Overview of rodenticide poisoning

INTRODUCTION — This topic reviews the types of rodenticides that may lead to toxic exposures and provides agent-specific information on toxicity, clinical manifestations, and initial management.

●The clinical manifestations, diagnosis, and management of long-acting anticoagulant rodenticide poisoning are discussed separately. (See "Anticoagulant rodenticide poisoning: Clinical manifestations and diagnostic evaluation" and "Anticoagulant rodenticide poisoning: Management".)

●The general evaluation and management of the poisoned patient are discussed separately. (See "General approach to drug poisoning in adults" and "Initial management of the critically ill adult with an unknown overdose" and "Approach to the child with occult toxic exposure".)

We encourage the clinician to contact a regional poison control center or consult a medical toxicologist for all serious rodenticide exposures. (See 'Additional resources' below.)

RODENTICIDE CONCEPTS — Throughout history, rodent control has been essential to the survival and health of populations. Rodents carry disease and affect food supply, and multiply rapidly when left unchecked. The process of eradicating rodent populations, however, is not without challenges. For example, rodents will avoid some toxic compounds by taste alone (primary bait refusal), will not feed twice on a substance that causes illness (bait shyness), and learn to avoid certain supplies of food or water if they cause death in other rodents [1]. For this reason, one-dose rodenticides are often used because using a toxin that must accumulate after multiple feedings will kill only a fraction of target animals.

Moreover, finding an agent that is easy to spread, highly toxic to rodents, but low in toxicity to nontarget species (such as humans and domesticated animals) is not straightforward. An ideal rodenticide has the following qualities:

●It must be effective in small enough amounts that adding it to food or water supply will not cause bait refusal.

●It must not partially sicken rodents who ingest it, lest it cause bait shyness for future encounters.

●The manner in which it kills the rodents cannot arouse suspicion in the surviving animals.

●The substance should be specific to rodents in toxicity and less toxic to humans and domestic animals [1].

The anticoagulant rodenticides best meet these criteria.

Rodenticides are utilized in a number of formulations, depending on the circumstances and location of use. Edible baits must be ingested by the target species, whereas tracking powders and contact dusts are picked up on the fur during transit and subsequently ingested during grooming. Edible solid baits may be in the form of pellets, wax blocks, or loose "cereal" baits, which can be mixed in with or sprinkled on food. Pellet baits are often used as a packet or sachet that remains fresh until opened by the rodent, as is seen with household anticoagulant rodenticides. Edible liquid baits are mixed with water and best placed in a dry area where they are likely to entice thirsty rodents. Extreme care is required in the placement of liquid baits to avoid ingestion by children and pets [2].

EPIDEMIOLOGY — Rodenticides account for approximately 0.5 percent of the approximately 2.3 million human exposures reported annually to regional poison control centers in the United States [3]. The majority of these exposures involve long-acting "superwarfarin" anticoagulants, warfarin, bromethalin, cholecalciferol, and phosphides [3]. Poisoning patterns in the United Kingdom are very similar, with a vast predominance of long-acting and warfarin anticoagulant rodenticides, followed by cholecalciferol, phosphides, and alpha-chloralose [2]. Fortunately, the use of highly toxic rodenticide agents in these countries is largely restricted only to commercial exterminators. Thus, mortality from rodenticide exposure is low.

However, global rodenticide exposures vary widely. For example, according to national poison center data in India, zinc phosphide, barium carbonate, and aluminum phosphide remain the most common cause of household and agricultural rodenticide poisoning, and deaths frequently occur [4,5]. Illegal rodenticides must also be considered, as in the case of outbreaks of tetramine poisoning in mainland China [6,7]. In the event that the exposure cannot be clearly identified, the practitioner evaluating a patient after rodenticide exposure should be aware of the regional differences in both household and agricultural pesticide use. Consultation with a regional poison control center can assist with identifying the likely rodenticide and is strongly encouraged. (See 'Additional resources' below.)

DEFINITION AND CLASSIFICATION — Rodenticides or "rat poisons" refer to any product commercially available and designed expressly to kill rodents, mice, squirrels, gophers, and other small animals. Although toxicity varies widely among these agents, most rodenticides produce their toxic effect in humans by ingestion of a large single dose [8].

The most clinically helpful categorization of rodenticides utilizes the amount of poison that causes death in 50 percent of patients following exposure (lethal dose₅₀ or LD₅₀) and a corresponding "signal word", which in some regions (eg, the United States) appears on the product label by law and reflects the highest possible toxicity of the product as follows [9]:

●Highly toxic – LD₅₀: 0 to 50 mg/kg, signal word "Danger"

●Toxic – LD₅₀: 50 to 500 mg/kg, signal word "Warning"

●Less toxic – LD₅₀: 500 to 5000 mg/kg, signal word "Caution"

APPROACH — The clinician should make every effort to identify the specific rodenticide and the circumstances of the exposure to guide care. The clinician is encouraged to contact a regional poison control center to assist with identification and interpretation of rodenticide labeling. (See 'Regional poison control centers' below.)

Identify the poison — Regional poison control centers are a valuable resource when identifying rodenticides; contact information is provided below. (See 'Regional poison control centers' below.)

Proper identification of the rodenticide involves collection of the following information:

●Location of ingestion

●Rodenticide description (eg, appearance, color, and odor)

●Packaging information

Whenever possible, the rodenticide package should be inspected for the brand name, the full chemical name of the product, the "signal word" (eg, "Danger", "Warning", or "Caution"), and any other relevant warning labels, such as a skull and crossbones. Of note, the brand name alone is insufficient for correct identification of the rodenticide because it can correspond to several rodenticides sold by one manufacturer.

Symptomatic patients — Consultation with a regional poison control center and/or medical toxicologist is advised for clinicians managing symptomatic patients following rodenticide poisoning. (See 'Regional poison control centers' below.)

When the poison is not known, clinical features can help with identification and guide treatment as follows (table 1) (see 'Highly toxic ("Danger")' below and 'Toxic ("Warning")' below and 'Less toxic ("Caution")' below):

●Cardiac arrhythmias, refractory shock, or cardiac arrest – Cardiovascular toxicity suggests the following rodenticides which can be further classified by when signs appear after exposure:

•Early: Zinc or aluminum phosphide, white (yellow) phosphorus, or barium carbonate

•Late: Arsenic, thallium, sodium monofluoroacetate (SMFA), or fluoroacetamide

●Seizures – SMFA, fluoroacetamide, tetramine, or arsenic

●Muscle rigidity, opisthotonus, trismus, and facial grimacing (risus sardonicus) – Strychnine

●Cranial neuropathy, lethargy, or coma – Thallium, arsenic, alpha-chloralose, bromethalin, Vacor (pyriminil, N-3-pyridylmethyl-N-p-nitrophenylurea, PNU)

●Bruising or bleeding – Anticoagulants (warfarin, superwarfarin compounds)

Asymptomatic patients — Asymptomatic patients may still develop serious toxicity. The clinician should be especially cautious when managing patients with intentional ingestions.

Known poison — Management depends upon the agent as follows:

●Highly toxic agents (signal word: "Danger") – Ingestions of highly toxic agents require close monitoring and warrant consultation with a regional poison control center and medical toxicologist (see 'Regional poison control centers' below). Compound appearance, minimum lethal dose, clinical manifestations, and specific management by poison are provided below and in the table (table 1). (See 'Highly toxic ("Danger")' below.)

Delayed toxicity in initially asymptomatic patients is most characteristic of poisoning with thallium, arsenic, sodium monofluoroacetate (SMFA), and fluoroacetamide. Thus, exposure to these agents usually warrants hospital admission to a unit with intensive care capability.

Patients who are asymptomatic after possible ingestion of highly toxic agents that do not cause delayed poisoning should undergo the following treatment:

•Gastrointestinal decontamination as appropriate for the specific agent (table 1).

•Pertinent ancillary testing (eg, continuous electrocardiogram monitoring for barium carbonate, phosphide compounds, and phosphorus compounds; serum lactate and blood gas analysis for SMFA/fluoroacetamide; serum calcium in patients possibly exposed to elemental phosphorus; serum potassium following barium carbonate exposure or phosphide compound ingestion; or glucose monitoring after Vacor ingestion).

•Observation for a minimum of six hours after exposure. If the patient has any symptoms of poisoning or abnormal findings on ancillary testing, then hospitalization is warranted. Otherwise, these patients may be discharged home after six hours of observation, as long as the clinical picture is unchanged and the possibility of exposure to any delayed-toxicity agents such as thallium, arsenic, SMFA, or fluoroacetamide can be excluded. However, given the high toxicity of all of these agents, a low threshold for admission and observation is appropriate for exposure to any highly toxic rodenticide.

●Other agents (signal word "Warning" or "Caution") – Small ingestions of agents such as alpha-naphthyl thiourea, cholecalciferol, bromethalin, or anticoagulant rodenticides are unlikely to cause any toxicity. In these cases, patients may be discharged home with further management determined according to the specific compound. (See 'Toxic ("Warning")' below and 'Less toxic ("Caution")' below.)

Serious poisoning has been described after large, intentional ingestions of anticoagulant and bromethalin rodenticides and is theoretically possible with other rodenticides such as red squill and cholecalciferol. These patients warrant gastrointestinal decontamination (eg, gastric lavage if presenting within one hour of ingestion and activated charcoal administration) and appropriate observation or follow-up depending upon the agent. (See 'Less toxic ("Caution")' below.)

Unknown poison — If the clinician strongly suspects ingestion of a highly toxic rodenticide other than elemental phosphorus, then we suggest that asymptomatic patients who have presented within one hour of ingestion should undergo gastric lavage followed by administration of activated charcoal with appropriate precautions to protect the airway and prevent aspiration as needed. Gastric lavage should not be performed in patients who have already vomited spontaneously. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Gastric lavage' and "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)

This recommendation is based upon trials that show improved outcomes with early gastric lavage in patients with potentially life-threatening ingestions and following administration of activated charcoal to agents that bind to charcoal (see "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects' and "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects'). However, benefit from this approach is variable for highly toxic rodenticides for which most evidence is observational. (See 'Highly toxic ("Danger")' below.)

All asymptomatic patients with exposure to an unknown rodenticide warrant the following studies:

●12-lead ECG and continuous monitoring

●Plain radiographs of the chest and abdomen

●Complete blood count

●Prothrombin time and international normalized ratio (PT and INR) and partial thromboplastin time (PTT)

●Blood glucose

●Serum electrolytes

●Venous or arterial blood gas

●Serum calcium and phosphorus

●Blood urea nitrogen (BUN) and serum creatinine

●Liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and bilirubin

Abnormal results can suggest specific rodenticides as follows:

●QTc prolongation on ECG – Arsenic, white (yellow) phosphorus, sodium monofluoroacetate (SMFA), or fluoroacetamide

●Hypocalcemia – White (yellow) phosphorus, SMFA, or fluoroacetamide

●Lactic acidosis – SMFA or fluoroacetamide

●Hyperphosphatemia – White (yellow) phosphorus

●Hypokalemia – Zinc or aluminum phosphide or barium carbonate

●Radiopaque substance on abdominal radiograph – Arsenic, thallium, or barium carbonate

●Elevated liver enzymes, BUN, or creatinine – Thallium, white (yellow) phosphorus, arsenic, or zinc or aluminum phosphide

●Hyperglycemia with ketoacidosis – Vacor

●Elevated PT and INR – Anticoagulant

Patients with any abnormality on ancillary testing warrant hospital admission for observation and supportive care of evolving toxicity. Specific treatment may also be indicated (table 1). (See 'Highly toxic ("Danger")' below and 'Anticoagulants (superwarfarins and warfarins)' below.)

Patients who remain asymptomatic with normal ancillary studies warrant hospital observation for up to 24 hours to exclude poisoning from SMFA or fluoroacetamide. Furthermore, all asymptomatic patients should undergo measurement of PT with INR and PTT at approximately 48 hours after exposure to identify anticoagulant rodenticide poisoning.

HIGHLY TOXIC ("DANGER") — These rodenticides can cause death in low doses and frequently require aggressive intensive care for patient survival. In some countries, they may be labelled with the signal word "Danger."

Thallium — Although banned for use in the United States and many other countries, thallium sulfate is a highly toxic yet effective rodenticide, which may be used in other parts of the world [10,11]. When used as a pesticide, it is a granular powder with no taste or odor. Thallium is well absorbed orally, via inhalation, and through intact skin. Ingestion of as little as 8 mg/kg has caused death in humans [12,13].

Despite rare use as a rodenticide, thallium poisonings do occur annually worldwide. They are usually caused by accidental contamination of grain or rice [14-16], intentional homicidal adulteration of food [17,18], and occupational exposures. The toxicity of thallium sulfate (and other inorganic thallium salts) stems from its displacement of potassium in enzyme systems and ion channels, causing global disruption of cellular energy production [19].

●Clinical manifestations and diagnosis – Based upon case reports and case series, a single large thallium exposure, as typically occurs with thallium-containing rodenticide poisoning, is associated with the following findings [14-17,19-22]:

•Early signs (up to 48 hours) – Abdominal pain, vomiting, constipation, and, less commonly, diarrhea are frequently noted within a few hours of ingestion. Tachycardia, hypertension, and chest pain may also occur.

•Intermediate signs (two days to two weeks) – Neurologic symptoms predominate later including the following:

-Very painful stocking-glove paresthesias

-Cranial nerve dysfunction with ptosis and nystagmus

-Optic neuritis

-Ataxia

-Choreoathetosis

-Cognitive and memory deficiency

-Delirium

-Psychosis

-Lethargy and coma

Other common findings include alopecia, classically sparing the inner third of the eye brows and axilla, darkening of hair roots, erythematous changes of the palms and soles, and hyperpigmentation with eczematous skin changes.

Acute kidney injury, hepatotoxicity, anemia, with thrombocytopenia, and hyperchloremic metabolic acidosis less commonly occur.

•Late – Permanent vision defects including optic atrophy with vision loss, central scotomata, cataracts, and blue vision loss are late effects of thallium poisoning.

Poisoning victims may die from sudden cardiac death or multi-organ failure weeks after exposure [12,17,23].

The diagnosis of thallium exposure is confirmed by atomic absorption spectrometry of a 24-hour urine sample [24]. Because it is radiopaque, thallium can be detected on radiographs of the abdomen [21]. Radiographs have also been used to identify adulterated food in cases of attempted homicide [23].

●Management – The management of thallium poisoning is based upon case reports and case series [14-17,19,20]. Clinicians managing patients with thallium poisoning are encouraged to consult a regional poison control center or medical toxicologist. (See 'Regional poison control centers' below.)

Treatment of thallium poisoning consists of the following:

•Supportive care – Provide supportive care of airway, breathing, and circulation as needed.

•Gastric emptying – Although rarely useful in most poisonings, gastric lavage is warranted for patients who present within one hour of ingestion of a large dose of thallium, based upon the high risk the patient will develop irreversible toxicity not amenable to standard therapy. However, gastric lavage is not necessary if spontaneous vomiting has already occurred. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Indications'.)

•Enhanced elimination – Gastrointestinal elimination of thallium is enhanced by one of the following regimens and should be performed [15,19,25,26]:

-Prussian blue (potassium ferric hexacyanoferrate, dose: 250 mg/kg per day divided into two or four doses) – Prussian blue may be administered with a cathartic, such as 15 percent mannitol in patients with constipation.

-Multiple dose activated charcoal (MDAC) with cathartic given with the first dose – Unlike most other heavy metals, thallium is well adsorbed to activated charcoal (AC). Thallium also undergoes significant enterohepatic circulation. Thus, MDAC may confer some benefit in removing thallium from the circulation and promoting fecal excretion [25,26].

Prussian blue is preferred by many experts because it has been shown to bind to thallium better than AC in vitro [25]. However, Prussian blue may not be immediately available in many health care facilities. In that situation, MDAC administration should be started as soon as possible until Prussian blue can be obtained.

•Whole bowel irrigation (WBI) – Although there is no proven benefit to whole bowel irrigation (rapid instillation of polyethylene glycol-electrolyte solution via NG or OG tube at 1 to 2 L/hr), this treatment may have a role in thallium poisoning when MDAC or Prussian blue administration are not possible. WBI cannot be performed simultaneously with MDAC, and should be reserved for patients in which this therapy cannot be tolerated. Moreover, in patients getting oral Prussian blue therapy, WBI cannot be given as it will limit absorption of the antidote.

•Extracorporeal removal – Based upon case reports, hemodialysis, charcoal hemoperfusion, and continuous renal replacement therapy can be used to enhance thallium clearance [27]. Of these techniques, hemodialysis is typically most readily available, the most effective means of expeditious toxin removal, and should be instituted as soon as possible for maximal clinical benefit [28].

Sodium monofluoroacetate and fluoroacetamide — Sodium monofluoroacetate (SMFA), also designated compound 1080 in the United States, is a highly lethal rodenticide [29]. It occurs naturally in a variety of poisonous plant species indigenous to Brazil, South Africa, and West Africa. As a rodenticide, it is used in several countries (eg, New Zealand, Australia, Mexico, and Israel) to control invasive mammal species (eg, possums in New Zealand and foxes in Australia) [29,30]. Collars impregnated with SMFA are used on livestock in the United States to protect them from coyotes. Although rare, poisonings with SMFA has been reported worldwide [30].

SMFA is an odorless, tasteless, water-soluble, white powder that has a very low LD₅₀ (2 mg/kg) [31]. It is easily absorbed through ingestion, inhalation, ocular exposure, and contact with open wounds. Very small exposures have caused fatalities in young children. It has also has gained mention as a potential agent of chemical terrorism [32].

Fluoroacetamide (compound 1081) is chemically and mechanistically similar to SMFA, with a slightly higher fatal dose and a more delayed onset of action.

Because they have chemical structures that mimic acetate, both SMFA and fluoroacetamide irreversibly inhibit the Krebs cycle. The mechanism of toxicity involves transformation of the parent compound to fluorocitrate which binds to the enzyme, aconitase, and stops the cycle [30]. As a result, cellular aerobic metabolism ceases and a variety of enzymatic systems are inhibited including fatty acid oxidation, gluconeogenesis, and the urea cycle. Blocking of the Krebs cycle at this step also causes accumulation of citrate which complexes with extracellular calcium leading to hypocalcemia and worsening metabolic acidosis [30,31]. Thus, the clinical consequences of SMFA and fluoroacetamide poisoning are far reaching, but the major clinical effects consist of severe lactic acidosis, hypocalcemia with seizures and dysrhythmias, and shock that is refractory to fluid resuscitation and inotropic support [30].

●Clinical manifestations and diagnosis – Because clinical toxicity is exclusively due to the fluorocitrate metabolite, even the most severe poisonings will exhibit a latent period until metabolite formation has occurred; the latent period is usually 30 to 180 minutes after SMFA exposure, but potentially delayed up to 20 hours after fluoroacetamide exposure [31].

Clinical findings include [30,33-35]:

•Respiratory distress

•Nausea and vomiting

•Diarrhea

•Abdominal pain

•Agitation

•Seizures

•Coma

•Hypotension that may be refractory to fluid resuscitation and inotropic support

•Lactic acidosis, hypokalemia, and hypocalcemia on measurement of blood gases and serum electrolytes

•QT segment prolongation on electrocardiogram (ECG) secondary to hypocalcemia

•Nonspecific ST and T wave abnormalities on ECG

•Arrhythmias, primarily ventricular tachycardia but including a variety of types, such as supraventricular tachycardia, atrial fibrillation, ventricular fibrillation, and asystole

Delayed sequelae may include acute kidney injury, hepatic dysfunction, cerebellar degeneration, cerebral atrophy, and neuropathy [30,35].

When fatal, SMFA toxicity has a fulminant clinical course; death usually ensues within 72 hours and is secondary to persistent shock or cardiac arrhythmias [30]. The best predictors of mortality in one case series were elevated creatinine, decreased pH, and hypotension [33].

Both SMFA and fluoroacetamide are detectable in blood and urine using thin layer chromatography or gas chromatography with mass spectrophotometry [36]. However this testing cannot be performed quickly enough to be clinically useful. Thus, the diagnosis is usually made based upon clinical features.

●Management – A regional poison control center or medical toxicologist should be consulted for all exposures. (See 'Regional poison control centers' below.)

Treatment of SMFA and fluoroacetamide toxicity is primarily supportive as follows [30,36]:

•Gastric lavage for patients who present for treatment less than one hour after ingestion. Lavage is not necessary if spontaneous vomiting has occurred. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Gastric lavage'.)

•Activated charcoal (AC) administration for patients in whom it can be given safely; SMFA and fluoroacetamide bind to activated charcoal and may be beneficial. However, the airway should be secured in unstable patients (eg, altered mental status, hypotension, or respiratory distress), prior to giving AC. It has the greatest benefit if given within one hour of ingestion. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)

•Repeated measurement of venous or arterial blood gases and electrolytes; hypocalcemia should be treated with intravenous calcium. Metabolic acidosis is frequently severe enough to require treatment with sodium bicarbonate. Hypokalemia from frequent vomiting requires potassium repletion.

•Cardiac arrhythmias should be treated according to Advanced Cardiac Life Support and Pediatric Advanced Life Support guidelines (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Correction of hypocalcemia, hypokalemia, and/or acidosis is frequently needed for successful treatment.

•Shock often requires fluid resuscitation and, if hypotension persists, inotropic support. (See "Shock in children in resource-abundant settings: Initial management", section on 'Clinical and physiologic targets' and "Definition, classification, etiology, and pathophysiology of shock in adults".)

•Seizures secondary to hypocalcemia warrant prompt intravenous infusion of calcium. Otherwise, they should be initially treated with benzodiazepines (eg, lorazepam 0.1 mg/kg intravenous; maximum dose 4 mg) (table 2 and algorithm 5 and algorithm 6).

Specific antidotal agents to counteract the biochemical effects, such as ethanol, sodium succinate, and glycerol monoacetate, are purely experimental and have only been used in animal studies [30-32]. They should be administered only after consultation with a regional poison control center or medical toxicologist, whenever possible. (See 'Regional poison control centers' below.)

Asymptomatic patients who present after SMFA exposure should be observed for up to 24 hours to ensure any latent period has expired.

Strychnine — Strychnine is still used worldwide as a rodenticide in pellet form, with specific indications for both mice and gophers. Some rodenticide formulations of strychnine are sold as bright pink tablets, making them appealing to small children. Most commonly found in crystalline or powder form, strychnine is both colorless and odorless, but is known for its bitter taste when dissolved in water.

The mechanism of strychnine toxicity involves competitive inhibition of glycine receptors at the postsynaptic and motor neuron level. Because glycine is an inhibitory neurotransmitter, this receptor blockade leads to a subsequent increase in the downstream firing of muscle fibers and involuntary muscle contraction. (See "Strychnine poisoning", section on 'Pharmacology and cellular toxicology'.)

●Clinical manifestations and diagnosis – The onset of symptoms from strychnine poisoning usually occurs within 10 to 20 minutes of ingestion. However, injection or inhalation may result in more rapid development, and dermal exposure may produce a delayed onset. Physical findings consist of the following (see "Strychnine poisoning", section on 'Clinical features of overdose'):

•Prodromal signs may include mydriasis, hypervigilance, anxiety, hyperreflexia, clonus, and stiffness of the facial and neck muscles.

•Classic findings consist of repetitive facial grimacing (risus sardonicus), trismus, and full-body opisthotonus, which can be mistaken for seizure activity. Because strychnine's effects occur primarily at the level of the spinal cord, the patient is often awake during and after the episodes. Complications of toxicity result from excessive muscle activity and include rhabdomyolysis, lactic acidosis, and hyperthermia. Spasm of respiratory muscles may lead to respiratory failure and inability to mechanically ventilate, resulting in death.

The diagnosis of strychnine poisoning relies on clinical findings. Strychnine can be detected in blood and urine for forensic purposes.

●Management – Early consultation with a regional poison control center or medical toxicologist is advised for all patients. (See 'Regional poison control centers' below.)

The management of strychnine poisoning is discussed separately. (See "Strychnine poisoning", section on 'Management'.)

Zinc and aluminum phosphide — Commonly found in powder, pellet, or tablet form, the metallic phosphides, zinc and aluminum phosphide, are both low-cost and highly toxic rodenticides. Metallic phosphides are used worldwide to protect grains from rodents and other pests during transportation and storage [37]. Trade names of preparations include Gopha Rid, Mouse-con, and Mr. Rat Guard.

Inhalation of phosphine gas, produced when aluminum or zinc phosphide is exposed to moisture in stored grain, represents the most common form of exposure. Oral exposures from deliberate suicidal ingestions with aluminum phosphide are common in northern India [38,39]. Risk factors for death after intentional poisoning include dose (≥500 mg of phosphides), hypotension, acidosis, hypoxia, global left ventricular hypokinesis, and left ventricular ejection fraction <40 percent [40]. Ingestion of fresh phosphide rodenticide in the original packaging is most potent. Metallic phosphides that have been opened become less toxic with time because water in the air causes conversion of the phosphides to phosphine gas which dissipates [39].

Although phosphine gas is known to have an odor similar to rotten fish and is detectable to some at a concentration of 2 ppm, it is not a reliable early warning sign of exposure [41]. While the odor is neither sensitive nor specific for phosphide poisoning, it may help substantiate the diagnosis of metallic phosphide poisoning when obtained on history or present on evaluation of patient emesis.

Upon ingestion, phosphides are converted by gastric acid to phosphine gas, the primary toxic agent [42]. Subsequently phosphine gas is absorbed from the gastrointestinal tract into the blood stream. Phosphine gas released from treated grains in silos and other agricultural sites can cause toxicity through inhalation and dermal exposure. Several mechanisms of toxicity have been proposed, including inhibition of oxidative phosphorylation, free radical production with promotion of lipid peroxidation, and cholinesterase inhibition but none fully explain the clinical features of poisoning [39,43]. Mortality often occurs rapidly within the first day of severe metallic phosphide poisoning regardless of therapy. Death typically results from cardiac arrhythmias or refractory shock and cardiac failure [39,44-46].

●Clinical manifestations and diagnosis – Phosphide toxicity occurs rapidly, typically within 30 minutes of exposure. Clinical findings of zinc phosphide ingestion consist of the following [39]:

•Gastrointestinal (GI) irritation marked by nausea, vomiting, hematemesis, and retrosternal chest and abdominal pain

•Shock with refractory hypotension caused by direct cardiac toxicity

•Cardiac arrhythmias, including bradycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular arrhythmias

•Hemorrhagic pulmonary edema with tachypnea, cough, acute respiratory distress syndrome, and respiratory failure

•Less common features include hepatotoxicity, intravascular hemolysis with methemoglobinemia and/or renal failure

The diagnosis of phosphide poisoning is made by history and characteristic clinical signs. Exposed patients may also exhibit hypokalemia and elevated lactate concentrations, although these findings are not diagnostic. Based upon case reports, zinc phosphide is radiopaque and, when positive, abdominal radiographs can help confirm the diagnosis and support specific management [47,48].

●Management – Early consultation with a regional poison control center or medical toxicologist is advised for all patients. (See 'Regional poison control centers' below.)

Of note, phosphine may be released as a gas from emesis, feces, or lavage material and can cause respiratory distress in health care providers and other exposed persons [49]. Thus, these patients should be managed in negative pressure rooms and emesis and feces from the poisoned patient should be disposed of in closed containers. However, serious toxicity in health care providers caring for patients poisoned with metallic phosphides has not been described [39]. The management of phosphide ingestion is based upon limited evidence derived from case reports.

For phosphide ingestion, supportive care is the mainstay of treatment and consists of the following [39]:

•Provide supplemental oxygen and ventilation as needed and dictated by the degree of respiratory compromise. Tracheal intubation may be performed in standard fashion.

•Provide fluid resuscitation with rapid infusions of isotonic normal saline to replace obvious fluid losses and to treat hypovolemic shock.

•Treat hypoglycemia and correct hypokalemia and hypomagnesemia as indicated. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Severe or symptomatic hypokalemia' and "Approach to hypoglycemia in infants and children", section on 'Treatment' and "Hypomagnesemia: Evaluation and treatment".)

•Treat cardiogenic shock with vasoactive medications as needed in patients unresponsive to isotonic fluid resuscitation. (See "Treatment of acute decompensated heart failure: Specific therapies" and "Use of vasopressors and inotropes" and "Shock in children in resource-abundant settings: Initial management".)

•Manage atrial and ventricular arrhythmias according to Advanced Cardiac Life Support and Pediatric Life Support guidelines (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4).

Additional therapies have been described but we strongly encourage consultation with a regional poison control center or medical toxicologist, whenever possible, before giving these treatments. Of these, magnesium infusion appears to be of greatest potential benefit.

Adjunct therapies include the following (see 'Regional poison control centers' below):

•Magnesium infusion – Case series have documented hypomagnesemia in some patients poisoned with metallic phosphides. Hypomagnesemia should be corrected in all patients with metallic phosphide poisoning. Nevertheless, studies of treatment with intravenous magnesium have yielded mixed results [39,50]. Small trials suggest intravenous magnesium administration can decrease mortality, if hypomagnesemia is identified and the regimen chosen raises the magnesium concentration [51,52]. In these trials, the regimen with the best effect was as follows: 1 g magnesium sulfate, intravenously followed one hour later by 1 g given as a continuous infusion over three hours and then 1 g every six hours until recovery or a maximum duration of five days.

•Insulin and dextrose infusion – Insulin infusion combined with maintenance of normal blood glucose using a continuous dextrose infusion was associated with survival in four of five patients with large ingestions of aluminum phosphide [39]. Thus, this therapy may be beneficial in patients who are not responding to supportive care and who are unlikely to benefit from magnesium infusion.

•Gastrointestinal decontamination – Case reports and animal studies describe the use of a variety of measures to prevent absorption of phosphine including coconut oil lavage to prevent phosphine gas production, oral or gastric tube administration of sodium bicarbonate, lavage with potassium permanganate, or administration of activated charcoal [39,53]. However, none has demonstrated clear benefit, and we avoid routine use of these interventions. Furthermore, vomiting often precludes or preempts any attempts at gastrointestinal decontamination.

•Other therapies – Individual case reports describe the use of N-acetylcysteine (NAC) as an antioxidant and the antianginal agent trimetazidine to maintain oxidative phosphorylation [54,55]. Additional study is needed to determine the role of either agent in the treatment of phosphide poisoning.

Elemental phosphorus — Elemental phosphorus is a nonmetallic substance that exists in two common forms, red and white (or "yellow" phosphorus). The red form, commonly used in match-tip production, is not absorbed and has very limited toxicity. The white form, a yellowish, waxy solid, is highly toxic and was formerly used worldwide in a large number of rodenticide preparations. Despite the decrease in use, rodenticides remain the most readily available source of yellow phosphorus today, containing 2 to 5 percent yellow phosphorus [56]. Intentional ingestion of firecrackers by suicidal patients and exploratory firework ingestion in children has also been reported [57,58]. Phosphorous is known for its luminescent properties, once exposed to oxygen, as well as a faint garlic odor. It causes significant local as well as systemic toxicity [59]. The LD₅₀ for acute exposure is approximately 1 mg/kg [60].

Phosphorus is readily and most commonly absorbed via the gastrointestinal (GI) tract. Dermal exposure causes burns and systemic effects. Once in the bloodstream, renal and hepatic phosphorus concentrations are elevated within hours [61]. The mechanism by which ingested (white) phosphorus causes tissue damage are direct tissue toxicity caused by an exothermic reaction, local production of phosphoric acid leading to tissue corrosion, and formation of phosphorus pentoxide which reacts with organic molecules [62,63]. Phosphorus is also caustic to the skin and eyes and poses a significant risk of fire and explosion when exposed to air. In the circulation, phosphorus binds to calcium and can cause life-threatening hypocalcemia [64].

●Clinical manifestations and diagnosis – Clinical manifestations are classically described in three phases as follows [57]:

•Phase one occurs minutes to hours after the ingestion. Initial findings consist of perioral and mucosal burns, nausea, vomiting, and diarrhea. A garlic odor on the breath may also be noted. The feces or vomitus may exhibit phosphorescence, sometimes labeled the "smoking stool syndrome" [59]. Mortality in this stage is due to cardiovascular collapse and ventricular dysrhythmias.

•Phase two, if present, consists of a latent period of up to several weeks in which symptoms seem to resolve.

•Phase three is marked by systemic toxicity that involves multiple organ systems such as the GI tract, liver, heart, kidneys, and brain [65]. Hepatotoxicity with jaundice and hypoglycemia and acute kidney injury with renal failure are most commonly described [57].

Individual patients may or may not display all phases of toxicity. Overlap of toxic findings between phase I and phase III or absence of a latent period is common.

Inhalation of white phosphorus can cause lung irritation and respiratory distress [57].

Diagnostic testing for phosphorus toxicity is of limited utility, and focus should instead be on detailed history and physical exam in cases where clinical suspicion is high. Monitoring of vital signs as well as electrolytes, especially serum potassium, calcium and phosphorus, is essential [60].

●Management – Early consultation with a regional poison control center or medical toxicologist is advised for all patients. (See 'Regional poison control centers' below.)

If dry and exposed to air, white phosphorus poses a risk of burns and fire. Health care providers should ensure that all clothing is removed and soaked with water to prevent spontaneous ignition. Elemental phosphorus on the patient's skin should be copiously irrigated with water or saline. Wounds should be covered with saline-soaked gauze to prevent drying. White phosphorus particles embedded in wounds must be kept wet; particles will reignite if allowed to dry. Immediate surgical debridement is often necessary and repeated debridements may be needed to remove all phosphorus particles. (See "Topical chemical burns: Initial evaluation and management", section on 'White phosphorus'.)

Healthcare providers must take special precautions to be sure that they do not handle dry white phosphorus or get it on their clothing. In addition, patient emesis and feces should be disposed of carefully in concert with institutional policies for disposition of hazardous waste.

Further management consists of the following:

•Although gastric lavage and activated charcoal are recommended by some experts for "large" ingestions [66], these should be cautiously employed, if at all, because vomiting caused by these treatments may cause additional mucosal burns. Also, spontaneous vomiting frequently occurs and preempts any need for gastric emptying. In addition, a case report describes a fire and an explosion associated with an attempt at passing a nasogastric tube [67].

•Patients warrant close monitoring of serum potassium, calcium, and phosphorus concentrations with rapid treatment of hypocalcemia or hyperkalemia. (See "Treatment of hypocalcemia", section on 'Therapeutic approach' and "Treatment and prevention of hyperkalemia in adults", section on 'Patients with a hyperkalemic emergency' and "Management of hyperkalemia in children", section on 'Initial emergent therapy'.)

•Liver failure frequently occurs and requires supportive management. (See "Acute liver failure in adults: Management and prognosis", section on 'General management' and "Acute liver failure in children: Management, complications, and outcomes", section on 'General management principles'.)

•N-acetylcysteine has been suggested as theoretically beneficial but limited evidence does not show improved outcomes in poisoning [68].

Arsenic — Arsenic-based rodenticides have been in use since the 1860s, although many have been banned in developed countries [69]. Most arsenical pesticides contain the soluble salt, arsenic trioxide, a highly toxic inorganic compound with an LD₅₀ of 14 mg/kg [70].

●Clinical manifestations and diagnosis – After an acute ingestion, patients initially exhibit gastrointestinal symptoms such as nausea, vomiting, and watery diarrhea over the first one to three hours. Clinicians may detect a garlic odor on the breath and in stools after large ingestions. These symptoms are soon followed by dehydration and hypotension. Acute arsenic poisoning can also result in QTc prolongation with subsequent torsades de pointes. In severe cases, patients may experience cardiac arrhythmias, shock, acute respiratory distress syndrome, and sometimes death. In some cases, acute encephalopathy can develop and progress over several days, with delirium, coma, and seizures. There have also been reports of persistent central nervous system symptoms such as headache, confusion, and memory problems. Renal injury can lead to proteinuria, hematuria, acute tubular necrosis, and anuria.

Chronic effects can occur as the sequelae of acute poisoning (as discussed above) or as the result of chronic longer-term exposure to lower arsenic doses. The clinical effects of chronic toxicity can have an insidious onset and thus be more difficult to diagnose. The findings of chronic arsenic exposure are discussed separately. (See "Arsenic exposure and chronic poisoning", section on 'Clinical features and latent effects of chronic exposure'.)

In the case of an acute ingestion, abdominal radiographs may demonstrate gastrointestinal radiopaque material soon after ingestion, although the absence of opaque material does not rule out exposure. An electrocardiogram should be obtained to assess the QTc interval and continuous cardiac monitoring performed for rapid detection of tachyarrhythmias. In general, measurement of arsenic concentrations in urine is preferable to blood, since blood arsenic is cleared rapidly. In the emergent situation, a spot urine arsenic can be obtained prior to beginning chelation therapy. The urine creatinine in the spot sample should also be obtained to correct for urine concentration. During treatment, 24-hour urine arsenic monitoring is usually performed to follow the amount of arsenic excretion over time.  

The diagnostic evaluation for suspected chronic exposure is discussed separately. (See "Arsenic exposure and chronic poisoning", section on 'Diagnosis'.)

●Management – Acute arsenic toxicity can be life-threatening, requiring decontamination, aggressive cardiopulmonary support, and possible administration of chelation therapy. Since arsenic concentration results are typically not immediately available, treatment decisions must be based upon the history, physical examination, and the degree of clinical toxicity and suspicion for arsenic poisoning [71,72]. (See "Arsenic exposure and chronic poisoning", section on 'Management'.)

Early consultation with a regional poison control center or medical toxicologist is advised for all patients. (See 'Regional poison control centers' below.)

Barium carbonate — In contrast to barium sulfate, the insoluble salt used in radiographic contrast medium, the soluble salts of barium are highly toxic due to their easy dissolution to ionic barium in the presence of water [73]. These include barium carbonate, sulfide, chloride, chlorate, and nitrate, of which barium carbonate has been most often used as a rodenticide. It has largely fallen out of use. Exposures still occur, however, with ingestion of a rodenticide product or food-poisoning outbreaks [74,75]. Toxicity has occurred from ingestion of as little as 200 mg of soluble barium [73].

Barium competitively inhibits potassium efflux channels, causing sequestration of total body potassium stores in the intracellular compartment. The sodium-potassium adenosine triphosphate (ATP) pump function continues unchanged, however, causing further potassium influx and severe hypokalemia [76,77]. As a result, the decreased resting potential of cell membranes renders myocardial cells more prone to arrhythmias and causes skeletal muscle paralysis. Vascular smooth muscle may also be affected. Hypertension is also a common finding.

●Clinical manifestations and diagnosis – Clinical signs of toxicity occur soon after ingestion. They begin with vomiting, diarrhea, and abdominal pain, and progress to generalized weakness, muscle twitching, and focal or generalized paralysis [73,76-82]. Hypertension is often seen, as are malignant ventricular arrhythmias that arise from severe hypokalemia. Treatment of hypokalemia is essential for the management of cardiac arrhythmias but, based upon case reports, may not treat muscle weakness or hypertension [75,78].

Laboratory assessment of the patient with barium poisoning should begin with immediate measurement of electrolytes, repeated hourly, for hypokalemia and other electrolyte disturbances. A mild lactic acidosis is often present.

Electrocardiogram (ECG) findings include diffuse ST-segment depressions, flattened T waves, and U waves (figure 1), as would be expected in patients with hypokalemia [73,76]. Abdominal radiography may show opaque material, but not reliably so.

Barium concentrations in the blood, serum, and urine can be obtained, but neither correlate with toxicity nor provide timely information to guide management. Thus, history of ingestion along with characteristic clinical findings, especially profound hypokalemia, most frequently provide the diagnosis.

●Management – Early consultation with a regional poison control center or medical toxicologist is advised for all patients. (See 'Regional poison control centers' below.)

Patients often have existing or progressive paralysis that requires endotracheal intubation and mechanical ventilation. Additional treatment consists of the following [73,75,76,78-82]:

•Oral administration of magnesium or sodium sulfate solutions is recommended to promote the precipitation of ionic barium into nontoxic barium sulfate. For this indication, the oral dose of magnesium sulfate is 250 mg/kg for children and 30 g for adults. Activated charcoal has no role as it does not bind barium salts. Intravenous administration of magnesium sulfate is not recommended because precipitation in renal tubules has led to acute kidney injury.

•Beyond this, correction of hypokalemia is the mainstay of therapy in barium poisoning. Extremely high doses of IV potassium may be required; multiple reports exist of patients getting over 300 mEq of IV potassium supplementation over 24 hours with incomplete resolution of toxicity or persistent hypokalemia [76].

•In the patient with refractory hypokalemia or persistent respiratory muscle paralysis despite potassium therapy, renal replacement therapy is warranted and can significantly accelerate removal of barium and produce more rapid resolution of hypokalemia and recovery. Both intermittent hemodialysis and continuous venovenous hemodiafiltration have been successful.

Survival is likely if aggressive treatment of respiratory failure and electrolyte imbalances is provided. Toxicity generally resolves in one to two days after ingestion [73,75,81].

Rarely used or banned compounds — Although certain agents are infrequently used or outright banned for use in much of the world, cases of poisoning do occasionally occur from these agents, and the clinician should be aware of their toxicity.

Tetramethylene disulfotetramine (TETS, tetramine) — Globally banned for use and illegal for sale, this Chinese rodenticide is easy to synthesize and, according to some reports, is still the most common cause of fatal rodenticide poisoning in mainland China [83-85]. Often sold under the name "Dushuquiang" ("very strong poison"), it is more toxic to humans than compound 1080, the most toxic pesticide registered by the World Health Organization, with a lethal dose (LD₅₀) of 0.1 to 0.3 mg/kg in mammals [86]. As little as 7 mg (or a small taste) may be lethal in humans [85]. Most poisoning cases occur via malicious exposures, such as in the case of a Chinese restaurant owner who poisoned a competing restaurant in 2002, sickening dozens and killing 48 [6,7]. Similar to picrotoxin, tetramine is an irreversible antagonist of the GABA receptor.

●Clinical manifestations – Features of poisoning include vomiting, headache, dizziness, perioral paresthesias, weakness, and lethargy [85]. Severe poisoning causes tachycardia, palpitations, cardiac arrhythmias, and refractory status epilepticus. Onset of symptoms may begin within 10 minutes of ingestion or be delayed up to 13 hours after exposure. Other acute clinical sequelae include liver failure with coagulopathy and rhabdomyolysis with acute kidney injury [85,87]. Long-term follow-up of patients sickened by tetramine suggests that patients may develop chronic seizure disorders, cognitive impairment, and cortical blindness [87,88].

●Management – Consultation with a regional poison control center and/or medical toxicologist is strongly encouraged. (See 'Regional poison control centers' below.)

Treatment is based upon case reports and should be directed at gastrointestinal decontamination and control of seizures as follows [85,87]:

•If spontaneous vomiting has not already occurred, patients who present within one hour of ingestion should undergo gastric lavage with protection of the airway by endotracheal intubation as needed.

•Activated charcoal (AC) should be given to all patients who present within one hour of ingestion and, after consultation with a regional poison control center or medical toxicologist, may be appropriate in selected patients who present more than one hour after ingestion. Safe administration of AC in patients with altered mental status or seizures warrants endotracheal intubation for airway protection prior to administration via a gastric tube.

•Seizure management consists of first-line treatment with benzodiazepines. Continued seizures should be treated with phenobarbital and then continuous infusion of an anti-epileptic agent (eg, midazolam or, in patients older than two years of age, propofol) per recommended regimens for status epilepticus (algorithm 6 and table 2). High doses of pyridoxine (eg, 70 mg/kg, maximum dose 5 g) are also appropriate when ingestion of isoniazid is a possibility and, when given with chelation therapy, have been associated with significantly decreased mortality in one animal model of tetramine poisoning [89] and 100 percent survival in two small human case series [85]. (See "Isoniazid (INH) poisoning", section on 'Pyridoxine'.)

•Based upon studies in animals and human case series [85,89], acute administration of 2,3-dimercaptopropane-1-sulfonate, if available, may be beneficial in cases of refractory status epilepticus. Dosing in adults is as follows: DMPS, 125 to 250 mg intramuscularly every 30 minutes to one hour until convulsions stop. No dosing information is available for children with tetramine poisoning.

While DMPS is not available as a medication in the United States, oral succimer (DMSA) is a potential alternative However, the practical limitations of administering an oral drug to a seizing patient may limit its usefulness.

•Extracorporeal removal with hemodialysis or charcoal hemoperfusion have been reported but evidence is insufficient to suggest that either method is associated with improved outcomes. [85,87]

Aldicarb — Although not legal for use as a rodenticide, the potent carbamate cholinesterase inhibitor, aldicarb, has been associated with outbreaks of rodenticide poisoning both in the United States and elsewhere [90-92]. It is often sold under the name "Tres Pasitos" and imported unlawfully from Latin American countries, where it is legal for sale. The name, meaning "three little steps," denotes the rapidly lethal effects on mice rendered unable to stumble more than three steps from ingestion to death.

An extremely potent cholinesterase inhibitor, aldicarb is rapidly and well absorbed orally [93], with an LD₅₀ in humans of 0.8 mg/kg. In one series of aldicarb rodenticide poisonings, the case-fatality rate was 4 percent and included both suicidal ingestions as well as an exploratory ingestion in a young child [92]. Symptoms after exposure include the cholinergic toxidrome, similar to that seen after organophosphorus insecticide poisoning (table 3). Treatment is the same as for other cholinesterase inhibitor poisoning and includes high doses of atropine and pralidoxime. Death occurs from severe bronchorrhea and respiratory muscle weakness, but usually only when the diagnosis and/or treatment is delayed.

The management of aldicarb and other carbamate poisonings is discussed in detail separately. (See "Organophosphate and carbamate poisoning", section on 'Management'.)

Alpha-chloralose — Used primarily in Europe as a rodenticide and avicide, alpha-chloralose is a central nervous system (CNS) depressant and veterinary anesthetic. Reports of severe human toxicity are rare, but do occur, usually with massive ingestions [94-96]. Clinically, patients exhibit CNS depression, coma, and myoclonus. Patients may die from respiratory insufficiency [94,95].

Management consists of gastric lavage if the patient presents within one hour of ingestion and aggressive treatment of seizures (table 2). Patients with altered mental status warrant endotracheal intubation for airway protection prior to lavage. Activated charcoal may also be of benefit in the patient with a protected airway and recent ingestion. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Gastric lavage'.)

Salmonella-based rodenticides — Although generally regarded as unjustifiably hazardous to human health, the use of Salmonella enteritidis-coated rice grains as a rodenticide still persists in some regions, most notably in South America. Originally sold under the name Ratin in Europe and the United States, it was withdrawn from use due to the pandemic infectious hazard posed to human populations. However, Biorat, the preparation still in use, contains the same strain of S. enteritidis as previously used and is likely equally unsafe [97,98].

The clinical manifestations and treatment of S. enteritidis infection is discussed separately. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage", section on 'Management'.)

Vacor — Vacor (Pyriminil, N-3-pyridylmethyl-N-p-nitrophenylurea, PNU) is no longer available due to its severe human toxicity. It was originally released in 1975 as Vacor Rat-Killer (Rohm and Haas Company, Philadelphia) as a single-dose rodenticide and tracking powder, but was withdrawn for general use in 1979. Its appearance is similar to cornmeal, and both intentional and accidental exposures were reported up until the 1980s because of availability of old product in some households [99]. Symptoms have occurred with as little as 5 mg/kg exposure and death reported after ingestion of less than one, 3 g packet.

Vacor is similar to streptozocin and pentamidine in that it destroys pancreatic beta islet cells, bringing about diabetic ketoacidosis within hours of exposure. A nicotinamide antagonist, it impairs the synthesis of NAD and NADH required for cellular energy metabolism, which may explain its ability to cause global autonomic, peripheral, and CNS dysfunction [9,100].

●Clinical manifestations and diagnosis – Acutely, the patient with Vacor exposure has hyperglycemia, acidosis, and significant postural hypotension, which can persist for months or indefinitely. Peripheral and cranial neuropathies, weakness, pupillary dysfunction, anhidrosis, and impotence have all been reported [9,100]. Mental status changes can range from mild somnolence to overt encephalopathic delirium [9].

Diagnosis of Vacor ingestion is made based upon history and clinical findings.

●Management – Vacor is a very rare poisoning. Consultation with a regional poison control center or medical toxicologist is advised for all exposures. (See 'Regional poison control centers' below.)

Activated charcoal (AC) effectively binds to Vacor and should be given to all patients who present within one hour of ingestion. After consultation with a regional poison control center or medical toxicologist, administration of AC more than one hour after ingestion may be appropriate in selected patients. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)

Specific therapy of Vacor poisoning is directed towards preventing nicotinamide antagonism, by administration of nicotinamide 500 mg IV slow push initially, then 100 to 200 mg IV every four hours for 48 hours [9,100]. Smaller doses are advised in pediatric patients, but no specific dosing guidelines exist. If niacinamide is unavailable, niacin may be substituted, but will exacerbate hypotension and may be less effective. Orthostatic hypotension has been successfully treated with fluids, mineralocorticoids (eg, hydrocortisone), and dihydroergotamine mesylate [101].

TOXIC ("WARNING") — Although potentially toxic after an acute ingestion, alpha-naphthyl thiourea and cholecalciferol are unlikely to cause more than minor effects, even in large doses. Small exposures which occur under clear circumstances can be managed at home, or if presenting to a healthcare facility can be observed for only a brief period.

The appearance, clinical findings, and management for these compounds are as follows:

●Alpha-naphthyl thiourea – Alpha-naphthyl thiourea (ANTU) is a selective rodenticide, lethal only to adult Norway rats and some species of dog. A greyish, heat-stable, odorless powder, ANTU mixes easily with cereal or corn baits to induce respiratory failure after one feeding [102]. In target species, disruption of vascular endothelium causes rapid onset of pulmonary edema and pleural effusions. Although human pulmonary toxicity is possible, there is a remarkable absence of severe cases in the literature, despite widespread use [103]. One case series describes patients with suicidal ingestion of ANTU and chloralose who manifested more pulmonary hypersecretion than would have been expected with chloralose alone; however, all patients survived, despite large amounts ingested [1]. The LD₅₀ in man is quite high, approximately 4 g/kg [104].

Supportive care is the mainstay of treatment after ANTU exposure. Activated charcoal will bind to ANTU and should be given if the patient presents for care within one hour of ingestion and is awake and alert.

●Cholecalciferol – Cholecalciferol, vitamin D3, was first developed by Bell Laboratories as a rodenticide in 1984 and sold under the brand names Quintox and Rampage. Exploiting the rodent's specific vulnerability to small changes in calcium homeostasis, it causes death within two to five days from dehydration, organ calcification, and dysrhythmias. Because death is not immediate and it does not impart an unusual taste or appearance to food, it does not induce bait shyness, as is seen with phosphides, strychnine, and alpha-naphthyl thiourea. It is used by both the general public as well as commercial exterminators, and often sold in 30 g packs of pellets. One pellet contains approximately 2300 International Units (IU) of vitamin D.

Vitamin D3 brings about hypercalcemia by promoting calcium mobilization from bone and increasing intestinal absorption. Although there are no human case reports of hypervitaminosis D from a rodenticide exposure, it is well described with vitamin D supplementation errors. Usually, human toxicity involves a chronic ingestion of >50,000 IU daily. Calcium concentrations over 11.5 mg/dL cause anorexia, fatigue, disorientation, polyuria, vomiting, nephrocalcinosis, and renal insufficiency [105].

If there is a history of only a small ingestion, no further evaluation is indicated. After a significant exposure (ie, daily dose >50,000 IU) patients should be monitored for symptoms of hypercalcemia, and serum calcium concentrations obtained at presentation. A normal serum calcium concentration at 48 hours after exposure precludes the development of toxicity. Patients with hypercalcemia should be managed according to the degree of serum calcium elevation as discussed separately. (See "Treatment of hypercalcemia", section on 'Preferred approach'.)

LESS TOXIC ("CAUTION") — These agents are typically nontoxic when ingested in small amounts such after an exploratory ingestion in a child. However, anticoagulant rodenticides and bromethalin can cause serious toxicity when consumed in large amounts such as after a suicidal overdose in an adolescent or adult.

Anticoagulants (superwarfarins and warfarins) — The clinical manifestations, diagnosis, and management of anticoagulant rodenticide (also called long-acting anticoagulant rodenticide; LAAR) poisoning is discussed separately. (See "Anticoagulant rodenticide poisoning: Clinical manifestations and diagnostic evaluation" and "Anticoagulant rodenticide poisoning: Management".)

Bromethalin — Bromethalin was developed by Eli Lilly in the mid-1970s and first became commercially available approximately 10 years later. It was not until the late 1990s that bromethalin was widely available for use and, thus, had its first reports of human toxicity [106]. Sold under trade names including Assault, Vengeance, and Trounce, bromethalin is considered a very effective single-feeding rodenticide, causing death within 15 to 60 hours of exposure [107]. Although the LD₅₀ for humans has not been established, a number of animal studies exist showing a LD₅₀ ranging from 1.8 mg/kg in the common house cat to 13 mg/kg in a field rabbit [108]. Of note, guinea pigs exposed to a dose greater than 1000 mg/kg demonstrated no signs of toxicity.

●Toxicity – Based upon animal studies in the dog and rodent, bromethalin and its more active metabolite, desmethyl-bromethalin, exert their toxic effects by the uncoupling of mitochondrial oxidative phosphorylation, leading to a decrease in the production of adenosine triphosphate (ATP). The lack of ATP causes increased fluid around the neuron myelin sheaths in the brain and spinal cord [107,108]. Increased intracranial pressure (ICP) subsequently develops [109]. In a fatal case of bromethalin ingestion in a human, microscopic evaluation of the brain showed vacuolization of the white matter consistent with findings in other animal species [110]. Animal models indicate that seizures may occur as well [107-109].

●Clinical manifestations – Most patients with a low-dose, unintentional bromethalin exposure will develop no symptoms [111]. When present, the most common symptoms reported to poison control centers after unintentional ingestions are minor and include vomiting, nausea, mild drowsiness, lethargy, and/or abdominal pain. Among adolescents and adults with intentional bromethalin exposure, most are also asymptomatic or have minor symptoms as previously described for unintentional ingestion.

However, serious neurologic toxicity can occur, including agitation, hallucinations/delusions, coma, seizures, and, rarely, death [111]. For example, after an intentional ingestion of about 17 mg of bromethalin, a 21-year-old male developed progressive coma, increased intracranial pressure, and cerebral edema; and ultimately died [110].

Patients with intentional exposure and any patients who develop symptoms after exposure warrant referral to a health care facility.

●Management – Management of bromethalin ingestion depends upon the estimated dose and circumstances surrounding the exposure:

•Pediatric unintentional exposure – Unintentional bromethalin exposures in children usually result in no symptoms and may be monitored at home [111,112]. For example, in a retrospective study of almost 2500 unintentional bromethalin exposures reported to United States regional poison control centers, about 93 to 98 percent of children (≤12 years of age) were asymptomatic, and none had more than moderate effects [111].

•Intentional and symptomatic exposures – Although the likelihood of serious toxicity is low, all patients with intentional and symptomatic exposures require evaluation at a health care facility. Awake and alert, symptomatic patients and those with large or intentional ingestions who present within one hour of ingestion warrant treatment with a single dose of activated charcoal.

Otherwise, management is supportive [111]:

-Antiemetics (eg ondansetron) for vomiting

-Intravenous fluid as needed for dehydration associated with vomiting and diarrhea

-Benzodiazepines as initial treatment for seizures

-Protection of the airway in patients with altered mental status or coma and management of intracranial pressure [113] (see "Evaluation and management of elevated intracranial pressure in adults" and "Elevated intracranial pressure (ICP) in children: Management")

Other low toxicity rodenticides — Other low toxicity rodenticides that rarely result in serious poisoning include norbormide, and red squill. Norbormide and red squill have no reports of death after ingestion.

Clinical manifestations of these compounds are as follows:

●Norbormide – Introduced by McNeil Laboratories in 1964 under the trade names "Shoxin" and "Raticate," norbormide is known for its selective toxicity to rats, but is virtually harmless to humans, animals, and other rodent species. The mechanism by which it exerts its effects is through severe and irreversible vasoconstriction of the small caliber vessels, leading to tissue hypoperfusion and subsequent organ failure [114]. Although the LD₅₀ for the Norway rat is known to be 5 to 15 mg/kg [115], reports of human volunteers ingesting up to 300 mg/kg showed no clinical effect, other than slight decreases in both temperature and systolic blood pressure. Because this agent is essentially nontoxic, no specific treatment is needed after ingestion. We typically counsel parents to watch the child in the home for four hours. All suicidal ingestions warrant prompt evaluation for psychiatric intervention.

●Red squill (Urginea maritime) – Red squill (Urginea maritime) has been used commercially as a rodenticide for over 75 years [116] and has been sold under brands, such as Deathdiet, Rodine, and Rat Snax. It is a botanically derived compound, containing two different cardiac glycosides as its active ingredients, scillaren A and scillaren B, whose effects are similar to those of digitalis. U. maritime has a very bitter taste and also acts as a potent emetic, which often prevents toxicity in most animals. Since rats are incapable of emesis, they cannot rid themselves of red squill and thus readily absorb the potent glycoside analogs [117]. A LD₅₀ has not been identified for this compound.

Although no serious toxicity from red squill ingestion in humans has been reported, clinical manifestations of acute ingestion might include abdominal pain, vomiting, cardiac arrhythmias, and seizure activity. Once ingested, U. maritime would produce effects similar to digitalis; thus, treatment for symptomatic patients would be the same as for digoxin toxicity and consists of activated charcoal administration and digoxin immune Fab. In the rare instance of cardiac toxicity, although serum digoxin concentrations may confirm a significant red squill ingestion, the assay does not have complete crossreactivity for all cardiac glycosides; thus, signs and symptoms may exceed what would be predicted from the concentration [118]. As such, dosing of digoxin-specific immune fragments should be based upon symptomatology and not serum concentrations. (See "Digitalis (cardiac glycoside) poisoning", section on 'Management' and "Digitalis (cardiac glycoside) poisoning", section on 'Fab fragment dosing'.)

Although the risk of toxicity is very low, we typically advise activated charcoal administration to all patients who present within one hour of ingestion and perform cardiac monitoring for four hours.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Classification – Rodenticides or "rat poisons" refer to any product commercially available and designed expressly to kill rodents, mice, squirrels, gophers, and other small animals. Toxicity of these agents can be categorized by the amount of poison that causes death in 50 percent of patients following exposure (lethal dose₅₀ or LD₅₀) and a corresponding "signal word", which in some regions (eg, the United States) appears on the product label as follows (see 'Definition and classification' above):

•Highly toxic – LD₅₀: 0 to 50 mg/kg, signal word "Danger"

•Toxic – LD₅₀: 50 to 500 mg/kg, signal word "Warning"

•Less toxic – LD₅₀: 500 to 5000 mg/kg, signal word "Caution"

●Identify the poison, if possible – When managing patients with rodenticide exposure, the clinician should make every effort to identify the specific rodenticide and the circumstances of the exposure to guide care. The clinician is encouraged to contact a regional poison control center to assist with identification and interpretation of rodenticide labeling. (See 'Identify the poison' above and 'Regional poison control centers' above.)

Compound appearance, minimum lethal dose, clinical manifestations, and specific management by poison are provided (table 1).

●Management

•Symptomatic patients – A patient who develops symptoms after a toxic rodenticide poisoning should undergo emergency evaluation and receive supportive care and/or specific treatment guided by the compound that was ingested or is suspected by clinical findings. (See 'Symptomatic patients' above.)

•Gastrointestinal decontamination – In an asymptomatic patient who presents within one hour following a strongly suspected ingestion of a highly toxic rodenticide other than elemental phosphorus, we suggest performing gastric lavage followed by administration of activated charcoal (Grade 2C). We take appropriate precautions to protect the airway and prevent aspiration as needed. Gastric lavage should not be performed in a patient who has already vomited spontaneously. (See 'Unknown poison' above.)  

•Ancillary studies – Warranted studies to identify early signs of exposure to highly toxic rodenticides are discussed in the text. (See 'Unknown poison' above.)

•Asymptomatic patient with highly toxic agent ingestion – This patient requires close monitoring and warrants consultation with a regional poison control center or medical toxicologist. (See 'Highly toxic ("Danger")' above and 'Regional poison control centers' above.)

•Asymptomatic patient with anticoagulant ingestion – A patient with a small anticoagulant ingestion (less than one packet) requires no testing or therapy. The clinician should be cautious when managing patients with suicidal ingestions, where quantification of the ingestion is notoriously unreliable. Since rare asymptomatic patients who have reported ingested small quantities of anticoagulant rodenticides, may actually have consumed larger amounts than suspected, the families should receive careful instructions to observe these individuals for any signs of bleeding. (See 'Asymptomatic patients' above and "Anticoagulant rodenticide poisoning: Management".)

•Bromethalin ingestion – Unintentional bromethalin exposures in children usually result in no symptoms and may be monitored at home. Although the likelihood of serious toxicity is low, all patients with intentional and symptomatic exposures require evaluation at a health care facility. Awake and alert, symptomatic patients and those with large or intentional ingestions who present within one hour of ingestion warrant treatment with a single dose of activated charcoal. Otherwise, care is supportive. (See 'Bromethalin' above.)

•Other less toxic ingestions – Small ingestions of agents such as alpha-naphthyl thiourea or cholecalciferol are unlikely to cause any toxicity. (See 'Toxic ("Warning")' above.)