AU2009100350A4 - Vertebrate Pest Control - Google Patents

Vertebrate Pest Control Download PDF

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AU2009100350A4
AU2009100350A4 AU2009100350A AU2009100350A AU2009100350A4 AU 2009100350 A4 AU2009100350 A4 AU 2009100350A4 AU 2009100350 A AU2009100350 A AU 2009100350A AU 2009100350 A AU2009100350 A AU 2009100350A AU 2009100350 A4 AU2009100350 A4 AU 2009100350A4
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vertebrate
aminophenyl
papp
toxic
formulation
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AU2009100350A
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Charles Thomas Eason
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CHARLES EASON
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CHARLES EASON
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Description

C01.002 AU VERTEBRATE PEST CONTROL TECHNICAL FIELD 5 The invention relates to vertebrate toxic agents including formulations of 1-(4-aminophenyl)-1-alkanone for use in the control of vertebrate pests. In particular, the invention relates to vertebrate toxic agents including formulations of 1-(4-aminophenyl)-1-alkanone in 10 combination with other methemoglobinaemia inducing agents and their use in the control of species of the genus Rattus. BACKGROUND ART 15 Control methodologies for vertebrate pest control currently rely largely on labour-intensive trapping or the use of increasingly unpopular vertebrate toxic agents. These agents are linked with secondary poisoning or 20 considered inhumane. The toxins used in vertebrate toxic agents may be classified as anticoagulants or non-anticoagulants. Anticoagulants comprise toxins such as warfarin, pindone, 25 diphacinone, coumatetralyl, difenacoum, bormadiolone, broadifacoum, flocoumafen or difethalione. Non anticoagulants comprise toxins such as cyanide, zinc phosphide, sodium monofluoroacetate (1080) or cholecalciferol. 30 The worldwide use of 1080 occurs mostly in Australia and New Zealand. In New Zealand there has been a heavy reliance on the use of anticoagulants and the non 1 C01.002 AUJ anticoagulant monofluoroacetate (1080) for vertebrate pest control. Public support for the use of 1080 declined by 8% in the 5 period 2003 to 2006 (URM (2006)). The use of 1080 has been reassessed by New Zealand's Environmental Risk Management Authority (ERMA(2007)). Whilst being highly effective the use of 1080 is considered inhumane (Sherley (2004); Cooper et al (2007)). 10 There is a need for new vertebrate toxic agents. However, the use of new vertebrate toxic agents including alternative toxins, such as second-generation anticoagulants, have resulted in non-target wildlife 15 contamination in New Zealand (Eason et al (2002)) and internationally (Young and de Lai (1997)). The problems associated with the existing use of toxins are compounded by use in conjunction with outdated bait 20 technology (Eason et al (2002); Litten et al (2004)). For example, fragmentation of the dosage form may result in ingestion by the target pest of a low dosage and ultimately lead to resistance (Eason et al (1997)). 25 1-(4-aminophenyl)-1-propanone (synonyms: para aminopropriophenone; PAPP) is regarded as a humane toxin. Vertebrate toxic agents including this toxin cause methaemoglobinaemia and oxygen deprivation to the brain in feral cats and stoats. 30 PAPP is highly toxic to canids (Savarie et al (1983)). The United States Fish and Wildlife Service investigated the use of PAPP as a toxin for the vertebrate pest Canis 2 C01.002 AU latrans (coyote). However, a limitation on the use of PAPP is the nausea and vomiting that may occur pursuant to ingestion of the toxin. 5 The use of PAPP for the control of vertebrate pests has been investigated in Australia and New Zealand (Fisher et al (2005); Fisher & O'Connor (2007); Fleming et al (2006); Marks et al (2004) and Murphy et al (2005)). However, a vertebrate toxic agent including this toxin has yet to be 10 registered for sale. It is an object of the invention to provide improved vertebrate toxic agents for use in the control of vertebrate pests. This object is to be read disjunctively 15 with the object of to at least provide a useful choice. DISCLOSURE OF INVENTION In a first aspect the invention provides a vertebrate 20 toxic agent including a formulation of an amount of a 1 (4-aminophenyl)-1-alkanone where the formulation excludes an antiemetic. Preferably, the vertebrate toxic agent is in a discreet 25 dosage form where the amount of the 1-(4-aminophenyl)-1 alkanone is less than 200 mg per dosage form. Preferably, the 1-(4-aminophenyl)-1-alkanone is selected from the group consisting of: 1-(4-aminophenyl)-1 30 ethanone, 1-(4-aminophenyl)-1-propanone, 1-(4 aminophenyl)-1-pentanone, 1-(4-aminophenyl)-1-hexanone, 1 (4-aminophenyl)-1-heptanone, 1-(4-aminophenyl)-1-octanone, 1-(4-aminophenyl)-1-nonanone and 1-(4-aminophenyl)-1 3 C01.002 AU decanone. Most preferably, the 1-(4-aminophenyl)-l alkanone is selected from the group consisting of: 1-(4 aminophenyl)-1-propanone, 1-(4-aminophenyl)-1-pentanone and 1-(4-aminophenyl)-1-hexanone. 5 Preferably, the vertebrate is a species of the genus Rattus. More preferably, the vertebrate is a species of the genus Rattus selected from the group consisting of: Rattus norvegicus and Rattus rattus. 10 Preferably, the dosage form is a capsule, pellet or tablet. Preferably, the dosage form has a volume less than 1 ml. 15 In a first embodiment of the first aspect the invention provides a vertebrate toxic agent including a formulation of an amount of 1-(4-aminophenyl)-1-propanone where: 20 the vertebrate is a species of the genus Rattus; the amount of the 1-(4-aminophenyl)-1-propanone is less than 200 mg per 1 ml; and the formulation excludes an antiemetic. 25 In a second aspect the invention provides a method of controlling a vertebrate pest including the step of applying to the environment of the vertebrate pest the vertebrate toxic agent of the first aspect of the invention. 30 4 C01.002 AU In the description and claims of the specification the following terms and phrases have the meaning provided: "1-(4-aminophenyl)-1-alkanone" means a chemical of the 5 structure: 0 H2N where R 1 is a an alkyl substituent. 10 "Antiemetic" means an ingredient used in the preparation of a formulation to be effective against nausea or vomiting following ingestion of the formulation. 15 "Discreet dosage form" means in the context of a vertebrate toxic agent an aliquot of the formulation including a capsule, pellet or tablet. "Product" means a formulation identified and packaged for 20 a specified use or uses. "Vertebrate toxic agent" means a product used to kill or reduce the viability of vertebrate pests, including the induction of methemoglobinaemia. 25 5 C01.002 AU DETAILED DESCRIPTION The toxic effects of 1-(4-aminophenyl)-1-alkanones appear to be related to the rapid formation of methemoglobin in 5 some species (Vandenbelt et al. (1944)). High methemoglobin levels reduce the oxygen-carrying capacity of the blood. At toxic doses 1-(4-aminophenyl)-1-alkanones induce a 10 rapid methemoglobinaemia. Hypoxia and central nervous system depression precede death. Carnivore species appear to be much more susceptible to 1 (4-aminophenyl)-1-alkanones than birds (Savarie et al. 15 (1983); Shafer et al. (1983)). Accordingly, 1-(4 aminophenyl)-1-alkanones, in particular 1-(4-aminophenyl) 1-propanone, 1-(4-aminophenyl)-1-pentanone and 1-(4 aminophenyl)-1-hexanone, have some degree of target specificity, especially in the Australian and New Zealand 20 environments. Formulations including 1-(4-aminophenyl)-1-alkanones such as 1-(4-aminophenyl)-1-propanone typically require the additional inclusion of an antiemetic to prevent the 25 target pest vomiting following ingestion of the formulation. The vertebrate toxic agents of the invention where the target vertebrate is a species of the genus Rattus are 30 particularly advantageous. These vertebrate toxic agents may comprise a formulation of an amount of 1-(4 aminophenyl)-1-alkanone where the formulation excludes an antiemetic. 6 C01.002 AU The exclusion of an antiemetic provides a number of advantages including a reduction in the cost of preparing the vertebrate toxic agent, reduced concern associated 5 with the release of chemical substances into the environment, and reduced cost associated with obtaining regulatory approval. In addition to an amount of 1-(4-aminophenyl)-1-alkanone, 10 the formulation will typically contain sodium nitrite as a second methemoglobinaemia inducing agent. The selection of the amount of 1-(4-aminophenyl)-1 alkanone (with or without sodium nitrite) in combination 15 with the volume of a discreet dosage form may further permit the use of a vertebrate toxic agent that is effective against vertebrate pests in addition to species of the genus Rattus despite the exclusion of an antiemetic from the formulation. 20 If necessary, the discrete dosage form may be dimensioned to prevent, or at least mitigate, the likelihood of the vertebrate toxic agent being ingested by non-target species such as indigenous fauna. 25 EXPERIMENTAL Study Animals Laboratory rats, males and females were housed 30 individually in cages and fed a maintenance diet of cereal pellets with access to water ad libitum. After at least a week of acclimatisation the toxic section of the trial was initiated. 7 C01.002 AU Observations After dosing, rate of onset of symptoms, duration of symptoms and time to death were determined. The induction of methemoglobinaemia was assessed by observation of 5 blueness (cyanosis) of ears, mouth, tongue or lips. Dosing regimen - PAPP only Six acclimatised rats were presented with 4 g of feed containing 125 mg of PAPP. Three of the rats had PAPP mixed with EPA diet. Three of the rats had PAPP mixed 10 with 213 rodent bait. The amount of bait eaten was assessed and the dose of PAPP ingested on a mg/kg body weight basis determined. Dosing regimen - PAPP and sodium nitrite Four acclimatised rats were presented with 5 g of feed 15 (213 rodent bait) in two groups (Group 1 & Group 2). The rats were lightly fed for two nights and then fasted for 24 hours. After fasting the two rats from Group 1 each received 188 mg of microencapsulated sodium nitrite. After fasting the two rats from Group 2 each received 94 20 mg sodium nitrite with 12 mg PAPP. The toxic compounds were mixed with 213 rodent bait. RESULTS Dosing regimen - PAPP only 25 Initial studies were conducted with PAPP at dose rates ranging from 103 mg/kg body weight to 420 mg/kg body weight (Table 1). Signs of methemoglobinaemia were observed in some animals, but none were killed. 8 C01.002 AU Weight Feed Amount eaten mg/kg body weight Observations 295 213 2.7 278 Sluggish pale eyes 305 213 1.6 160 Sluggish pale eyes 297 213 4.1 420 Sluggish pale eyes 290 EPA 1.9 202 Sluggish pale eyes 288 EPA 2.8 295 Sluggish pale eyes 290 EPA 1.0 103 Sluggish pale eyes Table 1. Rat weights, feed, amount eaten, mg/kg ingested and subsequent observations according to dosing regimen - PAPP only. 5 Dosing regimen - PAPP and sodium nitrite The rats presented with 5 gm feed containing a combination of microencapsulated sodium nitrite and PAPP all ate the bait. The relevant dose rates are provided in Table 2. Signs of methemoglobinaemia were observed in some animals, 10 but none were killed. Amount eaten mg/kg body Amount eaten weight Sex Weight (sodium weight (PAPP, mg) (sodium nitrite, mg) (PAPP) nitrite) Male 554 187.5 338.4 Male 414 93.75 12 226.4 29.0 Female 251 187.5 747.0 Female 370 93.75 12 253.4 32.4 Table 2. Rat weights, feed, amount eaten, mg/kg ingested and subsequent observations according to dosing regimen - PAPP and sodium nitrite. 9 C01.002 AU SUMMARY Rats will consume PAPP alone or in combination with sodium nitrite in quantities sufficient to induce 5 methemoglobinaemia. The onset of PAPP induced methemoglobinaemia is rapid. It is plausible to maximise the induction methemoglobinaemia by co-administration of relatively low doses of PAPP and increasing doses of sodium nitrite. Alternatively or in addition more toxic 10 1-(4-aminophenyl)-1-alkanones may be substituted for PAPP for use in the vertebrate toxic agents of the invention. Although the invention has been described in detail with reference to specific features it should be appreciated that variations and modifications may be made without 15 departing from the scope of the invention. Furthermore where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred to in this specification. 20 10 C01.002 AU REFERENCES Beutler and Mikus (1961) The effect of sodium nitrite and para aminopropriophenone administration on blood methemoglobin levels and 5 red blood cell survival, Blood 18, 455-67 Cooper et al (2007) 1080 and wildlife: ethical issues raised by its use on Australian animals, Royal Zoological Society of New South Wales, 229-232 10 Eason et al (1997) Product stewardship, animal welfare, and regulatory toxicology constraints on vertebrate pesticides, Proceedings of the Fiftieth New Zealand Plant Protection Conference, 206-213 15 ERMA (2007) The reassessment of 1080: and informal Guide to the August 2007 Decision of the Environmental Risk Management Authority, ISBN 978-0-478-231538-0, p 28 . 20 Fisher et al (2002) Acute and oral toxicity of aminopropiophenome to stoats, New Zealand Journal of Zoology, 32, 163-169 Pan et al (1983) Acute oral toxicity of p-aminophenones, General Pharmacology 14, 465-467 25 URM (2006) Public acceptance of 1080 programme, URM Research Ltd., Report for Animal Health Board, p9 Saverie et al (1983) Comparative acute oral toxicity of para 30 aminopropiophenone, Bulletin of Environmental Contamination and Toxicology, 30, 122-126 Scawin et al (1984) The acute oral and intravenous toxicity of p aminopropiophenone (PAPP) to laboratory rodents, Toxicology Letters 35 23, 359-365 Sherley (2004) The traditional categories of fluoroacetate poisoning signs and symptoms belie substantial underlying similarities, Toxicology Letters, 151, 399-406 40 11 C01.002 AU Young & de Lai (1997) Population declines of predatory birds coincident with the introduction of Klerat Rodenticide in North Queensland, Australian Bird Watcher, 17, 160-167 5 12
AU2009100350A 2008-04-17 2009-04-17 Vertebrate Pest Control Expired AU2009100350A4 (en)

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NZ567602 2008-04-17
NZ567602A NZ567602A (en) 2008-04-17 2008-04-17 Vertebrate pest control comprising a 1-(4-aminophenyl)-1-alkanone, particularly PAPP

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2010202590B2 (en) * 2009-06-22 2013-11-14 Animal Control Technologies (Australia) Pty Ltd Formulations for Vertebrate Pest Control

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2010202590B2 (en) * 2009-06-22 2013-11-14 Animal Control Technologies (Australia) Pty Ltd Formulations for Vertebrate Pest Control

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