Clinicians participating in this CME activity gain essential knowledge and skills for managing rodenticide toxicity. Specifically, they learn to identify and differentiate the diverse mechanisms of action and clinical presentations of various rodenticides, ranging from anticoagulant-induced bleeding to neurological and metabolic disturbances. This training also emphasizes the importance of promptly identifying the specific rodenticide involved through detailed history-taking, physical examination, and searching for packaging or other indicators. Participants can also assess and implement immediate stabilization techniques, apply specific antidotes, and provide supportive care. They also gain proficiency in interpreting laboratory and diagnostic test results and recognizing abnormalities associated with rodenticide ingestion.
This activity reviews the critical role of consultation with poison control centers and toxicologists for treatment guidance. Clinicians learn to develop and strategize effective treatment plans, incorporating collaboration with multidisciplinary teams to enhance patient outcomes. By the end of the activity, clinicians are also better prepared to coordinate follow-up care and recommend preventive measures to reduce accidental rodenticide exposures. This comprehensive approach improves clinicians' ability to provide timely and accurate diagnosis and management of rodenticide toxicity, ultimately enhancing patient care and safety.
Objectives:
Identify the diverse mechanisms of action and clinical presentations of various rodenticides.
Screen patients for potential rodenticide exposure through detailed history-taking and physical examination.
Select appropriate laboratory and diagnostic tests to confirm rodenticide ingestion and identify associated abnormalities.
Collaborate with multidisciplinary teams to develop and strategize effective treatment plans for rodenticide toxicity.
Rodenticide toxicity is a significant public health concern due to the diverse mechanisms of action and the variety of available rodenticides. Most commonly, human exposure to rodenticides is accidental, often occurring in young children. The clinical presentation of rodenticide toxicity varies widely. Common symptoms range from anticoagulant-induced bleeding to neurological and metabolic disturbances. Prompt identification of the ingested rodenticide is critical for effective treatment and involves obtaining a detailed history, performing a thorough physical examination, and searching for packaging or other indicators of the specific rodenticide(s) involved. Management of rodenticide toxicity focuses on stabilizing the patient and providing specific antidotes or supportive care. Consultation with poison control centers or toxicologists is essential for guidance on appropriate treatment of rodenticide toxicity.
Although anticoagulants are the most commonly used rodenticides today, many other rodenticide agents are available. Thus, symptoms of rodenticide poisoning vary depending on the specific agent(s) ingested. Rodenticide registration, distribution, sale, and use are regulated by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), which is enforced by the Environmental Protection Agency (EPA).[1] FIFRA regulates the labeling of rodenticides and requires the prominent display of specific information, including a signal word that indicates an agent's degree of toxicity.
Rodenticides labeled with the signal word danger are highly toxic and include thallium, sodium monofluoroacetate (SMFA, fluoroacetate), strychnine, zinc phosphide, aluminum phosphide, elemental phosphorus, arsenic, and barium carbonate. Rarely used or banned agents with this labeling include tetramethylenedisulfotetramine (TETS or tetramine), aldicarb, alpha-chloralose, and pyrinuron. Rodenticides labeled with the signal word warning are moderately toxic and include alpha-naphthylthiourea and cholecalciferol. Finally, rodenticides labeled with the signal word caution pose low to very low risks for toxicity and include superwarfarin, warfarin, norbormide, bromethalin, and red squill.
According to the Annual Report of the American Association of Poison Control Centers, more than rodenticide ingestions were reported in the United States.[2] More than half of these rodenticide ingestions were in children younger than 6. Anticoagulant rodenticides were identified as the ingested agents in more than cases. Bromethalin was the second most commonly ingested agent and was identified in cases.[2]
Rodenticides consist of a wide variety of xenobiotics with different mechanisms of action. The pathophysiologic effects of several common rodenticides are summarized below.
Thallium
Thallium is a tasteless and odorless powder that can be absorbed through inhalation or the skin. This chemical acts by substituting for potassium in sodium-potassium adenosine triphosphatase and the sulfhydryl or thiol group of mitochondrial membranes. Thallium inhibits pyruvate kinase and succinate dehydrogenase, which disrupts the Krebs cycle, oxidative phosphorylation, and energy production.[3] Please see StatPearls' companion resource, "Thallium Toxicity," for more information.
Fluoroacetamide (Compound ) and Sodium Monofluoroacetate
Both fluoroacetamide and SMFA are metabolized into monofluoroacetyl coenzyme A, which is subsequently converted into fluorocitrate. Fluorocitrate irreversibly binds aconitase and inhibits the citric acid cycle. Inhibition of the citric acid cycle leads to lactic acidosis and the buildup of substrates that are otherwise broken down by aconitase, including citrate.[4] The buildup of citrate can bind cations and lead to electrolyte abnormalities, including clinically relevant hypocalcemia.[5] In addition, inhibition of fatty acid oxidation can lead to ketosis. Hyperammonemia may also result from associated inhibition of the urea cycle.[6]
Strychnine
Strychnine is an odorless and colorless powder. Strychnine toxicity commonly causes involuntary muscle contraction, resulting from strychnine's competitive inhibition of glycine receptors of postsynaptic and motor neurons within the spinal cord.[7] Please see StatPearls' companion resource, "Strychnine Toxicity," for more information.
Zinc and Aluminum Phosphide
When zinc or aluminum phosphide is ingested, gastric acid releases phosphine gas, which is absorbed into the bloodstream. Zinc and aluminum phosphides inhibit the cytochrome C oxidase system, which disrupts the formation of adenosine triphosphate (ATP).[8]
Elemental Phosphorus
Elemental phosphorus exists in red or white forms, with white phosphorus used as a rodenticide. White phosphorus is very toxic and can cause damage both locally and systemically. When ingested, it causes direct tissue damage through exposure to phosphoric acid and phosphorus pentoxide. In circulation, phosphorous binds to calcium and can lead to clinically significant hypocalcemia.[9]
Arsenic
Arsenic is a toxic, inorganic compound whose exact mechanism of action is unknown. Proposed toxic mechanisms of arsenic include inhibition of hexokinase in glycolysis, inhibition of pyruvate dehydrogenase in the Krebs cycle, and aberrant vasodilation due to the formation of sulfhydryl compounds.[10] Please see StatPearls' companion resource, "Arsenic Toxicity," for more information.
Barium Carbonate
Barium carbonate dissolves easily in water and is highly toxic. The barium ion inhibits potassium diffusion out of cells, which can result in clinically significant hypokalemia.[11]
Tetramethylenedisulfotetramine (Tetramine)
Tetramine is odorless, colorless, and tasteless and is a reversible and noncompetitive antagonist of the gamma-aminobutyric acid type A (GABA-A) receptor.[12] Through antagonism of the GABA-A receptor, tetramine may induce seizures and other neurotoxic effects.
Aldicarb
Originating from Latin America, aldicarb is also known as tres pasitos, which refers to the 3 little steps mice take before aldicarb causes death. Aldicarb is a potent cholinesterase inhibitor and causes a cholinergic toxidrome.[13]
Alpha-chloralose
Originating from Europe, alpha-chloralose is used as a veterinary anesthetic and rodenticide. Alpha-chloralose's mechanism of action is not clearly defined but is believed to be similar to that of barbiturates.[14]
Pyriminil
Pyriminil causes swift destruction of pancreatic beta cells through nicotinamide antagonism and impairment of NAD and NADH synthesis.[15][16]
Cholecalciferol (Vitamin D3)
Cholecalciferol mobilizes calcium from the bones and increases intestinal calcium absorption, which causes hypercalcemia.[17][18] Large ingestions of cholecalciferol may cause clinically significant hypercalcemia, leading to dehydration, anorexia, renal failure, and calcification of vital organs.
Anticoagulants (Superwarfarins and Warfarin)
Superwarfarins, including brodifacoum, difenacoum, bromadiolone, and chlorophacinone, are anticoagulant rodenticides that are structurally similar to warfarin but contain terminal phenyl groups instead of terminal methyl groups. Substituting a terminal phenyl group makes superwarfarins 100-fold more potent compared to warfarin.[19] Warfarin and superwarfarins are competitive inhibitors of the vitamin K epoxide reductase complex 1 (VKORC1). VKORC1 inhibition prevents the synthesis of clotting factors II, VII, IX, and X. Please see StatPearls' companion resource, "Warfarin Toxicity," for more information.
Norbormide
Norbromide causes extreme peripheral vasoconstriction, leading to ischemia, organ failure, and death. However, it is not toxic to humans.[20]
Bromethalin
Bromethalin uncouples oxidative phosphorylation, leading to decreased ATP production. This lack of ATP causes edema around neuron sheaths, leading to toxic effects in the central and peripheral nervous systems. Bromethalin is rarely toxic to humans because it takes significant ingestion to exert toxic effects.[21]
Red Squill (Urginea maritima or Drimia maritima)
Red squill contains scillaren A and B, which are cardioactive glycosides.[22] Thus, red squill's mechanism of toxicity is very similar to digoxin and involves inhibition of the sodium-potassium ATPase pump. Inhibition of the sodium-potassium ATPase pump leads to gastrointestinal, cardiac, and central nervous system toxicity.[23]
Children are more susceptible to rodenticide toxicity due to accidental ingestion, whereas adults who attempt suicide with rodenticides represent a significant subset of affected patients.[24] The most common rodenticides used in the United States are anticoagulants. Symptoms consistent with ingesting anticoagulant rodenticides include hematuria, hemoptysis, epistaxis, flank pain, bruising, and petechiae under the blood pressure cuff.[25] However, the symptoms of rodenticide toxicity vary depending on the rodenticide(s) involved. Because of the wide range of potential toxicities, every effort should be made to identify the rodenticide(s) exposed to the patient. Accurate and timely identification of rodenticides may involve having friends or family of the patient or law enforcement search the patient's last known location to find rodenticide packaging or other indicators of what specific rodenticide(s) were involved in the exposure.
The toxicity of rodenticides is categorized by the amount of poison required to cause death in 50% of those animals exposed, which is known as lethal dose 50 (LD50). In some regions, including the United States, the toxicity of a rodenticide is denoted by signal words on product labels, such as danger, warning, or caution. Rodenticides labeled as danger are considered to be very toxic (LD50 is 0-50 mg/kg). Rodenticides labeled as warning are considered to be toxic (LD50 is 50-500 mg/kg). Finally, rodenticides labeled as caution are considered to be less toxic (LD50 is 500- mg/kg).
Symptoms of toxicity for specific rodenticides are described below:
Thallium
Acute exposure to thallium can cause acute gastroenteritis, cranial nerve dysfunction, painful peripheral neuropathy, seizures, alopecia, and hyperpigmentation. Chronic exposure to thallium can cause tremors, ataxia, distal motor weakness, diplopia, nystagmus, seventh cranial nerve palsy, and ocular lens opacities.[3][26]
Fluoroacetamide (Compound ) and Sodium Monofluoroacetate
Exposure to compound and SMFA may cause seizures, metabolic acidosis, shock, dysrhythmias, and hypocalcemia. Acute kidney injury, hepatic dysfunction, and cerebral or cerebellar atrophy may develop as late complications of compound or SMFA exposure.
Strychnine
Exposure to strychnine may cause muscle spasms, trismus, risus sardonicus, opisthotonos, lactic acidosis, and hyperthermia. Rhabdomyolysis may also develop due to muscle damage caused by strychnine exposure.[27]
Zinc and Aluminum Phosphide
Exposure to zinc and aluminum phosphide may cause acute gastroenteritis, acid-base disorders, cardiac arrhythmias, renal failure, hemorrhagic pulmonary edema, respiratory failure, hepatotoxicity, and intravascular hemolysis with methemoglobinemia.[28][28]
Elemental Phosphorus
Symptoms of elemental phosphorus toxicity include acute gastroenteritis, burns on the skin or mucosa, phosphorescent emesis or feces (smoking stools), dysrhythmias, renal failure, and hepatotoxicity.[29][30]
Arsenic
Symptoms of arsenic exposure include garlic taste, vomiting, bloody diarrhea, hypotension, prolonged QTc, acute kidney injury, delirium, and seizures. Arsenic may also cause coma in patients with significant exposure.[31][32]
Barium Carbonate
Exposure to barium carbonate may cause gastroenteritis, hypertension, arrhythmias, shortness of breath, and muscle paralysis.[33]
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Tetramethylenedisulfotetramine (Tetramine)
Symptoms of TETS or tetramine exposure include gastroenteritis, arrhythmias, and convulsions. TETS or tetramine may cause respiratory failure or coma in patients with significant exposure.[12]
Aldicarb
Exposure to aldicarb may cause cholinergic symptoms, including excessive salivation, lacrimation, urination, and diarrhea. Aldicarb also commonly causes gastrointestinal upset and emesis.[34][35]
Alpha-chloralose
Symptoms of alpha-chloralose toxicity include convulsions, hypothermia, and respiratory depression.[36]
Pyriminil
Symptoms of pyriminil toxicity include hypoglycemia, Kussmaul breathing, hypotension, lethargy, and encephalopathy.
Cholecalciferol (Vitamin D3)
Exposure to toxic doses of cholecalciferol may cause polyuria, polydipsia, abdominal pain, vomiting, renal failure, and encephalopathy.[18]
Anticoagulants (Superwarfarins and Warfarin)
Symptoms of superwarfarin and warfarin toxicity include hematuria, hemoptysis, epistaxis, flank pain, and bruising. Some patients can experience intracranial bleeding as a result of toxic superwarfarin or warfarin exposures.
Norbormide
Evidence suggests that norbormide is safe in non-rat species, given its rat-selective mechanism of toxicity.[37][20] There are no reported cases of toxicity in humans.
Bromethalin
Symptoms of bromethalin exposure may include altered mental status and delirium that are secondary to severe cerebral edema.[38]
Red Squill (Urginea maritima or Drimia maritima)
Similar to digitalis toxicity, exposure to red squill can cause abdominal pain, vomiting, seizures, hyperkalemia, and cardiac arrhythmias.
Accurate and timely identification of the ingested rodenticide(s) is crucial when assessing patients suspected of rodenticide toxicity. Laboratory or diagnostic tests may be ordered to help identify or confirm the effects of an ingested rodenticide. However, abnormalities that laboratory or diagnostic tests detect may not be specific to a singular rodenticide. Thus, in the setting of unknown rodenticide ingestion, abnormal laboratory or diagnostic test results cannot definitively identify or confirm the ingested rodenticide. Commonly associated test abnormalities and their corresponding testing modalities are listed below.
Comprehensive Metabolic Panel
A comprehensive metabolic panel can detect hypoglycemia induced by zinc or aluminum phosphide; hyperglycemia caused by pyriminil; hypocalcemia caused by ingesting white phosphorus, SMFA, or fluoroacetamide; hypokalemia caused by barium carbonate, zinc phosphide, or aluminum phosphide; elevated blood urea nitrogen or creatinine caused by thallium, arsenic, white phosphorus, zinc phosphide, or aluminum phosphide; or elevated liver enzymes caused by thallium, arsenic, white phosphorous, zinc phosphide, or aluminum phosphide.[33][4]
Serum Phosphate
A serum phosphate can detect hyperphosphatemia caused by ingesting white phosphorus.
Creatine Phosphokinase
An elevated creatine phosphokinase may provide evidence of strychnine-induced muscle damage.[39]
Serum Lactate
An elevated serum lactate level can detect lactatemia. Along with an arterial blood gas showing anion gap metabolic acidosis, it may provide evidence of SMFA- or fluoroacetamide-induced lactic acidosis.[4]
Serum Lipase
Elevated serum lipase levels may signify the ingestion of pyriminil.
Troponin
Elevated troponin levels may signify cardiac myocyte damage caused by zinc and aluminum phosphide.
Complete Blood Count
A complete blood count can detect anemia caused by zinc or aluminum phosphide.
International Normalized Ratio and Activated Partial Thromboplastin Time
Elevated international normalized ratio (INR) and activated partial thromboplastin time (aPTT) may signify ingesting anticoagulant rodenticides, including warfarin and superwarfarins.
12-Lead Electrocardiogram
A 12-lead electrocardiogram can detect QTc interval prolongation caused by SMFA, fluoroacetamide, white phosphorous, or arsenic.[40]
Chest and Abdominal X-Rays
Chest and abdominal x-rays may show the presence of radiopaque rodenticides, including barium carbonate, arsenic, and thallium.
Initial Care
Immediate management of rodenticide toxicity involves supporting the patient's airway, breathing, and circulation. Once stabilized, the patient's clothing should be removed, and the skin should be washed with water to remove any residual rodenticide. In addition, consultation with a poison control center or toxicologist should be initiated immediately after stabilization. Gastric decontamination strategies, including gastric lavage, activated charcoal, and whole bowel irrigation, should not be used before consultation with a regional poison control center or a medical toxicologist. Only limited data show that these interventions decrease mortality. Other essential treatments to consider after the patient is stabilized include isotonic fluid repletion for dehydration, cooling for hyperthermia, and antiemetic medication administration, such as ondansetron, for nausea or vomiting. Patients experiencing cholinergic toxicities after aldicarb exposure may benefit from the early administration of anticholinergic agents such as atropine, glycopyrrolate, and pralidoxime.
Specific Medical Treatment
After initial treatment of rodenticide toxicity, further treatment is largely supportive. However, medical treatments that should be considered for specific rodenticide poisonings are reviewed below.
Renal replacement therapy: Hemodialysis, continuous renal replacement, or charcoal hemoperfusion may benefit patients with heavy metal poisonings from thallium, arsenic, or barium.
British anti-Lewisite/dimercaprol: British anti-Lewisite may be an effective chelator for patients with arsenic poisoning.[41]
Meso-2,3-dimercaptosuccinic acid or 2,3-dimercapto-1-propane sulfonate: These medications may be effective chelators for patients with chronic arsenic poisoning.[41]
Prussian blue: Prussian blue may be used as an ion exchanger in patients with thallium poisoning.[42][43]
Sodium or magnesium sulfate: Sodium and magnesium sulfates may be used for acute barium carbonate ingestion. These compounds render barium carbonate as a non-absorbable barium sulfate compound.[11]
Benzodiazepines: Benzodiazepines may be effective in treating muscle spasms and seizures caused by strychnine poisoning.[44]
Nicotinamide: Intravenous nicotinamide may be used in cases of pyriminil poisoning to replenish NAD and NADH for cellular energy metabolism.[16]
Mineralocorticoids: Mineralocorticoid drugs, including fludrocortisone, may be used to treat orthostatic hypotension caused by pyriminil poisoning.
Digoxin immune fab: Digoxin immune fab binds cardiac glycoside agents and may be used to treat patients with red squill poisoning.[23]
Patients with rodenticide toxicity can have a wide range of clinical presentations. If rodenticide exposure is confirmed and the patient experiences symptoms consistent with rodenticide exposure, treatment for rodenticide toxicity should begin immediately. If rodenticide exposure is uncertain or unconfirmed, clinicians should work to rule out other conditions that may be the cause of the patient's symptoms, including acute viral gastroenteritis, Clostridioides difficile infection, foodborne toxin exposure, acute hepatitis, alcohol withdrawal, opioid withdrawal, diabetic ketoacidosis, disseminated intravascular coagulation, organophosphate or carbamate toxicity, epilepsy, intracranial hemorrhage, stroke, or rattlesnake bite.
The prognosis of rodenticide toxicity depends on the specific rodenticide and the amount ingested. Patients who receive treatment for acute rodenticide toxicity early have a better prognosis compared to those for whom treatment is delayed. The benefit of early treatment of rodenticide toxicity again underscores the importance of a detailed history, a thorough physical examination, and prompt rodenticide identification. Chronic rodenticide toxicity is associated with more morbidity compared to acute toxicity. However, large, acute rodenticide exposures are associated with high rates of death.
The complications of rodenticide toxicity vary depending on the rodenticide ingested. Severe complications of rodenticide toxicity include renal and hepatic failure, permanent neurological damage, and death.
Consultation with a regional poison control center or medical toxicologist is vitally crucial to the effective diagnosis and management of rodenticide toxicity. Toxicology experts can help determine to which rodenticide(s) the patient was exposed and can assist clinicians in determining whether the patient needs to be admitted to the hospital. Additionally, toxicology experts can assist with determining the most effective treatment(s) for the patient, including the role of gastric decontamination, extracorporeal toxin elimination, and toxin-specific treatments.
When using rodenticides, instructions should always be followed, and steps should be taken to avoid exposing humans to them. All rodenticides should be kept out of reach of children and pets and stored in appropriate containers with sufficient labeling. Unfortunately, some rodenticides are brightly colored and may be mistaken for food. In addition, tamper-resistant rodent traps should be used to prevent accidental rodenticide ingestion. Poisoned rodents should be placed in secure bins, and individuals disposing of these rodents should always use gloves to avoid contact with rodenticides.
Rodenticide toxicity requires an integrated approach by healthcare professionals to enhance patient-centered care, outcomes, safety, and team performance. Clinicians, advanced practitioners, pharmacists, and other healthcare providers must develop skills in promptly identifying the ingested rodenticide through detailed history-taking, physical examinations, and identifying packaging or other indicators. They should strategize effective management plans that focus on stabilizing the patient and administering specific antidotes or supportive care. Responsibilities include ordering and interpreting laboratory and diagnostic tests, which provide critical information for patient management.
Interprofessional communication is essential, involving consultation with poison control centers and toxicologists for guidance on diagnosis and treatment protocols. Care coordination ensures that each team member understands their role in the patient's care, from initial assessment and stabilization to ongoing monitoring and support. This collaborative approach improves patient safety by avoiding delays in treatment and ensuring that all aspects of the patient's condition are addressed comprehensively. By working together, healthcare teams can improve patient outcomes and enhance team performance in managing rodenticide toxicity.
Disclosure: Bobbisue Isackson declares no relevant financial relationships with ineligible companies.
Disclosure: Lisandro Irizarry declares no relevant financial relationships with ineligible companies.
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