior to 1994; however, none have been reported killed by 1080. Hochstetters frog populations were monitored after possum control in the Hunua Ranges in 1994, and no short-term detrimental effect was observed. Whilst the primary focus on non-target species monitoring has been on birds, selected invertebrate populations were also monitored in five 1080 poisoning operations. No impact was detected on populations of weta in Waipoua Forest, a range of invertebrate species on Rangitoto Island, predatory insects in Mapara Reserve, or ground-dwelling invertebrates in Puketi Forest and Titirangi Reserve (Spurr 1994a). Recent observations of the numbers of species and number of individual invertebrates found feeding on 1080 baits has led to the prediction that vertebrate pest control operations are unlikely to have any long-term deleterious impacts on invertebrate populations (Sherley et al. 1999; Spurr & Drew 1999). However, concerns remain because of the number of taxa identified on baits, and changes in the number of invertebrates interfering with baits containing 1080. Sherley et al. (1999) suggested that the risk from carrot bait is small when compared with cereal bait. This conclusion is based on the mistaken assumption that ‘rain washes 1080 from carrots faster than from pollard’ and is incorrect as 1080 leaches more slowly from carrot bait than it does from cereal bait (Bowen et al. 1995). Regardless of these findings, efforts to reduce non-target exposure through the use of new bait materials, repellents, and colour continue (Morgan & Goodwin 1995; Hartley et al. 1999; Morgan 1999).


It has recently been suggested that a food-web approach may be a more rational way to evaluate 1080 movement and impact in ecosystems. Priorities suggested include measuring net ecological outcomes at the community level (Innes & Barker 1999) to provide a clearer assessment of risk versus benefit.

Dogs are extremely susceptible to 1080 and must be kept away from toxic baits and possum carcasses which can remain toxic for many months (Meenken & Booth 1997). Predators, such as stoats, ferrets, and cats, are also susceptible to secondary poisoning (Heyward & Norbury 1999; Murphy et al. 1999). Livestock must also be kept well away from baits, and even partially degraded baits should be regarded as hazardous to sheep and cattle. Although possum kills are routinely monitored, particularly for large-scale aerial 1080 operations, there have been few scientific studies of any associated deer mortality. One study in the northern part of Pureora Conservation Park in 1988 found that 43% of the red deer population were killed. Simultaneous carcass searches over the poisoned area confirmed the pellet-count result. The other study in the Hauhungaroa Range in 1994 gave deer kills in three areas of 30–40% of the population (Fraser et al. 1995). However, in a recent report 1080 carrot baits are reported to have reduced deer populations by >90% (Fraser & Sweetapple 2000). Pig mortality might also be expected but has not been reported.

There has been a sustained international trend to increase target specificity and reduce bait application rates when using any pesticide (Greig-Smith 1993; Morgan 1994a,b; Veltman & Pinder 2000) and minimum bait application rates (e.g. 5kg/ha) should be used. Pest control operators should guard against the careless use of 1080, poor-quality control operations, or use of poor-quality baits. Non-target mortality can be minimised by well-planned operations using high-quality baits and by the increased use of bait stations. Provided that control operations are well planned and carefully executed by trained professionals using high-quality baits, adverse effects on ecosystems, water quality and safety, livestock, and human health can be minimised. No significant hazards exist to people drinking water from poisoned areas unless substantial amounts of 1080 have been dropped into a small stream. Nevertheless, the continued use of aerial sowing techniques is bound to cause community concern. Greater use of ground control including trapping, cyanide, and 1080 bait enclosed within bait stations has reduced the conflict between communities and pest control operators. When conducting aerial control, operators should be aware of a recent review of aerial control operations that indicate they will be significantly more successful when conducted in cold conditions. These observations are consistent with acute toxicity studies in possums that have demonstrated that the toxicity of 1080 is temperature-dependent (Veltman & Pinder 2000).


1.1.7 Summary

Advantages

Disadvantages

Highly effective for achieving a rapid reduction in possum numbers

Controversial, especially aerial operations

The only poison available for aerial application

Secondary-poison risk from possum carcasses (especially to dogs)

Cheap compared to most other poisons

No effective antidote

Biodegradable in the environment

Generates bait shyness if target animal gets sub-lethal dose

Can achieve consistently high kills

Poor-quality bait causes bird deaths

High-quality efficacy data and extensive field experience underpin both aerial and ground-baiting techniques





  • Ten-eighty is the main poison currently used for possum and rabbit control, either aerial application or ground-based operations.


  • Monofluoroacetate, the active ingredient of 1080, occurs naturally in toxic plants in Australia, South Africa, and South America.

  • Since 1080 is highly water-soluble, it will be dispensed in the environment by rain and stream water. Some micro-organisms, such as Pseudomonas species, in the soil will defluorinate 1080.

  • Sodium monofluoroacetate is a relatively stable molecule that will not break down in water unless living organisms, such as aquatic plants or micro-organisms, are present. Water-monitoring surveys, conducted during the 1990s, have confirmed that significant contamination of waterways following aerial application of 1080 bait is unlikely.

  • Sodium monofluoroacetate is a broad-spectrum poison that acts by interfering with the energy-producing tricarboxylic acid cycle in the mitochondria.

  • Dogs are extremely susceptible to poisoning.

  • If an animal has ingested a sub-lethal dose of 1080, toxin residues will not persist in meat, blood, the liver, or fat (in contrast with brodifacoum – Talon® or Pestoff®).

  • Cellular and organ damage from multiple exposure to sub-lethal doses (e.g. myocardial necrosis) could be cumulative.

  • If livestock become exposed to 1080 bait, a minimum withholding period of 5–10 days should be enforced to allow for excretion of 1080, so that residues will not occur in meat.
  • High-quality baits reduce non-target impacts on birds. Current evidence suggests that populations of common bird species and invertebrates are not adversely affected, but further monitoring of rarer species after aerial application of baits is still underway.

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