Background to PAPP

Since the middle of last century, Australia has largely relied on one very effective toxin for control of foxes and wild dogs. The toxin used is sodium fluoroacetate. It was the 1080th compound tested in a search for a new rodenticide, so its common name is ‘1080’.

While found to be unsuitable as a rodenticide, 1080 was highly toxic to foxes, rabbits and wild dogs but less toxic to native animals. It continues to be a proven effective tool in the battle against damaging pest animals in Australia. 1080 is used in reliable manufactured baits and in freshly prepared baits, but agricultural industries recognised the need for additional control tools.

What is PAPP

PAPP Molecule

PAPP Molecule

PAPP is the short name given to para-amino propiophenone. PAPP was selected as the next chemical to provide the required efficacy, safety and humaneness for a new bait.

Though difficult to synthesize, it is a relatively simple molecule. It has no other known use apart from its capacity to induce methaemoglobin.

PAPP is a chemical toxin that is suitable for control of foxes and wild dogs (but not rabbits). It has been developed as an additional tool and not as a replacement to 1080. Both chemicals have strengths and weaknesses that are useful in different pest management situations.

The development of PAPP arose from studies in the 1970’s and 80’s that assessed its ability to cause the formation of methaemoglobin in blood. When the toxicity of PAPP was tested in primates, rodents and dogs, the dogs were found to be much more susceptible than other species. The reason for the higher risk is that dogs and foxes metabolise PAPP by a different pathway that causes abnormally high concentrations of methaemoglobin in the blood.

Animals affected by PAPP show few clinical signs

Animals affected by PAPP show few clinical signs

Methaemoglobin contains oxidised iron Fe+++ (or ferric) but normal haemoglobin is Fe++ (or ferrous). Normal haemoglobin carries oxygen very well, but methaemoglobin does not carry oxygen at all.

An animal that experiences high levels of methaemoglobin is unable to deliver oxygen to tissues such as the heart, brain and diaphragm. An affected animal will quickly become unconscious and die, but an animal that suffers only a mild amount of methaemoglobin experiences temporary lethargy then recovers to normal within hours.

The unusual metabolic pathway in canid animals (wild dogs and foxes) makes them highly susceptible to PAPP, so studies tested PAPP as a new poison that can be used to target these pests. It has taken some 10 years and several million dollars of industry funding to obtain registration of PAPP baits. As PAPP has not been used or registered for any other product, the regulatory authorities required a very extensive data and information package in order to be properly able to evaluate the risks and benefits of the new chemical. In early 2016 final product labels were approved to allow PAPP to be used in baits to assist the targeted control efforts on foxes and wild dogs in Australia.

Though PAPP has many benefits that distinguish it from other pesticides, it also carries some risks that need to be understood and managed.

This page, the use instructions on http://www.animalcontrol.com.au/foxecute2.htm, http://www.animalcontrol.com.au/dogabait2.htm and the accompanying booklets, supporting documents and advisory notes (see also http://www.pestsmart.org.au and industry publications) seek to give all users the correct understanding of PAPP and the right ways to use PAPP baits to achieve effective fox and wild dog control, with minimal risk to domestic dogs, users and non-target wildlife.

Mode of action of PAPP

PAPP is absorbed rapidly from the gastrointestinal tract and is transported to the liver. Foxes and dogs have liver enzymes that convert PAPP to a hydroxylated version, PHAPP (Para hydroxyamino propiophenone). PHAPP is taken up by red blood cells where it causes the rapid conversion of haemoglobin to methaemoglobin.

Schematic of the process of PAPP acting on the Heamaglobin

 

If levels of methaemoglobin in blood exceed about 80% the affected animal dies quietly from oxygen depletion. This is known as metabolic anoxaemia and is totally painless. Thus, PAPP poisoning is a very humane pest control technique. Metabolically the effect can be likened to carboxy haemoglobinaemia that is caused by carbon monoxide poisoning. Thus, PAPP poisoning is amongst the most humane pest control techniques known.

The process of absorption of PAPP, its metabolic transformation to PHAPP and then action in the red blood cell is fast. Peak methaemoglobin concentrations occur about 30–60 minutes after peak PAPP levels. Typically, a fully dosed fox dies within 1–2 hours of ingesting a single FOXECUTE® bait . This is shorter than the time taken for 1080, which is approximately 4.5 hrs for a fox that receives a 3 mg 1080 fox bait or up to several hours for a wild dog affected by a 6mg 1080 bait. However, during this lag phase there are few clinical signs until the final stages of toxicosis with 1080.

PAPP doses exceeding about 25 mg/kg liveweight will kill most dogs and foxes. However, the difference in average liveweight of foxes (5-7kg) versus dogs (typically 15 to 30 kg) mean that much higher doses of PAPP are needed in wild dog baits than for fox control. Baits are dosed with an overage to ensure high efficacy.

While action of PAPP is fast, death only occurs if sufficient quantities of the toxin are eaten and absorbed quickly. If the toxin is absorbed slowly this will allow time for detoxification mechanisms to work and the animal will not reach the critical levels of methaemoglobin to cause death. The FOXECUTE® and DOGABAIT® baits achieve this rapid delivery. However, if small amounts of bait are eaten slowly, this will allow time for detoxification mechanisms to work and haemoglobin levels will not reach lethal levels. An under-dosed or slowly dosed animal may become lethargic or may show symptoms like blue/grey (cyanotic) gums and tongue, but can recover without treatment and with no long-term effects.

Both PAPP and PHAPP are metabolised and excreted quickly, mainly via the kidneys into urine. So if the animal does not die from the acute overdose, recovery is fast. Moreover, there is no bioaccumulation, so repeated small doses would have little or no impact. There are no long-term effects from sub-lethal exposure to PAPP.

% Blood Haemoglobin Levels after PAPP Ingestion

 

Most animals possess a protective enzyme called methaemoglobin reductase that naturally reverses methaemoglobinaemia. This enzyme is a safety mechanism to convert methaemoglobin back into normal haemoglobin.

How does PAPP differ from 1080

The mode of action of PAPP (see above) is different from the mode of action of 1080. Sodium flouroacetate (1080) is a naturally occurring plant toxin. It is found in several plants but especially in Gastraolobium and some Acacia species. It is a simple molecule that is deceptively similar to normal acetate which is an essential intermediate in the breakdown of sugar into energy.

1080 Molecule

1080 Molecule

1080 works by blocking the action of a critical enzyme (aconitase), which is one of a series of enzymes responsible for converting sugar into chemical energy in all animal cells. This enzyme sequence occurs in the mitochondria (“energy factories”) of cells and is known as the Tri Carboxylic acid, or TCA cycle. 1080 works as a “spanner” in the gears of the energy factory, so all other biochemical processes that require energy cease, as metabolic energy is depleted.

Enzymes in some species are less able to be blocked by 1080, so reptiles are generally less susceptible than birds and birds are less susceptible than mammals. Even between mammals there are large differences in susceptibility. One reason for this is that 1080 occurs naturally in some toxic plants in Australia, so Australian native herbivores that eat such plants have been naturally selected for resistance.

Thus, 1080 can be used selectively to control introduced pest animals, since the introduced pests have not had the evolutionary time to adapt, while posing limited risk to the vast majority of native species.

Risks are further reduced by using baits that are preferred by the pests but not palatable to the non-target species and by using baiting techniques such as “buried baits”, (where possible) that reduce the risk of nontarget animals taking baits.

These practices have been well developed and tested over many decades and enable pest animals to be controlled while posing limited risk to non-targets.

However, 1080 is highly toxic not just for foxes and wild dogs but also for pets and working dogs. For this reason many landowners are reluctant to use this effective chemical as widely as is needed to manage the pest wild dogs and foxes.

While the action of 1080 is only to block an enzyme in the mitochondria, the resultant biochemical disruption of sugar metabolism, into carbon dioxide and energy, causes a build-up of citrate in blood. Citrate binds up calcium ions that are necessary for normal muscle function and coordination. Therefore, during the last phases of poisoning with 1080, while the animal is unconscious, an affected animal exhibits muscle spasms that can be distressing for an owner to witness. Moreover, there is no proven antidote to poisoning with 1080 so most dogs that accidentally take a bait will succumb, even despite veterinary intervention.


Animal Control Technologies (Australia) Pty Ltd
46-50 Freight Drive
Somerton, Victoria, 3062
Australia
Telephone +61 3 9308 9688
Fax +61 3 9308 9622

E-mail: enquiries@animalcontrol.com.au