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METALDEHYDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Metaldehyde is a cyclic polymer (tetramer) of acetaldehyde prepared by low temperature polymerization in the presence of hydrochloric and sulfuric acids.

Specific Substances

    1) Acetaldehyde, tetramer
    2) META, Meta-fuel
    3) Metacetaldehyde
    4) CAS 9002-91-9
    5) Meta-acetaldehyde
    6) Polymerized Acetaldehyde
    1.2.1) MOLECULAR FORMULA
    1) C8-H16-O4

Available Forms Sources

    A) FORMS
    1) Most commonly sold in the United States as a protein-rich, cereal-based slug and snail bait in granular or pellet form for deposition around trees or outdoor plant containers. It may also be sold as a paste or foam. These preparations generally contain less than 4% metaldehyde.
    a) It is also sold in the US as a solution, and as a dust that can be prepared as a liquid suspension and sprayed over crops or landscaping.
    2) Metaldehyde is available in Europe and Japan as a solid tablet or block for use as a fuel source in portable stoves. These preparations may contain 100% metaldehyde.
    3) Metaldehyde is also sold in Japan in tablet form for the purpose of producing brightly colored flames used in entertaining (eg, Engelfire(TM), Partyfire(TM), and Bigengel(TM)).
    a) These tablets vary slightly in composition depending on the color flame that it produced, but all contain 90% to 100% metaldehyde.
    b) The tablets are typically wrapped in brightly colored cellophane and contain two tablets per package.
    B) SOURCES
    1) Metaldehyde is prepared by polymerization of acetaldehyde in the presence of hydrochloric acid and sulfuric acid (HSDB , 2000).
    C) USES
    1) It has no therapeutic use in humans and is primarily sold and used in the United States as a molluscicide. There are currently 58 slug and snail bait products containing metaldehyde registered with the Environmental Protection Agency.
    a) Trade names include the following: Antimilice, Anotox, Cekumeta, Deadline, Halizan, Limatox, Limeol, Meta, Metason, Mifaslug, Namekil, Slug Death, Slug Fest Collogel 25, Slugit and Slug-tox.
    b) The concentration in the US is generally less than 4%. Baits are sometimes mixed with other herbicides and pesticides.
    c) The greatest use in California in 2005 was in citrus orchards and outdoor container nurseries.
    d) In Europe and Japan, it is used in its compressed form as a solid fuel for small portable camping stoves. Ingestion may occur by children who confuse the fuel tablets, solid blocks or powder for candy.
    e) In Japan, it is also sold as a colored flame tablet (Engelfire(R)) used for entertaining (Shintani et al, 1999).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) OVERDOSE: Initial signs and symptoms of acute metaldehyde toxicity generally include salivation, facial flushing, nausea, vomiting, abdominal pain, tachycardia and drowsiness. In high doses metaldehyde may cause muscular rigidity and spasms, tremor, seizures, coma and death.
    B) Toxicity may occur via inhalation, ingestion or from dermal exposure. ONSET of symptoms after acute ingestion is generally within 1 to 3 hours.
    C) IRRITANT: Metaldehyde is a strong irritant to skin, eyes and mucous membranes.
    0.2.3) VITAL SIGNS
    A) WITH POISONING/EXPOSURE
    1) Profound hyperthermia has been noted in both human and animal exposures.
    0.2.5) CARDIOVASCULAR
    A) WITH POISONING/EXPOSURE
    1) Metaldehyde has no known direct effects on myocardial conduction or contractility. It may cause hypotension as part of a disulfiram-like reaction as it is metabolized to acetaldehyde, or as a sequelae of dehydration and multiorgan dysfunction in severe or protracted intoxications.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Tracheobronchial secretions are increased after acute ingestion. Respiratory failure may occur 24 to 40 hours after ingestion and is imputed to be the proximate cause of death in most reported fatalities.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Initial lethargy (sometimes protracted) may be followed by seizures, muscle spasms, and coma.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Salivation, nausea, vomiting, diarrhea and severe abdominal pain are characteristic symptoms.
    0.2.9) HEPATIC
    A) WITH POISONING/EXPOSURE
    1) Elevated liver enzymes were reported in one human case, and liver damage has developed in experimental animals.
    0.2.10) GENITOURINARY
    A) WITH POISONING/EXPOSURE
    1) Transient renal impairment has been reported in one human case report, and this was most likely a reflection of dehydration and not directly attributable to metaldehyde toxicity.
    0.2.11) ACID-BASE
    A) Metabolic acidosis and respiratory alkalosis have been reported.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH POISONING/EXPOSURE
    1) Metabolic acidosis is seen in moderate to severe cases, and is most likely a reflection of dehydration and increased neuromuscular activity. Hyperkalemia may ensue in cases which progress to rhabdomyolysis and/or renal impairment.
    0.2.15) MUSCULOSKELETAL
    A) Increased muscle tone, fasciculations and spasms are a prominent feature of moderate to severe metaldehyde poisoning in both humans and animals.
    0.2.20) REPRODUCTIVE
    A) Dietary concentrations of 1000 ppm and 5000 ppm given to rats interfered with reproductive performance, but were not teratogenic.

Laboratory Monitoring

    A) Metaldehyde concentrations in plasma or urine are not clinically useful.
    B) Obtain baseline electrolytes, urinalysis, hepatic enzymes and renal function tests in symptomatic patients. Serum creatinine phosphokinase should be tested in severely symptomatic patients due to the risk of rhabdomyolysis from muscular rigidity and prolonged seizure activity.
    C) Metaldehyde is not known to affect the cardiac conduction system directly, but a screening electrocardiogram may be useful in ruling out other potential co-ingestants, and continuous cardiac monitoring should be considered for all potentially hemodynamically unstable patients or patients with severe electrolyte disturbances.
    D) EEG monitoring may be useful in patients with prolonged or recurrent seizures.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis is NOT recommended due to the potential for aspiration in patients who may develop a depressed level of consciousness or seizures.
    B) Metaldehyde ingestion can typically produce severe vomiting with a depressed mental status followed by recurrent seizures; the risk of aspiration in these patients is extremely high. Although judicious use of activated charcoal may have a role in these ingestions, clinicians should be aware of the potential for the patients condition to deteriorate and exercise appropriate caution.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    F) Good supportive care with aspiration and seizure precautions is paramount in ensuring a favorable outcome. required.
    G) Monitor fluid and electrolyte status carefully with special attention to dehydration and acidosis. Correct dehydration and acidosis with appropriate intravenous fluids.
    H) Forced diuresis probably does not significantly enhance the renal elimination of metaldehyde.

Range Of Toxicity

    A) The minimum lethal or toxic dose of metaldehyde is not well established in the literature. An acute lethal dose in the range of 100 milligrams/kilogram has been suggested for adults. A man ingested approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate) and recovered following supportive care.
    B) One adult female died within 26 hours of ingesting 12 grams metaldehyde from multi-organ failure.
    C) Adults have survived ingestions of 16 to 19 grams.
    D) Most reported exposures in children have been unintentional low-dose ingestions with few sequelae. Death has been reported following acute ingestions of 3 to 4 grams in children.

Clinical Effects

Summary Of Exposure

    A) OVERDOSE: Initial signs and symptoms of acute metaldehyde toxicity generally include salivation, facial flushing, nausea, vomiting, abdominal pain, tachycardia and drowsiness. In high doses metaldehyde may cause muscular rigidity and spasms, tremor, seizures, coma and death.
    B) Toxicity may occur via inhalation, ingestion or from dermal exposure. ONSET of symptoms after acute ingestion is generally within 1 to 3 hours.
    C) IRRITANT: Metaldehyde is a strong irritant to skin, eyes and mucous membranes.

Vital Signs

    3.3.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Profound hyperthermia has been noted in both human and animal exposures.
    3.3.3) TEMPERATURE
    A) HYPERTHERMIA - Profound hyperthermia has been noted in both human and animal exposures. It may be seen in the absence of seizure activity, but may be related to the degree of muscle hypertonia and spasms, in association with seizures (Booze & Oehme, 1985; Moody & Inglis, 1992).

Heent

    3.4.3) EYES
    A) Metaldehyde is an irritant. Conjunctivitis may occur with either acute or chronic exposure to metaldehyde (HSFS , 2000; EPA, 1980).
    B) Reversible blindness has been reported in some poisoned animals (Grant & Schuman, 1993).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Metaldehyde has no known direct effects on myocardial conduction or contractility. It may cause hypotension as part of a disulfiram-like reaction as it is metabolized to acetaldehyde, or as a sequelae of dehydration and multiorgan dysfunction in severe or protracted intoxications.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension (cause uncertain) was noted in cases of children poisoned by metaldehyde (Booze & Oehme, 1985). Profound hypotension in the setting of coma, metabolic acidosis, severe rhabdomyolysis, and ventricular dysrhythmias were reported in a woman who ingested 12 g metaldehyde. Despite aggressive therapy, death occurred 26 hours after exposure (Shih et al, 2004).
    B) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypertension (BP 222/117) was reported in adult man who ingested metaldehyde and alcohol (Keller et al, 1991).
    C) TACHYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Tachycardia (114 bpm) developed in a 38-year-old man after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). An ECG revealed sinus tachycardia with normal PR, QRS and QTc intervals. His hospital course was complicated with a profound metabolic acidosis, recurrent seizures and dystonia. Following supportive care, he recovered and was extubated on day 8 (Bleakley et al, 2008).

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Tracheobronchial secretions are increased after acute ingestion. Respiratory failure may occur 24 to 40 hours after ingestion and is imputed to be the proximate cause of death in most reported fatalities.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Death may result from respiratory failure at 24 to 40 hours following ingestion (Booze & Oehme, 1985). Respiratory distress requiring intubation occurred in a woman within 2 hours of ingesting 12 g metaldehyde. Despite aggressive supportive care, the patient died 26 hours after exposure (Shih et al, 2004).
    B) COPIOUS SPUTUM
    1) WITH POISONING/EXPOSURE
    a) Excessive tracheobronchial secretions are a prominent feature of early intoxication in both human and animal exposures (Booze & Oehme, 1985; Longstreth & Pierson, 1982).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Inhalation of smoke produced by a novelty item, Snow Storm(R) tablets, resulted in pneumonitis in a 14-year-old girl. Symptoms included: paroxysmal cough, inspiratory pleuritic chest pain, rhinorrhea, lacrimation, tachypnea, and bilateral wheezing. Chest x-ray demonstrated, an interstitial pattern consistent with acute lung injury (ALI). The tablets were subsequently found to contain metaldehyde and sodium carbonate. It was speculated that smoking metaldehyde in the presence of a base resulted in production of crotonaldehyde (Jay et al, 1988).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Initial lethargy (sometimes protracted) may be followed by seizures, muscle spasms, and coma.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) Initial lethargy has been reported in some cases followed by coma (Longstreth & Pierson, 1982; Moody & Inglis, 1992).
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures are a prominent feature of moderate to severe metaldehyde poisoning. They may occur shortly after exposure and be protracted, continuing for 3 days or more depending on the amount ingested (Shih et al, 2004; Longstreth & Pierson, 1982).
    b) CASE REPORT - An 18-month-old girl bit into a troche-like tablet of metaldehyde (used during parties to produce a colored flame when lighted) and developed drowsiness followed by nausea and seizures. The child made a complete recovery following supportive care and was discharged to home on hospital day 3 (Shintani et al, 1999).
    c) CASE REPORT - A 38-year-old man developed a generalized tonic-clonic seizure after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). Although his seizure was successfully treated with lorazepam, he experienced dystonia of the facial muscles with jaw clenching and superior lateral gaze fixation. His dystonia resolved within 10 minutes of receiving benztropine 2 mg. He experienced several more seizures over the next 4 hours, which were treated with IV infusion of phenytoin for 7 days, followed by oral preparation of phenytoin. An EEG revealed a right hemispheric ictal focus accompanied by postictal slowing. Computerized tomography of the brain showed no intracranial abnormalities (Bleakley et al, 2008).
    C) DYSTONIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 38-year-old man developed a generalized tonic-clonic seizure after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). Although his seizure was successfully treated with lorazepam, he experienced dystonia of the facial muscles with jaw clenching and superior lateral gaze fixation. His dystonia resolved within 10 minutes of receiving benztropine 2 mg (Bleakley et al, 2008)
    D) SEQUELA
    1) WITH POISONING/EXPOSURE
    a) After recovery, temporary or short-term memory loss and psychomotor impairment have followed poisoning (Bleakley et al, 2008; Longstreth & Pierson, 1982).
    E) INCREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) Increased muscle tone, fasciculations and spasms are prominent features of moderate to severe metaldehyde poisoning in both human and animal exposures.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) OPISTHOTONUS
    a) Opisthotonus has been reported after metaldehyde poisoning in birds, as well as mammals. One horse reportedly experienced muscular contractions so severe as to separate the left latissimus dorsii muscles from their vertebral attachments (Booze & Oehme, 1985).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Salivation, nausea, vomiting, diarrhea and severe abdominal pain are characteristic symptoms.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Initial effects following exposure include salivation, nausea, vomiting, and abdominal pain (Lewis et al, 1939; Longstreth & Pierson, 1982).
    b) Metaldehyde is non-corrosive, but is a strong irritant to mucosal tissues; gastrointestinal hemorrhage has been reported after large ingestions in animals (Booze & Oehme, 1985).
    c) CASE REPORT - Nausea and seizures were reported in an 18-month-old girl after ingesting a troche-like tablet (used to produce a colored flame when lighted) which contained metaldehyde. The child had an uneventful recovery following supportive care (Shintani et al, 1999).
    d) CASE REPORT - A 38-year-old man was found unconscious with chalky white vomitus after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate) (Bleakley et al, 2008).

Hepatic

    3.9.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Elevated liver enzymes were reported in one human case, and liver damage has developed in experimental animals.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Transient elevation of AST was reported in the course of one human case of acute oral overdose (Moody & Inglis, 1992).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Liver damage has been reported following acute ingestion in animals (Booze & Oehme, 1985).

Genitourinary

    3.10.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Transient renal impairment has been reported in one human case report, and this was most likely a reflection of dehydration and not directly attributable to metaldehyde toxicity.
    3.10.2) CLINICAL EFFECTS
    A) BLOOD UREA ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Transient elevation of blood urea nitrogen was reported in one case of acute oral overdose (Moody & Inglis, 1992).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) Kidney injury has been noted in animals (Booze & Oehme, 1985).

Acid-Base

    3.11.1) SUMMARY
    A) Metabolic acidosis and respiratory alkalosis have been reported.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) Metabolic acidosis is sometimes severe; concomitant respiratory alkalosis has also been reported (Bleakley et al, 2008; Shih et al, 2004; Keller et al, 1991; Longstreth & Pierson, 1982) .
    2) CASE REPORT - A 38-year-old man developed profound anion gap metabolic acidosis (pH 6.944, pO2 30.35 kPa, pCO2 3.46 kPa, base excess -25.8 mmol/L, standard bicarbonate 5.5 mmol/L, anion gap 48.6 mmol) after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). Following supportive care, he recovered and was extubated on day 8 (Bleakley et al, 2008).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION DISORDER
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A mildly deranged coagulation screen (prothrombin time, 18.2 seconds; activated partial prothrombin time, 45.6 seconds; fibrinogen, 7.68 g/L) was reported in a 38-year-old man after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). His hospital course was complicated with a profound metabolic acidosis, recurrent seizures and dystonia (Bleakley et al, 2008).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) BLOOD COAGULATION DISORDER
    a) There is evidence of coagulopathy from metaldehyde toxicity in several avian and mammalian species found postmortem (Booze & Oehme, 1985).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Metaldehyde is a strong irritant to skin and mucous membranes (Sax & Lewis, 1987; HSFS , 2000).

Musculoskeletal

    3.15.1) SUMMARY
    A) Increased muscle tone, fasciculations and spasms are a prominent feature of moderate to severe metaldehyde poisoning in both humans and animals.
    3.15.2) CLINICAL EFFECTS
    A) INCREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) Muscular rigidity and spasm may occur (Wilkinson, 1968; Longstreth & Pierson, 1982; HSFS , 2000).
    B) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 39-year-old woman intentionally ingested 12 g metaldehyde and alcohol (amount unknown), and developed metabolic acidosis along with severe rhabdomyolysis (CPK peaked at 51,238 U/L; MB fraction 3.4%). Despite aggressive intensive care, the patient died 26 hours after exposure from multi-system failure (Shih et al, 2004).

Reproductive

    3.20.1) SUMMARY
    A) Dietary concentrations of 1000 ppm and 5000 ppm given to rats interfered with reproductive performance, but were not teratogenic.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) No morphologic abnormalities were noted in second and third generation rats (Verschuuren et al, 1975).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS108-62-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.3) HUMAN STUDIES
    A) LACK OF EFFECT
    1) RATS - A two-year feeding study at concentrations of 5000 ppm in the diet of rats failed to demonstrate carcinogenic potential (Verschuuren et al, 1975).
    2) Currently, no evidence exists that metaldehyde is carcinogenic to animals (HSFS , 2000), and no studies to assess the risk of carcinogenesis have been performed in humans.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Metaldehyde concentrations in plasma or urine are not clinically useful.
    B) Obtain baseline electrolytes, urinalysis, hepatic enzymes and renal function tests in symptomatic patients. Serum creatinine phosphokinase should be tested in severely symptomatic patients due to the risk of rhabdomyolysis from muscular rigidity and prolonged seizure activity.
    C) Metaldehyde is not known to affect the cardiac conduction system directly, but a screening electrocardiogram may be useful in ruling out other potential co-ingestants, and continuous cardiac monitoring should be considered for all potentially hemodynamically unstable patients or patients with severe electrolyte disturbances.
    D) EEG monitoring may be useful in patients with prolonged or recurrent seizures.

Methods

    A) EEG
    1) EEG monitoring may be useful in patients with prolonged or recurrent seizures, particularly if they require intubation and paralysis for control.
    B) OTHER
    1) Bait that contains metaldehyde can be detected by placing the substance in a test tube and gently warming. Metaldehyde sublimes to form copious "artificial snow."

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Metaldehyde concentrations in plasma or urine are not clinically useful.
    B) Obtain baseline electrolytes, urinalysis, hepatic enzymes and renal function tests in symptomatic patients. Serum creatinine phosphokinase should be tested in severely symptomatic patients due to the risk of rhabdomyolysis from muscular rigidity and prolonged seizure activity.
    C) Metaldehyde is not known to affect the cardiac conduction system directly, but a screening electrocardiogram may be useful in ruling out other potential co-ingestants, and continuous cardiac monitoring should be considered for all potentially hemodynamically unstable patients or patients with severe electrolyte disturbances.
    D) EEG monitoring may be useful in patients with prolonged or recurrent seizures.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Emesis is NOT recommended due to the potential for seizures.
    B) ACTIVATED CHARCOAL
    1) Metaldehyde ingestion can typically produce severe vomiting with a depressed mental status followed by recurrent seizures; therefore, the risk of aspiration in these patients is extremely high, and most likely outweighs the benefit of decreased absorption of metaldehyde. Activated charcoal should generally NOT be administered in the prehospital setting if a metaldehyde ingestion is suspected.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS
    1) Emesis is NOT recommended due to the potential for aspiration in patients who may develop a depressed level of consciousness or seizures.
    B) ACTIVATED CHARCOAL
    1) Activated charcoal adsorbs metaldehyde. There is evidence from an animal study that activated charcoal given as a 5:1 ratio to ingested metaldehyde may significantly reduce absorption of toxin when administered early after ingestion.
    a) However, metaldehyde ingestion typically produces severe vomiting with depressed mental status followed by recurrent seizures. Therefore, the risk of aspiration in these patients is extremely high. Although judicious use of activated charcoal may have a role in these ingestions, clinicians should be aware of the potential for the patients condition to deteriorate and exercise appropriate caution.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    4) ANIMAL DATA - In a study of Wistar rats, the quantitative adsorption capacity of activated charcoal was determined following acute exposure to metaldehyde (Shintani et al, 1999). The detoxifying effect of activated charcoal and the inhibition of metaldehyde absorption was examined, and it was found that a ratio of 5:1 (activated charcoal was given 30 minutes after dosing to 400 mg metaldehyde/kg orally) prevented metaldehyde toxicity.
    a) The authors concluded that activated charcoal given as an adsorbent-to-metaldehyde ratio of 5:1, significantly reduced the gastrointestinal absorption of metaldehyde in rats. Other findings based on gas chromatographic studies suggested that acetaldehyde may not have a role in producing metaldehyde toxicity.
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) No specific antidote is available; therefore, good supportive care with aspiration and seizure precautions is paramount in ensuring a favorable outcome.
    2) Monitor fluid and electrolyte status carefully with special attention to dehydration and acidosis. Obtain baseline electrolytes, urinalysis, complete blood count, hepatic enzymes and renal function tests in symptomatic patients. Correct dehydration and acidosis with appropriate intravenous fluids.
    3) Obtain a baseline ECG and continuous cardiac monitoring as indicated.
    4) Forced diuresis probably does not significantly enhance the renal elimination of metaldehyde.
    5) EEG monitoring may be useful in patients with prolonged or recurrent seizures.
    B) SEIZURE
    1) Status epilepticus may develop in patients with metaldehyde poisoning.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) EXPERIMENTAL THERAPY
    1) Several compounds have been tested in animals or suggested for use as antidotes including: D-penicillamine; N-acetylcysteine; thiamine; and ascorbic acid. None of these have been of proven benefit in animals and none have been tested in humans for this indication.
    2) These agents have been investigated because they may lower blood acetaldehyde levels in acetaldehyde-poisoned animals.
    3) N-ACETYLCYSTEINE - Intravenous N-acetylcysteine was administered to a 38-year-old man after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). On admission, he was obtunded and pale, with chalky white vomitus, diaphoresis, and tachycardia. His hospital course was complicated by profound metabolic acidosis, a mildly deranged coagulation screen, recurrent seizures and dystonia. Following supportive care, he recovered and was extubated on day 8 (Bleakley et al, 2008).

Enhanced Elimination

    A) DIURESIS
    1) A kinetic study of metaldehyde poisoning in dogs found negligible amounts of metaldehyde in the urine, suggesting that elimination is primarily via non-renal routes (Booze & Oehme, 1986). Forced diuresis probably does not significantly enhance the renal elimination of metaldehyde.

Abstracts

Case Reports

    A) ADULT
    1) A 44-year-old man who consumed alcohol with one cup 4% metaldehyde bait presented 10 hours postingestion with vomiting, seizures, hypertension, and severe acidosis.
    a) Treatment with phenytoin and phenobarbital were required to control seizures. Serum and urine metaldehyde-specific acetaldehyde levels (as measured by the Smith hydrolysis method) were 1 mg/dL and 3 mg/dL at 16 hours postingestion, respectively. The patient recovered uneventfully (Keller et al, 1991).
    2) A 39-year-old woman ingested 200 g of "slug death" which contained 12 g metaldehyde and developed seizures, coma, and respiratory distress 2 hours after exposure. The patient was intubated and transferred to intensive care where she remained comatose along with profuse diaphoresis and slowly reactive pupils (4 mm), muscle rigidity, hyperthermia, and recurrent clonic seizures. Despite the use of hemodialysis and hemoperfusion along with aggressive supportive care, the patient's condition deteriorated. Approximately 7 hours after exposure, the patient developed profound hypotension, ventricular dysrhythmias, metabolic acidosis with severe rhabdomyolysis (CPK peaked at 51,238 U/L; MB fraction 3.4%), hyperkalemia (peaked at 8.5 mEq/L) and gastrointestinal bleeding (hemoglobin decreased to 5.1 g/dL). The patient died 26 hours after ingestion (Shih et al, 2004).
    3) A 37-year-old man presented in coma and developed hyperpyrexia and status epilepticus controlled with diazepam and phenytoin. Initial serum electrolytes, glucose and renal and liver function tests were all within normal limits. He was treated with intravenous normal saline, but developed mild renal and hepatic impairment which normalized within a week. After relatives found two empty containers of Slugit in his home, serum and urine specimens were tested for the presence of metaldehyde, which was confirmed by gas chromatography (Moody & Inglis, 1992).
    4) A 32-year-old woman drank approximately 18.9 grams (330 mg/kg) of metaldehyde (470 mL of a 4% liquid molluscicide preparation) and developed immediate nausea and vomiting followed by the onset of convulsions 2 hours later. She was treated with endotracheal intubation for airway protection, gastric lavage, charcoal and diazepam, but remained in status epilepticus throughout the day. Serum chemistries were remarkable for an anion gap of 23 mEq/L. Her hospital course was complicated by recurrent generalized convulsions over the course of 3 days despite diazepam, phenytoin and phenobarbital administration. She developed rhabdomyolysis and pneumonia and remained comatose for 7 days. After extubation she exhibited profound memory loss and cognitive slowing which gradually improved to baseline over the course of a year (Longstreth & Pierson, 1982).
    B) PEDIATRIC
    1) A 14-year-old girl smoked several Snow Storm tablets containing metaldehyde over the course of a day. She had embedded the tablets within tobacco cigarettes. Within 48 hours, she developed dizziness, paroxysmal cough, and pleuritic chest pain. Her physical examination was significant for lacrimation, rhinorrhea, edema of the oropharynx and respiratory distress. She became hypoxic and arterial blood gas determination demonstrated a pO2 of 63. Chest radiography was consistent with acute lung injury. Her respirations were assisted with continuous positive airway pressure by mask. She recovered without permanent pulmonary sequelae after 3 days of treatment (Jay et al, 1988).

Range Of Toxicity

Summary

    A) The minimum lethal or toxic dose of metaldehyde is not well established in the literature. An acute lethal dose in the range of 100 milligrams/kilogram has been suggested for adults. A man ingested approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate) and recovered following supportive care.
    B) One adult female died within 26 hours of ingesting 12 grams metaldehyde from multi-organ failure.
    C) Adults have survived ingestions of 16 to 19 grams.
    D) Most reported exposures in children have been unintentional low-dose ingestions with few sequelae. Death has been reported following acute ingestions of 3 to 4 grams in children.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) An acute lethal dose in the range of 100 milligrams/kilogram has been suggested for adults (von Burg & Stout, 1991). There is no systematic data to support this guideline.
    B) CASE REPORTS
    1) PEDIATRIC
    a) Death of a child has resulted from the ingestion of 4 grams (Lewis et al, 1939).
    2) ADULT
    a) A 39-year-old woman ingested 12 g of metaldehyde (258 mg/kg) and an unknown quantity of ethanol. Within 2 hours of ingestion, the patient developed seizures, coma, cyanosis and respiratory distress. Despite aggressive intensive care, the patient developed multi-system failure (CNS depression, recurrent seizures, hyperthermia, persistent hypotension, hyperkalemia (peaked at 8.5 mEq/L), metabolic acidosis with rhabdomyolysis (CPK peaked at 51,238 U/L), gastrointestinal bleeding (hemoglobin 5.1 g/dL) and ventricular dysrhythmias) and died 26 hours after ingestion (Shih et al, 2004).
    b) A 53-year-old man died after ingesting 6 tablets (containing 24,000 milligrams) of metaldehyde (Vischer, 1935).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) PEDIATRIC
    a) Survival has occurred after a reported ingestion of 2 grams by a 2.8-year-old child (Belfrage, 1927).
    b) An 18-month-old girl developed seizures after biting a troche-like tablet that contained 90% metaldehyde (Shintani et al, 1999). Recovery was uneventful following supportive care.
    2) ADULT
    a) Survival has reportedly occurred with ingestion of 3000 to 24,000 milligrams in adults (Lewis et al, 1939; Booze & Oehme, 1985).
    b) A 38-year-old man was found unconscious after ingesting approximately 600 mg/kg of a liquid solution of 20% metaldehyde (slug killer concentrate). On admission, he was obtunded and pale, with chalky white vomitus, diaphoresis, and tachycardia. His hospital course was complicated by profound metabolic acidosis, a mildly deranged coagulation screen, recurrent seizures and dystonia. Following supportive care, he recovered and was extubated on day 8 (Bleakley et al, 2008).
    B) OTHER
    1) DOSE-RESPONSE GUIDELINES
    a) In a review by Borbely (1970; referenced in Booze and Oehme, 1985), 213 cases of metaldehyde exposures were reported to the Swiss Toxicological Information Center between 1966 and 1969. He proposed the following dose-response relationships, based on his retrospective review of 20 intentional overdoses in adults who became symptomatic after ingestion (Booze & Oehme, 1985)
    1) The following should serve as a guideline only; individual variability may exist:
    a) A few mg/kg: May produce nausea, vomiting, cramps, fever, flushing, and drooling.
    b) Up to 50 mg/kg: May include all the above symptoms, as well as drowsiness, tachycardia, irritability, and muscle spasms.
    c) 50 to 100 mg/kg: All of the above, and an increase in muscle tone and ataxia.
    d) 100 to 150 mg/kg: All of the above, and an increase in seizures and reflexes.
    e) 150 to 200 mg/kg: All of the above and muscle twitching may be seen.
    f) 400 mg/kg or higher: May produce coma and death.

Workplace Standards

    A) ACGIH TLV Values for CAS108-62-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS108-62-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS108-62-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS108-62-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2000 Sax & Lewis, 1989 Vonburg & Stout, 1991 Budavari, 1996)
    1) LD50- (ORAL)MOUSE:
    a) 200 mg/kg
    2) LD50- (ORAL)RAT:
    a) 630 mg/kg
    3) LD50- (SKIN)RAT:
    a) 2275 mg/kg

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) SUMMARY
    a) There is no systematic data linking serum or urine concentrations of metaldehyde with specific clinical effects in humans. Case reports in which serum or urine concentrations are reported should be interpreted as having confirmed exposure. Correlation between measured metaldehyde concentrations and toxicity must be viewed with caution, since metaldehyde is rapidly metabolized and time to assay may affect results.
    2) ACUTE
    a) Toxic concentrations are not well established. Determination of toxicity is based on the development of clinical signs and symptoms, and not on measured metaldehyde or acetaldehyde concentrations in blood or urine.
    b) A case of metaldehyde poisoning in an adult with severe clinical signs also reported acetaldehyde concentrations specific for metaldehyde as measured by the Smith hydrolysis method. Serum acetaldehyde concentration was 1 mg/dL and urine concentration was 3 mg/dL (Keller et al, 1991).
    c) Concentrations on admission in one seriously ill patient following acute oral overdose included: metaldehyde (serum), 113 mg/L; acetaldehyde (serum), less than 1 mg/L. Urine metaldehyde concentration, 14 hours post-admission was 53 mg/L (Moody & Inglis, 1992).
    d) A study of metaldehyde toxicity in 8 dogs dosed orally with 600 mg/kg metaldehyde showed slight tremors in all dogs at plasma concentrations above 8 ng/microliter, ataxia and hyperesthesia at concentrations above 20 ng/microliter, and increased salivation at levels between 40 and 58 ng/microliter. The one dog that reached a plasma concentration greater than 60 ng/mL had seizures and died after 4.5 hours. The other dogs appeared clinically recovered after 24 hours (Booze & Oehme, 1986).

Pharmacology Toxicology

Toxicologic Mechanism

    A) In general, metaldehyde is thought to kill mollusks by causing dehydration and paralysis. The mechanism of action in either invertebrates or higher animals is not well established.
    B) Metaldehyde is a cyclic polymer of acetaldehyde (4 molecules arranged in an 8-membered ring) similar to paraldehyde (3 molecules). The prevailing theory is that acetaldehyde, produced by the degradation of metaldehyde, is responsible for the toxic effects of metaldehyde ingestion. While the clinical pathology seen with metaldehyde and acetaldehyde poisoning is similar, there are several lines of evidence that suggest metaldehyde is directly toxic to mammals, or that acetaldehyde is not the sole or primary agent involved in its toxicity.
    C) Metaldehyde is hydrolyzed to acetaldehyde in the presence of hydrochloric acid (Selim & Seiber, 1973). Gastric contents of acutely poisoned dogs demonstrated both metaldehyde and acetaldehyde (Booze & Oehme, 1986; Udall, 1973). It is unclear whether significant conversion to acetaldehyde occurs after absorption from the gastrointestinal tract.
    D) Acetaldehyde is rapidly oxidized to acetic acid and carbon dioxide. Driesbach (1983) hypothesized that the rate of degradation of metaldehyde to acetaldehyde is significantly faster that the rate of acetaldehyde clearance, leading to accumulation of acetaldehyde. However, studies with paraldehyde suggest that the opposite is true, and that the rate at which acetaldehyde is oxidized and cleared is up to four times faster than the rate of formation of acetaldehyde (Zaleska & Gessner, 1983; Hitchcock & Nelson, 1943).
    E) A comparative study of metaldehyde and acetaldehyde toxicity in dogs found that while metaldehyde levels were measurable in blood and urine in metaldehyde-poisoned dogs, acetaldehyde could not be detected in either blood or urine from the same animals. In addition, the metaldehyde and acetaldehyde poisoned dogs exhibited different symptomatology, with more vomiting in the acetaldehyde group, and more ataxia and tremors in the metaldehyde group (Booze & Oehme, 1986).
    F) The specific pharmacology of metaldehyde has been investigated in the mouse model. Two mouse studies have been performed in which 1000 mg/kg of metaldehyde was given orally, and neurotransmitter concentrations were measured postmortem.
    G) One study found a significant decrease in the brain concentration of gamma-aminobutyric acid (GABA), and a significant increase in monoamine oxidase (MAO) activity. The GABA effects correlated with survival, while the increased MAO activity appeared unrelated (Homeida & Cook, 1982). Decreased inhibitory GABA activity may be responsible for the convulsions seen with severe metaldehyde toxicity.
    1) A second study was then conducted which found a significant decrease in noradrenaline (NA), 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroindole-acetic acid (5-HIAA levels) (Homeida & Cook, 1982).
    H) Studies in animal models of acetaldehyde toxicity are not entirely in concordance with these findings. Acetaldehyde has been shown to competitively inhibit rather than increase MAO activity. However, studies have shown an increase in NA clearance in rats given acetaldehyde, and in vitro study found that acetaldehyde decreased 5-HIAA levels (Booze, 1985).

Physicochemical

Physical Characteristics

    A) Metaldehyde is a white crystalline material (prism) that easily fractures into fibers giving it a powdery appearance (Budavari, 1989; Sax & Lewis, 1987; HSDB , 2000).
    B) It is tasteless substance with a mild characteristic odor (HSDB , 2000).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 176.24

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) GEESE - Extreme opisthotonus with the beak touching the tail was seen after ingestion of approximately 800 mg/kg by 6 week old goslings (James, 1955).
    B) DUCKS and CHICKENS - Similar symptoms were seen in both chickens and ducks exposed to metaldehyde in one experimental study. Symptoms included incoordination, torticollis, tremors, rigidity, spasms, and hyperpnea (Booze & Oehme, 1985; Delak & Marzan, 1958).
    C) BIRDS - Postmortem examination of metaldehyde poisoned birds have revealed dilated and engorged blood vessels in the mesentery and intestinal serosa. The lungs were edematous with some areas of blood-tinged fluid surrounding the air sacs. The gizzards had petechiae and the spleen and liver were edematous and hyperemic with coagulation necrosis of hepatocytes noted (Booze & Oehme, 1985).
    11.1.2) BOVINE/CATTLE
    A) Signs of toxicity are reported to be similar to those seen in dogs. The following signs/symptoms have been observed:
    1) SIGNS/SYMPTOMS - A mildly poisoned animal will demonstrate profuse salivation, ataxia, and hypernea. More serious poisoning involves severe ataxia, tremors, seizures and muscle fasciculations, which progress from the rear of the animal and move forward. They have been so severe to pitch the animal forward onto their muzzles (Booze & Oehme, 1985).
    a) Blindness and torticollis have been reported (Stubbings et al, 1976; Longbottom & Gordon, 1979; Williams & Thomas, 1976).
    b) Bloody diarrhea was a prominent finding in one dairy herd that broke into an old barn and fed on grain containing both metaldehyde and arsenic. Although gastrointestinal irritation and hemorrhage has been reported in other species after metaldehyde poisoning, this feature is a well-established clinical consequence of acute arsenic poisoning and cannot be clearly attributed to metaldehyde in this case (Valentine et al, 2007).
    c) PATHOLOGICAL LESIONS - Postmortem lesions identified in cattle after metaldehyde ingestion have included acute lung injury, hypocoagulability, petechial and ecchymotic hemorrhages along the trachea, bronchi, epicardium, myocardium, and throughout the gastrointestinal tract (Stubbings et al, 1976; Longbottom & Gordon, 1979; Williams & Thomas, 1976).
    11.1.3) CANINE/DOG
    A) SIGNS/SYMPTOMS - Acute consequential ingestions in dogs have been frequently reported. Dogs will often eat all of the snail bait that is available. Symptoms may start immediately or may be delayed for up to 3 hours.
    B) Initial symptoms include tachycardia, anxiety, nystagmus, mydriasis, panting, and excessive salivation which may appear frothy. The animals then become ataxic with stiff legs.
    C) Severe poisoning is characterized by the development of severe muscle fasciculations, vomiting, and seizures resulting in cyanosis, acidosis, and dehydration. Hyperthermia frequently develops, but may be related to the increased muscular activity. Late in the poisoning, depression following by coma may occur.
    1) Death is usually due to respiratory failure and occurs between 4 and 24 hours after an ingestion. If the acute phase is survived, recovery can be expected within 3 days to several weeks. Long term affects may include memory loss, and blindness (in one case) (Booze & Oehme, 1986).
    11.1.5) EQUINE/HORSE
    A) Horse poisoning by metaldehyde is unusual. Symptoms reportedly have included colic, restlessness, tremors of the legs, diarrhea, sweating, and increased breathing rates. Tachycardia, clonic spasms, incoordination, severely fluted nostrils, and generalized seizures may also develop.
    1) Horses near death may have violent muscle spasms with ventriflexion of the spine (Sutherland, 1983; Harris, 1975; Miller, 1972).
    11.1.6) FELINE/CAT
    A) At least one death has been reported. Symptoms were similar to those reported with dogs (Booze & Oehme, 1985; Turner, 1962).
    11.1.9) OVINE/SHEEP
    A) Poisoning of sheep by metaldehyde is unusual. Salivation, epileptiform seizures and tremors of the fore and hind legs and of the neck have been noted. Other symptoms have included ataxia, nystagmus, dyspnea, liver damage, and coma (Booze & Oehme, 1985).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Animal treatment is primarily directed at removal of the poison from the stomach, control of seizures, and combating acidosis and dehydration.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) In small animals, apomorphine may be used as an emetic. Induce emesis only within 30 minutes of ingestion, and only in an asymptomatic animal. Gastric lavage under light sedation may be the preferred method of gastric decontamination because aspiration may occur during vomiting in an animal with an altered mental status or seizures.
    b) With larger animals mineral oil has been used as a laxative. Do not attempt to induce emesis or gastric lavage in horses or ruminants (eg, cattle).
    c) Stomach contents and lavage washings can be frozen and submitted for acetaldehyde content.
    11.2.5) TREATMENT
    A) SEIZURES
    1) The use of diazepam or triflupromazine has been recommended in dogs. Acepromazine has also been used to control seizures after metaldehyde poisoning in dogs with a decrease in the death rate and less need for supervision and ventilatory support (Mull, 1983; Booze & Oehme, 1986).
    2) The use of xylazine in combination with acepromazine may be of value in horses with metaldehyde poisoning. Xylazine has also been used in cattle metaldehyde poisonings.
    3) Prolonged anesthesia with pentobarbitone or thiopentone sodium may be of value in controlling seizures in severe cases of poisoning (Duff, 1986; Webster & Webster, 1986; Rose, 1986).
    B) GENERAL
    1) HORSES - The use of xylazine in combination with acepromazine was of value in horses. Xylazine has been used in cattle metaldehyde poisonings. Enterogastric lavage or activated charcoal (250 to 500 grams in a water slurry via stomach tube) may be given. Do not attempt emesis in ruminants or horses. Severe cases: maintain on gas anesthesia with artificial respiration.
    2) Acidosis and dehydration should be treated with Lactated Ringers solution.
    3) Calcium gluconate successfully controlled seizures in a metaldehyde-poisoned puppy (Hayes, 1970). Two severe cases of metaldehyde poisoning recovered after treatment with apomorphine followed by acepromazine, and glucose and calcium gluconate (Davies & Lawrence, 1989).
    4) Prolonged anesthesia with pentobarbitone or thiopentone sodium may be of value in controlling seizures in severe cases of poisoning (Duff, 1986; Webster & Webster, 1986; Rose, 1986).
    5) Monitor the surviving animal for several days after recovery: hepatic failure may occur.

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) GENERAL
    1) MINIMUM LETHAL DOSE (Booze & Oehme, 1985)
    Chicken500 mg/kg
    Cow200 mg/kg
    Dog100 mg/kg
    Donkey360 mg/kg
    Duck300 mg/kg
    Geese800 mg/kg
    Goat783 mg/kg
    Guinea Pig175 mg/kg
    Horse360 mg/kg
    Mouse200 mg/kg
    Rabbit290 mg/kg
    Rat227 mg/kg
    Sheep300 mg/kg

    2) LD50 (Booze & Oehme, 1985)
    Dog100 to 1000 mg/kg
    Guinea Pig175 to 700 mg/kg
    Mice200 mg/kg
    Rabbit290 to 1250 mg/kg
    Rat227 to 690 mg/kg

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Animal treatment is primarily directed at removal of the poison from the stomach, control of seizures, and combating acidosis and dehydration.
    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) In small animals, apomorphine may be used as an emetic. Induce emesis only within 30 minutes of ingestion, and only in an asymptomatic animal. Gastric lavage under light sedation may be the preferred method of gastric decontamination because aspiration may occur during vomiting in an animal with an altered mental status or seizures.
    b) With larger animals mineral oil has been used as a laxative. Do not attempt to induce emesis or gastric lavage in horses or ruminants (eg, cattle).
    c) Stomach contents and lavage washings can be frozen and submitted for acetaldehyde content.

References

General Bibliography

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