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Norbormide is a uniquely selective rat toxicant for Rattus species, with rats being 100- to 150-fold more sensitive to norbormide toxicity than most other mammals and birds. Previously we reported that on completion of a 10-year program of targeted fundamental and applied synthetic chemistry and toxicology, taste aversion associated with this compound had been overcome. In 2020-2022, trials have been successfully completed on poultry farms with Norway rats and larger scale field trials were undertaken targeting ship rats using 1% norbormide paste baits. Firstly, the efficacy of norbormide-containing paste baits targeting rat infestations on poultry farms was proven with a 100% reduction of Norway rat populations on three different farms. Secondly, 100% reduction in ship rat abundance was achieved at two large field test sites; and no reduction was achieved at the untreated control site. These larger field trials are described in depth in this publication. Plans are progressing to complete product development and registration.

Rodenticides such as brodifacoum are more potent than first-generation anticoagulants. However, their field, farm, and outdoor use in urban settings have been linked to bioaccumulation and non-target impacts for more than three decades. Product development strategies focused on baits that yield good control of pests without residue risks to wildlife are few. To fill this gap, a bait containing a combination of diphacinone at 0.005% and cholecalciferol at 0.06% (D+C bait) has been developed as a multispecies bait for NZ use, that is effective at killing rodents and also possums (Trichosurus vulpecula), which are resistant to the toxin effects of first-generation anticoagulants. This bait was approved by the NZ Environmental Protection Agency and the product registered by the NZ Ministry of Primary Industries in 2019. A new bait is being considered with a lower dose of cholecalciferol. A bait containing half or a quarter of the loading concentration of cholecalciferol would have an even better safety profile for rodent control alone. Cage trials indicate that cholecalciferol at 0.03% with diphacinone 0.005% is as effective as brodifacoum as a single exposure bait. Amounts of cholecalciferol as low as 0.015% significantly improve the effectiveness of diphacinone.

Field trials are reported in this paper on a new bait containing 1% norbormide. Two separate field trials were recently completed on commercial chicken farms in South Auckland, New Zealand. Norway rats were abundant both inside the farm sheds and around the surrounding farmland. Monitoring undertaken before toxic baiting recorded high levels of rat activity. Post-treatment monitoring found no rat paw prints in any of the tracking tunnels from Site 1, and in only one tunnel at Site 2. The decrease of 100% and 96%, respectively, represented a marked reduction in the Norway rat population at both sites.

Norbormide is a rat specific toxicant. It causes vasoconstriction of small arteries and vasodilation of large arteries in rats, which results in a rapid fall in blood pressure and death from heart failure. It is an extraordinary compound in that it is only toxic to rats. The lack of toxicity of this compound to birds and other mammals is unique. It was originally researched in the 1960s and initially marketed in the USA. Problems with taste aversion slowed its continued use and sales it and was largely forgotten when anticoagulant rodenticides became more effective and popular. Following the emergence of anticoagulant resistance in some populations of rodents, residues of the second-generation anticoagulants in wildlife and concerns regarding humaneness, interest in non-anticoagulants, such as norbormide, has revived. Research has been conducted to help identify and understand a formulation of norbormide which is palatable, effective, and fast acting in rats. Further research is underway to determine methods for large scale synthesis of an improved form of norbormide. Field trials are planned in 2018/19. The ability to target rats with no risk to non-target species presents considerable advantages in many settings and warrants further investment and completion of the current scale-up phase of research and development.

Internationally, over the last 20 years the number of tools available for the control of small mammals has declined. Through the efforts of research we have bucked this trend and retained and developed new tools. Three new toxins have been extensively researched and registered, namely para-aminopropiophenone (PAPP) in 2011 for stoats and feral cats; zinc phosphide for possums in 2012; and encapsulated sodium nitrite (ESN) in 2013, for possums and feral pigs. The development of PAPP and ESN, coined red blood cell toxins, developed for humaneness, represent the first new vertebrate pesticides registered for field control of mammalian pests anywhere in the world for >30 years. Research on rodenticides including diphacinone with the additive cholecalciferol (D+C) and a palatable form of norbormide continues. A New Zealand EPA application for D+C was filed in June 2015. More effective killing systems are being researched, and the first successful field trials of resetting toxin delivery devices for possum and stoat control were completed in 2013 and 2014. Improved deployment strategies, integration of humane and selective toxins, lures of greater potency, and improved killing devices aided by species’ recognition will transform ground control for endangered species protection. Sodium fluoroacetate (1080) and other important tools have been retained as new tools are emerging from a research and development pipeline. It is important for the future of New Zealand’s biodiversity that this focused research continues and we continue to learn and advance new technologies. Our goals are shifting to enable reduction in density of rat, stoat, and possum populations to zero over large scales (i.e., elimination at landscape scale), and to hold these at zero through detection and response, including the use of new technologies for perimeter control as part of barrier systems for conservation.

PAPP is short for para-aminopropiophenone and is a new vertebrate pesticide. It is a compound with the formula C9H11NO, it is comparative humane, has low secondary poisoning risk, and has an antidote. PAPP was originally trialed in the 1960s as an antidote for human radiation and cyanide poisoning. In the USA, it has been investigated as a tool for coyote control and was found to be specifically much more toxic to carnivores than to birds and humans. In Australia, it will be used for field control of foxes, wild dogs, and feral cats. In New Zealand, PAPP was registered in 2011 for the control of stoats and feral cats, following the completion of pen and field trials and submission of extensive dossiers covering its effectiveness as a pest control agent and on its ecotoxicology, toxicology, and metabolism.

Introduced rats continue to have a major impact on biodiversity around the world, and improved control techniques are required to avoid further extinctions. We are trialing re-setting toxin-delivery systems (Spitfires) targeting a range of predators, including rats. The rat Spitfire works by firing 800 mg of a toxic paste onto the belly of the rat as it passes through a tunnel; the device then resets. When the rats groom the paste from their fur, they ingest the toxin. Each Spitfire is capable of approximately 100 doses and is fitted with a counter and a delay mechanism. We trialed 0.55% 1080 paste in the Spitfire and 15 of 15 wild Norway rats and 14 of 15 black rats died. Further trials are planned with a range of toxins to allow flexibility of use. Resetting devices that are expected to work for long periods without being serviced also require long-life lures. Preliminary trials showed urine and scats from female Norway rats were attractive to both male and female Norway rats. The volatile components from these and further trials will be identified to aid in developing a long-life lure. The long-term, effective control of introduced rats will require a range of toxins with different modes of action, a number of different delivery systems, and long-life lures.

Anticoagulant compounds are likely to play an important role in the control of commensal rodents for crop protection and conservation for the foreseeable future. However, there are concerns regarding their persistence and the development of more widespread resistance. We are seeking to retrieve and retain older alternatives as well as developing novel rodenticides. Our three-pronged approach is, firstly, to improve the performance of older non-anticoagulant rodenticides, such as sodium fluoroacetate (1080) and zinc phosphide; secondly to optimise the performance of 1st-generation anticoagulants; and thirdly, to identify alternatives to anticoagulant rodenticides with the same mode of action as para-aminopropiophenone (PAPP), which was registered in New Zealand as a predacide in April 2011. Zinc phosphide was also registered in New Zealand for the first time in 2011, and combinations of ultra-low-dose cholecalciferol with first generation anticoagulants are being advanced to provide the performance characteristics of a 2nd-generation anticoagulant with a lower risk of bioaccumulation and secondary poisoning.

To achieve long-term suppression of pest populations, devices capable of continued control over extended timeframes are needed. Creating new pest management tools to achieve this goal requires the integration of animal ecology, toxicology, and design engineering. This research outlines the development and testing of a long-life, resetting, toxin delivery system for vertebrate pest control, coupled with advances in novel species recognition systems. Such devices have the potential to offer advantages over current labor-intensive control techniques. Resetting systems have been developed to target several of the most destructive vertebrate pest species in New Zealand, including stoats and weasels. Results of enclosure trials for these two species showed similar responses after a paste containing 40% para-aminopropiophenone was delivered onto the chest and stomach, following triggering by a treadle operated system. Both species groomed the paste off shortly after application and death occurred after an average of 42 minutes for stoats and 57 minutes for weasels. The applications of these resetting devices are now being extended for the control of brushtail possums, another major vertebrate pest in New Zealand. Coupled with this, developments in species identification systems are ensuring that risks to non-targets are substantially minimized. Resetting, long-life toxin delivery systems could be deployed to control a variety of pest species, and further enhancement of these tools are ensuring their use for widespread field applications in a cost-effective, safe and reliable manner.

Compound 1080 has been used to control native wallabies and possums in Tasmania for over 50 years. Public concern in relation to humaneness and its effects on domestic dogs and nontarget species has led to opposition to its use. Feratox®, a form of encapsulated cyanide pellet registered for brushtail possum control in New Zealand, was considered as a replacement toxin. Trials in New Zealand showed that the material is fast-acting and humane in wallabies. In Tasmania, protocols were developed using bait stations that would minimise access by nontarget macropods and wombats. In field trials using Feratox®, however, there was excessive spillage of toxic pellets and variation in bait take between seasons by Tasmanian pademelons. Further work is under way to resolve these issues to see if protocols can be developed for the safe and effective use of cyanide pellets in areas where nontarget mammals are prevalent.

Feral cat and stoat control is conducted in New Zealand to protect a number of threatened native species, including kiwi, from predation. Para-aminopropiophenone (PAPP) is being developed for predator control. Previously reported cage trials have shown PAPP presented in a meat bait was palatable and effective, while symptoms observed demonstrated PAPP to be humane. Subsequent field trials on stoats were undertaken in two blocks of native forest and achieved 83% and 87% reductions in the stoat abundance index, and a field trial on a population of radio-collared feral cats had an 84% kill. PAPP represents one compound from a new class of active ingredients, which we are calling red blood cell toxins. These vertebrate pesticides have humaneness, and low secondary and non-target poisoning risks, as their primary consideration. The dose is optimised to be effective in the field and reduces oxygen supply to the brain such that animals become lethargic, sleepy and unconscious prior to death within 1-2 hours. Results from these field trials on stoats and feral cats indicate that PAPP will be a useful additional tool for predator control.

In New Zealand, sodium fluoroacetate (1080) has been used for vertebrate pest control for several decades. Since the 1990s, some 1080 users have switched to brodifacoum for possum and rodent control because of its ready availability and ease of use. An awareness that field use of brodifacoum results in persistent residues provides the impetus to develop alternatives and provide new tools and greater flexibility. Looking to the future, we seek toxins which increasingly combine “low-residue” characteristics with humaneness, and more selective bait and delivery systems enabling better and more acceptable control of possums, wallabies, mustelids, rodents, feral cats, and rabbits. Experience gained in the 1990s with the introduction of cholecalciferol (Feracol®) and a cyanide pellet (Feratox®), which both kill possums without secondary poisoning, underpins the extension in 2009 of the Feratox® registration to include introduced Dama wallabies. To date, zinc phosphide has not been registered in NZ, despite its field use in Australia and the U.S. and low secondary poisoning risk compared with 1080. Research and registration dossiers are being assessed in 2009-10 for zinc phosphide containing products for possum and rodent control. Registration documents are also being prepared for a combination of cholecalciferol and coumatetralyl to provide a slow-acting alternative to brodifacoum for the field control of possums, rodents, and rabbits with low risk of bio-accumulation. Anticipated timelines for product availability are 2010 (zinc phosphide) and 2011-13 (cholecalciferol and coumatetralyl). Our intention now is to move beyond these conventional rodenticides and develop new vertebrate pesticides. For example, we are pursuing the registration of para-aminopropiophenone (PAPP) for humane control of stoats and feral cats, and a series of related novel toxins and other compounds that target the red blood cell for other pest species including rodents. PAPP products should be available in 2010, subject to registration approvals. New research initiatives in 2010 will increasingly result in a shift in focus to the development of novel rodenticides aided by new international research collaborations.

Considerable effort has been put into retaining older vertebrate pesticides and improving the effectiveness and safety of pest control. Nevertheless, conventional control targeting single species is sometimes still associated with non-target impacts, bioaccumulation of toxins, fluctuating pest numbers, and unexpected ecological consequences. To counter this, we are developing multi-species bait types for sustained field use that are more palatable to vertebrate pest species. We are incorporating “low-residue” toxicants, namely zinc phosphide, cholecalciferol, diphacinone, and a combination of coumatetralyl and cholecalciferol, in new bait formulations. Looking to the future, we seek to increasingly combine “low-residue” characteristics with humaneness. New humane formulations of cyanide are being developed for a variety of pest species, and para-aminopropiophenone is being introduced for predator control in New Zealand as part of the product development and registration pipeline.

Potent second-generation anticoagulant rodenticides such as brodifacoum have been used as more effective alternatives to first-generation anticoagulants, such as warfarin. A combination of diphacinone at 0.005% and cholecalciferol at 0.06% produces a slow-acting bait that is effective at killing possums (Trichosurus vulpecula) and rodents. Cage trials with groups of possums and ship rats (Rattus rattus) achieved a mortality of 87% and 86% for possums and ship rats, respectively. Two field trials, each 200 hectares in size, targeting possums, ship rats and mice achieved an average reduction in the abundance of 94% for possums, 94% for ship rats and 80% for mice. The combination of diphacinone and cholecalciferol appears effective and has a favourable risk profile compared with second-generation anticoagulant rodenticides, such as brodifacoum. Approval of this new bait by the New Zealand Environmental Protection Agency was granted in 2018 and final registration obtained from the Ministry of Primary Industries in 2019. [ABSTRACT FROM AUTHOR]

BACKGROUND Invasive mammalian pests have inflicted substantial environmental and economic damage on a worldwide scale. RESULTS Over the last 30 years there has been minimal innovation in the development of new control tools. The development of new vertebrate pesticides, for example, has been largely restricted due to the costly and time-consuming processes associated with testing and registration. CONCLUSION In this article we discuss recent progress and trends in a number of areas of research aimed to achieve long-term population suppression or eradication of mammalian pest species. The examples discussed here are emerging from research being conducted in New Zealand, where invasive mammalian pests are one of the greatest threats facing the national environment and economy. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]