Vertebrate Pesticide Toxicology Manual (Poisons)

Cholecalciferol (Campaign®, FeraCol®)


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1.3 Cholecalciferol (Campaign®, FeraCol®)

Chemical Name: 9,10-Secocholesta-5,7,10 (19)-trien-3-ol.

Synonyms: Vitamin D3

This is a relatively new poison and was introduced in New Zealand in 1995. It poses a low risk of secondary poisoning. Introduced initially for possum control, it is also a rodenticide.

1.3.1 Physical and chemical properties

The empirical formula is C27H44O and the molecular weight is 384.62. The melting point is 84–85ºC. It is practically insoluble in water, soluble in the usual organic solvents, and only slightly soluble in vegetable oils. Pure cholecalciferol is oxidised and inactivated by moist air within a few days. Commercially produced cholecalciferol concentrate and baits are formulated to overcome oxidation and ensure stability.

1.3.2 Historical development, use, and occurrence in nature

Cholecalciferol (vitamin D3) was developed in the 1980s as a rodenticide (Marshall 1984; Tobin et al. 1993). It is registered under the trade name of Quintox® (0.075% cholecalciferol) in the USA, and in Europe it has been added to baits (Racumin® plus) to overcome anticoagulant resistance in rats and mice (Pospischil & Schnorbach 1994). In 1995 a cereal bait containing 0.8% cholecalciferol (Campaign®) was registered for possum control in New Zealand. This was followed in 1999 by the development of a paste bait containing 0.8% cholecalciferol (FeraCol®). Two strengths of FeraCol® paste will be available from 2000, 0.8% for possums and 0.08% for rats and mice. Cholecalciferol is synthesised in animal skin by the action of sunlight on its precursor, 7-dehydrocholesterol. Natural dietary sources of vitamin D3 include liver, fish oils, egg yolk, and milk fat. Vitamin D exists in two forms, vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol), each sharing the same steroid nucleus, but having different side chains. Both forms of vitamin D appear to be identically metabolised and express similar biological activity in mammalian species. Cholecalciferol seems to be more widely used as toxin, probably because it is more readily available and less expensive than ergocalciferol.

Because Vitamin D3 is naturally occurring and is involved in calcium homeostasis, there has on occasion been a tendency to consider baits containing cholecalciferol as safe to non-target species. However, the relatively lower sensitivity of cats and dogs compared with rodents does not make this product ‘safe’ for pets. Inappropriate marketing of cholecalciferol-containing rodenticides in Australia in the late 1980s produced a spate of poisoning incidents and subsequent backlash against its use. While target species for cholecalciferol are amongst the most sensitive, all bait containing cholecalciferol must be treated as potentially poisonous to non-target species, and must be handled and dispensed as carefully as other types of toxic bait.

1.3.3 Fate in the environment

There are no published data on the fate of cholecalciferol in soil and water. The manufacturers of Campaign® (Aventis) have suggested that cholecalciferol residues will be degraded by sunlight. Proper use of cholecalciferol-containing baits will limit the contamination of soil. Some baits may be spilt from bait stations. Cholecalciferol leaches from cereal baits very slowly and trace amounts will be found in soil immediately underneath disintegrating baits (Booth et al. 1999a). Once cereal baits have disintegrated, low-level residues of cholecalciferol in soil are unlikely to present a significant hazard. Since cholecalciferol is licensed for use only in bait stations, any contamination will be localised. Cholecalciferol is most unlikely to be found in waterways when used in a proper manner in appropriately designed bait stations.

1.3.4 Toxicology and pathology

Onset of symptoms

Possums that receive a lethal dose of cholecalciferol bait usually die within 4–7 days. Clinical signs commonly expressed include loss of appetite, constipation, lethargy, tachypnea (rapid and shallow breathing), and death. Death is thought to result from hypercalcaemia, tissue calcification, and renal or cardiac failure (Jolly et al. 1993; Beasley et al. 1997a).

The occurrence, speed of onset, and severity of signs is dose-dependent. There appears to be some species variation in the clinical signs of poisoning and target organs affected by cholecalciferol (Jolly et al. 1993). The clinical signs reported in cats and dogs include nausea, vomiting, and diarrhoea, but these do not occur in possums.

Mode of action

In order to gain biological and toxicological activity, cholecalciferol must undergo metabolic conversion to 25-hydroxycholecalciferol. At toxic doses, this active metabolite mobilises calcium stores from bones into the bloodstream, and decreases calcium excretion by the kidneys. The net result is dangerously high concentrations of blood calcium (hypercalcaemia) and tissue calcification. Tissue calcification can occur in the cardiovascular system, kidneys, stomach, lungs, and muscles. Mineralisation and blockage of blood vessels, with death probably from heart failure, appears to be the mode of action of cholecalciferol in the possum, as in rodents. In other species, including cats and dogs, renal failure (caused by vessel blockage and nephrocalcinosis) and gastrointestinal haemorrhage appear more prominent (Gunther et al. 1988; Moore et al. 1988; Jolly et al. 1993).

Sub-lethal poisoning of target species can cause prolonged anorexia and wasting, which creates ethical and animal welfare concerns. Therefore, current baits are designed with the appropriate concentration of cholecalciferol to ensure maximum potency. Calcium has been added to cereal baits in New Zealand to increase their effectiveness (Jolly et al. 1995). To avoid sub-lethal poisoning, it is particularly important for cholecalciferol baits that adequate palatability and efficacy of any new formulations are established using reliable quality assurance procedures.

Pathology and regulatory toxicology

Post-mortem examination of possums poisoned with cholecalciferol-containing bait has revealed pale, mottled hearts, oedema, and lung congestion. Histological examination has revealed widespread mineralisation of cardiac muscle fibres and calcification of blood vessel walls in the heart, kidneys, and lungs. In other species (cats and dogs) nephrocalcinosis and gastrointestinal haemorrhage appear more prominent. Necropsy shows a swollen liver with patchy congestion, pale enlarged kidneys with congested cortical vessels, pale blotching of the intestines, areas of gritty mucosa in the stomach, and pallid heart musculature. Histopathology shows widespread metastatic calcification of soft tissue e.g. renal tubules, submucosal and mucosal regions of stomach and small intestine, heart, and arterial walls of viscera.

The authors were unable to access data from regulatory toxicology studies on cholecalciferol. Regulatory toxicology studies are conducted in in vitro test systems and laboratory animals to assess risk to humans with regard to issues such as mutagenicity, teratogenicity, and define to no-effect levels.

Fate in animals
Absorption, metabolism, and excretion

Cholecalciferol after absorption from the intestine is transported to the liver, where it is metabolised to 25-hydroxycholecalciferol (25OHD). This metabolite is then transferred to the kidney and converted to 24,25-, or 1,25-dihydroxycholecaliferol. The latter metabolite is the most biologically active form of the vitamin.

Half-lives of cholecalciferol of 0.8–7.9 days have been observed in vitamin D-deficient humans and rats and 3–36 days in normal humans. The half-lives of the active metabolite 25OHD are 10.5–12 days in vitamin D-deficient humans, 15–36 days in humans when vitamin D status was normal, and 25–68 days in humans and cattle during vitamin D toxicity. Interestingly the half-life of 25OHD is shorter in seals than in other mammals, which probably explains the resistance of this species to cholecalciferol toxicity (Keiver et al. 1988). The fate of the 25OHD has been studied in a dog undergoing treatment for poisoning. Levels of 25OHD decreased from >250 ng/mL to normal (i.e. <50 ng/mL) within 30 days (Dougherty et al. 1990). After possums have received a lethal dose (20 mg/kg) of 0.8% cholecalciferol, the mean concentrations of the active metabolite in the blood increased from <50 to between 600 and 1000 ng/mL (Eason et al. 1996c).

Persistence studies in possums with cholecalciferol indicated that elevated concentrations of 25OHD are likely to persist for several weeks in animals that had received sub-lethal doses. In comparison to other examples of cholecalciferol excretion in the literature, the clearance of elevated 25OHD in poisoned possums appeared to be quite slow. This is perhaps not surprising since it has been shown in other animals that clearance of 25OHD is dose-dependent (Keiver et al. 1988) and target animals poisoned with cholecalciferol receive extremely high near-lethal doses. Clearly 25OHD is more persistent than rapidly eliminated poisons like 1080 (Eason et al. 1996a), but is less persistent than second-generation anticoagulants (Eason et al. 1996b).

Species variation in response to cholecalciferol

The single-dose LD50 for cholecalciferol in Norway rats and house mice is very similar but there is considerable species variation in susceptibility amongst other mammals and birds (Table 7). Possums and rabbits appear to be particularly sensitive to cholecalciferol (Eason 1993; Eason et al. 1994a; Henderson et al. 1994; Jolly et al. 1995; Henderson & Eason 2000) and recent studies overseas have shown cholecalciferol to be effective in controlling rock squirrels, gophers, and ground squirrels (Beard et al. 1988; Tobin et al. 1993). Cats appear to be less susceptible than possums, but toxicity was less consistent with some cats surviving doses up to 200 mg/kg, while others died at 50 mg/kg (Eason 1991).

Table 7. Acute oral toxicity (LD50 mg/kg) of cholecalciferol (Eason 1993; Eason et al. 1994a; Jolly et al. 1995)

Species LD50(mg/kg)

Rabbit 9.0

Possum 16.8 (reduced to 9.8 when administered with calcium)

Rat (Norway) 42.5

Mouse 43.6

Dog 80.0

Duck 2000.0

The relatively high LD50 in ducks suggests that cholecalciferol is less toxic to birds than the other toxins used for possum control. If the LD50 in ducks were applicable to other species, then a 500-g bird would need to eat approximately 100–150 g of bait to receive a lethal dose. However, mortalities in canaries and chickens at 2000 mg/kg indicate that some species may succumb to toxicosis after eating <100 g of bait containing cholecalciferol (Eason et al. 2000), and there are reports that calciferol (Vit D2), which is closely related to cholecalciferol, has killed song birds when used in bait for rodent control (Quy et al. 1995). These articles suggest some level of vulnerability of non-target birds to cholecalciferol.

Aquatic toxicology

There are no published data on the aquatic toxicity of cholecalciferol. In the unlikely event of significant amounts of cholecalciferol bait being applied directly to a small stream, poisoning of some aquatic organisms might result. However, fish are naturally rich in cholecalciferol and animals that exclusively eat fish (e.g. seals) appear to be able to cope with levels of vitamin D that would be toxic to most mammals (Keiver et al. 1988).

1.3.5 Diagnosis and treatment of cholecalciferol poisoning

Diagnosis of non-target poisoning in domestic animals

Diagnosis of cholecalciferol toxicosis is based on exposure history, clinical signs, development of hypercalcaemia, and in lethal cases, lesions. Veterinarians should note that differential diagnoses in dogs include hypercalcaemia secondary to paraneoplastic syndrome (especially with lymphosarcoma), juvenile hypercalcaemia, and hyperparathyroidism.

Clinical signs

Clinical signs in companion animals can be divided into neurologic, cardiovascular, gastrointestinal, and renal effects (Beasley et al. 1997a). Signs of poisoning usually develop within 12B36 hours after consumption of a toxic dose. Initial signs may be non-specific and moderate, and include anorexia, lethargy, weakness, nausea, vomiting ( blood), diarrhoea ( blood), polyuria (increased urination), polydipsia (increased water consumption), and rarely neurological abnormalities (e.g. seizures). Clinical signs become more severe 24B36 hours after onset, as serum calcium levels increase. Renal effects, including polyuria, hyposthenuria (decreased urine specific gravity), and azotemia (increased blood urea nitrogen (BUN) and creatinine) become more pronounced. Hypercalcaemia can result in electrocardiogram (ECG) changes, (Dorman & Beasley 1989). Heart sounds are slowed and prominent, and animals become progressively more depressed. Death usually occurs in 2 to 5 days from the onset of clinical signs.

Laboratory diagnosis

The most significant and specific clinical pathology alteration is hypercalcaemia. Serum calcium concentration begins to increase about 24 hours after exposure, and values of >11.5 mg/dL in adult dogs are highly suggestive of cholecalciferol poisoning. Elevations of serum phosphate may proceed hypercalcaemia by 12 hours, and may serve as a non-specific indicator of exposure. Renal azotemia and hyposthenuria (urine specific gravity in the 1.002B1.006 range) are common, and proteinuria and glucosuria may be seen in some acute cases. Increased tissue 1, 25-dihydroxycholecalciferol is a sensitive indicator. Kidney calcium concentrations may reach 1000 ppm in poisoned animals, compared with about 100 ppm in normal dogs (Osweiler 1996a; Beasley et al. 1997a).


Gross lesions include roughened, raised plaques in the intima of large vessels, petechial haemorrhages in various tissues; enlarged, pale thyroid glands; and pale, mineralised streaks in renal cortical surfaces. Histopathologically, calcification and necrosis of intramural coronary arteries, gastric mucosa, intestinal wall, parietal pleura, pulmonary bronchioles, pancreas, thyroid, muscles, and bladder have been observed. Degeneration, necrosis, and mineralisation may occur in the myocardium and especially the renal tubular epithelium (Beasley et al. 1997a; Jones et al. 1997).

Treatment of cholecalciferol toxicosis in domestic animals

Cholecalciferol poisoning is a medical emergency. Treatment of animals presented with severe or advanced clinical signs is difficult and prolonged, and the prognosis is guarded. Therefore, treatment should be initiated rapidly in order to maximise the probability of survival. Therapeutic goals are (1) to decrease cholecalciferol absorption; (2) to correct fluid and electrolyte imbalances; and (3) to prevent or reduce hypercalcaemia. Current recommendations for the treatment of cholecalciferol toxicosis in companion animals are as follows (treatment should be followed in order) (Dorman & Beasley 1989; Beasley et al. 1997a):

  • If ingestion was recent (< 3 hours), induce emesis with household salt solution or washing soda crystals, or perform gastric lavage.

  • Administer activated charcoal (1B2 g/kg) with a saline cathartic (magnesium sulphate at 250 mg/kg in 5–10 times as much water).

  • Continue activated charcoal (at 0.5B1.0 g/kg t.i.d.) for 1B2 days to reduce enterohepatic recirculation of vitamin D and its active metabolites.

  • Determine baseline serum calcium as soon as the animal is presented (to rule out normally occurring juvenile hypercalcaemia — values up to 14 mg/dL reported in some puppies), and continue to monitor serum calcium levels every 24 hours to determine if specific therapy to reduce serum calcium is required.

  • Monitor BUN and creatinine, urine specific gravity, heart sounds, and ECG parameters, beginning 24 hours after exposure.

  • Hypercalcaemia is treated with:

  • Diuresis with IV normal saline and frusemide (5 mg/kg initial IV bolus, followed by 3B4 mg/kg orally t.i.d.) to enhance renal calcium excretion. Thiazide diuretics are contraindicated since they may decrease urinary calcium. Early diuresis (initiate within the first 24 hours) is highly recommended in all animals with potentially serious exposures.

  • Corticosteroid administration (prednisone at 2B4 mg/kg, divided, b.i.d.) to inhibit the release of osteoclast-activating factors, reduce intestinal calcium absorption, and promote renal calcium excretion.

  • If serum calcium is excessive (>14 mg/kg), or hypercalcaemia is prolonged and unresponsive, administer salmon calcitonin to inhibit osteoclast activity at 4B6 IU/kg subcutaneously every 2B3 hours initially, until serum calcium levels stabilise (may be increased to 10B20 IU/kg if needed). Long-term administration at increased doses may be required, and some animals become refractory to treatment. Animals should be monitored for foreign protein reactions.
  • Life-threatening (> 20 mg/dL) hypercalcaemia may be treated with IV sodium EDTA at 25B75 mg/kg/h (human doses), although EDTA is potentially nephrotoxic. Severely hypercalcaemic or uremic animals may also benefit from peritoneal dialysis with calcium-free dialysate solutions.

  • Treatment with diuretics (frusemide at 2B4 mg/kg PO b.i.d.) and corticosteroids (prednisone at 2B4 mg/kg divided b.i.d.) should continue until serum calcium concentrations stabilise in the normal range. It is also valuable to continue to monitor BUN as an indicator of renal function. Often treatment is administered for 2B4 weeks, followed by withdrawal of therapy, and retesting serum calcium after 24 hours. Continue treatment until serum calcium remains normal at 24, 48, and 72 hours after withdrawal.

1.3.6 Non-target effects

The use of cholecalciferol baits in bait stations should limit non-target effects. Baits in bait stations are likely to be less accessible to non-target species than baits on the ground. A reassessment of the non-target hazards associated with toxic bait containing cholecalciferol has been recently completed by Eason & Wickstrom (2000). Current and future research questions for cholecalciferol relate to further investigation of primary and secondary poisoning risks to non-target species, its relative humaneness, and its persistence in the environment and animals.

Acute toxicity

In comparison with 1080 or brodifacoum, there is limited information on the susceptibility of non-target species to cholecalciferol. Primary poisoning assessments to gauge non-target susceptibility were undertaken with weta, ducks, chickens, canaries, and weka. Following oral gavage of cholecalciferol concentrate at 2000 mg/kg, there were no adverse effects in ducks. Chickens and canaries were more sensitive and some deaths occurred at 2000 mg/kg. Weka ate over 50 g of (0.1%) cholecalciferol without ill effects. Weta were not affected by oral administration of a single dose of cholecalciferol. Campaign® baits are dyed green and contain a high concentration of cinnamon (0.5%) to deter birds. Domestic cats or farm dogs allowed access to baits containing cholecalciferol may be killed or exhibit symptoms of cholecalciferol toxicosis. Treatment of cholecalciferol toxicosis is difficult (see section 1.3.5) (Hatch & Laflamme 1989) and prevention of exposure is critical.

Secondary poisoning

Three secondary-poisoning studies are summarised in Table 8. These assessments involved the feeding of carcasses of poisoned animals to cats or dogs as their only food source for consecutive days. Dogs and cats fed these carcasses were therefore exposed to concentrations of 25OHD residues usually encountered by scavengers after poisoning operations. In addition, in order to create a worst-case secondary-poisoning scenario, some dogs were fed possums 48 hours after dosing with cholecalciferol (Eason & Wickstrom 2000). The feeding study in cats appeared to confirm earlier work with dogs (Marshall 1984), which indicated that the risk of secondary poisoning with cholecalciferol is low. This is despite the presence of elevated concentrations of 25OHD in possum carcasses. Research in rats has previously demonstrated that 25OHD is active when administered orally (Rambeck et al. 1990), but is partially degraded in the intestinal tract (Frolick & Deluca 1973). Hence not all the 25OHD present in poisoned carcasses will be bioavailable to cats and dogs. The study by Eason & Wickstrom (2000) demonstrated repeated consumption of poisoned carcasses by dogs over 5 days induced hypercalcaemia and calcium deposition in the kidney. This was accompanied by partial anorexia and lethargy. Nevertheless, all affected dogs began to recover without veterinary intervention by about 14 days after exposure.

Low risks of secondary poisoning with cholecalciferol does not imply no risk, and all pets and farm dogs should be discouraged from eating animals that have been poisoned with cholecalciferol. Given that mild toxicosis can occur in dogs eating possum meat, a precautionary approach should be followed, and it would be extremely unwise for hunters to take game from areas where cholecalciferol has been used in the previous 1–3 months. Game species, particularly if they have gained direct access to bait, would be potentially hazardous to humans since they would be likely to contain abnormal levels of 25OHD for 1–2 months.

Table 8. Summary of secondary poisoning studies

Non-target species





Dogs fed rat carcasses for 14 days (after poisoning with 0.08% cholecalciferol baits)

No clinical signs of toxicosis

No pathological abnormalities

Marshall 1984


Cats fed possum carcasses for 5 days (after poisoning with 0.8% cholecalciferol baits)

No toxicosis

Non-significant increase in plasma Ca++

Eason et al. 1996a,c


Variable from single to multiple feeding of dogs with possum carcasses (after poisoning with 0.8% cholecalciferol baits)

No toxicosis in dogs receiving 1 or 2 carcasses.

Exposure to 5 carcasses resulted in moderate, sub-lethal toxicosis.

Eason & Wickstrom 2000

1.3.7 Summary



Available to general public

Expensive compared to 1080 and cyanide

Can rapidly reduce possum numbers (an acute toxin)

Not registered for aerial application

Low risk of secondary poisoning

Treatment for accidental poisoning of pets is available, but is complex – use of secure bait stations is essential

Less toxic to birds than 1080

A useful single-dose alternative to 1080

No long-term residue risks in sub-lethally exposed animals

  • The active ingredient of cholecalciferol is vitamin D3.

  • Cholecalciferol occurs in fish, liver, eggs, and milk.

  • Cholecalciferol is practically insoluble in water.

  • Possums and rodents that receive a lethal dose of cholecalciferol usually die within 4–7 days after ingestion.

  • Possums, rats, and rabbits are particularly susceptible to cholecalciferol; however, cholecalciferol will be toxic to all mammals that eat baits intended to kill possums or rodents. Post-mortem pathological changes in possums are consistent with heart failure. In other species kidney damage and gastrointestinal haemorrhage are more prominent.

  • After ingestion, cholecalciferol is converted to 25-hydroxycholecalciferol (25OHD), which acts to increase serum calcium concentrations by multiple mechanisms. The persistence of the active metabolite increases with increasing dose levels. For example, in humans the half-life of 25OHD is normally 15–36 days, but this increases to 25–68 days in humans during vitamin D toxicity. Elevated levels of 25OHD are likely in possum carcasses. Cholecalciferol poisoning can be diagnosed by elevated blood 25OHD and calcium concentration, and at post-mortem by evidence of calcification.

  • The risk of secondary poisoning would appear to be low; however, poisoned carcasses are likely to contain active metabolites of cholecalciferol. These metabolites will be partially degraded in the intestine of an animal eating poisoned possums. Domestic pets and farm dogs should always be discouraged from eating poisoned carcasses.

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