Development of a Novel Vertebrate Pesticide for the Invasive Small Indian Mongoose

Small Indian mongooses are detrimental introduced predators in the United States, where they depredate native species, serve as vector of disease, and threaten public safety. Due to the risk of accidental introduction to mongoose-free islands, high cost and limitations to trapping, and no national (Section 3) Environmental Protection Agency (EPA)-registered toxicants for mongoose control, there is a need for an efficacious toxic bait for mongooses for use in conservation areas and at points of entry in the United States. Over the last five years, the National Wildlife Research Center (NWRC) worked to develop a toxic bait for mongooses for registration with the EPA. This paper outlines the development pathway to registration of a toxic bait for mongooses in the United States

An evaluation of the registration and use prospects for four candidate toxicants for controlling invasive mongooses (Herpestes javanicus auropunctatus)

The eradication or control of invasive small Indian mongooses from islands likely requires toxic baiting when removal by trapping proves insufficient. The one toxic bait currently registered for mongooses in the United States has relatively low palatability and efficacy for mongooses. Developing and registering a new pesticide can be very expensive, while funding for developing toxicants for mongooses is limited. Once registered, use of a toxic bait may be hindered by other factors, such as public opposition to an inhumane toxicant, poorer efficacy than expected, or if the toxic bait is difficult for applicators to apply or store. Therefore, we conducted a product feasibility assessment comparing the registration and use potential of toxic baits for mongooses containing either bromethalin, diphacinone, para-aminopropiophenone (PAPP), or sodium nitrite (SN). We estimated that a diphacinone bait would be the cheapest and fastest to register, and more application methods may be allowed compared to the others. On the negative side, we ranked diphacinone as the least humane toxicant of the four, largely due to a prolonged time to death following exposure and onset of symptoms. However, this interval also increases the probability that the antidote can be administered following an accidental exposure. If an alternative toxicant is required, use of a bromethalin, PAPP, or SN bait would likely be limited to bait stations or burrow baiting due to primary risks to non-target species. A bromethalin bait would be the cheapest and fastest to register of the three, particularly if a bait that is already commercially available proved efficacious for mongoose. However, we ranked bromethalin lower than PAPP or SN for overall humaneness. A PAPP bait would be slow and the most expensive to register. An SN bait would be challenging to formulate into a palatable bait with a reasonable shelf life. Although we focused on the U.S., mongooses are invasive in many parts of the world and the regulatory and use requirements for pesticides in other countries are generally comparable. In addition, our feasibility assessment can serve as a template or starting point for managers considering development of toxicant products for vertebrate pests

Embracing Dynamic Models for Gene Drive Management

Robust methods of predicting how gene drive systems will interact with ecosystems is essential for safe deployment of gene drive technology. We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation. Gene drive technologies, although diverse in design and mode of action, are molecular architectures that promote the transmission of genetic information between generations. In theory, the release of one gene-drive-modified organism (GDMO) has the potential to irreversibly alter species, ecosystems, and environmental processes at a global scale (although in practice numerous mechanisms can limit invasiveness) [1]. This alarming and tremendous potential is an unprecedented challenge to biotechnology management that demands a different scope of oversight and coordination between public stakeholders, developers, and regulators [2,3]. Responsible management of GDMOs needs robust methods of risk assessment that account for and reduce uncertainties across different geographic and ecological contexts [1–3]

The Ground View of Navigating FIFRA and the ESA: One Pesticide Registrant's Perspective

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), enacted in 1947 and amended in 1972, 1978, and 1988, established federal regulation of pesticides in order to protect human and environmental health. FIFRA has been under the jurisdiction of the U.S. Environmental Protection Agency (EPA) since the EPA’s inception in 1970. Although FIFRA requires EPA to consider the benefits of a pesticide’s use, EPA must ensure that the pesticide is used without posing unreasonable adverse effects to human health or the environment. Furthermore, the Endangered Species Act (ESA), enacted in 1973, requires federal agencies to protect species vulnerable to extinction without consideration of costs. The amendments to FIFRA in 1972, 1978, 1988, and 1996 mandated the EPA review and reevaluate the eligibility of older pesticide products for reregistration under the updated FIFRA standard, while also complying with the new environmental laws of the 1970s. Today EPA’s goal is to review existing pesticide product registrations at least every 15 years under “Registration Review.” To meet their responsibilities under the ESA, EPA is initiating consultations with the U.S. Fish and Wildlife Service (USFWS) during the Registration Review process. The first pesticide active ingredients to advance to consultations under Registration Review are those in gas cartridge products. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) holds two gas cartridge product registrations. As a federal agency, APHIS also must comply with the ESA and consults with the USFWS on wildlife damage management activities, including tools such as pesticide products. This discussion presents APHIS’ unique ground view as a federal agency navigating the EPA’s ESA consultations during the Registration Review process, and describes the mitigation measures and their impacts on APHIS Wildlife Services’ activities

The Ground View of Navigating FIFRA and the ESA: One Pesticide Registrant's Perspective

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), enacted in 1947 and amended in 1972, 1978, and 1988, established federal regulation of pesticides in order to protect human and environmental health. FIFRA has been under the jurisdiction of the U.S. Environmental Protection Agency (EPA) since the EPA’s inception in 1970. Although FIFRA requires EPA to consider the benefits of a pesticide’s use, EPA must ensure that the pesticide is used without posing unreasonable adverse effects to human health or the environment. Furthermore, the Endangered Species Act (ESA), enacted in 1973, requires federal agencies to protect species vulnerable to extinction without consideration of costs. The amendments to FIFRA in 1972, 1978, 1988, and 1996 mandated the EPA review and reevaluate the eligibility of older pesticide products for reregistration under the updated FIFRA standard, while also complying with the new environmental laws of the 1970s. Today EPA’s goal is to review existing pesticide product registrations at least every 15 years under “Registration Review.” To meet their responsibilities under the ESA, EPA is initiating consultations with the U.S. Fish and Wildlife Service (USFWS) during the Registration Review process. The first pesticide active ingredients to advance to consultations under Registration Review are those in gas cartridge products. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) holds two gas cartridge product registrations. As a federal agency, APHIS also must comply with the ESA and consults with the USFWS on wildlife damage management activities, including tools such as pesticide products. This discussion presents APHIS’ unique ground view as a federal agency navigating the EPA’s ESA consultations during the Registration Review process, and describes the mitigation measures and their impacts on APHIS Wildlife Services’ activities

Development and Testing of a Matrix for Mongoose Toxic Bait: Nontoxic Bait Acceptance Cage Trials

The only pesticide currently registered for mongoose control is a product developed for rats that consists of a hard-cereal bait block. Although the active ingredient (diphacinone) is known to be highly effective for mongoose, previous studies indicate that carnivorous and omnivorous mongooses do not readily consume the hard bait matrix designed for gnawing rodents. A palatable bait matrix with a consistency more appropriate to mongoose dentition and feeding behavior will be required to develop a more effective mongoose pesticide. We evaluated the acceptance and consumption of nontoxic versions of four candidate bait matrices: FOXECUTE® and FOXSHIELD® (Animal Control Technologies, Australia; ACTA); HOGGONE® (ACTA); and a potted pork shoulder loaf containing artificial dead mouse scent developed by WS-NWRC as a bait for invasive brown treesnakes (hereafter ‘BTS bait’). We offered test groups of six mongooses one of the candidate bait matrices alongside dry dog kibble dog food as a challenge diet for five days. Because the potential active ingredients para-aminopropiophenone and sodium nitrite require accumulation of the toxicant within a relatively brief period of time to affect lethal toxicity before they are metabolized, we conditioned mongooses to feeding within only a four-hour window rather than slowly sampling the bait throughout the day. We estimated rate and amount of consumption through review of time-lapse photography of feeding trials and measured total consumption by weighing uneaten portions of bait. From the first day offered, most mongooses readily consumed ample amounts of all four bait matrices and consumed almost no challenge diet. Overall, consumption was highest and most consistent with the BTS bait. Although this trial did not clearly discriminate an optimal bait matrix, this result is highly encouraging in that we have multiple palatable options. The final selection will be based on other characteristics of the bait matrix such as longevity in the field, compatibility with the selected toxicant, and ease of manufacture, storage, and use. We provide an overview of some of these characteristics for each candidate bait type

A Decision Support Tool for Determining Federal Regulatory Authority over Products for Vertebrate Animals

Products developed for vertebrate animals, including toxicants, repellents, contraceptives, vaccines, drugs, antimicrobials, diagnostic kits, and some devices, are regulated under a suite of federal laws. Authorization for the production, sale, and use of these products is primarily controlled by three federal agencies: the U.S. Environmental Protection Agency’s (EPA) Office of Pesticide Programs, the U.S. Food and Drug Administration’s (FDA) Center for Veterinary Medicine, and the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS). Furthermore, regulatory oversight of these products extends to research activities conducted during their development. However, determining the regulatory jurisdiction of new products can be confusing for researchers and product developers. In fact, the same product could be regulated under different laws and by more than one agency depending on its intended target population, function, product claims, and route of administration. Adding to this complexity, EPA, FDA, and APHIS have reached a series of formal and informal agreements on which agency will have primary oversight for a number of novel product types that do not clearly fall into established product categories. Here, we present a decision support tool that helps researchers and product developers identify the regulatory jurisdiction of new products, allowing them to comply with federal laws and consult with the appropriate agency early in the research and development phase. Such consultations ensure that resources are spent on studies that satisfy agency-specific data requirements for product registration, approval, and licensing

A Decision Support Tool for Determining Federal Regulatory Authority over Products for Vertebrate Animals

Products developed for vertebrate animals, including toxicants, repellents, contraceptives, vaccines, drugs, antimicrobials, diagnostic kits, and some devices, are regulated under a suite of federal laws. Authorization for the production, sale, and use of these products is primarily controlled by three federal agencies: the U.S. Environmental Protection Agency’s (EPA) Office of Pesticide Programs, the U.S. Food and Drug Administration’s (FDA) Center for Veterinary Medicine, and the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS). Furthermore, regulatory oversight of these products extends to research activities conducted during their development. However, determining the regulatory jurisdiction of new products can be confusing for researchers and product developers. In fact, the same product could be regulated under different laws and by more than one agency depending on its intended target population, function, product claims, and route of administration. Adding to this complexity, EPA, FDA, and APHIS have reached a series of formal and informal agreements on which agency will have primary oversight for a number of novel product types that do not clearly fall into established product categories. Here, we present a decision support tool that helps researchers and product developers identify the regulatory jurisdiction of new products, allowing them to comply with federal laws and consult with the appropriate agency early in the research and development phase. Such consultations ensure that resources are spent on studies that satisfy agency-specific data requirements for product registration, approval, and licensing

Treatment with the Immunocontraceptive Vaccine, GonaCon, Induces Temporary Fertility Control in Free-ranging Prairie Dog Populations in Colorado, USA

Context Prairie dogs (Cynomys spp.) are rodents enjoyed by some humans; yet, they cause crop and property damage, and carry zoonotic disease. Non-lethal control of prairie dogs is of interest in urban/suburban settings. The injectable immunocontraceptive vaccine GonaCon (active ingredient is gonadotropin-releasing hormone [GnRH]) has been shown to be effective at reducing fertility in equine and deer, and is a US EPA-registered vaccine for use in these ungulate species. Aims To conduct a replicated field study to test efficacy of GonaCon in black-tailed prairie dogs (C. ludovicianus), and if found to be efficacious, to help facilitate the EPA registration of this product for prairie dog management in urban/suburban areas. Methods Prairie dogs were live-trapped in October–December 2018 in three treatment and three control sites. Every captured female ≥660 g was injected with 0.4 mL of either GonaCon (0.032% w/w GnRH) at treatment sites or a sham vaccine (absent of GnRH) at control sites. Juveniles and adults were counted at all six sites to establish juvenile:adult (ratio) and juvenile density in May–June 2019 (determining initial GonaCon effectiveness) and 2020 (determining persistence of contraception). Key results In 2019, the juvenile:adult ratio was significantly reduced (P = 0.0022) in GonaCon (mean ± s.e.: 0.23 ± 0.01) relative to the sham (1.10 ± 0.58) sites. Juvenile density was three times greater in sham than GonaCon sites. In 2020, GonaCon sites produced equal offspring to nearby sham sites. Conclusions GonaCon is highly effective during the first year (2019) but not in the second year (2020) if only a small area (0.6–2.8 ha) or small proportion of females in a colony is treated, such as was undertaken in this study. Implications In 2022, GonaCon− Prairie Dogs was EPA-registered. Treating whole colonies of prairie dogs at once is favored; yet, if small or partial colony treatment is desired, then annual GonaCon treatment may be needed

Development of a Novel Vertebrate Pesticide for the Invasive Small Indian Mongoose

Small Indian mongooses are detrimental introduced predators in the United States, where they depredate native species, serve as vector of disease, and threaten public safety. Due to the risk of accidental introduction to mongoose-free islands, high cost and limitations to trapping, and no national (Section 3) Environmental Protection Agency (EPA)-registered toxicants for mongoose control, there is a need for an efficacious toxic bait for mongooses for use in conservation areas and at points of entry in the United States. Over the last five years, the National Wildlife Research Center (NWRC) worked to develop a toxic bait for mongooses for registration with the EPA. This paper outlines the development pathway to registration of a toxic bait for mongooses in the United States