Vertebrate Pesticide Toxicology Manual (Poisons)

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2.6 Pindone

Chemical Name: 2-pivaloyl-1,3-indandione.

Synonyms: Pindone is the approved common name.

Pindone is one of the earliest first-generation anticoagulant rodenticides developed in the 1940s.

2.6.1 Physical and chemical properties

The empirical formula for pindone is C14H14O3 and the molecular weight is 230.3. It is a yellow crystalline powder with a melting point of 108.5–110.5ºC and low solubility in water (18 mg/L) at 25ºC. A sodium salt (‘Pival’ or pindone-sodium) C14H13NaO3 with a molecular weight 252.3 is readily water soluble.

2.6.2 Historical development and use

Pindone, like diphacinone, belongs to the indandione class of anticoagulants, which differ chemically from coumarin anticoagulants such as brodifacoum or warfarin.

Pindone was synthesised in 1937 (Beauregard et al. 1955) and developed as a pesticide in the early 1940s. It was originally evaluated as an alternative to pyrethrin because of its insecticidal properties (Kilgare et al. 1942). Subsequently it was selected for extended study as it possessed the strongest insecticidal and anticoagulant characteristics of a series of 1,3 indandiones (Crabtree & Robinson 1953). In 1948 pindone was shown to be an effective alternative to DDT for the treatment of body lice (Eddy & Bushland 1948), but it has not been widely used as an insecticide.

Pindone has been used worldwide to control rodents, though its use for the control of rats and mice has decreased following the introduction of more potent anticoagulants such as brodifacoum. There are two other indandiones, diphacinone and chlorophacinone, which were synthesised in the 1950s and 1960s, and these two newer, more potent compounds have also contributed to a reduction in pindone use for rodent control.


In New Zealand pindone has been used to control wallabies and possums, but in both Australia and New Zealand it has proved most effective for rabbit control (Eason & Jolly 1993). Pindone is currently registered in New Zealand for the control of rabbits and possums. It is most effective for rabbit control.

2.6.3 Fate in the environment

There are no published data on the fate of pindone or its metabolites in soil and water. However, there are unpublished data that indicate that pindone is slowly degraded in soil and water (G. Wright, pers. comm.).

In comparative studies, pindone is more slowly leached from oat grain bait for rabbits when compared with 1080. The authors attribute this to the lower solubility of pindone in water (Wheeler & Oliver 1978). This has recently been confirmed by New Zealand researchers (Booth et al. 1999a), which may in part explain the higher than expected non-target mortality observed after broad-scale use of pindone.

A small survey of water samples in a catchment area where pindone baits had been aerially sown for rabbit control was completed in 1994 (G.R.G. Wright pers. comm.). No pindone residues were detected.

2.6.4 Toxicology and pathology

Onset of signs

As for other anticoagulants.

Mode of action

Pindone acts like the other anticoagulant toxicants by interfering with the normal synthesis of vitamin K-dependent clotting factors in the liver. The weaker potency of first-generation anticoagulants such as pindone is related to a generally lower binding affinity when compared to second-generation compounds (Parmar et al. 1987; Huckle et al. 1988). The mechanism by which pindone exerts insecticidal and fungicidal activity has not been described in the literature.


Pathology and regulatory toxicology

As with all other anticoagulant compounds, clinical signs of toxicosis in animals will usually reflect some manifestation of haemorrhage. Onset of signs may occur suddenly; this is especially true when haemorrhage of the cerebral vasculature or pericardial sac occurs. Clinical signs commonly include anaemia and weakness. Haemorrhaging may be visible around the nose, mouth, eyes, and anus and animals may pass bloody faeces. When pulmonary haemorrhage has occurred, blood-tinged froth may be visible around the nose and mouth. Swollen, tender joints are common and, if haemorrhage involves the brain or central nervous system, ataxia or convulsions can occur. Poisoned animals will die usually of multiple causes associated with anaemia or hypovolemic shock. Some possums receiving high doses of pindone have died without any signs of haemorrhaging, and necropsy has revealed liver damage (Jolly et al. 1994). The authors were unable to locate any regulatory toxicology data relating to pindone.

Fate in animals
Absorption, metabolism, and excretion:

Pindone is absorbed through the gastrointestinal tract. Tissue distribution of pindone seems to be somewhat different from other anticoagulants. Plasma concentrations remain higher than tissue concentrations for 8 days and concentrations in the liver and kidney are comparable (Fitzek 1978). Pindone is far less persistent than second-generation anticoagulants such as brodifacoum, and is less persistent than diphacinone, which is consistent with our understanding of the mode of action and relative potencies of these compounds.

In dogs this compound is fairly well absorbed (67%) and the plasma elimination half-life is approximately 100 hours after administration of 3 mg/kg (Fitzek 1978). In sheep, residues were detected in the liver and fat of animals dosed with 20 mg/kg for 8 days, but at 2 weeks none was detected (Nelson & Hickling 1994).


Species variation in response to pindone:

There are limited acute toxicity data available on pindone, but even these data show marked species variation. For first-generation anticoagulants such as pindone, either very large single doses or repeated smaller doses are generally needed to induce death. A single dose of approximately 18 mg/kg is, however, sufficient to kill rabbits (Table 21).

In rabbits the repeat dose (7 days) LD50 is 0.52 mg/kg/day, while all rabbits receiving 1 mg/kg for 7 days died. By contrast, pindone doses of up to 12 mg/kg/day do not cause clinical or post-mortem haemorrhage in sheep (Oliver & Wheeler 1978). Possums appear to be even more resistant to pindone than sheep. None of 12 possums dosed at 8 and 16 mg/kg/day for 5 days died. One of 12 possums died when dosed with 32 mg/kg/day for 5 days, and 9 of 14 possums died when dosed with 64 mg/kg/day for 5 days. From these data an LD50 of 51 mg/kg/day for 5 days was calculated (Jolly et al. 1994).

Non-target research conducted in Australia provides information on the susceptibility of horses, cattle, goats, chickens, dogs, and cats. All these species were less susceptible than rabbits. Daily doses of pindone, ranging from 0.3 to 2.5 mg/kg, were administered for 5 days. No mortalities occurred and susceptibility was assessed by using extension of prothrombin time as a biomarker of poisoning. In this study, cattle and cats appeared most susceptible out of the six species tested, and horses least susceptible to pindone toxicity (Martin et al. 1991). Nevertheless, the rabbit remains outstanding as the most susceptible mammalian species evaluated to date.


Table 21. Acute oral toxicity (LD50mg/kg) of pindone (Beauregard et al. 1955; Oliver & Wheeler 1978; Hone & Mulligan 1982; Eason & Jolly 1993).

Species LD50 ((mg/kg)

Rabbit 6–18

Dog 50

Norway rat 75–100

Sheep approx. 100

Possum >100
Aquatic toxicology:

There are no published aquatic toxicity data for pindone.

2.6.5 Diagnosis and treatment of poisoning

As for brodificoum, see Section 2.1.5 (pp. 57–60).

2.6.6 Non-target effects

No systematic studies have been conducted to monitor the non-target impact of baits. During 1992–94 the aerial application of pindone baits to control rabbits increased. There have been numerous anecdotal reports (E.B. Spurr, pers. comm.) of extensive bird kills from both primary and secondary poisoning following broad-scale rabbit control in New Zealand, but no monitoring to determine whether or not populations are being affected. Birds found killed included plovers, quails, rails, wrybills, silvereyes, grey warblers, black-back gulls, and Australian harriers (Sullivan 1994). Even less is known about the effects of pindone on invertebrates and reptiles.


In Australia similar rabbit poisoning operations have caused concern with wedge-tailed eagles, noted to be a species at risk. Doses as low as 1–4 mg/kg/day for 5–7 days have caused deaths in this species (D. King pers. comm.).

2.6.7 Summary

Advantages

Disadvantages

No licence required

Not as potent as second-generation anticoagulants or non-anticoagulant poisons such as 1080, cholecalciferol, or cyanide

Effective for rodent control

Not potent for possum control

Highly effective for rabbit control




Antidote




Less persistent than brodifacoum





  • Pindone is a synthetic pesticide that was first synthesised in 1937. Its insecticidal and rodenticidal properties were demonstrated in the 1940s.


  • Pindone is not readily water soluble, but the sodium salt of pindone (pival) is readily water soluble and is sometimes used in New Zealand instead of pindone.

  • Pindone is a first-generation anticoagulant with low potency compared to compounds like brodifacoum, a second-generation anticoagulant.

  • Pindone is moderately toxic to a range of species. Rabbits are extremely susceptible; by contrast sheep, possums, and horses are comparatively resistant. There are anecdotal reports that raptors are particularly susceptible to secondary poisoning.

  • Pindone is far more effective for rabbit control than it is for possums.

  • Pindone is moderately persistent; far more persistent in animals than 1080, but considerably less persistent than brodifacoum.

  • The toxicity and non-target impacts of pindone are poorly documented.


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