Vertebrate Pest Control Manual

Vertebrate Pesticide Toxicology Manual (Poisons) Information on Poisons Used in New Zealand as Vertebrate Pesticides

2nd Edition (formerly the ‘Toxins Manual’)

Charles T. Eason and Mark Wickstrom Acknowledgements This nomination has the endorsement of the New Zealand Conservation Authority and the Royal Forest and Bird Protection Society. © Crown copyright

Department of Conservation PO Box 10-420 Wellington New Zealand

Foreword This manual was first compiled in 1997 and published by the Department of Conservation as a scientific reference document designed to assist all those involved in the planning, and use of, registered poisons for the control of animal pests in New Zealand. It is appropriate that a second edition has been produced as the use of pest control products for conservation is a rapidly evolving field with numerous publications relating to their efficacy, advantages, and disadvantages appearing in the last 3 years. Please note that other documents will need to be referred to for details of the Health and Safety aspects of working with toxic substances. The Department recognises that the use of vertebrate pesticides to control animal pests will always be difficult for some members of the wider community to accept, especially the concept that the benefits of their use may outweigh any perceived or real deleterious environmental effects. New Zealand’s animal pest problems are unique. Unlike in Australia, where many native plants contain natural toxins (including monofluoroacetate, the active chemical for 1080) as defence against browsing animals, the New Zealand forests evolved in the absence of mammals and without a need for such chemical defences. Our forests are, therefore, extremely vulnerable to mammalian browsers. The application of toxic baits has been developed as one effective means of controlling animal pests. Continued access to, and acceptability of, poisons is essential if we are to maintain our economic health and meet our international obligations for biodiversity protection, to say nothing of maintaining the natural heritage of our forest landscapes. The maintenance of this access depends upon the continued responsible use of poisons by all who are required to use them. It must be appreciated that all poisons have advantages and disadvantages, which make them more or less appropriate for different use patterns. The information included in this manual is specifically relevant to the use of toxic baits for pest control as part of the management of conservation lands and protected species. It is, however, likely to be useful to all land managers who currently use or would consider the use of toxic baits to deal with animal pests; the Department expects, and welcomes its use by a wide range of agencies and individuals who have similar pest problems, or a need to understand the toxicology and safety issues associated with the use of vertebrate pesticides. The Vertebrate Pesticide Toxicology Manual (Poisons) contains details from the most recently published scientific data on the effects and impacts of specific poisons on the environment, target, and non-target species. This document should be used in conjunction with other documents such as the Department of Conservation’s National Possum Control Plan. We urge all users to acknowledge, however, that it can only be their personal responsibility to remain up-to-date in all aspects of law and current best practice in the use of these tools. If in any doubt, seek advice! Please note that this manual has been compiled independently of the Department of Conservation’s Quality Conservation Management (QCM) process, but should be used in conjunction with the proposed Animal Pest QCM. The emphasis in this edition is similar to that in the first edition. Those poisons used widely are reviewed in considerable depth, e.g. 1080, cyanide, brodifacoum, and cholecalciferol. Some, but 1

less complete, information is provided on other poisons and those no longer used in New Zealand. We trust that this manual when used in conjunction with the Animal Pest QCM will provide clear and concise information on the planning, use, and effects of poisons for animal pest control. Suggestions for the improvement of this manual are welcome.

Murray Hosking General Manager, Conservation Policy

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Contents Foreword .....................................................................................................................1 Contents ......................................................................................................................3 Introduction .................................................................................................................7 SECTION 1: ACUTE POISONS

9

1.1 Sodium monofluoroacetate (1080) ......................................................................9 1.1.1 Physical and chemical properties ................................................... 9 1.1.2 Historical development, use, and occurrence in nature .................. 9 1.1.3 Fate in the environment ................................................................ 10 1.1.4 Toxicology and pathology ............................................................ 16 1.1.5 Diagnosis and treatment of 1080 poisoning .................................24 1.1.6 Non-target effects ......................................................................... 26 1.1.7 Summary....................................................................................... 29 1.2 Cyanide (Feratox®) ........................................................................................... 30 1.2.1 Physical and chemical properties ................................................. 30 1.2.2 Historical development, use, and occurrence in nature ................ 30 1.2.3 Fate in the environment ................................................................ 32 1.2.4 Toxicology and pathology ............................................................ 32 1.2.5 Diagnosis and treatment of cyanide poisoning ............................. 36 1.2.6 Non-target effects ......................................................................... 38 1.2.7 Summary....................................................................................... 39 1.3 Cholecalciferol (Campaign®, FeraCol®) .......................................................... 40 1.3.1 Physical and chemical properties ................................................. 40 1.3.2 Historical development, use, and occurrence in nature ................ 40 1.3.3 Fate in the environment ................................................................ 41 1.3.4 Toxicology and pathology ............................................................ 41 1.3.5 Diagnosis and treatment of cholecalciferol poisoning ................. 44 1.3.6 Non-target effects ......................................................................... 46 1.3.7 Summary....................................................................................... 47 SECTION 2: ANTICOAGULANT POISONS

49

2.1 Brodifacoum (Talon®, Pestoff®) ......................................................................49 2.1.1 Physical and chemical properties ................................................. 49 2.1.2 Historical development and use .................................................... 49 2.1.3 Fate in the environment ................................................................ 50 2.1.4 Toxicology and pathology ............................................................ 50 2.1.5 Diagnosis and treatment of anticoagulant poisoning .................... 57 2.1.6 Non-target effects ......................................................................... 61 2.1.7 Summary....................................................................................... 65 2.2 Flocoumafen ......................................................................................................66 2.2.1 Physical and chemical properties ................................................. 66 2.2.2 Historical development and use .................................................... 66 2.2.3 Fate in the environment ................................................................ 66 3

2.2.4 2.2.5 2.2.6 2.2.7

Toxicology and pathology ............................................................ 66 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 69 Non-target effects ......................................................................... 69 Summary....................................................................................... 69

2.3 Bromadiolone (Rid Rat) ..................................................................................... 70 2.3.1 Physical and chemical properties ................................................. 70 2.3.2 Historical development and use .................................................... 70 2.3.3 Fate in the environment ................................................................ 71 2.3.4 Toxicology and pathology ............................................................ 71 2.3.5 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 72 2.3.6 Non-target effects ......................................................................... 72 2.3.7 Summary....................................................................................... 73 2.4 Coumatetralyl (Racumin®) ............................................................................... 73 2.4.1 Physical and chemical properties ................................................. 73 2.4.2 Historical development and use .................................................... 74 2.4.3 Fate in the environment ................................................................ 74 2.4.4 Toxicology and pathology ............................................................ 74 2.4.5 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 75 2.4.6 Non-target effects ......................................................................... 75 2.4.7 Summary....................................................................................... 75 2.5 Diphacinone (Ditrac®) ...................................................................................... 75 2.5.1 Physical and chemical properties ................................................. 75 2.5.2 Historical development and use .................................................... 76 2.5.3 Fate in the environment ................................................................ 76 2.5.4 Toxicology and pathology ............................................................ 76 2.5.5 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 78 2.5.6 Non-target effects ......................................................................... 78 2.5.7 Summary....................................................................................... 79 2.6 Pindone .............................................................................................................. 79 2.6.1 Physical and chemical properties ................................................. 79 2.6.2 Historical development and use .................................................... 79 2.6.3 Fate in the environment ................................................................ 80 2.6.4 Toxicology and pathology ............................................................ 80 2.6.5 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 82 2.6.6 Non-target effects ......................................................................... 82 2.6.7 Summary....................................................................................... 83 2.7 Warfarin ............................................................................................................. 83 2.7.1 Physical and chemical properties ................................................. 83 2.7.2 Historical development and use .................................................... 84 2.7.3 Fate in the environment ................................................................ 84 2.7.4 Toxicology and pathology ............................................................ 84 2.7.5 Diagnosis and treatment of poisoning (see 2.1.5) ........................ 86 2.7.6 Non-target effects ......................................................................... 86 2.7.7 Summary ....................................................................................... 86

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SECTION 3: TOXINS NO LONGER USED BY THE DEPARTMENT

87

3.1 Phosphorus 3.1.1 3.1.2 3.1.3 3.1.4 3.1.5

......................................................................................................87 Physical and chemical properties ................................................. 87 Historical development and use .................................................... 87 Fate in the environment ................................................................ 87 Toxicology and pathology ............................................................ 88 Current use .................................................................................... 89

3.2 Arsenic 3.2.1 3.2.2 3.2.3 3.2.4 3.2.5

......................................................................................................90 Physical and chemical properties ................................................. 90 Historical development and use .................................................... 90 Fate in the environment ................................................................ 90 Toxicology and pathology ............................................................ 90 Current use .................................................................................... 91

3.3 Strychnine ......................................................................................................91 3.3.1 Physical and chemical properties ................................................. 91 3.3.2 Historical development and use .................................................... 92 3.3.3 Fate in the environment ................................................................ 92 3.3.4 Toxicology and pathology ............................................................ 92 3.3.5 Current use .................................................................................... 93 SECTION 4: COMPARATIVE RISK ASSESSMENT FOR COMMONLY USED VERTEBRATE PESTICIDES

94

4.1 What and where are the exposure and non-target risks .....................................94 4.1.1 Persistence in water, soil, plants ................................................... 94 4.1.2 Susceptibility and risk reduction for pets and livestock ............... 97 4.1.3 Risk of exposure and toxicity to non-target vertebrates (wildlife)98 4.1.4 Risk of exposure and toxicity to invertebrates ........................... 100 4.1.5 Risk of exposure to humans........................................................ 101 4.1.6 Toxic effects and humaneness in non-target species .................. 104 4.1.7 Humaneness in target species ..................................................... 106 4.1.8 Summary of characteristics of poisons used for possum control108 Acknowledgements .................................................................................................109 References ............................................................................................................... 110 Address list for suppliers of pest control products.................................................. 135 APPENDICES

135

Appendix 1

Glossary of terms ......................................................................... 135

Appendix 2

Quality specifications for 1080 pellet baits .................................139

Appendix 3

Quality specifications for 1080 carrot baits .................................141

Appendix 4

Possum baits per lethal dose (LD) ............................................... 144

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LIST OF TABLES Table 1:

Water analysis after major 1080 operations............................................ 13

Table 2:

Toxicology studies on 1080 relevant to human health: current status ....19

Table 3:

Acute oral toxicity (LD50 mg/kg) of sodium monofluoroacetate ............. 22

Table 4:

Plants with cyanogenic potential ........................................................... 31

Table 5:

Acute oral toxicity (LD50mg/kg) of cyanide ............................................ 35

Table 6:

Acute toxicity (96-hour LD50) of cyanide to daphnia and fish from aquaria ............................................................................................ 35

Table 7:

Acute oral toxicity (LD50mg/kg) of cholecalciferol ................................ 43

Table 8:

Summary of secondary poisoning studies............................................... 47

Table 9:

Acute toxicity (LD50mg/kg) of brodifacoum in rats ................................ 52

Table 10: Persistence of first-generation anticoagulants ........................................ 54 Table 11: Persistence of second-generation anticoagulants ....................................54 Table 12: Acute oral toxicity (LD50mg/kg) of brodifacoum for mammal species...56 Table 13: Acute oral toxicity (LD50mg/kg) of brodifacoum for bird species .......... 57 Table 14: Acute oral toxicity (LD50mg/kg) of flocoumafen ....................................67 Table 15: Occurrence of peak plasma concentrations in animals after oral ingestion of anticoagulants .....................................................................68 Table 16: Acute oral toxicity (LD50mg/kg) of bromadiolone ..................................72 Table 17: Acute oral toxicity (LD50mg/kg) of coumatetralyl ..................................74 Table 18: Radioactivity in the tissue of female rats 8 days after oral administration of a single dose of 14C-diphacinone ................................ 77 Table 19: Detectable diphacinone residues in tissue of cattle.................................77 Table 20: Acute oral toxicity (LD50mg/kg) of diphacinone ....................................78 Table 21: Acute oral toxicity (LD50mg/kg) of pindone ........................................... 82 Table 22: Acute oral toxicity (LD50mg/kg) of warfarin ........................................... 85 Table 23: Acute oral toxicity (LD50mg/kg) of phosphorus ......................................89 Table 24: Acute oral toxicity (LD50mg/kg) of arsenic ............................................. 91 Table 25: Acute oral toxicity (LD50mg/kg) of strychnine ....................................... 93 Table 26: Summary of mean times to onset of clinical signs of toxicosis ............ 107 FIGURE Figure 1: Relationships of aspects of the science of ecotoxicology and toxicology and the different levels of biological organisation. ............. 104

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Introduction The focus of this manual is on the properties of poisons used for mammalian pest control. Intensive measures have been devised, and implemented on an unprecedented scale in New Zealand, to control a wide variety of introduced mammals. These include aerial application of 1080 bait on mainland New Zealand, and baits containing brodifacoum to kill rodents on islands. Such measures are amongst the most aggressive taken worldwide to control introduced mammals. The risk to non-target species, from the compounds, will be determined by their intrinsic susceptibility, the properties of the poisons used, such as the toxicokinetics of these chemicals, as well as bait design and the way in which toxic baits are used in the field, which may limit or exacerbate the exposure of non-target species. The manual documents in detail the different properties of the different poisons. All have advantages and disadvantages, which make them more or less effective or appropriate for different use patterns. There is a massive literature on these compounds generated around the world, which is complemented by New Zealand-based research. A review was undertaken of the first edition of this manual and additional details with regard to the treatment of poisoning incidents were requested (Moffat 1999). In response to this review, the second edition contains more details on symptoms, diagnosis, and treatment for those poisons extensively used: 1080, cyanide, cholecalciferol, and brodifacoum. There is a greater emphasis on comparative toxicokinetics, and a new section at the end of the manual on the comparative risks associated with different poisons. The first edition of this manual has frequently been referred to as the ‘Toxins Manual’ (Haydock & Eason 1997). This reflects some confusion with regard to the following terms: toxins, toxicants, poisons, and vertebrate pesticides. Toxic substances of natural biological origin, principally derived from microbes, plants, and animals are usually described as toxins (e.g. cholecalciferol (vitamin D3), cyanide, and 1080). Toxicants are considered to be substances that are toxic in relatively small doses and do not originate from microbes, animals, and plants (e.g. brodifacoum, phosphorus, and pindone). The term ‘poison’ or ‘vertebrate pesticide’ can be used to cover both toxins and toxicants. In the context of this manual, compounds such as cholecalciferol and warfarin are considered as vertebrate pesticides, whereas the former is commonly regarded as a vitamin and the latter as a drug used to treat blood clotting disorders in humans. This should not be that surprising since ‘All substances are poison and it is only the dose that makes a distinction between one which is a poison and one which is a remedy.’ (Paracelsus c. 1500) Vertebrate pesticides (sometimes referred to as rodenticides) are distinguished from insecticides (toxic to insects), herbicides (toxic to plants), and fungicides (toxic to fungi). In this regard 1080 is unusual as it is known to be toxic to both insects and mammals and could therefore be classified as an insecticide, a vertebrate pesticide, or a rodenticide. We1 hope that compiling the significant toxicological features of these vertebrate pesticides in one document will assist all those directly or indirectly involved in the application of toxic baits for wildlife management. The focus of the document is the 1

Dr C.T. Eason is a Wildlife and Environmental Toxicologist Dr M. Wickstrom is a Veterinary Toxicologist formerly working for Landcare Research, currently at the University of Saskatchewan, Canada

7

toxins and toxicants commonly used by the Department of Conservation (DOC) in New Zealand, e.g. 1080, brodifacoum, cyanide and cholecalciferol. Other, less widely used, anticoagulants and poisons no longer used by the Department are covered only briefly. Toxicology is the study of the fate and effects of compounds with a toxic potential. The manual follows the same general structure as that requested by the Department of Conservation in the first edition. However, a new section has been added to assist with the comparison of the key features of the different toxins and toxicants. A glossary of terms is provided in Appendix 1. Note that many common names for animals are used throughout the manual. Those interested are referred to the original research for the scientific names where these are not cited.

Dr Charles T. Eason CENTOX Centre for Environmental Toxicology Landcare Research, Lincoln

While every care has been taken to ensure its accuracy, the information obtained in this report is not intended as a substitute for specific specialist advice. Landcare Research accepts no liability for any loss or damage suffered as a result of relying on the information, or applying it either directly or indirectly.

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SECTION 1 : ACUTE POISONS 1.1

Sodium monofluoroacetate (1080)

Chemical Name: Sodium monofluoroacetate. Synonyms: monofluoroacetate or Compound-1080 or 1080 (“ten-eighty”) Sodium monofluoroacetate (1080) is still the most widely used poison for possum control in New Zealand (in carrot, cereal, paste, and gel baits) for situations where possum numbers need to be reduced rapidly over large areas. Carrot baits are screened to remove small pieces so that the risks of birds eating baits is reduced. Cereal baits are used for both aerial and bait station control. Paste baits, and more recently gel bait, are used for ground-based follow-up maintenance control. Cinnamon is usually added to baits to mask the taste of 1080, and may be a partial deterrent to birds. Sodium monofluoroacetate can only be used by licensed operators. 1.1.1

Physical and chemical properties

The empirical formula for 1080 is C2H2FNaO2 and the molecular weight is 100.3. It forms an odourless, white, non-volatile powder that decomposes at about 200ºC. Although the compound is often said to be tasteless, dilute solutions are thought to taste like weak vinegar. Sodium monofluoroacetate is very water-soluble but has low solubility in organic solvents such as ethanol and oils. Monofluoroacetates are chemically stable, hence 1080 as a pure compound in powder form—or when prepared in an aqueous stock solution—will not readily decompose. 1.1.2

Historical development, use, and occurrence in nature

Sodium monofluoroacetate was first used in the United States about 50 years ago to control gophers, ground squirrels, prairie dogs, field mice, and commensal rodents. In New Zealand it is a pivotal component of pest control and has been developed specifically for aerial control of possums (Morgan 1994a,b), though it is increasingly being used for predator control through primary (pers. comm. E.B. Spurr) and secondary poisoning (Alterio 2000). Currently in New Zealand the principal target species are possums (Thomas 1994) and rabbits. Overuse of 1080 baits may result in bait shyness, but this may be avoided or mitigated by adherence to high-quality baiting practices and use of different bait types (Morgan et al. 1996b; Ogilvie et al. 2000; Ross et al. 2000) or additives to the baits (Cook 1999; Cook et al. 2000) Despite this risk of ‘shyness’ 1080 remains a highly effective tool for possum control. Manufactured 1080 for use in toxic baits has been shown to be chemically identical to the toxic compounds found in a poisonous plant; naturally produced 1080 induces the same signs and symptoms in animals (de Moraes-Moreau et al. 1995). Highly toxic fluoroacetate-producing plants are globally distributed with species on several major continents. Research in the 1940s identified monofluoroacetate, the active toxin in 1080, as the toxicant in the South African plant gifblaar (Dichapetalum cymosum), long recognised as a hazard to livestock. Since this discovery, monofluoroacetate has 9

been identified as the toxic agent in many other poisonous plants, such as rat weed (Palicourea margravii), native to Brazil (de Moraes-Moreau et al. 1995); and ratsbane (Dichapetalum toxicarium), native to West Africa (Atzert 1971). Monofluoroacetate also occurs naturally in some 40 plant species in Australia. Airdried leaves of Gastrolobium bilobum (heart-leaf poison) and G. parviflorum (box poison), for example, can contain up to 2600 mg/g of monofluoroacetate, and seeds of G. bilobum can have in excess of 6500 mg/kg of monofluoroacetate (Twigg 1994; Twigg et al. 1996a,b; 1999). The highest monofluoroacetate concentration so far reported from a living source is 8000 mg/g in the seeds of Dichapetalum braunii (Meyer 1994). Monofluoroacetate would appear to be one of the many secondary plant compounds that have evolved at high concentrations as a defence mechanism against browsing invertebrates and vertebrates. Most studies assessing monofluoroacetate concentrations in plants have focused on those species that are overtly toxic to mammals. However, it would appear that the ability of plants to synthesise monofluoroacetate is more widespread than generally supposed, since monofluoroacetate occurs at extremely low concentrations in some Finnish plants (Vartiainen & Kauranen 1980), in tea leaves (Vartiainen & Kauranen 1984), and guar gum (Vartiainen & Gynther 1984; Twigg et al. 1996b). In addition some plants, when exposed to fluoride ion, can biosynthesise fluoroacetate, albeit at very low levels. Fluorocitrate, the toxic metabolite of monofluoroacetate, has also been detected in tea leaves (Peters & Shorthouse 1972). Fluoroacetate biosynthesis can also occur in some bacteria, notably Streptomyces cattleya (O’Hagan & Harper 1999). Resistance in mammals, birds, and insects occurs in areas where there is continued exposure to the toxin. Interestingly, the caterpillar moth, Sindrus albimaculatus, which feeds on Dichapetalum cymosum, can not only detoxify fluoroacetate, but also accumulate it (probably in vacuoles) and uses it as a defence against predation (Meyer & O’Hagan 1992). 1.1.3

Fate in the environment

Persistence in soil Presumably, naturally occurring monofluoroacetate is diluted by rainwater and breaks down in soil after leaves and seeds drop to the ground or when the plants die. Not all micro-organisms can readily defluorinate monofluoroacetate and the rate of metabolism differs with different species of soil bacteria and fungi (King et al. 1994). Sodium monofluoroacetate, the sodium salt of this natural toxin, can certainly be metabolised by some soil micro-organisms, such as Pseudomonas and Fusarium species (Walker & Bong 1981; King et al. 1994). Enzymes capable of defluorinating fluoroacetate have been isolated from several micro-organisms. The active site of the enzyme attacks fluoroacetate. The fluoride carbon bond is cleaved and ultimately enzyme-bound intermediates form non-toxic metabolites such as glycolate (O’Hagan & Harper 1999). Sodium monofluoroacetate derived from baits will also be dispersed by water since it is highly water soluble and mobile (Parfitt et al. 1995). In older literature, it was suggested that 1080 is retained in solid particles and does not leach. This conclusion was based on the mistaken assumption that 1080 would not be held on cation-

10

exchange sites in soil. However, monofluoroacetate is an anion and New Zealandbased research has demonstrated that it could potentially be leached through soil by water (Parfitt et al. 1995). If heavy rainfall follows the use of 1080 baits, dilution to unmeasurable concentrations (300

Veenstra et al. 1991

Kamil 1987

55

Brodifacoum

Species

Blood t½ (hours)† (except where specified)

Liver (days)

retention‡

Rat

156

>80

Bachmann & Sullivan 1983

Rat

-

t½ 130

Parmar et al. 1987

Rabbit

60

-

Breckenridge et al. 1985

Dog

6 days

-

Woody et al. 1992

Dog

0.9–4.7 days

-

Robben et al. 1998

References

(mean 2.8)

Difethialone

Possum

20–30 days

>252

Eason et al. 1996c,d

Sheep

-

>250

Laas et al. 1985

Human

16–36

Rat

2.3 days

Dog

2.2–3.2 days

Weitzel et al. 1990 t½ 108 §

Lechevin & Poche 1988 Robben et al. 1998

† t½ for plasma or liver is the elimination half-life. It is standard convention to report the elimination t½ (-phase) rather than the -phase. ‡ Liver retention is expressed as the time period for which residues are reported to persist in the liver unless the value is preceded by t½. Plasma is t½ unless otherwise specified. § The half-life hepatic elimination for difethialone reported by Lechevin & Poche (1988) is unusually short for a secondgeneration anticoagulant, which suggests that difethialone may be unique.

Brodifacoum was detected in the liver of sheep 128 days after oral administration (0.2 and 2.0 mg/kg body weight) in concentrations of 0.64 and 1.07 mg/kg dry weight (equivalent to 0.22 and 0.36 mg/kg wet weight), respectively. The peak levels which occurred at 2 days in the high-dose group and at 8 days in the low-dose group, were 6.50 and 1.87 mg/kg dry weight (2.21 and 0.64 mg/kg wet weight), respectively (Laas et al. 1985). Parmar et al. (1987) found that elimination of radio-labelled brodifacoum, bromadiolone, and difenacoum from rat liver was biphasic, consisting of a rapid initial phase lasting from days 2 to 8 after dosing and a slower terminal phase when the elimination half-lives were 130, 170, and 120 days, respectively. Elimination of coumatetralyl was more rapid, with a half-life of 55 days. Similar results for difenacoum were found by Bratt (1987). After a single oral 14Cdifenacoum dose of 1.2 mg/kg body weight, the highest concentration of radioactivity (41.5% of the dose) was found in the rat liver 24 hours after dosing. The elimination from the liver was biphasic. The half-life of elimination of the radioactivity during the first rapid phase was 3 days, and for the slower phase was 118 days. A similar biphasic elimination was also apparent in the kidney. In the pancreas the concentration declined more slowly than in any of the other tissues (182 days). The parent compound was the major component in the liver 24 hours after dosing (42%). 56

Unchanged flocoumafen comprised the major proportion of the hepatic radioactivity in rats and was eliminated with a half-life of 220 days (Huckle et al. 1989). Veenstra et al. (1991) found retention of about 8% of an administered flocoumafen dose of 0.4 mg/kg in the liver of beagle dogs 300 days after dosing. Despite the more rapid metabolism of flocoumafen in Japanese quail, a proportion of the administered dose is retained in the liver, with a elimination half-life of 155 days after oral dosing (Huckle & Warburton 1989). There are limited data on the persistence of anticoagulants in New Zealand native species. In a study in weta, brodifacoum persisted for approximately 1 week after dosing (Morgan et al. 1996a). Species variation in response to brodifacoum For second-generation anticoagulants like brodifacoum only a single dose is needed to induce death, if sufficient toxicant is ingested, and brodifacoum is extremely toxic in a number of animal species. The toxicity of brodifacoum varies between mammal species (Table 12) and bird species (Table 13). In most mammals LD50 values are 1 mg/kg or less. Some higher values are reported in sheep and dogs, but there is considerable variability in these reports (LD50 in sheep 5– 25 mg/kg and in dogs 0.25–3.56 mg/kg). It has been suggested that anticoagulants are unlikely to affect invertebrates, which have different blood-clotting systems from vertebrates (Shirer 1992) and a New Zealand-based study has shown that brodifacoum lacks insecticidal properties in weta (Morgan et al. 1996a).

Table 12. Acute oral toxicity (LD50mg/kg) of brodifacoum for mammal species (Godfrey 1985; Eason et al. 1994a, Eason & Spurr 1995)

Species

LD50 (mg/kg)

Pig

0.1

Possum

0.17

Rabbit

0.2

Cat

0.25–25

Dog

0.25–3.56

Rat

0.27

Mouse

0.4

Bennett’s wallaby

1.3

Sheep

5–25

57

Table 13: Acute oral toxicity (LD50mg/kg) of brodifacoum for bird species (Godfrey 1985)

Bird species

LD50 (mg/kg)

Southern black-backed gull

3.0‡

California quail

3.3

Mallard duck

4.6

Black-billed gull

6.0‡

Silvereye

>6.0‡

Australasian harrier

10.0

Ring-necked pheasant

10.0

Paradise shelduck

† Lowest dose tested

>20.0‡

‡ Highest dose tested

Small birds such as silvereyes, sparrows, blackbirds, and California quail are considered more resistant to brodifacoum than some larger birds such as southern black-backed gulls, Canada geese, and pukeko (Godfrey 1985). However, some large birds, including Australasian harriers, ring-necked pheasants, and paradise shelducks, are also relatively resistant. Aquatic toxicology There are limited data on the aquatic toxicology of brodifacoum. In the unlikely event of a significant amount of brodifacoum bait being applied directly to a small stream, poisoning of aquatic invertebrates and fish could result. The EC50 from Daphnia magna (first instar) was 1.0 mg/kg after 24 hours of exposure and 0.34 mg/kg after 48 hours using 50 ppm pelleted baits. The LC50 (24 hours) for rainbow trout is 0.155 mg/L. The LC50s (96 hours) for rainbow trout and bluegill are 0.05 and 0.165 mg/L, respectively (World Health Organisation 1995. 2.1.5

Diagnosis and treatment of anticoagulant poisoning

Diagnosis of non-target poisoning in domestic animals Diagnosis of anticoagulant toxicosis is based on exposure history, clinical signs, response to treatment, laboratory analyses, and in lethal cases, lesions. Differential diagnoses vary with the species involved, and include other causes of coagulopathy (clotting disorders) such as autoimmune thrombocytopenia (reduced platelet numbers), liver disease, and hereditary clotting factor deficiencies like Von Willebrand’s disease or Haemophilia A (Beasley et al. 1997d).

58

Clinical signs Although in some cases signs have been observed within 24 hours of ingestion, there is usually a lag period of 3–5 days between exposure and the onset of clinical signs of anticoagulant toxicosis. This delayed onset represents the time required to deplete hepatic stores of vitamin K, and reduce preformed vitamin K-dependent, clotting factor concentration in the plasma to the point of functional deficiency. Initial clinical signs of anticoagulant poisoning are usually characterised by depression/lethargy and anorexia, followed shortly by anaemia with pale mucous membranes, dyspnoea, exercise intolerance, and haemorrhaging from numerous sites, as evidenced by haematemesis (vomiting blood), epistaxis (blood from the nose), haemoptysis (bronchial or pulmonary bleeding), melaena (‘tarry’ faeces), and haematomas in various locations. Periarticular or intraarticular haemorrhage causing swollen joints and lameness is especially common in pigs, and abortion induced by placental haemorrhaging has been reported in cattle. Convulsions indicate bleeding into the central nervous system. Animals experiencing prolonged toxicosis may be icteric (jaundiced). Similar clinical signs occur in humans and include haematuria, bleeding gums, and easy or spontaneous bruising (Park et al. 1986). As blood loss continues, cardiac murmurs, irregular heart beat, weak peripheral pulses, ataxia, recumbency, and coma will be observed. Death due to hypoxia and hypovolemic shock may occur from 48 hours to several weeks after exposure. Animals may occasionally be found dead with no premonitory signs, especially if severe haemorrhage occurs in the cerebral vasculature, pericardial sac, abdominal cavity, mediastinum, or thorax (Murphy & Gerken 1989; Felice & Murphy 1995). Laboratory diagnosis Laboratory evaluation of suspect anticoagulant exposures in domestic animals includes measurement of packed cell volume (haematocrit), clotting parameters, and residue analysis. The activity of vitamin K-dependent clotting factors (II, VII, IX, and X) is commonly measured using a suite of tests, including prothrombin time (PT), activated coagulation time (ACT), and activated partial thromboplastin time (APTT). Abnormal prolongation of PT is usually the earliest indicator of anticoagulant-induced coagulopathies, due to the involvement of factor VII in the coagulation pathway assessed by this clotting parameter. Factor VII has the shortest half-life of the vitamin K-dependent factors (6.2 hours in dogs), and is therefore the first to be depleted in plasma (Murphy & Gerken 1989). Elevations of PT from 2–6 times normal may occur within 24–48 hours of ingestion of a toxic dose. This is followed several hours later by elevation in APTT to 2–4 times normal values in cases of significant exposure. In general, changes in clotting parameter times are suggestive of anticoagulant exposure if they are prolonged beyond 25% of normal values. Assessment of coagulation parameters requires a sample of fresh, non-haemolysed blood collected in a sodium citrate (Blue Top) tube, stored at 4C, and submitted immediately. The diagnostic laboratory may require submission of a parallel sample from a ‘normal’, unexposed animal of the same species to serve as a control. The onset and severity of clinical signs of anticoagulant toxicosis are usually linked with declines in packed cell volume, except in cases of massive, acute haemorrhage.

59

Therefore, regular assessment of this end point is a useful tool to determine the appropriate course of treatment and to monitor progress. Suspect anticoagulant exposures can often be confirmed by laboratory identification of toxicant residues in vomitus (only in cases of very recent ingestion, prior to the onset of clinical signs) or tissue. The antemortem sample of choice is whole blood or serum (residues are protein-bound), while liver is the best post-mortem sample. Blood samples should be stored at 4C. Liver specimens should be wrapped in foil, sealed in plastic, and shipped frozen. Response to treatment Anticoagulant-induced coagulopathies (clotting disorders) can be distinguished from other types of coagulopathies by clinical response to treatment with the specific antidote, vitamin K1. Tests used to assess coagulation time should indicate significant improvement in clotting ability within 12–24 hours of initiation of treatment, and should return to normal within 36–48 hours (Murphy 1999). Lesions Post-mortem lesions resulting from anticoagulant rodenticide exposure are characterised grossly by generalised haemorrhage, especially in the thoracic or abdominal cavities, mediastinal space, periarticular tissues, subcutaneous tissues, subdural space, and gastrointestinal tract. Sudden deaths are often marked by massive haemothorax, haemopericardium, and pulmonary oedema or haemorrhage. The heart is often flaccid, with subepicardial and subendocardial ecchymoses. Centrilobular hepatic necrosis secondary to anaemia and hepatocellular hypoxia may be observed histologically (Osweiler 1996b; Beasley et al. 1997d). Treatment of anticoagulant toxicosis in domestic animals Companion animals usually present with signs of haemorrhage or anaemia, or with a history of recent ingestion of anticoagulant bait but no clinical effects. In the latter cases, either the dose ingested is insufficient to cause significant inhibition of vitamin K-dependent clotting factor production, or insufficient time has elapsed to deplete pre-exposure plasma clotting factor concentrations to the point of deficiency. Because treatment of anticoagulant toxicosis can be expensive (especially with large dogs exposed to second-generation products requiring prolonged therapy), animals presenting with a history of exposure but no clinical signs should be assessed carefully before treatment is initiated. Therapeutic goals for veterinarians in the treatment of anticoagulant poisoning are (1) to decrease toxicant absorption; (2) to correct low haematocrit and/or hypovolemia; and (3) to correct clotting factor deficiencies. Recommendations for the treatment of anticoagulant toxicosis in companion animals are as follows (Mount & Feldman 1983; Murphy & Gerken 1989; Osweiler1996b; Beasley et al. 1997d): 

Animal is presented asymptomatic, within several hours of suspected/confirmed oral exposure:  Induce emesis with household salt solution or washing soda crystals (if 9 months.  Non-target effects on individual birds of a number of species have occurred after brodifacoum use for rodent control.  Adverse effects on individual populations of a number of species of birds have been observed after brodifacoum use for rodent control. However, short-term losses are likely to be superseded by long-term gains once predators have been removed.

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2.2

Flocoumafen (Storm®)

Chemical Name: 4-hydroxy-3-[1,2,3,4-tetrahydro-3-[4(4-trifluoromethylbenzyloxy) phenyl]-1-naphthyl) coumarin Synonyms: Flocoumafen is the approved name, Storm® is the trade name. Flocoumafen and brodifacoum are extremely similar in terms of their chemistry, biological activity, potency, persistence, and risk of secondary poisoning. For further details on the toxicology, mode of action, etc. of flocoumafen see the previous section on brodifacoum.

2.2.1


Flocoumafen is an off-white solid with a melting point cis-isomer of 181–191C and a vaporisation point at 133 pPa (25ºC). Flocoumafen’s solubility is 1.1 mg/L in water and >10 g/L in acetone, alcohols, chloroform, and dichloromethane. It is stable to hydrolysis and does not undergo any detectable degradation when stored at pH7–9 for 28 days at 50ºC. 2.2.2

Historical development and use

Flocoumafen is a second-generation anticoagulant that was developed by Shell Research in the early 1980s. Flocoumafen has been used against a wide range of rodent pests including the principal commensal species. It is also effective against rodents that have become resistant to other anticoagulant rodenticides. It is currently registered for use in New Zealand as a rodenticide under the trade name ‘Storm’. Flocoumafen is not extensively used in the field in New Zealand. 2.2.3


Flocoumafen is not readily soluble in water. In physico-chemical terms flocoumafen is extremely similar to brodifacoum. Hence if flocoumafen-containing baits were to be used in the field, when these baits disintegrate flocoumafen is likely to remain in the soil where it will be slowly degraded by soil micro-organisms. Microbial degradation will be dependent on climatic factors such as temperature, and the presence of species able to degrade flocoumafen. 2.2.4 Toxicology and pathology Onset of symptoms Flocoumafen is a potent second-generation anticoagulent similar to brodifacoum. Its symptoms, time to onset of poisoning, mode of action, and toxicity to birds and mammals are like those of brodifacoum (Table 14). For practical considerations, species such as dogs, cats, and pigs, the risk of poisoning from baits or secondary poisoning from eating contaminated rodents will be similar to that for brodifacoum.

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Table 14. Acute oral toxicity (LD50mg/kg) of flocoumafen (Hone & Mulligan 1982)

Species

LD50 (mg/kg)

Dog

0.075–0.25

Gerbil

0.18

Rat

0.25

Rabbit

0.70

Sheep

>5.0

Cat

>10.0

Goat

>10.0

Pig

60.0

Mode of action Like other anticoagulant toxins, flocoumafen acts by interfering with the normal synthesis of vitamin K-dependent clotting factors in the liver of vertebrates (Hadler & Shadbolt 1975). In the liver cells the biologically inactive vitamin K1-2,3 epoxide is reduced by a microsomal enzyme into biologically active vitamin K, which is essential for the synthesis of prothrombin and other clotting factors. Flocoumafen antagonism of the enzyme vitamin K1-epoxide reductase in the liver causes a gradual depletion of the vitamin and consequently of vitamin K-dependent factors, which results in an increase in blood-clotting time until the point where no clotting occurs. Pathology and regulatory toxicology Pathological lesions in animals poisoned with flocoumafen are similar to those for brodifacoum and other anticoagulants. In regulatory studies flocoumafen has been shown to lack genetoxicity in a range of in vitro and in vivo regulatory toxicology studies evaluating the potential of this toxicant to induce chromosomal damage or genetic mutation. In a teratogenicity study in rats some deaths or signs of haemorrhaging were reported at 0.4 mg/kg/day in females, but there were no reports of teratogenicity in foetuses. Hence regulatory studies indicate that flocoumafen lacks mutagenic or teratogenic effects at the doses tested (WHO 1995). Fate in animals (see section 2.1.4) Absorption, metabolism, and excretion The persistence of flocoumafen in sub-lethally exposed animals is as great, if not greater, than that of brodifacoum (see Table 11). In rats, absorption of flocoumafen is also rapid reaching a maximum concentration in blood after 4 hours (Huckle et al.

68

1989) (see Table 15). Similar rapid absorption occurs for other anticoagulants (Kamil 1987) (Table 15). Table 15. Occurrence of peak plasma concentrations in animals after oral ingestion of anticoagulants

Anticoagulant and dose

Species

Tmax hours

Reference

Warfarin 50 mg/kg

Possum

6

Eason et al. 1999a

Bromadiolone 0.8 mg/kg

Rat

6–9

Kamil 1987

Flocoumafen 0.14 mg/kg

Rat

4

Huckle et al. 1989

Following administration of flocoumafen, liver residues in rats consisted mainly of unchanged flocoumafen, although in a repeat-dose study a polar metabolite was also detected, indicating some low level of metabolism is occurring (Warburton & Hutson 1985; Huckle & Warburton 1986). In rats, eight urinary metabolites have been detected after percutaneous exposure to 14 C-flocoumafen (Huckle & Warburton 1986). However, they represented only a small proportion of the total dose, with most excretion occurring in the faeces as unchanged flocoumafen. Unchanged flocoumafen comprised the major proportion of the hepatic radioactivity in rats and was eliminated with a hepatic half-life of 220 days (Huckle et al. 1989). Veenstra et al. (1991) found retention of about 8% of an administered flocoumafen dose of 0.4 mg/kg in the liver of beagle dogs 300 days after dosing. There are insufficient comparative data in different species to clarify whether or not there is a pattern of species variation in the metabolism of flocoumafen. However, it appears that quail are able to metabolise floucoumafen more effectively than rats (Huckle & Warburton 1989). The metabolism of flocoumafen by Japanese quail may be partly responsible for the shorter liver retentions of this toxicant in quail (hepatic half-life 155 days; Huckle & Warburton 1989) versus rats (hepatic half-life 220 days; Huckle et al. 1988). Up to 12 radioactive components were detected in the excreta of quail (Huckle & Warburton 1989). Faecal excretion of radio-labelled flocoumafen following an oral dose of 0.14 mg/kg body weight accounted for 23–26% of the dose over the 7-day period; approximately half of this was recovered within the first 24 hours. Less than 0.5% of the dose appeared in the urine within 7 days (Huckle et al. 1989). When oral14C-flocoumafen doses of 0.02 mg/kg body weight or 0.1 mg/kg body weight were given to rats, once weekly for up to 14 weeks, approximately one-third of each weekly low dose was eliminated through the faeces within 3 days, mostly within the first 24 hours. At the higher dose the faecal excretion ranged from 18% after the first dose to 59% after the 10th dose (Huckle et al. 1988).

69

Species variation in response to flocoumafen For a number of species the LD50 is less than 1 mg/kg and this is similar to brodifacoum (see Tables 12 and 14). However, there are several species with surprisingly high LD50 values, e.g. pigs. No aquatic toxicity data was found. 2.2.5

Diagnosis and treatment of poisoning

As for brodificoum, see Section 2.1.5 (pp. 57–60). 2.2.6

Non-target effects

Flocoumafen has the potential to cause both primary and secondary poisoning of nontarget species. However, the adverse effects of flocoumafen on wildlife are dependent more on how baits are used and the behaviour of non-target species than the susceptibility of individual species to the toxin. Baits in bait stations are less accessible to non-target species than baits on the ground. Secondary poisoning of birds (e.g. brown skua and harriers) is likely where target species (e.g. rabbits and rats) are a major constituent of the diet. Flocoumafen is extremely persistent in the livers of lethally and sub-lethally poisoned animals, which heightens the potential risk of secondary poisoning in non-target species. As the use of flocoumafen is largely restricted to commensal rodents, the risks of exposure of wildlife are lower, except when it is used around farm buildings. Livestock must not be allowed access to flocoumafen baits as residues are likely to persist in their livers for up to 9 months or more. There is very little detailed information available on the non-target impacts of this toxin. However, as the properties of this toxin are very similar to those found in brodifacoum, the potential for non-target impacts are likely to be very similar. 2.2.7

Summary

Advantages

Disadvantages

Generally available and no licence required

High risk of secondary poisoning of non-target species if used widely in the field

Effective for rodents

Persistent (>9 months) in liver of vertebrates (can enter food chain and put meat for human consumption at risk) if used in the field

Antidote available

Although an antidote (vitamin K) is available, long-term treatment is needed. Expensive compared to 1080 or cyanide

 Flocoumafen has chemical and biological effects that are almost indistinguishable from brodifacoum.  Flocoumafen is a synthetic pesticide that was first registered for use approximately 20 years ago.

70

 Flocoumafen is not readily soluble, it binds strongly to the soil, and is slowly degraded. It is most unlikely to contaminate waterways as it is used principally for controlling commensal rodents or in bait stations.  It is a potent second-generation anticoagulant, which acts by interfering with the synthesis of vitamin K-dependent clotting factors. Flocoumafen is toxic to mammals, birds, and reptiles.  When used near farms, livestock must not be allowed access to flocoumafen baits, as residues may persist in the survivors for >9 months.

2.3

Bromadiolone (Rid Rat®, Contrac®, Supersqueak®)

Chemical Name:

3-[3-(4'- bromobiphenyl-4-yl)-3-hydroxy-1phenylpropyl]-4-hydroxycoumarin.

Synonyms: Bromadiolone is the approved name Baits containing bromadiolone include Rid Rat®, Contrac®, Supersqueak®, and are targeted at rodents. Bromadiolone has chemical and biological effects that are similar to brodifacoum. However, it is slightly less potent than both brodifacoum and flocoumafen.

2.3.1


The empirical formula for bromadiolone is C30 H23 BrO4 and the molecular weight is 527.4. Technical grade bromadiolone (97% pure) is a yellowish powder with a melting point of 200–210ºC. Its solubility at 20ºC is 19 mg/L in water, 730 g/L in dimethylformamide, 8.2 g/L in ethanol, and 25 g/L in ethyl acetate. Bromadiolone is stable at temperatures 9 months.  Bromadiolone is effective against rodents that have become resistant to other firstgeneration anticoagulant rodenticides.

2.4

Coumatetralyl (Racumin®, No rats & mice®)

Chemical Name: 4-hydroxy-3-(1,2,3,4-tetrahydro-1-naphthyl) coumarin Synonyms: Coumatetralyl is the approved common name Coumatetralyl is classified as a first-generation anticoagulant. It is less potent than brodifacoum, flocoumafen, or bromadiolone, but more potent than warfarin and pindone. Internationally it is sold under the trade name Racumin®, No rats & mice®.

2.4.1


The empirical formula for coumatetralyl is C19H16O3 and the molecular weight is 292.6. It is practically insoluble in water, slightly soluble in ether and benzene, soluble in alcohol and acetone, and readily soluble in dimethyl formamide.

74

2.4.2


This rodenticide was developed in 1957 by scientists at Bayer, and is marketed worldwide. It is used as a tracking powder or as a cereal bait, wax block, and paste for rodent control. 2.4.3


No published information is available on the fate of this rodenticide in soil. It would be likely to be broken down slowly in soil by micro-organisms. 2.4.4

Toxicology and pathology

Onset of signs Coumatetralyl baits containing 1 mg/kg will kill rats in 5–8 days. In general, the symptoms of poisoning do not appear suddenly. Mode of action As for other anticoagulant rodenticides (see brodifacoum), post-mortem examinations reveal extensive multiple haemorrhages throughout the body with considerable quantities of unclotted blood in the chest and abdominal cavities. Rats can withstand single doses of 50 mg/kg of this toxicant, but are unable to survive doses of 1 mg/kg when that dose is ingested over 5 successive days. Pathology and regulatory toxicology We could not find any regulatory toxicology studies in the published literature. Fate in animals Coumatetralyl is markedly less persistent (in sub-lethally poisoned animals) than brodifacoum (see Table 11). The hepatic half-life of sub-lethally exposed rats is 55 days (Parmar et al. 1987). Species variation in response to coumatetralyl: There are comparatively few acute toxicity data for coumatetralyl (Table 17). Table 17. Acute oral toxicity (LD50 mg/kg) of coumatetralyl (Hone & Mulligan 1982; Worthing & Hance 1991)

Species

Rat

LD50 mg/kg

16.5 (single dose) 0.3 (5 days)

Pig

1.0–2.0 (1–7 days)

Hen

50.0 (8 days)

Fish

1000.0 (96 hours)

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2.4.5



Non-target effects

Other than pets gaining access to bait, there are few references to non-target deaths in other species. In recent studies coumatetralyl-poisoned rat carcasses were fed to weka and ferrets. One out of 10 ferrets died, but no weka were killed (O’Connor & Eason 1999).

2.4.7

Summary

Advantages

Disadvantages

No licence required

Not as potent as brodifacoum or other second-generation anticoagulants

Effective for rodent control Antidote Less persistent bromadiolone

than

brodifacoum,

flocoumafen,

and

 This compound was first introduced in 1957 and is sold as Racumin®, and is used as a tracking powder or as a cereal bait for rodent control.  This bait needs to be ingested over several consecutive days to be most effective.  As for other anticoagulants, rodents die within 5–7 days after ingesting a lethal dose of the toxin.  As for other anticoagulants, coumatetralyl interferes with the synthesis of vitamin K-dependent clotting factors. If ingested in large enough quantities, it is toxic to mammals, birds, and reptiles.

2.5

Diphacinone (Ditrac®, Liquatox®, PESTOFF® (for ferrets))

Chemical Name: 2-(diphenylacetyl-1,3-indandione Synonyms: Diphacinone is the approved common name Like coumatetralyl, diphacinone is classified as a first-generation anticoagulant. 2.5.1


The empirical formula for diphacinone sodium salt is C23H15O3 Na and the molecular weight is 362.4. It is soluble in water; more soluble in ethyl alcohol, acetone and hot water; insoluble in benzene and toluene.

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2.5.2


Diphacinone is a first-generation anticoagulant, of the indandione class, produced and primarily used in the USA where it is used to control mice, rats, prairie dogs (Cynomys spp.), ground squirrels, voles and other rodents (Hayes & Laws 1991); and in South America where cattle are treated with diphacinone to provide live baits for vampire bats (Mitchell 1986). Diphacinone is more toxic than warfarin or pindone to most rodents. In New Zealand it is registered primarily for rodent control, and more recently it has been incorporated into a fish-based bait for ferret control (Ogilvie et al. 1995). This anticoagulant was first introduced for use in New Zealand in the 1950s as a rodenticide. It is available in both a liquid concentrate (Liquatox®) on a limited-sale basis in 50-ml plastic envelopes that are mixed with a litre of water for use as a liquid rodent bait, and a Ditrac® All Weather Block. 2.5.3


Comparative soil absorption and mobility studies have shown diphacinone to be relatively immobile. When tested in the laboratory, the half-life of diphacinone in soil under aerobic conditions is about 30 days and under anaerobic conditions is about 60 days (WHO 1995). 2.5.4


Onset of signs Diphacinone baits at 3 mg/kg will kill rodents in 5–8 days. Rats can withstand relatively high single doses of this toxicant, but are unable to survive doses of 100

(

Aquatic toxicology: There are no published aquatic toxicity data for pindone. 2.6.5



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 wedgetailed 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.).

83

2.6.7

Summary

Advantages

Disadvantages

No licence required

Not as potent as second-generation anticoagulants or nonanticoagulant 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.

2.7

Warfarin

Chemical Name: 3-(-acetonylbenzyl)-4-hydroxycoumarin. Synonyms: Warfarin. Warfarin, like pindone, is one of the earliest first-generation anticoagulant rodenticides 2.7.1


The empirical formula for warfarin is C19H16O4 and the molecular weight is 308.3. It is a colourless, odourless, and tasteless crystalline powder with a melting point of 161ºC. It is insoluble in water and benzene, freely soluble in alkaline solution, readily soluble in acetone, and only moderately soluble in alcohols.

84

2.7.2


Warfarin baits are registered in New Zealand for rodent control, but bromadiolone, brodifacoum, and flocoumafen are often preferred by pest managers because of their greater potency. Warfarin is a first-generation anticoagulant that has been used in a range of rodent baits since it was first introduced in 1947. Cereal pig-baits containing warfarin are available from the Animal Control Products factory in Wanganui. As warfarin is a first-generation anticoagulant, for most animals the baits will need to be ingested regularly over several days before any of the symptoms of poisoning will occur. 2.7.3


There are no published data on warfarin degradation. However, significant contamination of soil and water following the use of bait stations is extremely unlikely. Minor contamination is likely around the bait station, which should not be a major risk to non-target species. Degradation by soil micro-organisms and slow dispersal of warfarin in the soil is probable: this is based upon data on the degradation of similar anticoagulant toxicants. 2.7.4


Onset of signs and pathology As for all anticoagulants, the onset of symptoms will depend on the dose, nature, and amount of bait consumed. Rats Warfarin baits administering 1 mg/kg will kill rats in 5–8 days. Rats can withstand single doses of 50 mg/kg, but are unable to survive doses of 1 mg/kg bodyweight when that dose is ingested for 5 successive days. In general the symptoms of poisoning do not appear suddenly, and will culminate in death within 5–7 days of the initial ingestion of a lethal dose. Pigs Approximately 3 days after poisoning, some pigs will become lame, depressed, and lethargic. Food consumption decreases and blood is commonly observed in faeces. There is a great deal of individual variation in the time it takes for pigs to die from warfarin poisoning, with some pigs dying before or soon after they have shown the initial symptoms of poisoning and others living up to 31 days, progressively weakening over time. Mode of action Warfarin, like the other anticoagulants, inhibits the synthesis of vitamin K-dependent clotting factors. In addition, warfarin is reported to induce capillary damage. Two different metabolites are thought to be responsible for these effects: 4-hydroxycoumarin inhibits the formulation of prothrombin and reduces the clotting power of the blood, whereas there is some evidence that, at sufficient dosage, benzalacetone produces capillary damage that exacerbates bleeding.

85

Pathology and regulatory toxicology Animals may be subjected to a hypovolemic crisis secondary to massive haemorrhage into body cavities, subcutaneous tissues, and the alimentary, respiratory, and urinary tracts in cases where large doses of the toxin have been ingested. Animals that receive a lower dose of the toxin may show signs of lethargy, anaemia, anorexia, bloody faeces, and abdominal pain. In pigs, extensive haemorrhages into the stomach and the small and large intestine are the most common signs of anticoagulant pathology, with skeletal muscle, peritoneum, and weight-bearing joints common sites of haemorrhage. There are limited regulatory toxicology studies on warfarin and no data relating to potential mutagenic effects. While all anticoagulant rodenticides are likely to be embryotoxic if ingestion occurs at a sufficiently high dose, warfarin is unique in this class of compounds and was found to be both embryotoxic and teratogenic when administered to rats (WHO 1995), causing internal hydrocephalus and anomalies of skeletal ossification. In humans undergoing continuous drug treatment with warfarin, defects have in the past been classified as warfarin embryopathy and include both skeletal and non-skeletal abnormalities. No cases of embryopathy from anticoagulants in their use as rodenticides have been reported. Fate in animals Absorption, metabolism, and excretion Warfarin is readily hydroxylated by rat microsomal enzymes to at least eight metabolites, including 6-,8- and especially 7-hydroxywarfarin (Sutcliffe et al. 1987). It is not persistent, and is readily excreted with an elimination half-life of about 18 hours in male rats and 28 hours in female rats (Pyrola 1968). The half-life in rat liver is reported to be 7–10 days for warfarin, which contrasts with half-lives exceeding 100 days for second-generation anticoagulants (Thijssen 1995) (see Tables 10 and 11). Species variation in response to warfarin The toxicity of warfarin varies according to species and whether exposure was a single or multiple dose (Table 22). For example, the single dose LD50 is 50–100 mg/kg in rats (species unspecified) versus 1 mg/kg for 5 days (Osweiler et al. 1985). Table 22: Acute oral toxicity (LD50mg/kg) of warfarin (Osweiler et al. 1985)

Species

Single dose (mg/kg)

Repeated dose (mg/kg)

Pig

3

0.5

Dog

50

5

Rat (unspecified)

50–100

1

Cat

50–100

1

86

Values for the acute oral LD50 of warfarin for Norway rats vary between 1.5 and 3.75 mg/kg (Hone & Mulligan 1982). The strain and sex of the test animals and the carrier used in the administration probably affected the results obtained. Aquatic toxicology There are no published data available for warfarin. 2.7.5



Non-target effects

Although less potent than 1080 or brodifacoum, warfarin still has the potential to cause primary poisoning of non-target species. Secondary poisoning is relatively uncommon (Osweiler et al. 1985; Prakash 1988). If warfarin baits are used for control of pest species, it is important that the baits are not positioned where livestock may eat them.

2.7.7

Summary

Advantages

Disadvantages

No licence required

Not as potent as second-generation anticoagulants or nonanticoagulant poisons such as cholecalciferol and 1080

Effective for rodent control Antidote Less persistent than brodifacoum

 Warfarin is a first-generation anticoagulant.  In order for a lethal dose to be ingested, the target species needs to consume either one large single dose or a small dose for several days in a row.  Because warfarin has a slow mode of action, bait shyness is not readily induced.  It is not persistent when compared to brodifacoum, but is considerably less potent than second-generation anticoagulants.

87

SECTION 3 : TOXINS NO LONGER USED BY THE DEPARTMENT OF CONSERVATION 3.1

Phosphorus

Chemical Name: P4. Synonym: Phosphorus. Phosphorus is used as a paste and is generally applied to turf spits on the ground. It is only available to licensed operators.

3.1.1


Phosphorus is a yellow solid with a waxy lustre that has a melting point of 44.1ºC. Phosphorus is mixed with water, bentonite, and magnesium oxide to produce an emulsion that is incorporated into a fruit paste for the control of rabbits and possums. Raw phosphorus is a corrosive dangerous product. Pastes have somewhat different properties.

3.1.2


Phosphorus was first used in rabbit control in New Zealand and Australia in the early 1920s. The initial use of this toxicant was in pollard pellets by dissolving the phosphorus sticks in carbon bi-sulphide or mixing phosphorus in boiled water and then adding pollard to make the pellets. It was also used on oats and wheat. In the 1950s phosphorus was incorporated into paste for rabbit control. In the 1960s phosphorus pellets were withdrawn from the market because the phosphorus broke down (oxidised) quickly in the bait, and was ineffective. Phosphorus paste is still used by regional councils and is publicly available. Under the Pesticides (Vertebrate Pest Control) Regulations 1977, the operator must either hold a licensed operators certificate or be working under the supervision of a certificate holder to use phosphorus for pest control. 3.1.3


Phosphorus is unlikely to be persistent in the environment. Phosphorus is usually added to paste bait for possum control. On exposure to air the phosphorus oxidises to phosphates, which are not poisonous. Accordingly, phosphorus is more stable in paste, which tends to ‘cake’ and protect the phosphorus from oxidation.

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3.1.4


Onset of signs In the veterinary literature, phosphorus poisoning is usually categorised in three phases: (1) An acute initial phase occurring within hours of ingestion characterised by gastrointestinal, abdominal, and circulatory signs. Initial signs generally involve vomiting and diarrhoea. If the dosage is sufficiently large, shock, cyanosis, incoordination and coma may develop, with death occurring before the second and third phases appear; (2) An interim or latent phase with apparent recovery occurs at lower doses approximately 48 hours to several days after initial clinical signs; (3) The third stage is characterised by recurrence of marked clinical signs involving the gastrointestinal tract. Liver failure then occurs. These literature reports suggest that death may occur in 1–2 days, or there may be improvement for 1–2 days before vomiting, diarrhoea, and other signs return. Death is usually due to liver necrosis and heart failure. There may be a delay of up to 3 weeks after ingestion before convulsions, coma, and death. Recent trials at Landcare Research have shown that possums eating phosphorus-paste baits die within 18 hours and do not experience the prolonged toxicosis commonly attributed to phosphorus in the scientific and veterinary literature (Eason et al. 1997, 1998b; O’Connor et al. 1998). There is no antidote to phosphorus, but with early diagnosis the poison may be removed by vomiting or gastric lavage, then treated with 0.1% potassium permanganate or 2% hydrogen peroxide (to oxidise the toxicant to harmless phosphates) and mineral oil (which prevents absorption). However, if there is bleeding or ulceration treatment is more difficult. Mode of action The mode of action is unknown. It has not been possible to associate the main clinical or pathological features of intoxication with inhibition of any particular enzyme or class of enzymes. Phosphorus is sometimes referred to as a protoplasmic poison, but it is difficult to distinguish its possible direct effects on the liver, kidney, brain, and heart from the effects of anoxia on those organs. The peripheral vascular dilatation, which is the first and most pervasive systemic effect of phosphorus, contributes to all the disorders that may be seen in various organs. However, the mechanism of this dilatation is not clear. Phosphorus not only leads to structural damage of vital organs, but also produces serious disruption of their metabolic function, as evidenced by hypoglycemia, azotemia, inhibition of glycogen formation in the liver, and many other disorders. Pathology and regulatory toxicology Pathological changes include gross evidence of fatty degeneration and swollen livers, as well as gastrointestinal irritation, necrosis, and haemorrhage. If death is sufficiently prompt, there is no pathology except irritation of the oesophagus and stomach. Perforation may occur. Following survival for several days, fatty degeneration is striking in the liver, heart, and kidney but may be found in all organs, including the brain. We were unable to locate any material relating to genotoxicity or teratogenicity, or data from other regulatory toxicology studies on phosphorus.

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Fate in animals Phosphorus is readily absorbed but its persistence in lethally and sub-lethally poisoned possums has not been elucidated. Species variation in response to phosphorus There is little species variation in response to phosphorus and most species are at risk if they eat bait (Table 23). Table 23.

Acute oral toxicity (LD50mg/kg) of phosphorus (Hone & Mulligan 1982)

Species

LD50 (mg/kg)

Sheep

1

Pig

1–6

Rabbit

4

Dog

3–6

Cat

3–6

Possum

6–10

Poultry (unspecified)

10

Aquatic toxicology Unknown. It is unlikely that significant amounts of phosphorus baits used for possum control will enter watercourses. 3.1.5

Current use

This poison has been in use since the 1920s and is one of the few poisons that is still available to the public as an acute poison for rabbit and possum control. It is also still used in some instances to poison pigs. It is not currently used by the Department of Conservation, but is used around houses and public areas by regional councils where there is a risk to dogs from 1080. However, use of phosphorus is also associated with secondary poisoning of dogs. Advantages

Disadvantages

Effective (kills of >90% achieved)

Has some animal welfare concerns‡)

Less public opposition than with 1080†

Secondary poisoning risk to dogs and birds Risk of fire Antidotes of limited value

† When farmers or the community oppose the use of 1080 they will often accept phosphorus as a replacement. ‡ Studies show that the symptoms of phosphorus poisoning in possums differ from those reported in the veterinary literature for other animals

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3.2

Arsenic

Chemical Name: Arsenic trioxide (As2 O3). Synonyms: White arsenic, arsenous oxide.

3.2.1


Arsenic is a naturally occurring toxin found in combination with other metals, particularly iron as arsenic pyrite (FeAs), and iron-arsenic sulphide. Two other forms of arsenic sulphide, orpiment and regular white arsenic (arsenic trioxide), are less common. 3.2.2


The first recorded use of arsenic in New Zealand and Australia was in the 1880s where it was used in a variety of baits including oats, wheat, root crops, apples, and pollard pellets. In the early 1970s arsenic was discontinued from use in rabbit control due to its inability to decompose. In addition to this, a number of people were reported to have been affected by arsenic’s cumulative properties. When still in use in the 1970s, arsenic was available to the public. Under the Pesticides (Vertebrate Pest Control) Regulations 1977, the operator had to either hold a licensed operator’s certificate or be working under the supervision of a certificate holder. All of these certificates were withdrawn by the Pesticides Board on the advice of the then Agricultural Pest Destruction Council when arsenic was withdrawn from use in New Zealand. 3.2.3


Arsenic from baits is converted into various inorganic and organic arsenic compounds, most or all of which will be toxic to a varying extent. Arsenic baits were not considered safe to livestock until they had decomposed or had been completely disintegrated by rain. 3.2.4


Onset of signs Death from a single dose appears to be a painful process occurring over several hours or days. Mode of action Arsenic causes severe gastroenteritis, vomiting, copious watery or bloody diarrhoea, with convulsions and coma preceding death. The corrosion of the gastrointesinal tract is thought to lead to shock as well as haemorrhage.

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Fate in animals Substantial elimination of a sub-lethal dose will occur in 1–6 weeks in most animals. Arsenic is well distributed throughout all tissues and remains for long periods in bone, skin, and hair. Species variation in response to arsenic: One of the main disadvantages of arsenic, in addition to its extremely inhumane mode of action, is its low toxicity to rats and possums as compared to its toxicity to humans (Table 24). Table 24. Acute oral toxicity (LD50mg/kg) of arsenic (Hone & Mulligan 1982)

3.2.5

Species

LD50mg/kg

Human

1.43

Possum

8.22

Mouse

45.00

Rat

138.00

Current use

Arsenic is no longer available for use in New Zealand.

3.3

Strychnine

Chemical Name: Strychnine alkaloid. Synonyms: Strychnine.

3.3.1


The empirical formula for strychnine is C21H22N2O2 and its molecular weight is 334.4. Strychnine is an odourless bitter white powder. Its melting point is 270º–290ºC. Strychnine has a solubility in water at room temperature of 143 mg/L. Its salts are more soluble in water; for example, the sulphate is soluble in water at 30 g/L at 15ºC. Strychnine is soluble in chloroform, slightly soluble in benzene, and less soluble in diethyl ether and petroleum ether.

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3.3.2


Strychnine is found in the seeds of the Indian tree Strychnos nux-vomica where it is one of a number of different alkaloids. It has a long history as a rodenticide (Schwartze 1922), being used first in Germany in the 16th Century. It affects the central nervous system, leading to paralysis a few minutes after intake and to death within half an hour in rodents (Prakash 1988). The first recorded use of strychnine in New Zealand and Australia was in the 1880s where it was used in conjunction with a variety of baits including oats, wheat, root crops, thistle roots, apples, and pollard pellets. It was also used in grain to control problem birds. In the early 1980s strychnine was withdrawn from use in New Zealand on the grounds that the type of death that it caused was inhumane. When strychnine was used in the early 1970s, an operator was required, under the Pesticides (Vertebrate Pest Control) Regulations 1977, to hold a licensed operators certificate or to be working under the supervision of a certificate holder. All licences were then cancelled by the Pesticides Board on the advice of the then Agricultural Pest Destruction Council on the grounds that the toxin was inhumane and dangerous to staff. 3.3.3


Strychnine is a stable alkaloid that retains its toxicity indefinitely in the bait and in the carcass of the poisoned animals. Strychnine bait must be completely decomposed or washed out before a poisoned area could be determined as toxin-free. 3.3.4


Onset of signs Poisoned animals often die in less than an hour as a result of respiratory failure (asphyxia), but death may take 24 hours or longer if the dose is low. The typical signs of strychnine poisoning are restlessness and muscular twitching that progresses to convulsive seizures continuing for 45 minutes or more before death. Violent muscular spasms extend the limbs and curve the neck upwards and backwards; the jaws fix and the eyes protrude (Osweiler et al. 1985). Poisoned animals are generally found close to the bait because of the poison’s rapid action. Strychnine and its salts (especially strychnine sulphate) are highly toxic to all mammals, less so to birds. The LD50 to the Norway rat is 5–6 mg/kg (Prakash 1988). The oral LD90 for strychnine in mice is approximately 5 mg/kg (Mutze 1989). Strychnine induces poison shyness in rats and similar shyness is thought to occur in other vertebrate pests (Prakash 1988). The bitter taste is usually masked by a sweetening agent (icing sugar) in baits. Mode of action Strychnine is a fast-acting poison that is readily absorbed into the circulatory system from the intestinal tract. Highest concentrations of strychnine are found in blood,

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liver, and kidney. Even though it is a neurotoxin, strychnine does not appear to concentrate preferentially in nervous tissues (Hayes 1994). Fate in animals Strychnine is highly persistent in baits and poisoned carcasses. Species variation in response to strychnine: Strychnine is highly toxic to most domestic animals and wildlife (Table 25). Studies in the USA have shown a 50% reduction in horned lark populations after using strychnine (Apa et al. 1991). Some individual non-target bird species have been reported killed in mouse control operations in Australia (Anthony et al. 1984; Mutze 1989). Table 25.

3.3.5

Acute oral toxicity (LD50mg/kg) of strychnine (Hone & Mulligan 1982; Osweiler et al. 1985)

Species

LD50mg/kg

Cow

0.5

Horse

0.5

Cat

0.75

Norway rat

6.8

Duck

2.9

Chicken

5.0

Pigeon

2.1

House sparrow

4.0

Current use

This toxin had been in use since the late 1800s for pest control but has now been banned from use in New Zealand. It is still used in Australia for mouse plagues and in the USA to control several pests, including skunks, targeted for control in rabies-infected areas, using strychnineinjected eggs. It is also used in Fiji and other islands in the Pacific.

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SECTION 4: COMPARATIVE RISK ASSESSMENT FOR COMMONLY USED VERTEBRATE PESTICIDES Here we review some of the information provided in the previous sections on individual poisons used for possum control, for comparative risk-assessment purposes.

4.1

What and where are the exposure and non-target risks? Risks = Hazard  Exposure

Risks to human health and non-target wildlife or livestock are dependent on the inherent toxicity of the pesticide (i.e. hazard) and the potential for exposure to either residues or toxic baits (Eason et al. 1997). Clearly all poisons used for vertebrate pest control are hazardous. Risks can be minimised by preventing exposusre of non-target species to these compounds. Some risks will be common for all types of toxic bait, e.g. the risk of a child eating toxic material if it is not stored in a secure location. Other risks, such as the risk of secondary poisoning, will vary dependent on the properties of the pesticide and how it is used Refer to the DOC ‘Information on the Animal Pest QCM Module, The Safe Handling of Pesticides’, published April 2000. 4.1.1

Persistence in water, soil, and plants

1080: Extensive research has demonstrated that 1080 may be degraded in most moist soils over 2 or more weeks by naturally occurring micro-organisms (e.g. Pseudomonas, Fusarium), although in climatic extremes (e.g. drought and extreme cold) the breakdown may take several months (Walker & Bong 1981; Wong et al. 1992; King et al. 1994; Parfitt et al. 1994; Walker 1994). After 1080 is leached from baits into soils, theoretically there may then be an uptake of the toxin into terrestrial plants. In a laboratory study a single bait containing 0.15% 1080 was placed on the soil in 130-mm pots containing perennial ryegrass and broadleaf. Mean 1080 concentrations peaked at 0.08 ppm in ryegrass after 3 days then declined below detection limits after 7 days; and broadleaf concentrations peaked at 0.06 ppm after 10 days and persisted at measurable concentrations (>3 ppb) for a further 28 days (Eason et al. 1998a). Although uptake of 1080 by plants in the field is likely to be much lower, there are currently no data available on 1080 in plants after baits have been aerially broadcast. Extremely low 1080 concentrations in plants for only short periods of time are thought to present an extremely low risk to animal health. Although it may be leached through some soils, to date no detectable amounts of 1080 have been measured in groundwater following control operations (Parfitt et al. 1994; C. Eason unpubl. data). Legislation requires that baits not be aerially broadcast within 100 m of streams, yet there have been incidents where measurable amounts of 1080 have been detected in stream water. The amounts recorded to date have usually been less than 9 ppb and were only detected over short periods after aerial application of 1080. Although 1080 95

is not degraded in distilled water, the concentration of 1080 will decline in stream water (Booth et al. 1999b), and these rates of degradation are about 60% higher when temperatures are increased from 11C to 21C (Ogilvie et al. 1996). Immediately following aerial control the Ministry of Health normally requires managers to collect and then send samples of stream water for laboratory analysis of 1080 concentration. Proper use of bait-station limits contamination of waterways. Cyanide: Cyanide paste is rapidly degraded by moisture and is therefore likely to remain in the environment for a short period only. Feratox® (pellets) may, however, persist for 2–3 months even when exposed to the weather (Warburton et al. 1996). Cyanide used in bait stations or as a paste is unlikely to contaminate waterways. Cholecalciferol: Cholecalciferol is used in bait stations and is therefore also unlikely to be found in waterways. It is degraded by sunlight and is also slowly oxidised when exposed to air. There is no published information on the fate of cholecalciferol in soils. However, its physico-chemical characteristics imply minimal leaching is probable. Brodifacoum: Environmental contamination by brodifacoum can be minimised by using it in well-constructed bait stations. Brodifacoum used in bait stations is unlikely to be detected in waterways, and is persistent in soils. Pindone: There is little published on the fate of pindone in soils. It is only slowly leached from baits, and no pindone was recovered from the soil under baits that were subjected to 200 mm of rain (Booth et al. 1999a). Rates of microbial degradation may be slow because of the insecticidal and fungicidal properties of pindone (Oliver & Wheeler 1978). Under standard conditions of use there was no pindone found in water samples following an aerial operation to control rabbits (Nelson & Hickling 1994). Phosphorus: This compound is readily oxidised. Baits that quickly dehydrate in hot, dry weather can ignite by spontaneous combustion and cause fires. Persistence of residues in animal tissues 1080: Residues of 1080 may persist in sub-lethally poisoned vertebrates for up to about 4 days (Eason et al. 1994c). However, residues of 1080 can persist in the carcasses of dead animals for at least 80 days (Meenken & Booth 1997), and these may be lethal to cats, dogs, rats, stoats, and ferrets (Hegdal et al. 1986; McIlroy & Gifford 1992), mustelids (Alterio 1996, 2000; Heyward & Norbury 1999; Murphy et al. 1999), and possibly some omnivores (e.g. hedgehogs). Furthermore, some insectivorous birds that feed on insects and larvae on carcasses (Hegdal et al. 1986) may be exposed to residues. Cyanide: Cyanide is comparatively rapidly metabolised and excreted over several days. The risks to non-target species associated with cyanide control of possums are therefore mainly through primary poisoning. However, animals recently poisoned with cyanide should be regarded as hazardous. (Mouth-to-mouth resuscitation of humans who have ingested cyanide is also dangerous.) 96

Cholecalciferol: Cholecalciferol is metabolised in possums to 25hydroxycholecalciferol which is toxic and will be present in the carcasses of poisoned possums. The risk to dogs and cats by secondary poisoning is low when compared with 1080. Dogs that ate one or two carcasses of possums poisoned with cholecalciferol (Campaign®) exhibited no ill effects, while dogs eating five carcasses over a period of 5 days showed moderate clinical signs of poisoning (Eason & Wickstrom 2000). Cats fed the carcasses of possums that had been killed by cholecalciferol had slightly higher serum calcium levels after eating possum meat for 5 days, but these returned to normal within a few weeks. Human consumption of game meat in areas where cholecalciferol baits have been used is not recommended since carcasses could contain significant amounts of 25-hydroxycholecalciferol for several weeks. Brodifacoum: Field use of brodifacoum will kill possums, rats, and mice (Gillies & Pierce 1999; Thomas 1998). Both rodent and possum carcasses will be predated by birds and mammals that eat carrion (Eason et al. 1999c) after eating brodifacoum baits as some die in the open (Cox & Smith 1992; Meenken et al. 1999). This has resulted in secondary poisoning of owls in New Zealand and overseas (Mendenhall & Pank 1980; Hegdal & Blaskiewicz 1984; Hegdal & Colvin 1988; Newton et al. 1990; Ogilvie et al. 1997; Stephenson et al. 1999), and raptors (Radvanyi et al. 1988), domestic cats and dogs (Dodds & Frantz 1984; Marsh 1985; Du Vall et al. 1989; Hoogenboom 1994; Young & De Lai 1997; Stone et al. 1999), and mustelids (Alterio 1996; Shore et al. 1999). In addition to the 33 species of indigenous birds at risk from primary poisoning, and eight species of indigenous birds at risk from secondary poisoning with brodifacoum (Eason & Spurr 1995), residues have recently been identified in dead whiteheads, parakeets, and kokako (Eason & Murphy 2000). Brodifacoum residues have also been identified in wild venison and pork from meat samples taken at processing factories. As brodifacoum will persist in the meat and livers of sub-lethally poisoned sheep and possums for at least 9 months (Laas et al. 1985; Eason et al. 1996a), there is a theoretical potential for humans to be exposed to brodifacoum residues (Eason et al. 1996a). Brodifacoum use should therefore be limited to bait-station control of rodents and low-density possum populations so that non-target predators or scavengers are placed at less risk of eating animals containing residues. The Department of Conservation has in January 2000 taken steps to reduce the mainland field use of brodifacoum. Pindone: Pindone, like other first-generation anticoagulants, is less persistent in animal tissues than second-generation anticoagulants such as brodifacoum (Parmar et al. 1987; Huckle et al. 1988). For example, in sheep, residues were detected in the liver and fat of animals dosed with 10 mg/kg for 8 days, but at 2 weeks none was detected (Nelson & Hickling 1994). Phosphorus: Phosphorus residues may persist for some time in the stomach or tissues of carcasses that have been poisoned with phosphorus, and this causes secondary poisoning of birds (Sparling & Federoff 1997) and dogs (Gumbrell & Bentley 1995).

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4.1.2

Susceptibility and risk reduction for pets and livestock

1080: Dogs are highly susceptible to 1080 (Eisler 1995). Residues in possum carcasses may be lethal to dogs for more than 80 days following 1080 poisoning (Meenken & Booth 1997). Dogs should therefore be excluded from control areas where 1080 has been applied for possum control for at least 3 months from the date of application or longer if dry. In areas frequently used by the public it may be necessary for managers to either caution dog owners about the need to fit muzzles to their dogs, or to use an alternative poison that does not present the same residue problems (e.g. cholecalciferol or cyanide). There have also been instances of livestock (e.g. sheep, deer, cattle) being poisoned by baits or by scavenging (e.g. cats, mustelids, and pigs) carcasses of animals that have been killed by 1080 (Annison et al. 1960; Gillies & Pierce 1999; Murphy et al. 1999; Alterio 2000). Most reported livestock deaths are as a result of baits being unintentionally applied in the wrong place, or of inadequate withholding periods before stock are reintroduced into control areas. Pregnant ewes are more susceptible than non-pregnant sheep; nevertheless, a single sub-lethal dose of 1080 had no long-term effects on the health or productivity of sheep (Wickstrom et al. 1997b; O'Connor et al. 1999). Cyanide: Cyanide is not a persistent toxin, but there have been several reports of sheep, cattle, and dogs (Hughes 1994) ingesting lethal amounts of recently laid baits. To minimise the exposure of non-target species to cyanide, paste baits should be placed sensibly and destroyed after they have been in the field for 2 nights. Uneaten Feratox® capsules should be retrieved. Cholecalciferol: There is a danger that baits containing cholecalciferol may be used less carefully than other bait types because cholecalciferol is known to be vitamin D3, and perceived to be ‘safe’. It is most important, therefore, to re-emphasize that cholecalciferol at the concentrations used in possum or rodent baits is potentially highly toxic to most animals. Cholecalciferol bait may be toxic to pets and domestic stock if they feed on sufficient amounts, and for this reason delivery in bait stations is recommended. The risks of secondary poisoning are low compared to 1080. Nevertheless, pets should be discouraged from eating carcasses as repeated exposure will induce toxicosis. Brodifacoum: Where bait stations are located along fence lines or in trees within the reach of animals, some livestock (especially cattle) are inclined to rub against bait stations and dislodge bait, which they then eat. Particular care is needed to exclude brodifacoum baits from livestock access. Other domestic animals feeding on carcasses containing brodifacoum residues may ingest lethal amounts of brodifacoum through secondary poisoning (e.g. dogs and cats). Antidotes are available (Vitamin K) for brodifacoum and pindone, but treatment of brodifacoum poisoning is prolonged. Pindone: Pindone is highly toxic to rabbits (LD50 = 6–18 mg/kg), but less toxic to dogs (LD50 = 75-100 mg/kg) and sheep (LD50 100 mg/kg) (Eason 1996). Evaluation of prothrombin times demonstrated that cats were the most susceptible domestic animal to pindone, that cattle may be affected by moderate doses, and horses are the least susceptible (Martin et al. 1991). Sheep administered sub-lethal amounts of pindone eliminated all of the toxicant within 2 weeks of dosing (Nelson & Hickling 1994).

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Phosphorus: Phosphorus is lethal to all domestic livestock that feed on paste baits. Cats, dogs, and pigs are also at risk from secondary poisoning. Although only 2–4 tonnes of phosphorus paste were used annually for possum control in New Zealand, between 1960 and 1976 there were 117 confirmed dog deaths by phosphorus compared to 254 deaths with 1080 (Rammell & Fleming 1978). 4.1.3

Risk of exposure and toxicity to non-target vertebrates (wildlife)

Non-target animals are principally at risk from eating baits or poisoned carcasses. 1080: The risk to non-target species during aerial control has been extensively studied (Spurr 1993a; Spurr 1994a; Fraser et al. 1995; Spurr & Powlesland 1997; Powlesland et al. 1999; Sherley et al. 1999; Fraser & Sweetapple 2000). Ongoing research is further evaluating species that may be at risk, and options that may further improve the safety of all possum control could include the use of more-potent bird repellents. Although most dead birds found following possum control have been exotic species (e.g. blackbird, chaffinch), native birds (e.g. whitehead, robin, tomtit, morepork) have also been killed (Spurr 1994a). The numbers of birds killed following aerial application of bait has declined since operators started routinely screening carrot bait to remove highly toxic fragments (Spurr 1994a); adding green dye (Caithness & Williams 1970) and cinnamon (Udy & Pracy 1981) as bird deterrents; and reducing sowing rates (Morgan et al. 1997). To date aerial control has had no long-term effects on populations of bats (Lloyd & McQueen 1998). The impact of aerial operations on lizard and skink populations has not been well assessed, but it would seem there is some mortality of these vertebrates when exposed to 1080 baits or to insects that have fed on baits (Whitaker & Loh 1991). The impact of aerial control on native frogs has not been assessed, but research conducted in Australia suggests that frogs are not very susceptible to 1080 (McIlroy 1986). The extent of non-target interference with baits in bait stations has not been well researched. Kaka may eat both plain cereal baits (Spurr 1993b) and baits dyed green and containing 0.1% cinnamon (Hickling 1997) when first exposed to them. However, cinnamon-lured baits are eaten less frequently and in significantly smaller amounts by kaka after they have been exposed to them two or more times (Hickling 1997). Although kiwi may eat cereal baits (Pierce & Montgomery 1992) but not carrot (MacLennan et al. 1992), there have been no kiwi deaths reported following 1080 operations (Spurr 1994a; Robertson et al. 1999b). Although rats and mice use bait stations (Thomas 1998) it is not known how many other species are at risk by primary poisoning. Possums, mice, rabbits and rats poisoned with 1080 are in themselves a hazard to other animals that eat them. Secondary poisoning of predators is commonly reported (Murphy et al. 1999; Heyward & Norbury 1999) and mortality in deer, usually 30–40% after aerial operations (Fraser et al. 1995) has been higher, i.e. >90% (Fraser & Sweetapple 2000). Cyanide: There are fewer reports of birds being killed by cyanide than by 1080 or traps (Spurr 1991). However, some ground-dwelling species are at risk, and unfortunately in some regions there have been reports of weka and kiwi being killed 99

where cyanide paste was used. For example, in 1984 some 66 hunters reported 37 kiwi poisoned by cyanide paste, about a quarter of the number caught in traps (Spurr 1991). In comparison no kiwi have been reported poisoned after 1080 operations. The risks that discarded cyanide capsules (i.e. Feratox®) present to non-target species has not been formally assessed. There are anecdotal reports of Feratox® killing hedgehogs, stoats, and cats, but not birds (J. Kerr, pers. comm.). Cholecalciferol: Cholecalciferol is less toxic to birds than 1080 (Wickstrom et al. 1997a; Eason & Wickstrom 2000), and is therefore likely to kill very few birds by either primary or secondary poisoning. Captive mallard ducks survived very high doses (2000 mg/kg) of cholecalciferol (Marshall 1984; Eason & Wickstrom 2000), but some canaries and chickens receiving the same dose subsequently died. Risk of exposure of non-target mammals or birds in the field has not yet been quantified. Brodifacoum: Brodifacoum is a potent second-generation anticoagulant that is toxic to many non-target species by both primary and secondary poisoning (Godfrey 1985; Eason & Spurr 1995). For example, most blackbirds on Red Mercury Island not killed by aerial application of brodifacoum baits were subsequently found to contain brodifacoum residues (Morgan & Wright 1996), and there are now extensive reports of other species of birds and mammals, including feral pigs, showing residues (Ogilvie et al. 1997; Empson & Miskelly 1999; Dowding et al. 1999; Stephenson & Minot 1999; Robertson et al. 1999a; Eason et al. 2000). A wide range of bird species (e.g. saddleback, silvereyes, paradise shelduck, morepork, skua, robin, and weka) have been found dead from poisoning after field use of brodifacoum in New Zealand (e.g. Taylor 1984; Taylor & Thomas 1993; Towns et al. 1993; Williams et al. 1986a,b; Stephenson et al. 1999). The manufacturer of brodifacoum concentrate (Zeneca) recommends that the pesticide should not be aerially broadcast for the control of pests, and that systems for controlled delivery of baits should be used. Further research in brodifacoum control areas is required to assess the risks to insectivorous birds feeding on invertebrates; the risks to predatory (e.g. New Zealand falcon, morepork) and omnivorous birds; the risk to folivores and seed-eating birds that may eat baits (e.g. Ogilvie et al. 1997); and the impacts of an exposure to brodifacoum on the breeding success of selected bird species. Detrimental effects on some individuals may, however, be counter-balanced by improved survival and breeding success in the absence of possums and rodents. In the short term a research priority is to establish whether or not the extent of brodifacoum transfer through the food web can be contained, for example, by using brodifacoum for rodents alone, or only using brodifacoum in pulses after 1080, cyanide, or cholecalciferol for initial control. Pindone: Research has demonstrated that pindone presents a risk of primary and secondary poisoning of birds (Martin et al. 1994). Scavengers such as the harrier hawk are likely to be most at risk from secondary poisoning (Calvin & Jackson 1991), and raptors tended to be more susceptible (0.25 mg/kg) than magpies, pigeons, parrots, and ducks (4–5 mg/kg) in dose-ranging experiments (Martin et al. 1994). However, the risks of inducing secondary poisoning are likely to be less pronounced than with brodifacoum, dependent of course on how the toxic baits are applied. In New Zealand there have been anecdotal reports (E.B. Spurr pers. comm.) of extensive bird kills from both primary and secondary poisoning after the use of pindone for

100

rabbit control, but there has been no monitoring to determine whether or not pindone has any long-term effects on the local abundance of bird populations. Phosphorus: Phosphorus is known to kill birds that feed on carrion. Although the non-target effects on indigenous birds in New Zealand have not been assessed, it is expected that morepork, New Zealand falcon, black-backed gull, skua, weka, and harriers will be at some risk from secondary poisoning. 4.1.4

Risk of exposure and toxicity to invertebrates

Invertebrates are at risk from contact with baits, eating baits or poisoned carcasses, or from exposure to residues in soil or other environmental media. 1080: There have been no significant changes in the relative abundance of different invertebrate taxa monitored before and after aerial poisoning that can be attributed to insect populations having been exposed to 1080 poison (Spurr 1994b; Spurr & Drew 1999). However, residues of 1080 have been measured in some insects (e.g. weta and cockroach) for up to 3 weeks following aerial application of 1080 baits (Eason et al. 1998a). Invertebrates with 1080 residues may present a risk to insectivorous birds (Hegdal et al. 1986). It has been shown that the addition of cinnamon to baits is a deterrent to some invertebrates (Spurr & Drew 1999). Recent research has confirmed that 1080 is not persistent in invertebrate species (e.g. Booth & Wickstrom 1999). Sherley et al. (1999) have raised concerns over the number of invertebrate species food in contact with 1080 baits, and research is now focusing on the incorporation of an invertebrate repellent into baits to enhance target specificity, and decrease the risk of secondary poisoning via species such as weta, which are known to eat 1080 baits. Cyanide: Although the effect of cyanide on invertebrates in New Zealand has not been researched, it is lethal to aquatic invertebrates at relatively low concentrations (i.e.