Anticoagulant Rodenticides: Deadly for Pests, Dangerous for Pets Valentina Merola, DVM
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TOXICOLOGY BRIEF PEER-REVIEWED Anticoagulant rodenticides: Deadly for pests, dangerous for pets Valentina Merola, DVM t’s fall, and mice and rats are able as grain-based pellets, wax heading indoors to escape the blocks, dusts, and tracking pow- Icooler weather, making them- ders and in a variety of other for- selves unwanted visitors. Many mulations and colors (Table 1). people put out rodenticide baits to Some people assume that if they keep these pests from becoming see a blue-green pellet it is an anti- permanent residents. Anticoagu- coagulant rodenticide. But be care- lant rodenticides are popular ful, because not every blue-green choices. But these rodenticides pellet is an anticoagulant rodenti- can harm other animals in the cide and not every anticoagulant house as well. The prognosis for rodenticide is a blue-green pellet. pets that have ingested anticoagu- Other rodenticide baits that contain lant rodenticides depends on the bromethalin, zinc phosphide, or length of time between exposure cholecalciferol can be indistin- and treatment, so you must diag- guishable from an anticoagulant nose and institute appropriate rodenticide. Second-generation an- therapy immediately. ticoagulant rodenticides are most commonly found at a concentra- Origin compound marketed as an antico- tion of 0.005% (difethialone is First-generation anticoagulant ro- agulant rodenticide. Rodents be- found at 0.0025%), while warfarin denticides were initially developed came resistant to the first-generation is most commonly found at during the 1940s and 1950s by the compounds over the next few 0.025%.3 When an animal is ex- Wisconsin Alumni Research Foun- decades, so second-generation anti- posed to an anticoagulant rodenti- dation (WARF). WARF was founded coagulant rodenticides, such as cide, always examine the package in 1925 as a nonprofit agency with brodifacoum, diphacinone, and to determine the concentration of the purpose of promoting, aiding, bromadiolone, were produced. The the active ingredient so that a dose and encouraging scientific research second-generation compounds can be calculated and appropriate and investigation at the University of were developed to work more treatment undertaken (Table 2). Wisconsin-Madison. Dicumarol was quickly and with greater efficacy the first anticoagulant that could be than the first-generation products. Risk factors and susceptibility given orally to people, and warfarin They were also formulated to be Dogs allowed to roam may be (named after WARF) was the first highly palatable to rodents.1 Be- more likely to encounter rodent cause of this, second-generation baits. These baits may be improp- “Toxicology Brief” was contributed by anticoagulant rodenticides are both erly placed in areas pets have ac- Valentina Merola, DVM, Department of appealing and extremely toxic to cess to, or rodents may drag baits Veterinary Biosciences, College of nontarget species, especially do- into these areas. Pets that live in Veterinary Medicine, University of mestic dogs (Table 1). rural or urban areas where rodent Illinois, Urbana, IL 61802. The depart- control is frequently used are also ment editor is Petra A. Volmer, DVM, Available products more likely to be exposed. An ani- MS, DABVT, College of Veterinary Anticoagulants are the most com- mal owner may be unaware that a Medicine, University of Illinois, Urbana, mon type of rodenticide produced pest control operator has placed IL 61802. Dr. Volmer is also a diplomate 2 of the American Board of Toxicology. and used in the United States. An- these baits if the owner lives in a ticoagulant rodenticides are avail- rental property or has recently 716 OCTOBER 2002 Veterinary Medicine TOXICOLOGY BRIEF moved to a new home. In general, toxicosis is possible in an animal interaction can cause more of either rodent baits are used most often in that frequently preys upon rodents drug to be available.3 The plasma the fall when rodents are most in an area where these baits are half-life varies among products. The likely to enter buildings. Finally, commonly used.3 first-generation rodenticides have a keep in mind that rodenticides are Animals that are elderly or juve- half-life of about 14 hours in dogs; commonly used in malicious poi- nile and those with liver disease, the second-generation rodenticides sonings, and must be considered if hypothyroidism, or other underly- have a half-life of up to six days.1 the clinical signs are consistent, ing illnesses are more susceptible The rodenticides are metabolized in even in animals that are thought to to anticoagulant rodenticides. the liver and excreted in the urine. be unlikely to have encountered the agent. Toxicokinetics Mechanism of action Relay toxicosis, the intoxication Anticoagulant rodenticides are Vitamin K is a necessary cofactor in by ingestion of a previously poi- rapidly and well-absorbed orally. activating clotting factors II, VII, IX, soned animal, is unlikely to occur They are highly protein-bound in and X by carboxylation (Figure 1). with these agents, because only a plasma. In an animal receiving an- Without vitamin K, these coagula- small amount of the rodenticide is other drug that is highly protein- tion proteins will remain in a non- in a rodent’s gut (in general, the bound, such as a nonsteroidal anti- functional, precursor state. Antico- LD50 in rodents is lower). But relay inflammatory drug, the displacement agulant rodenticides interfere with TABLE 1 Common Anticoagulant Products and Their Active Ingredient Concentrations, Formulations, and Acute LD50* Active Common Common Trade Names Ingredient Generation Concentrations Formulations Acute LD50 Rodex, Blitz, Rid-a-Rat, Warfarin First 0.025%–0.03% Pellets, others 20–300 mg/kg (dogs); Eagles, and many more** 5–30 mg/kg (cats) D-Con, Havoc, Jaguar, Brodifacoum Second 0.005% Chunks, blocks, 0.2–4 mg/kg (dogs); Warrior Chunks, Enforcer, pellets, others unknown in cats and many more Hawk, Maki, Boot Hill, Bromadiolone Second 0.005% Blocks, bars, 11–15 mg/kg (dogs); Just One Bite, Tomcat pellets, others unknown in cats Ultra, and many more D-Cease, Generation, Difethialone Second 0.0025% Pellets, others 4 mg/kg (dogs); Hombre > 16 mg/kg (cats) Assassin, Tomcat, Ditrac, Diphacinone Second 0.005%–0.2% Blocks, bars, powder, 0.9–8 mg/kg (dogs); Exterminator’s Choice, liquid concentrates 15 mg/kg (cats) and many more Enforcer Rat Bait, Pindone Second 0.03% Pellets, others 5–75 mg/kg (dogs); Duocide** unknown in cats *Source: References 1, 3, 4, and 12. **Products containing warfarin and pindone are older, and most have been replaced. But these older products could still be in use. Veterinary Medicine OCTOBER 2002 717 TOXICOLOGY BRIEF Continued TABLE 2 An Example of a Rodenticide Dose Calculation and Interpretation A 75-lb dog is seen consuming 4 oz of a bait that contains 0.005% brodifacoum. To calculate the dose of brodifacoum the dog ingested in mg/kg: 1. Convert the animal’s weight to kilograms: 75 lb 2.2 lb/kg ϭ 34 kg 2. Calculate how much bait the dog ingested: 1 oz ϭ approximately 30 g; 4 oz ϫ 30 g ϭ 120 g 3. Calculate the amount brodifacoum in each gram of bait: 0.005% ϭ 0.05 mg brodifacoum/g bait 4. Calculate how much brodifacoum the dog ingested: 0.05 mg/g ϫ 120 g ϭ 6 mg of brodifacoum ingested 5. Calculate the dosage in mg/kg: 6 mg 34 kg ϭ 0.18 mg/kg This dose is approaching the low end of the LD50 range (0.2–4 mg/kg; see Table 1). The LD50 is defined as the dose at which 50% of an experimentally exposed population will die. This means that nearly half of the exposed individuals die below the LD50. Because some animals are sensitive to doses between the LD50 1 10 and / of the LD50, it is recommended that any animal that received a dose in that range be decontaminated and monitored. In this case, the dose is high enough to warrant aggressive decontamination, monitoring, and treatment. 1 2 Animals that received doses less than / of the LD50 (in this case, less than 0.1 mg/kg) should be decontaminated, and the PT should be monitored every day for 72 hours. Previous administration of vitamin K1 may result in misleading PT results. In general, to be cautious and prevent clinical signs in the most sensi- tive individuals, it is recommended to decontaminate and monitor any animal that received a dose above 0.02 mg/kg. the activation process by inhibit- tive form. The net result is a coag- ing an animal’s ability to conserve ulopathy that begins as the natural vitamin K. Vitamin K is consumed breakdown of the clotting factors by carboxylation of the proteins occurs. The half-lives of factors II, and is present as vitamin K epox- VII, IX, and X are 41, 6.2, 13.9, and ide, which cannot activate clotting 16.5 hours, respectively; thus fac- proteins.4 Normally, the body con- tor VII will be depleted first.4 If an verts vitamin K epoxide back to external source of vitamin K is active vitamin K via the enzyme provided to an animal, normal ac- vitamin K epoxide reductase. Anti- tivation of the proteins can occur, coagulant rodenticides inhibit this and no clinical signs will develop. enzyme, resulting in a lack of ac- tive vitamin K.4 As a result, con- Clinical signs centrations of the clotting factors Clinical signs in an exposed ani- decrease, since no more precursor mal usually develop one to seven protein can be converted to an ac- days after ingestion as the active 718 OCTOBER 2002 Veterinary Medicine TOXICOLOGY BRIEF clotting factors are depleted, with FIGURE 1 three to five days being the most common time frame, depending CO2 on the agent consumed.1 The clin- ical signs can vary, but they are al- Precursor factor II, VII, IX, X Functional factor II, VII, IX, X ways due to the coagulopathy.