New Vertebrate Toxic Agents for Pest Species

Pesticides

New Vertebrate Toxic Agents for Pest Species

Rhian Cope, Lower Hutt, New Zealand

Given that most indigenous animal life in New Zealand evolved for millions of years in the absence of terrestrial mammalian predators, the continued preservation of most endemic species is heavily contingent on effective suppression of introduced vertebrate predators with the use of vertebrate toxic agents.

In New Zealand the most common method for the control of feral cats and stoats is trapping, which is effective but labor intensive. Sodium fluoroacetate (1080) is also currently registered for feral cat control in the form of a fish/meat meal pellet for either bait stations or hand-laying, although it is not approved for stoat control. Notably, 1080 operations directed against brush tailed possums (Trichosurus vulpecula), rabbits (Oryctolagus cuniculus), and other mammalian pest species often serendipitously result in secondary poisoning of feral cats and stoats. However, 1080 is controversial because of genuine concern regarding secondary poisoning in nontarget domestic species, as well as the general public’s concern over its use. Thus New Zealand has been placed in the position of seeking new toxicants and technologies for the control of vertebrate pest species.

New Zealand has recently approved a new vertebrate toxic agent for the control of feral cats (Felis catus) and stoats (Mustela erminea): para-aminopropiophenone (PAPP). The use of encapsulated sodium nitrite for the control of feral pigs (Sus scrofa domesticus) is currently in the final stages of regulatory approval. A third toxin, tutin, is currently under development. These toxins (toxicants) are the subjects of this chapter.

Para-Aminopropiophenone (PAPP)

PAPP was originally developed as a potential antidote for acute cyanide poisoning and for its radioprotective properties against X, gamma, and high-energy proton irradiation. PAPP is the most potent methemoglobin inducer of the para-aminoalkylphenones. It is capable of inducing clinically significant methemoglobinemia, oxidative hemolytic anemia, and Heinz body formation in a variety of vertebrate species including mustelids, cats, dogs, and rodents, as well as in various bird species.

In the United States, trials using PAPP for control of coyotes (Canis latrans) were conducted for the U.S. Fish and Wildlife Service. The coyote trials revealed problems with both formulation and regurgitation by dosed animals. Development of PAPP was not a priority after 1080 was registered for use in the Livestock Protection Collar. New Zealand PAPP formulations all contain an antiemetic. This addition decreases the risk that vomiting of the bait will reduce the effectiveness of these formulations in targeted species. Unfortunately, the inclusion of an antiemetic potentially increases the hazard of PAPP baits ingested by nontarget species.

PAPP is readily metabolized, is not bioaccumulative, and does not accumulate in the environment. The risk of secondary toxicity to nontarget species is regarded as low. However, nontarget burrowing seabirds are considered to be at risk of inadvertent poisoning because of the current design of the bait stations.

Lethal Doses

PAPP has some selective toxicity for felids, mustelids, and canids. The lethal doses are: cats, 20 to 34 mg/kg; stoats, 37.1 to 94.8 mg/kg; ferrets (Mustela furo), 13 to 25 mg/kg; and dogs (Canis familiaris), 21.4 to 42.9 mg/kg. Birds and rodents are somewhat less susceptible, although there is some variability in the response of different bird species.

Methods of Use as a Vertebrate Toxic Agent

Veterinarians should understand how these agents are deployed and how most exposures occur. PAPP is available as a 410 g/kg paste mixed with meat to produce meat boli that contain about 22 mg PAPP/g. The boli are placed in bait stations. PAPP is designed to be a single-feed vertebrate toxic agent. However, prefeeding with mince for 2 weeks prior to laying the PAPP baits is recommended. Prepared mince baits should be used within 24 hours of preparation and remain toxic for several days.

A device in which a concentrated PAPP preparation is sprayed onto the ventrum of the animal and subsequently ingested via grooming is currently under development. This device is capable of dosing more than 100 animals without having to be reset or recharged.

Disposition

PAPP is rapidly and nearly completely absorbed after oral exposure. It is a protoxicant that undergoes metabolic activation in vivo. In rodents, the putative methemoglobin-producing metabolite is 4-(N-hydroxy) aminopropiophenone (PHAPP). However, there are species differences in metabolism. In rats PAPP is metabolized predominantly by N-acetylation. In dogs metabolism is predominantly by ring and aliphatic hydroxylation, with lower rates of N-hydroxylation occurring in male dogs; consequently bitches produce more methemoglobin for a given dose of PAPP than male dogs. In primates both N-acetylation and oxidation occur. Elimination kinetics after oral dosing follows a two-compartment model. The elimination of PAPP metabolites appears to be dependent on glucuronidation, implying that species with low glucuronidation capacity, such as cats, may have greater difficulty eliminating the compound.

Mode of Action

PAPP and its putative active metabolite PHAPP produce acute oxidative damage to the erythron, with resultant methemoglobinemia, Heinz body formation, and oxidative hemolysis. This results in decreased blood oxygen carrying capacity and tissue hypoxia. Frank methemoglobinemia is compounded by a concurrent left shift of the hemoglobin : oxygen dissociation curve, which further exacerbates tissue hypoxia. Peak methemoglobinemia occurs between 1 and 3 hours postingestion.

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Tags: Kirks Current Veterinary Therapy XV

Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off

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