While there is broad agreement on the challenges facing the Aotearoa New Zealand food system now and in the near future, there is less agreement on the action to be taken. Poor agreement is fuelled by gaps in both our scientific understanding of the food system and data to support our decision making, particularly in the environmental and social spaces. Filling these gaps and being transparent about scientific confidence in future predictions will strengthen the evidence base for action.

Asparagopsis (A. taxiformis and A. armata) as a dry feed additive, and novel oil-based formulations containing bromoform are effective at reducing enteric methane emissions in ruminant livestock. An inclusion rate of Asparagopsis at 0.2%-0.5% of the daily diet for cattle of say 470 kg consuming 15 kg dry matter (DM) per day is equivalent to 30-75 g/day Asparagopsis delivering 180-450 mg/day bromoform (at 6 mg bromoform per gram of seaweed) per animal equivalent to 0.4-1.0 mg/kg/day of bromoform. This is a low dose when compared to those evaluated in animal toxicity studies. A response relationship in terms of emission reductions and the dosage of bromoform ingested, is established, as opposed to dose responses linked to seaweed biomass. Most of the research studies on bromoform as a methane mitigant have used Asparagopsis. Nevertheless, the primary interest from a regulatory perspective is bromoform, the most prevalent bioactive. Regulatory considerations to enable safe use of bromoform for methane mitigation in ruminants are described. A key conclusion is that bromoform, administered in very low doses, is not bioavailable at measurable levels. Hence the risk of residue transfer or toxicity in livestock and humans will be minimal.

A resetting toxin device (the "Spitfire") has been designed that delivers a toxic paste to a rat's ventral surface when it passes through a tunnel.The rat grooms off the paste and ingests the toxin.The system was assessed in cage trials and one field trial.The purpose of the cage trials was to investigate whether a range of toxins can be delivered by the Spitfire to rats (Rattus rattus and R. norvegicus), namely 0.55% sodium fluoroacetate (1080), 0.2% brodifacoum, 15% cholecalciferol, and 12.5% zinc phosphide.The trials with 1080, brodifacoum, and zinc phosphide were successful with > 85% of rats ingesting lethal doses.The trials with cholecalciferol were less successful with only 58% of rats dying.A one-month pilot field trial was undertaken using 1080 in the Spitfires.There was a knockdown in rat (and stoat Mustela erminea) abundance, establishing proof of concept for the Spitfire delivery system with this toxin.The long-term, effective control of introduced rats will require a range of toxins with different modes of action.The Spitfire could be a useful additional control tool for rats and is currently being re-engineered to be made more reliable.

The ongoing use of 1080 toxin for the control of mammal pests in New Zealand remains highly contentious. Several reviews over the last 25 years identified information gaps and areas of concern, both social and scientific. In this paper these areas of concern are discussed and the extensive scientific and social research that has been undertaken to clarify and address them is reviewed. Although there has been a major national investment in research aimed at finding an alternative to 1080, that has not yet been fully achieved because of low or inconsistent efficacy and/or low cost-effectiveness of alternatives, regulatory difficulties in obtaining approval for aerial delivery of any alternative, and toxic residue concerns. Finding an alternative that has similar efficacy while satisfying the demands for species-selectivity, no residues, and humaneness is a continuing challenge. The most promising prospect appears to be through understanding the genome of the target animals and opportunities for genetic manipulation, either by developing species-specific designer lethal toxicants based on genome mining, or by gene editing to develop non-lethal technologies. Both will require considerable time and funding for research, and considerable effort and engagement to address social and regulatory hurdles.

The Coronavirus Disease-2019 (COVID-19) pandemic urges researching possibilities for prevention and management of the effects of the virus. Carotenoids are natural phytochemicals of anti-oxidant, anti-inflammatory and immunomodulatory properties and may exert potential in aiding in combatting the pandemic. This review presents the direct and indirect evidence of the health benefits of carotenoids and derivatives based on in vitro and in vivo studies, human clinical trials and epidemiological studies and proposes possible mechanisms of action via which carotenoids may have the capacity to protect against COVID-19 effects. The current evidence provides a rationale for considering carotenoids as natural supportive nutrients via antioxidant activities, including scavenging lipid-soluble radicals, reducing hypoxia-associated superoxide by activating antioxidant enzymes, or suppressing enzymes that produce reactive oxygen species (ROS). Carotenoids may regulate COVID-19 induced over-production of pro-inflammatory cytokines, chemokines, pro-inflammatory enzymes and adhesion molecules by nuclear factor kappa B (NF-κB), renin-angiotensin-aldosterone system (RAS) and interleukins-6- Janus kinase-signal transducer and activator of transcription (IL-6-JAK/STAT) pathways and suppress the polarization of pro-inflammatory M1 macrophage. Moreover, carotenoids may modulate the peroxisome proliferator-activated receptors γ by acting as agonists to alleviate COVID-19 symptoms. They also may potentially block the cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin-converting enzyme 2 (ACE2). These activities may reduce the severity of COVID-19 and flu-like diseases. Thus, carotenoid supplementation may aid in combatting the pandemic, as well as seasonal flu. However, further in vitro, in vivo and in particular long-term clinical trials in COVID-19 patients are needed to evaluate this hypothesis.

The agricultural production of ruminants is responsible for 24% of global methane emissions, contributing 39% of emissions of this greenhouse gas from the agricultural sector. Strategies to mitigate ruminant methanogenesis include the use of methanogen inhibitors. For example, the seaweeds Asparagopsis taxiformis and Asparagopsis armata included at low levels in the feed of cattle and sheep inhibit methanogenesis by up to 98%, with evidence of improvements in feed utilisation efficiency. This has resulted in an increasing interest in and demand for these seaweeds globally. In response, research is progressing rapidly to facilitate Asparagopsis cultivation at large scale, and to develop aquaculture production systems to enable a high quality and consistent supply chain. In addition to developing robust strategies for sustainable production, it is important to consider and evaluate the benefits and risks associated with its production and subsequent use as an antimethanogenic feed ingredient for ruminant livestock. This review focuses on the relevant ruminal biochemical pathways, degradation, and toxicological risks associated with bromoform (CHBr3), the major active ingredient for inhibition of methanogenesis in Asparagopsis, and the effects that production of Asparagopsis and its use as a ruminant feed ingredient might have on atmospheric chemistry.

Norbormide[5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents/mammals.However, as an acute vasoactive, NRB has a rapid onset of action, often leading to sub-lethal uptake/bait shyness.Recently, it was brought to our attention that baits containing two independently sourced batches of NRB (which differed noticeably in their stereochemical composition) displayed markedly different palatability/efficacy profiles in rats.Accordingly, with a view to independently evaluating the individual isomers of NRB in rats by means of a palatability and efficacy bait trial, this research describes the isolation of the individual isomers of endo-NRB (Y, V, W and U) from the parent mixture, by means of a chemical derivatization strategy.

Greenshell™ mussel (GSM, Perna canaliculus) is New Zealand’s most important aquaculture species. They are a good source of long chain-polyunsaturated fatty acids (n-3 LC PUFA). Beyond a traditional food product, GSMs are also sold as mussel powders and oil extract formats in the nutraceutical markets. In this study, a four-sequence, single dose, randomized crossover human trial with eight evaluable healthy male participants was undertaken to determine the bioavailability of the n-3 LC PUFA in four different GSM formats (oil, powder, food ingredient and half-shell unprocessed whole mussel) by measuring area under the curve (AUC) and maximal concentration (CMax). Blood samples were collected at baseline and up to 48 h after initiation of product consumption in each administration period. There were minor differences between the bioavailability of FA (fatty acid) between the different GSM formats. Eicosapentaenoic acid (EPA) peak concentrations and plasma exposures were significantly lower with GSM oil compared to GSM half-shell and GSM powder formats, which resulted in AUC0–48 for the intake of GSM half-shell mussel and GSM powder being significantly higher than that for GSM oil (p = 0.013, f= 4.84). This equated to a 20.6% and 24.3% increase in the amount of EPA present in the plasma after consumption of half-shell mussels and mussel powder respectively compared to GSM oil. GSM oil produced the shortest median time to maximal plasma n-3 LC PUFA concentration of all evaluated products demonstrated by a shorter maximum measured plasma concentration (TMax = 5 h). Docosahexaenoic acid (DHA) and n-3 LC PUFA plasma exposure parameters were statistically comparable across the four GSM products evaluated.

Author(s): Shapiro, Lee; Eason, Charles; MacMorran, Duncan; Rennison, David; Brimble, Margaret; Jackson, Michael | Abstract: 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.

ABSTRACT 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.

New Zealand has many introduced mammalian species that are managed as pests of conservation and/or economic importance, including four rodent species.Vertebrate pesticides are the most important rodent management tool, largely dominated by anticoagulants such as brodifacoum, and by the metabolic disruptor, Compound 1080.There has been considerable opposition to these pesticides, primarily based on concerns about environmental persistence and non-target effects; Maori have been particularly vocal in opposition.Maori have place-based knowledge about naturally-occurring plant toxins that could be used as culturally-acceptable alternatives to existing rodenticides.In the context of the research presented here, the term 'culturally-acceptable' refers to new pest control options that have been co-designed with Matauranga Maori experts that inherently include Maori ways of thinking, being, and acting.Tuhoe researchers in our study wanted to pursue the most promising natural toxic compound found in native plants as a suitable alternative to current vertebrate pesticides.Therefore, we undertook an oral gavage trial to assess the toxicity of tutin, the toxin active in tutu (Coriaria arborea), to the Norway rat, (Rattus norvegicus).Tutin was toxic to this species at a dose of 55 mg kg -1 , with a quick, humane death compared to other existing rodenticides.At a dose rate of 55 mg kg -1 , all animals of both sexes died within an hour, and once neurological poisoning symptoms commenced these animals were unconscious within 5-10 minutes.We conclude it is warranted to take the next logical research step, which is to prove whether this dose rate would be technically attainable in the field.Although for now New Zealand remains reliant on 1080 and anti-coagulants for mammalian pest control, efforts should continue to develop more targeted toxins and delivery systems.We recommend incorporating Matauranga Maori to identify alternative control tools that could lead to more culturally acceptable pest control.

The history of discoveries in rodenticide development and control technology as well as current and future-focused research are explored. Traps and older poisons such as red squill, arsenic, and cyanide have been used for hundreds if not thousands of years. Between 1940 and 1980 there was a period of innovation with the discovery of new molecules, including acute toxins and slower acting anticoagulants. The period 1980 to 2018 has been a time for improved utilization of individual tools and research to retain registrations, develop new toxins and delivery systems, and explore non-lethal control options. However, despite these advances, decades old broad-spectrum toxins and traplines are still the mainstay of pest control. Technological leaps are needed to achieve much more precise, affordable, and socially acceptable pest control. The period 2018 to 2050 should be a time for accelerated innovation. There are exciting opportunities for transformational change based on the integration of existing and new tools, such as advances in automated species recognition systems, new self-resetting traps, and species-specific toxin-delivery systems. Over-reliance on 'silver bullet' technologies for small mammal pest control is the wrong approach to biodiversity conservation. This has been demonstrated through two decades of challenging research on viral vectored immunocontraception, and would apply if all pest control research focused on a single toxin, one new engineering-based technology, or on gene editing, which has potential, but will not be a panacea for all mammal pests. Balance is important, with research supporting the skill of pest control practitioners and supporting emerging technologies, as well as novel biocontrol or genetic research. There has been no focused research aimed at integrating a broad suite of new tools, and incorporating disruptive technologies from completely different fields. We believe that science and technology have now advanced such that automated, online, and real-time systems for monitoring and managing pests are achievable in the next decade.

Natural products have inspired over 60% of today's drugs and biocides, including rodenticides, with examples such as warfarin, fluoroacetate and cholecalciferol. Fluoroacetate is a toxic component of poisonous plants found in Australia, Africa, South America and India and is thought to deter herbivores. Together with other rodenticides it has medical applications. In relation to its use for the control of unwanted introduced animals in New Zealand, research has focused on mode of action, sub-lethal effects, welfare, reducing its risk to non-target species, and fate in the environment following use in baits. Less attention has been placed on its role in nature. In this paper the natural occurrence of bioactives that have stimulated the development of rodenticides are reviewed and links between biocidal and medical applications are explored.

The therapeutic benefits of Greenshell™ mussel (GSM; Perna canaliculus) preparations have been studied using in vitro test systems, animal models, and human clinical trials focusing mainly on anti-inflammatory and anti-arthritic effects. Activity is thought to be linked to key active ingredients that include omega-3 polyunsaturated fatty acids, a variety of carotenoids and other bioactive compounds. In this paper, we review the studies that have been undertaken in dogs, cats, and horses, and outline new research directions in shellfish breeding and high-value nutrition research programmes targeted at enhancing the efficacy of mussel and algal extracts. The addition of GSM to animal diets has alleviated feline degenerative joint disease and arthritis symptoms, and chronic orthopaedic pain in dogs. In horses, GSM extracts decreased the severity of lameness and joint pain and provided improved joint flexion in limbs with lameness attributed to osteoarthritis. Future research in this area should focus on elucidating the key active ingredients in order to link concentrations of these active ingredients with their pharmacokinetics and therapeutic effects. This would enable consistent and improved efficacy from GSM-based products for the purpose of improved animal health.

Author(s): Shapiro, Lee; Rennison, David; Brimble, Margaret; MacMorran, Duncan; Eason, Charles | Abstract: 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.

Brushtail possums (Trichosurus vulpecula) present an ongoing threat to New Zealand's environment and economy. Research into additional control techniques is vital to ensure that a variety of efficient tools are available to help achieve population suppression. Encapsulated sodium nitrite (NaNO2) has been developed in New Zealand as a new toxin for possum and feral pig (Sus scrofa) control. Its toxic effects at high doses are mediated through the induction of methaemoglobinaemia, a condition in which the carrying capacity of oxygen in red blood cells is reduced. This study investigated the potential secondary poisoning risks associated with NaNO2. Secondary poisoning risks were assessed for dogs, cats and chickens in small-scale trials. Trial groups for each species consisted of two treatment groups with four individuals per group and one non-treatment group with two individuals. For 6 consecutive days, the treatment groups of dogs, cats and chickens were fed entire or partial carcasses from possums lethally poisoned with paste bait containing encapsulated NaNO2. Individuals in each group were observed continuously for 3 hours following each daily feeding and blood samples were taken from dogs and cats. Individuals were observed for obvious physiological signs of NaNO2 poisoning and symptoms of methaemoglobinaemia specific to dogs, cats and chickens. None of the dogs, cats or chickens displayed any obvious physiological signs of poisoning or symptoms of methaemoglobinaemia. Blood chemistry and haematology parameters measured for dogs and cats were either within the range considered normal or when outside this range comparable levels were also recorded in the control group. No changes in histology relating to NaNO2 intoxication were observed in dogs or cats after being fed carcasses, minced meat, vital organs or stomachs of possums poisoned with NaNO2. Therefore, the secondary poisoning risk appears to be minimal.

Acute toxicity of sodium nitrite (NaNO2) was assessed in chickens (Gallus gallus domesticus) and domestic mallard ducks (Anas platyrhynchos domestica) by oral gavage and in free-feeding trials with chickens, domestic mallard ducks, pigeons (Columba livia f. domestica), budgerigars (Melopsittacus undulates) and weta (Family: Rhaphidophoridae). Free-feeding trials involved the presentation of toxic paste and pellet baits containing encapsulated NaNO2 developed for the control of common brushtail possums (Trichosurus vulpecula) and feral pigs (Sus scrofa). The oral gavage LD50 value for NaNO2 in solution was approximately 68.50 mg/kg (95% CI 55.00-80.00 mg/kg) for both chickens and ducks. In feeding trials, six out of 12 chickens consumed toxic paste bait and four of these birds consumed a lethal dose. When chickens consumed toxic paste bait, the LD50 value was approximately 254.6 mg/kg (95% CI 249.1-260.2 mg/ kg). Of the other three species of birds presented with toxic baits only one duck consumed a lethal dose of paste bait. There was no evidence of weta feeding on toxic baits.

Rodenticide and vertebrate pesticide registrations have declined worldwide over the last 30 years. New Zealand has not followed this trend, instead retaining essential toxins and traps, improving their use and exploring new mammal control tools. Looking to the immediate future, as well as continuing to improve the use of existing tools, there are opportunities for further advances in emerging technologies such as wireless technology for species recognition and aiding trapping programmes, self-resetting traps and toxin-delivery systems to be enhanced with advanced lures, and new toxins which increasingly combine low-residue' characteristics with selectivity and humaneness. More selective baiting and delivery systems will enable more targeted control of possums, mustelids and rodents. The use of new toxins with advantages in specific settings should be complemented by improvements in resetting trap technology, barrier approaches, and novel biocontrol and genetic concepts. Sodium fluoroacetate (1080) and other important tools have been retained; we have the ingredients for transformational change, and new tools are emerging from a research and development pipeline. However, there has been limited practical experience with emerging technologies compared with traditional or 1080 baits. Additional investment and practical experience is imperative, at this stage, to enable the potential of new toxins and other tools to reach their potential. It is also important for the future of New Zealand's biodiversity that research continues to be focused on emerging technologies as well as on completely novel ideas.

In New Zealand we need to develop new control tools for the overabundant brushtail possum, which is an agricultural and environmental pest. In this study we evaluated the performance of a new microencapsulated zinc phosphide (MZP) paste (1.5% w/w nominal conc.) in a captive study and at six North Island field sites. In the captive study 14 out of 16 possums fed MZP paste bait died (87.5% kill ± 8.3% SE) with death occurring on average 165.4 minutes (± 5.5 SE) after first eating the bait. At all field sites relative possum abundance was estimated using a residual trap catch index, and contractors were able to choose their preferred ground-control technique. Pre-feeding non-toxic paste (using 200-320 g/ha) was carried out over 2 weeks with at least one top- up after 7 days. Toxic bait was then deployed using the same baiting regime, and the average decline in possum abundance at the field sites was 82.2% (± 3.2% SE). This trial demonstrates that experienced contractors can get good kills using MZP and a refinement of best practice techniques could further improve control efficacy.