small animal toxicology essentials (poppenga/small animal toxicology essentials) || rodenticides

Section 3

Specifi c Toxicants

117

17 Rodenticides

INTRODUCTION

Rodenticides are pesticides that are intended to kill rodents and other small mammals. Frequently, however, dogs, cats, pet rodents, and other “ nontarget ” animals ingest the agent either unintentionally or due to malicious poisoning. At the ASPCA Animal Poison Control Center (APCC), rodenticides were the fourth most common ingestion in dogs (Meadows and Gwaltney - Brant 2006 ) while antico-agulant rodenticides (AR) were the ninth most common exposure reported in cats (Merola and Dunayer 2006 ).

There are several different rodenticides currently avail-able. They come in various forms including pellets, blocks, dust, and place packs (paper packages left out for the rodents to chew open). Some rodenticides are mixed with seeds or grain to attract the rodents. Many rodenticides are dyed green or blue, but other colors such as red, tan, and white are also common. Rodenticides cannot be identifi ed by their color or form; they can be identifi ed only by locat-ing their active ingredient or the Environmental Protection Agency (EPA) registration number (EPA Reg. no.) on the packaging. Properly identifying the agent is necessary for determining the appropriate treatment for the ingestion. However, even if the agent cannot be identifi ed, treatment should not be delayed while trying to obtain the information.

ANTICOAGULANT RODENTICIDES

Sources/Formulations

Anticoagulant rodenticides (AR) were originally derived from studying the effects of moldy clover on cattle. Mold infecting sweet clover ( Melilotus offi cinalis and M. alba )

converted the harmless chemical coumarin into the toxic metabolite dicoumarol. Chronic ingestion of the infected hay led to coagulopathy and death in cattle (Knight and Walter 2001 ). Warfarin, the fi rst commercially available anticoagulant rodenticide, was developed in the 1940s as a derivative of dicoumarol; it was named for the Wisconsin Alumni Research Foundation (WARF), the organization that uncovered the link between dicoumarol and coagu-lopathy (Merola 2002 ; Murphy 2007 ). Warfarin is also used therapeutically as an anticoagulant in human and veterinary medicine.

While warfarin was the original anticoagulant rodenti-cide, others were soon synthesized. Warfarin requires many days of ingestion to cause signs. Also, rodents devel-oped resistance to warfarin ’ s effects. To overcome these drawbacks, second - generation anticoagulant rodenticides were developed. These are capable of being lethal with a single feeding (Murphy 2007 ). The various compounds are listed in Table 17.1 .

AR are sold in various forms (as discussed in the intro-duction) and under dozens of trade names. Warfarin baits generally contain 0.025% of active ingredient or 7 mg of warfarin per ounce of bait. Second - generation anticoagu-lant rodenticides come as a 0.005% bait (1.4 mg of active ingredient per ounce of bait) with the exception of difethi-alone, which is 0.0025% (0.7 mg of difethialone per ounce of bait).

Due to the unintended poisoning of children, pets, and wildlife by rodenticides, the EPA in 2008 announced a regulation to ban the over - the - counter sale of second - generation anticoagulant rodenticides directly to consum-ers. The use of AR will be restricted to licensed Pest

Small Animal Toxicology Essentials, First Edition. Edited by Robert H. Poppenga, Sharon Gwaltney-Brant.© 2011 John Wiley and Sons, Inc. Published 2011 by John Wiley and Sons, Inc.

Eric Dunayer

118 Section 3 / Specifi c Toxicants

begins, signs depend on where the hemorrhage has occurred. For instance, hemorrhage into the chest can lead to signs of dyspnea. Heavier dogs, due to pressure on their joints, might bleed into joint spaces and subsequently develop lameness. Hemorrhage under the skin can cause swelling of limbs. Bleeding into the brain and spinal cord can cause a sudden onset of paralysis and seizures. Most commonly, hemorrhage occurs into body “ spaces ” such as pleural or peritoneal cavities. Some dogs die suddenly without any obvious signs. Bleeding generally will not start until 3 – 7 days after the exposure due to the require-ment that existing vitamin - K – dependent clotting factors be consumed. Younger animals, which have less of a reserve of coagulation factors, potentially start to develop coagulopathy sooner. Also, animals with preexisting liver disease are also more susceptible to intoxication (Merola 2002 ).

Laboratory

Depending on the length of time bleeding has occurred, the animal might be anemic with a decreased hematocrit. Platelet counts are often slightly decreased as platelets are consumed to try to stop the bleeding. Increases in the coagulation parameters prothrombin time (PT) and partial thromboplastin time (PTT) are the most consistent fi ndings. Factor VII (critical for the extrinsic coagulation pathway) has the shortest half - life in dogs (6.2 hours) and as it is depleted, the PT (which assesses both the extrinsic and common coagulation pathways) will become abnormal fi rst, generally by 48 – 72 hours (Murphy 2007 ). A second test known as PIVKA (proteins induced by vitamin K 1 antagonism) can be used instead of the PT to monitor the patient but it may not be as readily available.

Differential Diagnoses

Differential diagnoses include naturally occurring bleed-ing defects such as hemophilia, von Willebrand disease, and other inherited or acquired clotting disorders. Because the liver produces the clotting factors, liver failure can lead to spontaneous bleeding. Finally, bleeding due to trauma should be ruled out.

Diagnostics

Antemortem

A diagnosis of AR toxicosis is based on history and results of coagulation testing. In some cases, particularly where there is no history of exposure, analysis of whole blood or serum for the presence of a specifi c AR can confi rm expo-sure (Murphy 2007 ).

Control Operators, and the rodenticide must be in a tam-perproof bait station. Other rodenticides will still be avail-able for direct purchase by consumers, but they can only be sold in a bait station; loose pellet baits are banned (USEPA 2008 ).

Kinetics

Most AR are well absorbed after ingestion. Once absorbed, a large percentage is bound to plasma proteins. Ingestion of other highly protein - bound drugs (such as NSAIDs, thyroid supplements, and corticosteroids) can increase the toxicity of the anticoagulant by displacing it from the protein. The half - lives of the agents vary but, in general, fi rst - generation agents have a much shorter half - lives (14 hours) than second - generation products (up to 6 days) (Merola 2002 ).

Mechanism of Action

AR interfere with the ability of the liver to recycle vitamin K, which is necessary for the production of the active forms of clotting factors II, VII, IX, and X. Without con-tinuous production of new factors, the animal depletes those that are present in the blood. When the factors are depleted (generally 3 to 7 days or more after ingestion), spontaneous hemorrhage begins (Merola 2002 ).

Toxicity

The toxicity of these products varies greatly by compound and by form (Murphy and Talcott 2006 ). Often, when the chemical is incorporated into bait, its toxicity is greatly increased. Warfarin requires a much higher single dose to cause toxicosis compared to repeated daily ingestions. Because of the wide variation in toxic doses in the litera-ture, the APCC recommends using 0.02 mg/kg as a dosage of concern for all second - generation agents.

Clinical Effects

Signs

The initial signs of AR toxicosis are generally vague and include anorexia, weakness, and lethargy. Once bleeding

Table 17.1. Anticoagulant rodenticides

First - Generation Second - Generation

Warfarin Chlorophacinone Diphacinone Pindone

Brodifacoum Bromadiolone Difenacoum Difethialone

Chapter 17 / Rodenticides 119

since vitamin K 1 takes 6 – 12 hours before new clotting factors can be produced, the patient should receive a fresh frozen plasma an/or whole blood transfusions to supply clotting factors until the body manufactures a suffi cient quantity on its own (Murphy and Talcott 2006 ). Strict cage rest should be enforced. For animals that are dyspneic due to bleeding into the pleural cavity, the chest can be care-fully tapped to relieve pressure (Merola 2002 ). Blood from a thoracocentesis can be autotransfused back to the patient especially if anemia is present.

Prognosis

For asymptomatic animals, vitamin K 1 therapy is effective and should prevent signs from developing. If bleeding has begun, the prognosis is more guarded, depending on extent and location of the hemorrhage. However, most symptom-atic animals can recover with appropriate therapeutic intervention.

BROMETHALIN


Bromethalin was developed to kill AR - resistant rodents. Despite its name being similar to some of the AR (broma-diolone, brodifacoum), it is not an anticoagulant; it is neurotoxic. As with AR, bromethalin is sold in various forms and under many different brand names. It generally comes as a 0.01% concentration (2.84 mg bromethalin per oz of bait) (Dunayer 2003 ). For mole control, it is also sold in the form of a “ worm ” bait. In these products, the bro-methalin concentration is 0.025%.

Kinetics

Bromethalin is rapidly absorbed after ingestion and plasma levels peak in about 4 hours. In the liver, bromethalin is converted to a toxic metabolite desmethylbromethalin. Bromethalin is excreted in the bile and undergoes entero-hepatic recirculation. The half - life of bromethalin is about 6 days in rats (Dunayer 2003 ; Gupta 2007 ).

Mechanism of Action

Bromethalin and its metabolite desmethylbromethalin uncouple oxidative phosphorylation. This leads to decreased production of energy in cells so levels of ATP fall. Without ATP, Na - K ATPase pumps in the cell mem-brane are unable to pump sodium out of the cell. Because sodium builds up inside the cell, water is pulled in and the cell swells. Nerves cells are the most sensitive tissue and so signs of neurotoxicity are seen. In the CNS, myelin sheaths that surround nerve cells swell and vacuoles form

Postmortem

Typically, no microscopic lesions are noted. The animal will have widespread hemorrhage into body cavities, joints, skin, CNS, or other tissues. AR can be detected, most typically in liver tissue, to confi rm exposure (Murphy 2007 ).

Management of Exposures

In animals with recent exposures ( < 4 hours), emesis should be performed. This can be followed with a single dose of activated charcoal; multiple doses of activated charcoal have not been shown to be benefi cial. Next, one of two courses should be followed (Merola 2002 ). Vitamin K 1 can be started at a dose of 3 – 5 mg/kg divided twice a day. The length of treatment depends on the agent ingested. For warfarin, a minimum of 14 days is recommended; for bromadiolone, the recommended treatment period is 21 days; and for all other fi rst and second - generation agents, at least 30 days of treatment should be done. Injections of vitamin K 1 should not be used if possible as this increases the risk of allergic or anaphylactic reactions. Oral vitamin K 1 should be given with a small, fatty meal, such as canned dog or cat food, because this enhances absorption. For rodents and small puppies or kittens, the injectable vitamin K 1 solution can be given orally if appropriately sized tablets are not available. Approximately 48 and 72 hours after stopping the vitamin K 1 , a PT should be run to see if additional treatment is necessary (Merola 2002 ).

Alternatively, instead of starting vitamin K 1 immedi-ately, the patient ’ s PT can be monitored. A baseline PT level should be obtained and then rechecked at 48 and 72 hours after the exposure. If the PT becomes prolonged, vitamin K 1 therapy, as indicated above, should be insti-tuted (Merola 2002 ). As mentioned above, the PIVKA test, if available, can be used instead of the PT to monitor the patient.

A study done at the University of Pennsylvania showed that over 90% of dogs decontaminated with emesis and/or activated charcoal after anticoagulant ingestion did not need treatment with vitamin K 1 when their PT was moni-tored; none of the animals developed signs during the period that the PT was being run (Pachtinger et al. 2008 ). Therefore, waiting to monitor PTs rather than immediately starting vitamin K 1 is an acceptable treatment plan.

In patients that are actively bleeding, emesis should not be performed as exposure likely occurred several days before presentation. The animal should be stabilized for shock with fl uids. If the anemia is severe, a blood transfu-sion should be performed (Merola 2002 ). Vitamin K 1 therapy should be started as soon as possible. However,


Table 17.2. Toxicity of bromethalin in various species

Species Oral LD 50 (mg/kg)

Rat 2.0 Mouse 5.3 Rabbit 13.0 Guinea pig < 1000 Dog 4.7 Cat 1.8

Source : Van Lier and Cherry 1988 .

within the nerve cell. As the cells and the myelin sheaths swell with fl uid, internal pressure increases; there is also an increase in cerebrospinal fl uid pressure. Together, these changes cause nerve dysfunction (Dunayer 2003 , Gupta 2007 ).

Toxicity

For most species, the toxicity of bromethalin is very similar (see Table 17.2 ). However, cats are much more sensitive to the effects of bromethalin than dogs. Guinea pigs are relatively insensitive to bromethalin as they are unable to produce the toxic metabolite desmethylbro-methalin (Dunayer 2003 ). Interestingly, if guinea pigs are fed desmethylbromethalin, the toxic dose is similar to bro-methalin (Van Lier and Cherry 1988 ). Based on cases reported to the APCC, dogs have died at dosages of 0.95 mg/kg and cats have developed signs at 0.24 mg/kg (Dunayer 2003 ).

Clinical Effects

Signs

In dogs, the onset of signs depends on the dose ingested. At lower doses, the onset is slow, taking from 24 – 86 hours to be seen. Initial signs include hindlimb weakness, which can progress to paresis and paralysis. CNS depression also develops. Once signs develop, they may last for days to weeks before they resolve (Dorman et al. 1990b ). In dogs ingesting doses at or above the LD 50 , the onset of signs is more rapid, from 4 – 36 hours. In these dogs, hyperexcit-ability develops followed by tremors, seizures, and death (Dorman et al. 1990b ).

In cats, the most common sign is ataxia. Other signs include focal motor seizures, recumbency, abdominal dis-tension, decreased conscious proprioception, and a decer-ebrate posture. Onset of signs occurs from 3 – 7 days after exposure. As noted with dogs, higher ingested doses gen-erally lead to earlier onset of signs (Dorman et al. 1990a ).

Laboratory

There are no signifi cant laboratory changes expected with bromethalin toxicosis. (Dorman et al. 1990b ).


For the paralytic form of bromethalin toxicosis, toxic dif-ferentials include botulism, ivermectin toxicosis, and iono-phore toxicosis. In seizing patients, differentials include metaldehyde (snail bait), strychnine, zinc phosphide, and sodium fl uoroacetate (Compound 1080) intoxications.

Diagnostics

Antemortem

Antemortem diagnosis relies on a history of exposure and occurrence of compatible clinical signs. Although blood can be tested for the presence of bromethalin, this is not a standard test and results are typically not available prior to the need to institute treatment.

Postmortem

Bromethalin can be detected in various organs including the brain and liver. Histopathology of the CNS shows spongy degeneration of the white matter with an accu-mulation of fl uid within the myelin sheaths (Dunayer 2003 ).


There is no antidote for bromethalin, so the management of exposure is focused on decontamination. Decontamina-tion recommendations vary depending on the species, dosage, and time since ingestion. Tables 17.3a and b sum-marize the APCC ’ s recommendations for decontamination (Dunayer 2003 ). Since bromethalin is not an anticoagu-lant, vitamin K 1 is not indicated as a treatment.

Once signs begin, treatment is supportive and symptom-atic. Recumbent animals should be well padded to prevent pressure sores. Seizures should be controlled as needed. Mannitol, furosemide, and corticosteroids have been sug-gested to treat the cerebral edema. Although these might slow progression of signs, they do not prevent their occur-rence. In addition, when the treatment is stopped, the animal may deteriorate rapidly (Dunayer 2003 ).

Prognosis

Prompt decontamination can often prevent signs from occurring. In mild cases, recovery is possible but full recovery can take weeks. Animals who are paralyzed or having seizures have a guarded prognosis, although even these animals can recover with intensive care.


cholecalciferol is transported to the liver on vitamin D – binding proteins. In the liver, cholecalciferol is metabo-lized to 25 - hydroxycholecalciferol, also known as calcife-diol. Calcifediol circulates in the blood and, in the kidneys, is further metabolized to 1,25 - dihdroxycholcalcerifol or cacitriol, which is the most active form of vitamin D (Morrow 2001 ; Rumbeiha 2006 ).

Mechanism of Action

Calcitriol increases blood calcium and phosphorus levels via various mechanisms: increased gastrointestinal absorp-tion of calcium, increased calcium reabsorption by the kidneys, and increased bone resorption and release of phosphorus and calcium into the blood (Morrow 2001 ; Rumbeiha 2006 ). The overall effect is to increase blood phosphorus and calcium levels. When the calcium × phos-phorus product exceeds 60, soft tissue mineralization may occur. Mineralization of the kidneys can lead to acute renal failure although any tissue can be affected. (Morrow 2001 ).

Toxicity

In dogs dosages of 10 mg/kg have been fatal (Gupta 2007 ). Based on experience at the APCC, dosages of 0.5 mg/kg can cause signs (Morrow 2001 ). Therefore, the APCC

CHOLECALCIFEROL


Cholecalciferol is a form of vitamin D 3 . It is generally found in a 0.075% bait (21.3 mg cholecalciferol per oz of bait). As with other rodenticides, it is available in different forms and from different manufacturers (Morrow 2001 ). Vitamin D toxicosis can also occur due to chronic overdosing with vitamin D supplements or as a result of improperly formulated dog or cat foods. Although over - the - counter daily multivitamins contain vitamin D, it is generally present in such low concentrations ( < 1000 IU per capsule) that vitamin D toxicosis from acute overdoses of these products is rare. However, pre-scription products containing between 5,000 and 50,000 IU per capsule may result in toxicosis if suffi cient numbers are ingested. Additionally, certain medications that contain vitamin D analogs such as calcipotriene, a topical cream for treating psoriasis, can cause toxicosis similar to cho-lecalciferol (Rumbeiha 2006 ).

Kinetics

Cholecalciferol is rapidly absorbed after ingestion. It is mainly excreted by the liver and undergoes enterohepatic recirculation (Morrow 2001 ). Vitamin D 3 is highly fat - soluble so it can be stored in body fat. After absorption,

Table 17.3a. Decontamination recommendations for bromethalin ingestion: Recommendations for dogs

Time since Exposure

Dosage Ingested (mg/kg) Action

< 4 hours 0.1 – 0.49 Emesis or one dose of activated charcoal

> 4 hours 0.1 – 0.49 One dose of activated charcoal

< 4 hours 0.5 – 0.75 Emesis and three doses of activated charcoal over 24 hours

> 4 hours 0.5 – 0.75 Three doses of activated charcoal over 24 hours

< 4 hours > 0.75 Emesis and three doses of activated charcoal a day for 48 hours

> 4 hours > 0.75 Three doses of activated charcoal a day for 48 hours

Table 17.3b. Decontamination recommendations for bromethalin ingestion: Recommendations for cats

Time since Exposure

Dosage Ingested (mg/kg) Action

< 4 hours 0.05 – 0.1 Emesis or one dose of activated charcoal

> 4 hours 0.05 – 0.1 One dose of activated charcoal

< 4 hours 0.1 – 0.3 Emesis and three doses of activated charcoal over 24 hours

> 4 hours 0.1 – 0.3 Three doses of activated charcoal over 24 hours

< 4 hours > 0.3 Emesis and three doses of activated charcoal a day for 48 hours

> 4 hours > 0.3 Three doses of activated charcoal a day for 48 hours

Source : Dunayer 2003 .


hours) might increase clearance. Baseline levels of calcium, phosphorus, BUN, and creatinine should be obtained and monitored daily for at least 4 days (Morrow 2001 ).

In patients with elevated calcium and phosphorus con-centrations, intensive therapy is indicated to prevent renal failure and other signs. The animal should receive 0.9% saline IV at twice maintenance rates; sodium competes for reabsorption with calcium in the kidney and increases calcium loss. Furosemide should be administered as it increases calcium excretion by the kidneys. Corticoste-roids such as prednisone will decrease bone resorption and decrease intestinal absorption while increasing renal excretion of calcium. In addition, a low calcium/phosphorus diet should be fed and phosphate binders, such as alumi-num or magnesium hydroxide, can be given (Morrow 2001 ; Rumbeiha 2006 ).

If these measures are not successful in reducing calcium levels, other treatments should be initiated. Salmon calci-tonin is a hormone that lowers calcium levels. However, it must be given several times a day and some animals develop a tolerance to it. The preferred treatment is pami-dronate, a bisphosphonate used to lower serum calcium in people with hypercalcemia due to malignancy. Pamidro-nate is given in normal saline by slow IV infusion over 2 to 4 hours. Its effects can last up to a week. It can be repeated as needed. Other bisphosphonates such as clodro-nate also appear to be effective (Ulutas et al. 2006 ). Cal-citonin and pamidronate (or other bisphosphonates) should not be used together (Morrow 2001 ).

Treatment should be continued until the calcium × phos-phorus product is less than 60. At that point, treatments can be slowly reduced while the calcium and phosphorus values are watched closely for signs of recurrence over the course of several weeks (Morrow 2001 ).

Prognosis

The prognosis is good with prompt decontamination and if no signs develop. The prognosis is guarded once signs develop because mineralization is poorly reversible. Chronic renal failure can be a permanent sequela. Sudden deaths have occurred weeks later, probably due to cardiac arrhythmias from calcifi ed heart muscle or the rupture of a major artery like the aorta (Morrow 2001 ).

STRYCHNINE


Strychnine is an alkaloid obtained from the seeds and bark of the strychnine tree ( Strychnos nux - vomica and S.

recommends that decontamination and monitoring for signs be performed on dogs ingesting more than 0.1 mg/kg.

Clinical Effects

Signs

Onset of signs is usually within 12 to 36 hours of inges-tion. Initial signs include vomiting and diarrhea (possibly bloody). The animal will then show depression, polyuria, and polydipsia. Acute renal failure can occur in as little as 24 hours (Morrow 2001 ).

Laboratory

After ingestion, serum phosphorus usually increases fi rst, generally around 12 hours. The serum calcium increases by about 24 hours. Increases in BUN and creatinine con-sistent with renal failure can begin shortly after the phos-phorus and calcium product exceeds 60 (Morrow 2001 ).


Any condition that increases serum calcium levels should be considered as a differential. This includes primary hyperparathyroidism in which the parathyroid gland pro-duces excessive levels of parathormone (PTH), usually due to a tumor of the gland. In addition, certain tumors, such as lymphoma and anal gland carcinomas can secrete a protein that acts like PTH. In these syndromes, unlike cholecalciferol toxicity, phosphorus levels are usually normal (Rumbeiha 2006 ).

Diagnostics

Antemortem

In addition to measuring serum calcium, phosphorus, and assessing renal function, vitamin D 3 and calcitriol levels can be measured in blood. In cholecalciferol toxicosis, these are markedly elevated. In addition, PTH levels should be determined since they will be reduced (Rum-beiha 2006 ).

Postmortem

Lesions on postmortem examination include mineraliza-tion of soft tissues, especially the kidneys. However, this can occur with any condition that causes hypercalcemia. The bile and kidneys can be tested for calcifediol levels to confi rm toxicity (Rumbeiha 2006 ).


If ingestion is within 6 – 8 hours, emesis can be performed. Since cholecalciferol undergoes enterohepatic recircula-tion, multiple doses of activated charcoal (every 6 – 8


Laboratory

There are no specifi c changes associated with strychnine toxicosis (Talcott 2004 ).


Many toxicants and conditions can cause severe tremors similar to strychnine. These include metaldehyde, bro-methalin, tremorgenic mycotoxins, zinc phosphide, tetanus, organochlorine insecticides, anticholinesterase insecticides, and Brunfelsia spp. (Talcott 2006 ).

Diagnostics

Antemortem

Strychnine can be detected in urine and stomach contents from gastric lavage (Gupta 2007 ; Talcott 2004 ). However, some animals die so quickly that strychnine can ’ t be detected in their urine (Beasley et al. 1999 ). In addition, the results of the tests are not likely to be available before the patient has either died or recovered.

Postmortem

There are no specifi c lesions associated with strychnine toxicosis. Strychnine can be detected in stomach contents, urine, bile, liver, and kidney to confi rm exposure (Talcott 2004 ).


Emesis can be induced before the animal is symptomatic; however, due to rapid onset of signs in most cases, this may not be practical. Activated charcoal may be useful but care should be taken to avoid aspiration (Talcott 2004 ). In general, treatment is aimed at controlling the tremors and seizures. Barbiturates, methocarbamol, pro-pofol, and gas anesthesia may be used to control signs. In severe cases, the patient may need to be kept under anesthesia for 24 – 48 hours. IV fl uids to support hydra-tion should be administered. Sensory stimulation should be kept to a minimum to prevent worsening of the signs. Treatment should be continued until signs have resolved, which may take 24 – 72 hours (Talcott 2004 ; Gupta 2007 ).

Prognosis

Prognosis is guarded once signs have begun.

ZINC PHOSPHIDE


Zinc phosphide is an inorganic rodenticide that has been available for over 70 years (Albretson 2004 ). It is sold as

ignatti ). These trees grow in Southeast Asia and Australia (Gupta 2007 ). Strychnine is one of the oldest rodenticides; it was fi rst used in the 16th century (Talcott 2006 ). Strych-nine is sold in various formulations, usually mixed with grain. It is often dyed red or green. Formulations contain 0.5% – 3% strychnine. It is intended for killing rodents as well as porcupines, rabbits, and pigeons (Talcott 2004 ). Strychnine is labeled for use underground in animal burrows (Talcott 2004 ).

Kinetics

Strychnine is rapidly absorbed from the small intestine (Gupta 2007 ). It is metabolized in the liver, but up to 20% of the dose may be excreted in the urine unchanged (Talcott 2004 ). It rapidly distributes to many different tissues and has a half - life of about 6 hours (Gupta 2007 ).

Mechanism of Action

Strychnine competitively blocks the effects of the amino acid glycine, an inhibitory neurotransmitter in the spinal cord. Normally, glycine prevents repetitive nerve activity that stimulates muscle contractions. Without this inhibition, the nerve continues to fi re rapidly and leads to muscle spasms. Eventually, the animal develops muscle rigidity (tetanic spasms) (Talcott 2004 ; Gupta 2007 ). Because extensor muscles are stronger than fl exor muscles in the limbs and neck, an extensor rigidity develops.

Toxicity

Strychnine is considered extremely toxic. In dogs, the minimum lethal dosage is about 0.75 mg/kg (Gupta 2007 ); this is about 0.15 g/kg of a 0.5% bait or about 0.5 teaspoon in a 35 lb (16 kg) dog. In cats, the LD 50 is about 2 mg/kg (Talcott 2004 ).

Clinical Effects

Signs

Signs can occur from 10 minutes to 2 hours after ingestion depending on when the stomach empties since strychnine is better absorbed in the intestines (Talcott 2004 ). Vomit-ing is uncommon (Gupta 2007 ). Initially, the animal may be anxious, tachypneic, and salivating heavily. Signs then progress to ataxia followed by collapse with violent mus-cular seizures. The legs will be extended and rigid and the neck may be arched. Stimulation by noise or lights typi-cally causes signs to worsen. The animal can be hyperther-mic due to extreme muscle activity. Death is likely due to respiratory arrest from paralysis of the diaphragm (Talcott 2004 ; Gupta 2007 ).


Laboratory

There are no specifi c clinical laboratory changes noted (Albretson 2004 ).


The differential diagnoses are similar to those for strych-nine. These include metaldehyde, bromethalin, tremor-genic mycotoxins, zinc phosphide, tetanus, organochlorine insecticides, anticholinesterase insecticides, and Brunfel-sia spp.

Diagnostics

Antemortem

Diagnosis is based on history and the presence of the characteristic smell of phosphine gas. Stomach contents samples can be tested for the presence of phosphine.

Postmortem

Diagnosis can be made by the detection of phosphine in stomach contents.


If exposure was recent, the patient should be given oral liquid antacids to neutralize stomach acid and reduce the production of phosphine gas. Emesis can be performed early but a centrally active emetic such as apomorphine should be used rather than hydrogen peroxide, which could increase the production of phosphine gas (Albretson 2004 ). Emetics are not indicated in animals that have already vomited. In patients who are seizuring, gastric lavage can be considered. Activated charcoal has been recommended, but there is no proof of effi cacy (Knight 2006 ). In vomiting animals, activated charcoal may increase the risk of aspiration and it may delay healing of gastric erosions.

There are no antidotes for zinc phosphide toxicosis. Treatment should be directed to providing support and controlling signs such as fl uids for shock, seizure control, and correcting acid - base imbalances. Liver protectants such as n - acetylcysteine, B - vitamins, SAMe, and dextrose may be useful but proof of effi cacy is lacking (Albretson 2004 ; Knight 2006 ).

When presented with a poisoned animal, there is a real risk to attending medical staff. Phosphine gas coming from the patient ’ s stomach or vomitus can affect human person-nel in the room. The odor of phosphine gas can be detected by the human nose at about 2 ppm. However, levels of 1 ppm or less, depending on the length of exposure, can be toxic (Knight 2006 ). If possible, induction of emesis should be performed outdoors or in a well - ventilated

a 2% bait (566 mg zinc phosphide per oz of bait). Zinc phosphide can be found in several different forms such as in pellets, in place packs, and mixed with grains. In addi-tion to mice and rats, it is also used to kill voles, moles, rabbits, and other rodents (Gupta 2007 ).

Kinetics

After ingestion, zinc phosphide reacts with acids in the stomach to produce phosphine gas, which can be absorbed from the stomach or may be inhaled as it escapes the stomach (Albretson 2004 ). Intact zinc phosphide may be absorbed as well from the gastrointestinal tract.

Mechanism of Action

The exact mechanism of zinc phosphate and phosphine gas intoxication is not known. It is thought that phosphine gas blocks the enzyme cytochrome oxidase, which decreases energy production by cells. Without energy, cells are unable to maintain normal function and cell death occurs (Albretson 2004 ; Gupta 2007 ). Phosphine gas is also thought to be directly irritating, especially to the lungs (Albretson 2004 ).

In addition to its immediate effects, zinc phosphide can cause delayed liver and kidney failure. It is not known whether this is due to phosphine gas or the absorption of intact zinc phosphide.

Toxicity

The LD 50 of zinc phosphide is about 40 mg/kg in dogs and cats. The LD 50 in rats is 12 mg/kg. Because zinc phosphide is a strong emetic, dogs and cats are less sensitive to zinc phosphide than rodents because they can vomit and par-tially decontaminate themselves after ingestion (Albretson 2004 ).

Clinical Effects

Signs

The onset of signs varies from 15 minutes to 4 hours. Rapidity of onset appears to be infl uenced by whether or not the animal has food in its stomach. The presence of food increases the production of hydrochloric acid, which in turn increases the production of phosphine gas (Albret-son 2004 ). Vomiting, often bloody, is common. The ani-mal ’ s breath or its vomitus can have a garlicky or rotten fi sh smell from the phosphine gas (Knight 2006 ). Severe gastrointestinal pain can develop. CNS signs include anxiety, initial depression progressing to increased activ-ity, tremors, and seizures. Increased respiratory sounds and rate are common (Knight 2006 ).


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— — — . 2006 . Strychnine . In Small Animal Toxicology , 2nd ed. , edited by Michael E. Peterson and Patricia A. Talcott , pp. 1076 – 1082 . St. Louis : Elsevier Saunders .

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USEPA (U.S. Environmental Protection Agency) . 2008 . Final Risk Mitigation Decision for Ten Rodenticides. Accessed at http://www.epa.gov/pesticides/reregistration/rodenticides/fi nalriskdecision.htm#proposed on December 20, 2008.

Van Lier , Robert B.L. , Cherry , Linda D. 1988 . The toxicity and mechanism of action of bromethalin: A new single - feeding rodenticide . Fundamental and Applied Toxicology 11 : 664 – 672 .

room. Vomitus or gastric lavage material should be cleaned up rapidly and placed in an airtight bag. If the smell of phosphine gas is detected, personnel should be evacuated and the room aired out thoroughly.

Prognosis

In asymptomatic animals, the prognosis is good. If signs do develop, the prognosis is guarded especially for the fi rst 48 hours. Even those animals that survive the initial period may develop acute renal and hepatic failure over the next 2 weeks.

REFERENCES

Albretson , Jay C. 2004 . Zinc phosphide . In Clinical Veteri-nary Toxicology , edited by Konnie H. Plumlee , pp. 456 – 458 . St. Louis : Mosby .

Beasley , Val R. , Dorman , David C. , Fikes , James D. , Diana , Stephen G. , and Woshner , Victoria . 1999 . A Systems Affected Approach to Veterinary Toxicology . St Louis : Mosby .

Dorman , David C. , Parker , Alan J. , Dye , Janice A. , and Buck , William B. 1990a . Bromethalin neurotoxicosis in the cat . Progress in Veterinary Neurology 1 ( 2 ): 189 – 196 .

Dorman , David C. , Parker , Alan J. , and Buck , William B. 1990b . Bromethalin toxicosis in the dog: Part I: Clinical effects . Journal of the American Animal Hospital Associa-tion 26 : 589 – 594 .

Dunayer , Eric. 2003 . Bromethalin: The other rodenticide . Vet-erinary Medicine 98 ( 9 ): 732 – 736 .

Gupta , Ramesh C. 2007 . Non - anticoagulant rodenticides . In Veterinary Toxicology: Basics and Clinical Principles , edited by Ramesh C. Gupta , pp. 548 – 563 . New York : Elsevier .

Knight , Anthony P. and Walter , Richard G. 2001 . A Guide to Plant Poisoning of Animals in North America . Jackson, Wyoming : Teton New Media .

Knight , Michael W. 2006 . Zinc Phosphide . In Small Animal Toxicology, Second Edition , edited by Michael E. Peterson and Patricia A. Talcott , pp. 1101 – 1118 . St. Louis : Elsevier Saunders .

Meadows , Irina and Gwaltney - Brant , Sharon . 2006 . The 10 most common toxicoses in dogs . Veterinary Medicine 101 ( 3 ): 142 – 148 .

small animal toxicology essentials (poppenga/small animal toxicology essentials) || rodenticides

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