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ALDICARB

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Aldicarb is a carbamate pesticide.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C7-H14-N2-O2-S

Available Forms Sources

    A) FORMS
    1) It is formulated as granules (10-15% active ingredient) or in mixed formulations with lindane, PCNB, and ethazol(Hartley & Kidd, 1987a; Hayes, 1982a; Hayes & Laws, 1991a).
    B) SOURCES
    1) Aldicarb is produced by "isobutyraldehyde + hydroxylamine sulphate + methyl mercaptan + methyl isocyanate (alpha chlorination/oxime formation/sulphide formation/isocyanate addition)" (Ashford, 1994).
    C) USES
    1) Aldicarb is used as a systemic carbamate acaricide, insecticide, and nematicide. It is applied to soil to control insects and nematodes in ornamental plants, trees, and crops (Ashford, 1994; Budavari, 1996a; Lewis, 1997a; Lewis, 1998; Hartley & Kidd, 1987a; Hayes, 1982a).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) The following are symptoms from carbamate insecticides in general, which are due to the anticholinesterase activity of this class of compounds. All of these effects may not be documented for aldicarb, but could potentially occur in individual cases.
    B) USES: Aldicarb, a carbamate insecticide, is used as a systemic carbamate acaricide, insecticide, and nematicide. It is applied to soil to control insects and nematodes in ornamental plants, trees, and crops.
    C) TOXICOLOGY: Carbamate insecticides competitively inhibit pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess develop.
    D) EPIDEMIOLOGY: Exposure to carbamate insecticides is common, but serious toxicity is unusual in the US. Common source of severe poisoning in developing countries. Toxicity generally less severe than with organophosphates.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps may develop.
    2) SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, and acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, and respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, and seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia can also develop.
    3) CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (ie, secretions, bradycardia, fasciculations, and miosis) as compared with adults.
    4) INHALATION EXPOSURE: Vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic, and central effects if exposed to significant concentrations.
    0.2.20) REPRODUCTIVE
    A) Aldicarb was not teratogenic in rats or rabbits, but fetal rats were more sensitive to cholinesterase inhibition in the brain than the dams. Two stillbirths occurred after pregnant women consumed aldicarb-contaminated watermelons.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies were found on the possible carcinogenic activity of aldicarb in humans.

Laboratory Monitoring

    A) Monitor vital signs frequently. Obtain serial ECGs and Institute continuous cardiac and pulse oximetry monitoring.
    B) Monitor for respiratory distress (i.e. bronchorrhea, bronchospasm) and for clinical evidence of cholinergic excess (i.e. salivation, vomiting, urination, defecation, miosis).
    C) Determine plasma and/or red blood cell cholinesterase activities (plasma is generally more sensitive, but red cell correlates somewhat better with clinical signs and symptoms). Depression in excess of 50% of baseline is generally associated with cholinergic effects; in severe poisoning, cholinesterase activity may be depressed by 90% of baseline. Correlation between cholinesterase levels and clinical effects in milder poisonings may be poor.
    D) Monitor electrolytes and serum lipase in patients with significant poisoning.
    E) Monitor pulmonary function (i.e. forced vital capacity, expiratory volume in 1 second, negative inspiratory force) in symptomatic patients; may help anticipate need for intubation.
    F) Obtain a chest x-ray in all symptomatic patients.
    G) It is generally not useful to analyze biological or environmental samples for levels of aldicarb because it rapidly disappears.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TOXICITY
    1) A patient who is either asymptomatic or presents with mild clinical symptoms (i.e. normal vitals, pulse oximetry and an acetylcholinesterase greater than 80% of lower reference range), and remains stable for 12 hours can be discharged. Obtain appropriate psychiatric evaluation if an intentional exposure.
    B) MANAGEMENT OF MODERATE TO SEVERE TOXICITY
    1) Immediate assessment and evaluation. Airway management is likely to be necessary. Simple decontamination (i.e. skin and gastrointestinal, removal of contaminated clothes). Administer antidotes: atropine for muscarinic manifestations (e.g. salivation, diarrhea, bronchorrhea), pralidoxime for severe toxicity with nicotinic manifestations (e.g. weakness, fasciculations). Treat seizures with benzodiazepines. Admit to intensive care with continuous monitoring, titration of antidotes, ventilation, and inotropes as needed. Consult a medical toxicologist and/or poison center.
    C) DECONTAMINATION
    1) PREHOSPITAL: Activated charcoal is contraindicated because of possible respiratory depression and seizures and risk of aspiration. Remove contaminated clothing, wash skin with soap and water. Universal precautions and nitrile gloves to protect personnel.
    2) HOSPITAL: INGESTION: Activated charcoal for large ingestions. Consider nasogastric tube for aspiration of gastric contents, or gastric lavage for recent large ingestions, if patient is intubated or able to protect airway. DERMAL: Remove contaminated clothing. Wash skin thoroughly with soap and water. Universal precautions and nitrile gloves to protect staff from contamination. Systemic toxicity can result from dermal exposure. OCULAR: Copious eye irrigation.
    D) AIRWAY MANAGEMENT
    1) Immediately assess airway and respiratory function. Endotracheal intubation may be necessary because of respiratory muscle weakness or bronchorrhea. Avoid succinylcholine for rapid sequence intubation as prolonged paralysis may result. Monitoring pulmonary function (FVC, FEV1, NIF) may help anticipate need for intubation.
    E) ANTIDOTES
    1) There are two primary classes of antidotes: ATROPINE is used to antagonize muscarinic effects. OXIMES (pralidoxime in the US, or obidoxime in some other countries) are used to reverse neuromuscular blockade. Use of oximes is usually indicated for patients with severe toxicity and are used in conjunction with atropine.
    a) ATROPINE
    1) Atropine is used to treat muscarinic effects (e.g. salivation, lacrimation, defecation, urination, bronchorrhea). ADULT: 1 to 3 mg IV; CHILD: 0.02 mg/kg IV. If inadequate response in 3 to 5 minutes, double the dose. Continue doubling the dose and administer it IV every 3 to 5 minutes as needed to dry pulmonary secretions. Once secretions are dried, maintain with an infusion of 10% to 20% of the loading dose every hour. Monitor frequently for evidence of cholinergic effects or atropine toxicity (e.g. delirium, hyperthermia, ileus) and titrate dose accordingly. Large doses (hundreds of milligrams) are sometimes required. Atropinization may be required for hours to days depending on severity.
    b) PRALIDOXIME
    1) Treat moderate to severe poisoning (fasciculations, muscle weakness, respiratory depression, coma, seizures) with pralidoxime in addition to atropine; most effective if given within 48 hours. Administer for 24 hours after cholinergic manifestations have resolved. May require prolonged administration. ADULT DOSE: A loading dose of 30 mg/kg (maximum: 2 grams) over 30 minutes followed by a maintenance infusion of 8 to 10 mg/kg/hr (up to 650 mg/hr). ALTERNATE ADULT DOSE: 1 to 2 grams diluted in 100 mL of 0.9% sodium chloride infused over 15 to 30 minutes. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). In patients with serious cholinergic intoxication, a continuous infusion of 500 mg/hr should be considered. Intravenous dosing is preferred; however, intramuscular administration may be considered. A continuous infusion of pralidoxime is generally preferred to intermittent bolus dosing to maintain a target concentration with less variation. CHILD DOSE: A loading dose of 20 to 40 mg/kg (maximum: 2 grams/dose) infused over 30 to 60 minutes in 0.9% sodium chloride. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). ALTERNATE CHILD DOSE: An alternate loading dose of 25 to 50 mg/kg (up to a maximum dose of 2 g), followed via continuous infusion of 10 to 20 mg/kg/hr. In patients with serious cholinergic intoxication, a continuous infusion of 10 to 20 mg/kg/hr up to 500 mg/hr should be considered.
    F) SEIZURES
    1) IV benzodiazepines are indicated for seizures or agitation, diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV; repeat as needed.
    G) HYPOTENSIVE EPISODE
    1) IV fluids, dopamine, norepinephrine.
    H) BRONCHOSPASM
    1) Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine.
    I) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with unintentional trivial exposures who are asymptomatic can be observed in the home or in the workplace.
    2) OBSERVATION CRITERIA: Patients with deliberate or significant exposure and those who are symptomatic should be sent to a health care facility for evaluation, treatment and observation for 6 to 12 hours. Onset of toxicity is variable; most patients will develop symptoms within 6 hours. Patients that remain asymptomatic 12 hours after an ingestion or a dermal exposure are unlikely to develop severe toxicity. Cholinesterase activity should be determined to confirm the degree of exposure.
    3) ADMISSION CRITERIA: All intentional ingestions should be initially managed as a severe exposure. Determine cholinesterase activity to assess if a significant exposure occurred. Patients who develop signs or symptoms of cholinergic toxicity (e.g. muscarinic, nicotinic OR central) should be admitted to an intensive care setting.
    4) CONSULT CRITERIA: Consult a medical toxicologist and/or poison center for assistance with any patient with moderate to severe cholinergic manifestations.
    J) PITFALLS
    1) Inadequate initial atropinization. Patients with severe toxicity require rapid administration of large doses, titrate to the endpoint or drying pulmonary secretions.
    2) Monitor respiratory function closely, pulmonary function testing may provide early clues to the development of respiratory failure.
    3) Some component of dermal exposure occurs with most significant overdoses, inadequate decontamination may worsen toxicity.
    4) Patients should be monitored closely for 48 hours after discontinuation of atropine and pralidoxime for evidence of recurrent toxicity or intermediate syndrome.
    K) TOXICOKINETICS
    1) Well absorbed across the lung, mucous membranes (including gut), and skin; significant toxicity has been reported after all these routes of exposure.
    2) Most patients who develop severe toxicity have signs and symptoms within 6 hours of exposure, onset of toxicity is rarely more than 12 hours after exposure.
    3) Recurrence of toxicity after apparent improvement has been described.
    L) PREDISPOSING CONDITIONS
    1) Patients with chronic occupational exposure to carbamate insecticides may have chronically depressed cholinesterase activity and may develop severe toxicity after smaller acute exposures.
    2) Dermal absorption is enhanced in young children due to larger surface area to volume ratio and more permeable skin.
    M) DIFFERENTIAL DIAGNOSIS
    1) Gastroenteritis, food poisoning, asthma, myasthenic crisis, cholinergic excess from medications.
    0.4.3) INHALATION EXPOSURE
    A) Remove from exposure and administer oxygen if respiratory distress develops.
    B) Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine for bronchorrhea and bronchospasm. Inhaled beta agonists may be useful for bronchospasm unresponsive to anticholinergics.
    C) Monitor for the development of cholinergic toxicity and treat as in oral exposure.
    0.4.4) EYE EXPOSURE
    A) Irrigate exposed eyes with water or normal saline. Systemic toxicity is unlikely to develop from ocular exposure alone.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Systemic effects can occur from dermal exposure to carbamate insecticides. Remove contaminated clothing, wash skin thoroughly with soap and water. Use universal precautions and nitrile gloves to protect staff from contamination.
    2) Monitor for the development of cholinergic toxicity and treat as in oral exposure.
    0.4.6) PARENTERAL EXPOSURE
    A) Monitor for the development of compartment syndrome, tissue necrosis, cellulitis, and thrombophlebitis in addition to systemic cholinergic toxicity (which may be prolonged) after subcutaneous, intramuscular or intravenous injection.

Range Of Toxicity

    A) TOXICITY: A toxic dose has not been established. Aldicarb is considered the most toxic carbamate. Symptoms developed in patients receiving a dose of 0.0011 to 0.06 milligram/kilogram. The World Health Organization (WHO) has classified aldicarb as pesticide class IA (extremely hazardous). Carbamates are absorbed across the lung, mucous membranes (including gut), and skin. Poisoning depends upon inherent toxicity, dosage, rate of absorption, rate of metabolic breakdown, and prior exposure to other cholinesterase inhibitors. Generally carbamates are less toxic than organophosphates.

Clinical Effects

Summary Of Exposure

    A) The following are symptoms from carbamate insecticides in general, which are due to the anticholinesterase activity of this class of compounds. All of these effects may not be documented for aldicarb, but could potentially occur in individual cases.
    B) USES: Aldicarb, a carbamate insecticide, is used as a systemic carbamate acaricide, insecticide, and nematicide. It is applied to soil to control insects and nematodes in ornamental plants, trees, and crops.
    C) TOXICOLOGY: Carbamate insecticides competitively inhibit pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess develop.
    D) EPIDEMIOLOGY: Exposure to carbamate insecticides is common, but serious toxicity is unusual in the US. Common source of severe poisoning in developing countries. Toxicity generally less severe than with organophosphates.
    E) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps may develop.
    2) SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, and acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, and respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, and seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia can also develop.
    3) CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (ie, secretions, bradycardia, fasciculations, and miosis) as compared with adults.
    4) INHALATION EXPOSURE: Vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic, and central effects if exposed to significant concentrations.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTHERMIA: Slight or moderate hypothermia, not correlated with Glasgow Coma Score, was reported in 6 patients out of a series of 18 patients following acute aldicarb poisoning (Ragoucy-Sengler et al, 2000).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) MIOSIS and blurred vision may occur. Miosis, a muscarinic effect, is characteristic of severe and moderately severe poisonings, but may appear late (Tracqui et al, 2001; Flesch et al, 1999; Covaci et al, 1999).
    2) INCIDENCE: In a series of 26 children with methomyl or aldicarb poisoning, 21 (80%) developed miosis (Lifshitz et al, 1994). In a series of 18 aldicarb poisonings (all age groups), 17 patients developed miosis (Ragoucy-Sengler et al, 2000). In another case series of 35 pediatric and adult patients, 71% developed miosis following aldicarb poisoning (Nelson et al, 2001).
    3) CASE REPORT: A 2-year-old child became comatose with miotic pupils following accidental ingestion of aldicarb (Anon, 1997).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) Excessive salivation may occur as a cholinergic crisis effect following intentional ingestions (Flesch et al, 1999).
    2) INCIDENCE: In a series of 18 aldicarb poisonings (all age groups), 15 patients developed hypersalivation (Ragoucy-Sengler et al, 2000).
    3) INCIDENCE: In a case series of 35 patients (pediatric and adult), 54% developed salivation following aldicarb ingestion (Nelson et al, 2001).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Muscarinic effects may commonly include bradycardia (Covaci et al, 1999)
    b) INCIDENCE: In a series of 26 children with methomyl or aldicarb poisoning, 6 (23%) developed bradycardia (Lifshitz et al, 1994). In a series of 18 aldicarb poisonings (all age groups), 10 patients (55%) were reported to have bradycardia (Ragoucy-Sengler et al, 2000). In a case series of 35 patients (pediatric and adult), 22% developed bradycardia (hr <60) following aldicarb ingestion (Nelson et al, 2001)
    c) CASE REPORTS: A 43-year-old man with aldicarb poisoning presented with a heart rate of 50 beats/minute (Burgess et al, 1994). In another intentional aldicarb ingestion of 10 grams, heart rate of 40 beats/minute was reported in a 30-year-old woman (Flesch et al, 1999). Bradycardia with second degree AV block that resolved following 1 mg intravenous atropine was reported in a 63-year-old woman after ingesting aldicarb-contaminated coffee (Covaci et al, 1999).
    B) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Following ingestion of aldicarb, an 18-year-old man presented to the emergency department with tachycardia, tachypnea, diffuse muscle fasciculations and profuse bronchorrhea (Anon, 1997).
    b) CASE REPORT: Sinus tachycardia (100 bpm) was reported in a 29-year-old man who intentionally ingested an unknown amount of "Tres Pasitos", a rodenticide containing aldicarb (Waseem et al, 2010).
    c) INCIDENCE: In a case series of 35 patients (pediatric and adult), 63% developed tachycardia following aldicarb ingestion (Nelson et al, 2001).
    C) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Sinus tachycardia with ST segment depression may occur early in the course of poisoning. Repolarization abnormalities may occur and are generally transient (Tracqui et al, 2001).
    b) CASE SERIES: Conduction abnormalities were reported in 4 out of 18 aldicarb poisonings in one study (Ragoucy-Sengler et al, 2000). The abnormalities in these 4 patients were reported as heart block in 3 and torsade de pointes in one.
    c) Severe ST depression was reported in one pediatric carbamate poisoning (Sofer et al, 1989).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) Dyspnea is a common manifestation of carbamate insecticide exposure (Ragoucy-Sengler et al, 2000).
    b) Respiratory depression and rales may be noted. Dyspnea was reported in 7 of 8 children with carbamate poisoning (Sofer et al, 1989).
    c) ADULT CASE SERIES: Six men exposed to aldicarb in a sprayed field and working with sheep grazing in the contaminated field all experienced dyspnea and sore throats within 24 hours (Grendon et al, 1994).
    d) CASE REPORT: An adult was admitted 2 hours following development of pulmonary secretions and was found 13 hours later to have a blood aldicarb level of 0.1 mg/mL. Plasma cholinesterase was 6% of normal 3.5 hours after admission, and remained depressed for 56 hours (Burgess et al, 1994).
    e) CASE REPORT: A 29-year-old man developed respiratory distress with harsh breath sounds and rhonchi in both lung fields after intentionally ingesting an unknown amount of "Tres Pasitos", a rodenticide containing aldicarb (Waseem et al, 2010).
    B) BRONCHOSPASM
    1) Bronchoconstriction may occur (Morgan, 1993).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 2-year-old child was admitted to the hospital in a comatose state with miosis, muscle fasciculations and pulmonary edema following accidental ingestion of aldicarb. Intubation was required for respiratory insufficiency. The child recovered following supportive therapy and atropine and pralidoxime injections (Anon, 1997).
    D) PULMONARY ASPIRATION
    1) WITH POISONING/EXPOSURE
    a) Aspiration pneumonitis may occur after ingestion of carbamates in hydrocarbon vehicles. A complication of prolonged intubation and mechanical ventilation following pulmonary effects of poisoning is aspiration pneumonia (Aaron & Howland, 1998).
    E) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Respiratory depression along with acute pulmonary edema is usually the immediate cause of death from acute exposures to N-methyl carbamates such as aldicarb (Morgan, 1993).
    b) CASE SERIES: Respiratory insufficiency developed in 3 of 26 (11%) children with methomyl or aldicarb poisoning in one series (Lifshitz et al, 1994).
    F) SPUTUM ABNORMAL - AMOUNT
    1) WITH POISONING/EXPOSURE
    a) INCREASED BRONCHIAL SECRETIONS may occur secondary to muscarinic effects and may be significant requiring frequent suctioning (Tracqui et al, 2001; Covaci et al, 1999).
    b) INCIDENCE: In a case series of 35 patients (pediatric and adult), 34% developed bronchorrhea following aldicarb ingestion (Nelson et al, 2001).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures may occur in severe poisonings. Children may be more susceptible than adults. Incidences are shown as follows:
    1) CASE SERIES (PEDIATRIC): In a series of 26 children with aldicarb or methomyl poisoning, 3 (11%) developed seizures (Lifshitz et al, 1994). In a later expanded case series of 36 children, 3 (8%) developed seizures (Lifshitz et al, 1997).
    2) CASE SERIES (PEDIATRIC): In one series, 2 children poisoned by carbamates had seizures (Zwiener & Ginsburg, 1988).
    3) CASE SERIES: In a series of 18 aldicarb poisonings (all age groups), 4 patients (22%) developed seizures (Ragoucy-Sengler et al, 2000).
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) CNS depression leading to coma may occur after severe poisonings, with decreased or absent tendon and brainstem reflexes (Tracqui et al, 2001; Flesch et al, 1999).
    b) CASE SERIES (PEDIATRIC): In a series of 26 children with aldicarb or methomyl poisoning all developed stupor or coma (Lifshitz et al, 1994). In a later expanded case series, all 36 children developed stupor or coma, while 0 out of 24 adults with aldicarb or methomyl poisoning developed stupor or coma (Lifshitz et al, 1997).
    c) CASE SERIES (PEDIATRIC): In a series of 36 children intoxicated with methomyl and aldicarb, predominant symptoms were related to CNS depression and severe hypotonia. Absence of classic muscarinic effects was noted (Lifshitz et al, 1999).
    d) CASE SERIES: In a series of 18 aldicarb poisonings (all age groups), 8 patients (44%) developed coma (Ragoucy-Sengler et al, 2000).
    e) CASE SERIES: In a case series of 35 patients (pediatric and adult), 51% developed lethargy or coma following aldicarb ingestion (Nelson et al, 2001).
    C) DECREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) Hypotonia is a common nicotinic effect of carbamate insecticide poisoning (Ragoucy-Sengler et al, 2000).
    b) CASE SERIES: In a case series of 36 children and 24 adults with aldicarb or methomyl poisoning, all the children developed hypotonia, while none of the adults developed hypotonia (Lifshitz et al, 1997; Lifshitz et al, 1999).
    c) CASE SERIES: In a series of 18 aldicarb poisonings (all age groups), 7 patients developed hypotonia (Ragoucy-Sengler et al, 2000).
    D) SPASMODIC MOVEMENT
    1) WITH POISONING/EXPOSURE
    a) Muscle fasciculations may develop as a nicotinic effect (Ragoucy-Sengler et al, 2000; Flesch et al, 1999; Burgess et al, 1994).
    b) CASE SERIES (PEDIATRIC): Fasciculations developed in 1 of 26 (4%) children poisoned with methomyl or aldicarb (Lifshitz et al, 1994).
    c) CASE SERIES: In a series of 18 aldicarb poisonings (all age groups), 14 patients (78%) developed fasciculations (Ragoucy-Sengler et al, 2000).
    d) CASE SERIES: In a case series of 35 patients (pediatric and adult), 42% developed fasciculations following aldicarb ingestion (Nelson et al, 2001).
    E) ALTERED MENTAL STATUS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Seven farm workers presented to an emergency department with nausea, vomiting, diarrhea, abdominal cramping, and altered mental status. Interviews conducted with the patients revealed that they had each consumed a portion of a freshly picked watermelon from the farm prior to symptom-onset. Analysis of the uningested portion of the watermelon, as well as another watermelon from the same farm, detected the presence of aldicarb, aldicarb sulfone, and aldicarb sulfoxide. Six of the seven patients were discharged without sequelae following symptomatic and supportive therapy and 24 hours of observation. The seventh patient, a 53-year-old man with diabetes, hypertension, and hypokalemia, was admitted for electrolyte abnormalities and recovered uneventfully (D'Haenens et al, 2013).
    F) FATIGUE
    1) Protracted malaise and weakness may occur after apparent recovery from carbamate poisoning (Garber, 1987).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting and diarrhea are common muscarinic signs (Burgess et al, 1994).
    b) Following an incident of aldicarb food poisoning, gastrointestinal effects were most common, with abdominal cramps in 13 (93%), diarrhea in 12 (86%), and nausea in 13 (93%) (Anon, 1999).
    c) INCIDENCE: In a series of 18 aldicarb poisonings (all age groups), 13 patients developed vomiting (Ragoucy-Sengler et al, 2000).
    d) CASE SERIES: Diarrhea developed in 12 of 36 (33%) children compared with 0 of 26 adults poisoned with methomyl or aldicarb (Lifshitz et al, 1997; Lifshitz et al, 1999). In another series of 18 aldicarb poisonings (all age groups), 7 patients developed diarrhea (Ragoucy-Sengler et al, 2000).
    e) CASE SERIES: Seven farm workers presented to an emergency department with nausea, vomiting, diarrhea, abdominal cramping, and altered mental status. Interviews conducted with the patients revealed that they had each consumed a portion of a freshly picked watermelon from the farm prior to symptom-onset. Analysis of the uningested portion of the watermelon, as well as another watermelon from the same farm, detected the presence of aldicarb, aldicarb sulfone, and aldicarb sulfoxide. Six of the seven patients were discharged without sequelae following symptomatic and supportive therapy and 24 hours of observation. The seventh patient, a 53-year-old man with diabetes, hypertension, and hypokalemia, was admitted for electrolyte abnormalities and recovered uneventfully (D'Haenens et al, 2013).
    B) PANCREATITIS
    1) WITH POISONING/EXPOSURE
    a) In a series of 18 aldicarb poisonings (all age groups), 4 patients developed pancreatitis, with elevated lipase and amylase levels (Ragoucy-Sengler et al, 2000).
    b) CASE REPORT: Acute necrotic hemorrhagic pancreatitis occurred in a 29-year-old woman who attempted suicide by ingesting a carbamate pesticide (containing 10% aldicarb) (Moritz et al, 1994).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) A combined acidosis with very low oxygen saturation (arterial blood gases pH 7.22, O2 saturation 80.2%) was reported in a 63-year-old woman after consuming aldicarb-contaminated coffee (Covaci et al, 1999).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis may commonly develop as a muscarinic effect (Burgess et al, 1994).
    b) INCIDENCE: In a series of 18 aldicarb poisonings (all age groups), 9 patients developed sweating (Ragoucy-Sengler et al, 2000).
    c) INCIDENCE: In a case series of 35 patients (pediatric and adult), 58% developed diaphoresis following aldicarb ingestion (Nelson et al, 2001).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) Aldicarb was not irritating to the skin of rabbits and it did not cause a skin sensitization reaction in guinea pigs (Hayes & Laws, 1991).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Rhabdomyolysis with transient renal dysfunction has been reported in 2 adults following consumption of aldicarb-contaminated coffee. Both patients were treated with atropine injections over a 4-day period and recovered (Covaci et al, 1999).
    B) MUSCLE WEAKNESS
    1) WITH POISONING/EXPOSURE
    a) Acute muscle weakness may occur as a nicotinic effect.
    b) CASE REPORT (ADULT): An adult man was admitted 2 hours after development of weakness. Thirteen hours later the blood aldicarb level was 0.1 mg/mL. Plasma cholinesterase was 6% of normal 3.5 hours after admission, and remained depressed for 56 hours.
    1) The weakness improved after administration of pralidoxime 4 grams IV over 10 hours. Recovery was uneventful (Burgess et al, 1994).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) WITH POISONING/EXPOSURE
    a) Drinking water contamination with aldicarb was associated with an increase in CD8+ T-lymphocytes in a cohort of 23 women; exposures ranged from 1 to 61 ppb. When examined two years later, 2 women with continued exposure to water containing 1.2 to 5 ppb (mean average daily ingestion 0.022 mcg/kilogram/day) had no significant change in the CD8+ count, while 14 women who had discontinued exposure experienced decreased CD8+ counts. No clinical immune dysfunction was noted (Mirkin et al, 1990).
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    a) MIXED RESULTS IN ANIMALS: Immunosuppressant effects were seen in mice given aldicarb at levels of 1 to 1000 ppb in the drinking water, as measured by splenic plaque forming cell capacity in response to sheep erythrocytes (Olson et al, 1986). Similar studies have demonstrated time-dependant effects with stimulation at 30 and 60 days and inhibition at 90 and 180 days of exposure (Shirazi et al, 1990).
    1) In another study, levels up to 1000 ppm (1000 times higher than in the above study) did not affect antibody response to sheep red blood cells, levels of Ig-M, or lymphocyte blastogenesis (Thomas et al, 1987).
    2) A third study found no effect of aldicarb on splenic plaque forming response to sheep erythrocytes, NK cell function, and other immunologic parameters, when given at levels up to 1000 ppb in the drinking water for 34 days (Thomas & Ratajczak, 1988; Thomas et al, 1990). Other authors report time-dependant changes in various immune parameters (Hajoui et al, 1992). Results of these various investigations appear to be poorly reproducible.
    3) In C3H mice, aldicarb appears to interfere with macrophage stimulation of helper T-lymphocytes via inhibition of the production or release of interleukin-1 (Dean et al, 1990a; Dean et al, 1990b).

Reproductive

    3.20.1) SUMMARY
    A) Aldicarb was not teratogenic in rats or rabbits, but fetal rats were more sensitive to cholinesterase inhibition in the brain than the dams. Two stillbirths occurred after pregnant women consumed aldicarb-contaminated watermelons.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) Aldicarb was not teratogenic in rats in a 3-generation study at a dose of 0.7 mg/kg/day (EPA, 1988). It was also not teratogenic in rats at 1 mg/kg/day, or in rabbits at 0.5 mg/kg/day (EPA, 1988).
    3.20.3) EFFECTS IN PREGNANCY
    A) STILLBIRTH
    1) Two stillbirths out of 47 pregnancies occurred in the episode of mass poisoning by aldicarb from contaminated watermelons in California in 1985. These stillbirths were both from near-term pregnancies at the time of the poisoning (Goldman et al, 1990a).
    2) CASE REPORT - A 17-year-old pregnant woman (18 weeks gestation) ingested carbofuran, a related carbamate, to commit suicide. She arrived at a health care facility 2 hours after ingestion. She was treated with activated charcoal, gastric lavage and intensive symptomatic care. Fetal pulse was not audible on the second day of admission. Neither heart tones nor fetal movement could be detected by ultrasonography.
    a) Induction of delivery because of still pregnancy occurred on the seventh day of hospital admission. Concentration of carbofuran in the kidney, liver, and brain of the fetus was comparable with the concentration in the mother's blood (Klys et al, 1989).
    B) ABORTION
    1) A 46% incidence of spontaneous abortions was reported in areas on Long Island, NY, where water supplies had been contaminated with aldicarb (Schardein, 1993).
    C) ANIMAL STUDIES
    1) Aldicarb given in a single oral dose of 0.001, 0.001, or 0.1 mg/kg on day 18 of gestation inhibited cholinesterase in the brains, blood, and liver of fetal rats within one hour. Fetal enzymes were more severely affected than maternal enzymes (Cambon et al, 1979).
    2) Aldicarb at up to 0.7 mg/kg/d did not affect mortality, histopathology, fertility, gestation, viability or lactation in 3-generation studies in rats (Hayes & Laws, 1991).
    3) In evaluating the reproductive hazards of carbaryl (the dog is the most sensitive species, with an effective dose of 2 mg/kg), Cranmer (1986) concluded that there is a very large margin of safety for possible reproductive effects in humans, based on average human exposures.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Eleven metabolites of aldicarb, including the sulfone and sulfoxide, were detected in cow's milk (HSDB , 1997). Note that the sulfoxide has 76 times more anticholinesterase activity than aldicarb itself (HSDB , 1997).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) Administration of a mixture of pesticides including aldicarb to Swiss CD-1 mice and Sprague-Dawley rats resulted in no observed effects on fertility or general or developmental toxicity (Heindel, 1994).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS116-06-3 (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) IARC Classification
    a) Listed as: Aldicarb
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no studies were found on the possible carcinogenic activity of aldicarb in humans.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) No evidence for carcinogenicity in mice or rats was found in the NCI Carcinogenesis Bioassay (Feed) (RTECS , 1997). Aldicarb was also not carcinogenic in a 2-year feeding study in dogs (EPA, 1988).
    2) In chronic dietary studies aldicarb was not carcinogenic to rats at up to approximately 0.3 mg/kg/d or to mice up to approximately 0.9 mg/kg/d (Hayes & Laws, 1991).

Genotoxicity

    A) Aldicarb has been genotoxic in various short-term tests at the mutational and chromosomal level.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs frequently. Obtain serial ECGs and Institute continuous cardiac and pulse oximetry monitoring.
    B) Monitor for respiratory distress (i.e. bronchorrhea, bronchospasm) and for clinical evidence of cholinergic excess (i.e. salivation, vomiting, urination, defecation, miosis).
    C) Determine plasma and/or red blood cell cholinesterase activities (plasma is generally more sensitive, but red cell correlates somewhat better with clinical signs and symptoms). Depression in excess of 50% of baseline is generally associated with cholinergic effects; in severe poisoning, cholinesterase activity may be depressed by 90% of baseline. Correlation between cholinesterase levels and clinical effects in milder poisonings may be poor.
    D) Monitor electrolytes and serum lipase in patients with significant poisoning.
    E) Monitor pulmonary function (i.e. forced vital capacity, expiratory volume in 1 second, negative inspiratory force) in symptomatic patients; may help anticipate need for intubation.
    F) Obtain a chest x-ray in all symptomatic patients.
    G) It is generally not useful to analyze biological or environmental samples for levels of aldicarb because it rapidly disappears.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) If a blood sample can be obtained and analyzed within a short time after acute exposure to a carbamate such as aldicarb, determination of plasma pseudocholinesterase and/or red blood cell acetylcholinesterase activity may be useful in confirming exposure. A rapid method of analysis should be used, because the carbamylated enzyme is rapidly reactivated both in vivo and in vitro (Morgan, 1993).
    2) Depression of cholinesterase levels often does not correlate with severity of clinical symptoms.
    3) Cholinesterase levels can be done by specialized toxicology laboratories. Unless the patient has had extraordinary exposure to an N-methyl carbamate compound, IT IS UNLIKELY THAT BLOOD CHOLINESTERASE ACTIVITIES WILL BE DEPRESSED. Nonetheless, there is some merit in ordering cholinesterase levels to assess the approximate magnitude of toxicant absorption. In symptomatic patients, the red blood cell and serum cholinesterase activity correlated in 20 of 24 patients (Zweiner & Ginsburg, 1988).
    4) Serial monitoring of plasma pseudocholinesterase and erythrocyte acetylcholinesterase levels, in conjunction with reversal of clinical signs and symptoms, may be useful in determining when an occupationally-exposed person may return to work. In general, elevation of cholinesterase to 70% of pre-exposure value is considered sufficient recovery.
    5) The limit of sensitivities for aldicarb for different laboratories ranged from 0.01 to 0.2 parts per million (Witt & Wagner, 1986).
    6) Aldicarb was not detectable in a postmortem blood sample from a patient with occupational fatality where the primary cause of death was multiple trauma. Levels of aldicarb sulfoxide and sulfone were 0.108 and 0.374 ppm, respectively (Lee & Ransdell, 1984).
    4.1.3) URINE
    A) URINARY LEVELS
    1) Detection of phenolic derivatives of carbamates may be useful to confirm exposure to specific compounds, but is not sufficiently reliable for biological monitoring (Kuhr & Dorough, 1976).
    4.1.4) OTHER
    A) OTHER
    1) POSTMORTEM
    a) Postmortem levels of aldicarb found in body tissues in a patient with occupational fatality where the primary cause of death was trauma were (in ppm) - blood (not detected), liver (0.013), kidney (trace), skin--hand (0.492), skin--abdomen (0.005), skin--thigh (0.168) (Lee & Ransdell, 1984).

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Chest x-ray should be obtained in all symptomatic patients. The major cause of morbidity and mortality in carbamate insecticide poisonings is respiratory failure and associated pulmonary edema.

Methods

    A) CHROMATOGRAPHY
    1) Ragoucy-Sengler et al (2000) and Tracqui et al (2001) described the identification and quantification of aldicarb in human blood and urine by UV spectra and retention time after HPLC separation. The authors used a HPLC system with diode array detection. Limit of detection (assay on 1 mL blood) was 0.05 mcg/mL; limit of quantification was 0.10 mcg/mL (Tracqui et al, 2001; Ragoucy-Sengler et al, 2000).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) All intentional ingestions should be initially managed as a severe exposure. Determine cholinesterase activity to assess if a significant exposure occurred. Patients who develop signs or symptoms of cholinergic toxicity (e.g. muscarinic, nicotinic OR central) should be admitted to an intensive care setting.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with unintentional trivial exposures who are asymptomatic can be observed in the home or in the workplace.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist and/or poison center for assistance with any patient with moderate to severe cholinergic manifestations.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate or significant exposure and those who are symptomatic should be sent to a health care facility for evaluation, treatment and observation for 6 to 12 hours. Onset of toxicity is variable; most patients will develop symptoms within 6 hours. Patients that remain asymptomatic 12 hours after an ingestion or a dermal exposure are unlikely to develop severe toxicity. Cholinesterase activity should be determined to confirm the degree of exposure.

Monitoring

    A) Monitor vital signs frequently. Obtain serial ECGs and Institute continuous cardiac and pulse oximetry monitoring.
    B) Monitor for respiratory distress (i.e. bronchorrhea, bronchospasm) and for clinical evidence of cholinergic excess (i.e. salivation, vomiting, urination, defecation, miosis).
    C) Determine plasma and/or red blood cell cholinesterase activities (plasma is generally more sensitive, but red cell correlates somewhat better with clinical signs and symptoms). Depression in excess of 50% of baseline is generally associated with cholinergic effects; in severe poisoning, cholinesterase activity may be depressed by 90% of baseline. Correlation between cholinesterase levels and clinical effects in milder poisonings may be poor.
    D) Monitor electrolytes and serum lipase in patients with significant poisoning.
    E) Monitor pulmonary function (i.e. forced vital capacity, expiratory volume in 1 second, negative inspiratory force) in symptomatic patients; may help anticipate need for intubation.
    F) Obtain a chest x-ray in all symptomatic patients.
    G) It is generally not useful to analyze biological or environmental samples for levels of aldicarb because it rapidly disappears.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) PREHOSPITAL: Activated charcoal is contraindicated because of possible respiratory depression, seizures, and risk of aspiration. Remove contaminated clothing and wash skin with soap and water. Universal precautions and nitrile gloves to protect personnel. Vomiting should be contained and treated as hazardous material. Rescue personnel should avoid dermal exposure to vomiting because of the risk of intoxication.
    B) There are two primary classes of antidotes: ATROPINE (muscarinic antagonist); OXIMES (pralidoxime in the US, or obidoxime in some other countries) to reverse neuromuscular blockade. Use of oximes is generally indicated for patients with severe toxicity and are used in conjunction with atropine.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Activated charcoal with or without gastric lavage should be administered if ingestion has been recent. Seizures may occur; protect the airway.
    B) ACTIVATED CHARCOAL
    1) 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.
    2) 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).
    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) Monitor vital signs frequently. Obtain serial ECGs and institute continuous cardiac and pulse oximetry monitoring.
    2) Monitor for respiratory distress (ie, bronchorrhea, bronchospasm) and for clinical evidence of cholinergic excess (ie, salivation, vomiting, urination, defecation, miosis).
    3) Determine plasma and/or red blood cell cholinesterase activities (plasma is generally more sensitive, but red cell correlates somewhat better with clinical signs and symptoms). Depression in excess of 50% of baseline is generally associated with cholinergic effects; in severe poisoning, cholinesterase activity may be depressed by 90% of baseline. Correlation between cholinesterase levels and clinical effects in milder poisonings may be poor.
    4) Monitor electrolytes and serum lipase in patients with significant poisoning.
    5) Monitor pulmonary function (ie, forced vital capacity, expiratory volume in 1 second, negative inspiratory force) in symptomatic patients; may help anticipate need for intubation.
    6) Obtain a chest x-ray in all symptomatic patients.
    7) It is generally not useful to analyze biological or environmental samples for levels of aldicarb because it rapidly disappears.
    B) ATROPINE
    1) SUMMARY
    a) Atropine is used to treat muscarinic effects (e.g. salivation, lacrimation, defecation, urination, bronchorrhea).
    2) DOSE
    a) ADULT: 1 to 3 mg IV; CHILD: 0.02 mg/kg IV. If inadequate response in 3 to 5 minutes, double the dose. Continue doubling the dose and administering it IV every 3 to 5 minutes as needed to dry pulmonary secretions. Once secretions are dried, maintain with an infusion of 10% to 20% of the loading dose every hour. Monitor frequently for evidence of cholinergic effects or atropine toxicity (e.g., delirium, hyperthermia, ileus) and titrate dose accordingly. Large doses (hundreds of milligrams) are sometimes required. Atropinization may be required for hours to days depending on severity (Roberts & Aaron, 2007).
    3) MAINTAIN ATROPINIZATION: For hours or days, depending on estimated toxicity and dose of toxicant. Following a massive exposure, hundreds of milligrams of atropine may be needed. In one adult case, a total atropine dose of 970 milligrams was required (Nelson et al, 2001).
    4) ATROPINE INFUSION: An atropine drip may be compounded using the powdered form of the drug or using the 20 mL multidose vial. Use preservative-free atropine. In one adult case, an atropine drip was started at 6 mg/hr, then titrated up to 9 mg/hr in order to prevent recurrent bronchorrhea. This was continued for 5 days until a total dose of 970 mg had been administered (Nelson et al, 2001).
    5) ATROPINE WITHDRAWAL: Done gradually by lengthening interval between doses. Check lung bases for rales, and observe patient for return of cholinergic signs. Increase atropine dosage promptly if there are indications of relapse.
    6) PRESERVATIVE TOXICITY: Many parenteral atropine preparations are preserved with benzyl alcohol or chlorobutanol. High dose atropine therapy may result in excipient toxicity if these formulations are used. Preservative-free atropine injection is available.
    7) SUCTIONING: Careful suctioning of oral and tracheal secretions may be necessary until atropinization is achieved.
    C) PRALIDOXIME
    1) INDICATIONS
    a) USE IS CONTROVERSIAL: Critical reviews of the use of oximes in carbamate poisoning have been published (Pelfrene, 1986; Kurtz, 1990). Clinical experience in humans has not consistently confirmed the value of pralidoxime in carbamate poisoning.
    b) A consensus of experts concluded that 6 of 10 had or would use pralidoxime in conjunction with atropine for specific indications listed below. Four of 10 would not use pralidoxime. One expert presented anecdotal experience in two patients who appeared to worsen after receiving pralidoxime (Consensus, 1986).
    c) INDICATIONS: After adequate atropinization, pralidoxime may be indicated in the following situations (Consensus, 1986).
    1) Life-threatening symptoms such as severe muscle weakness, fasciculations, paralysis, or decreased respiratory effort.
    2) Continued excessive requirements of atropine.
    3) Concomitant organophosphate and carbamate exposure.
    2) INCREASED TOXICITY WITH USE
    a) In one human case report of carbaryl poisoning, pralidoxime was implicated in contributing to toxicity, but the patient appeared to be inadequately atropinized (Farago, 1969).
    b) ANIMAL STUDIES: In laboratory animals, when pralidoxime was given alone or an alternate oxime (obidoxime) was given with atropine, an increase in carbaryl toxicity (but not other carbamates) was seen. A total of 5 animals were studied(Natoff & Reiff, 1973).
    3) NO INCREASED TOXICITY WITH USE
    a) Pralidoxime was used in 5 of 13 patients with carbamate poisoning in one series, with no adverse outcome (Tsao et al, 1990).
    4) EFFICACIOUS USE
    a) CASE REPORT: Progressive weakness due to severe aldicarb poisoning, with a plasma cholinesterase 6% of normal, responded to administration of pralidoxime 4 grams over 10 hours (Burgess et al, 1992).
    b) CASE REPORT: Pralidoxime stopped muscle fasciculations in a severe carbamate poisoning caused by methomyl in a 52-year-old man. A total of 16 grams pralidoxime (2 grams in the emergency department and 0.5 gm/hr for 28 hours) and 18 mg atropine were given. Rapid and pronounced clinical improvement occurred (Ekins & Geller, 1994).
    c) ANIMAL STUDY: In laboratory animals, pralidoxime in combination with atropine decreased toxicity of various carbamates, including carbaryl. A total of 5 animals were studied (Natoff & Reiff, 1973).
    d) ANIMAL STUDY - In another study involving 6 animals, pralidoxime alone was effective in isolan and dimetilan, but not with carbaryl (Sanderson, 1961).
    e) ANIMAL STUDY: A study of effectiveness of atropine, pralidoxime, and HI-6 against carbaryl intoxication in rats demonstrated a decrease LD50 (intraperitoneally) when pralidoxime was used alone compared to control (39.4 milligrams/kilogram vs pralidoxime 69.9 milligrams/kilogram control).
    1) Pralidoxime used with atropine decreased the LD50 compared to atropine alone, but was still above control (244 milligrams/kilogram atropine + pralidoxime vs 460 milligrams/kilogram atropine vs 69.9 milligrams/kilogram control) (Harris et al, 1989).
    2) LD50 data for pralidoxime alone (no carbaryl) in rats was not done in this study.
    5) CASE SERIES
    a) OBIDOXIME: Twenty-six children were administered IV atropine and obidoxime during the first 5 hours of suspected organophosphate poisoning. Obidoxime was given in 2 doses of 6 mg/kg each, the first on admission and the second 3 to 4 hours later.
    1) Marked clinical improvement occurred within 2 to 4 hours and all children had recovered completely by 24 hours. Subsequently, all 26 children were confirmed to have carbamate poisoning. As rapid improvement within 24 hours is described in most reported cases of carbamate poisoning, there was no clear effect from obidoxime therapy. Secondary complications of oxime-related adverse effects were not observed (Lifshitz et al, 1994).
    6) DOSE
    a) PRALIDOXIME DOSE
    1) ADULT: A loading dose of 30 mg/kg (maximum: 2 grams) over 30 minutes followed by a maintenance infusion of 8 to 10 mg/kg/hr (up to 650 mg/hr) (Howland, 2011). In vitro studies have recommended a target plasma concentration of close to 17 mcg/mL necessary for pralidoxime to be effective, which is higher than the previously suggested concentration of at least 4 mcg/mL (Howland, 2011; Eddleston et al, 2002). ALTERNATE ADULT: An alternate initial dose for adults is 1 to 2 grams diluted in 100 mL of 0.9% sodium chloride infused over 15 to 30 minutes. Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). In patients with serious cholinergic intoxication, a continuous infusion of 500 mg/hr should be considered. In patients with acute lung injury, a 5% solution may be administered by a slow IV injection over at least 5 minutes (Howland, 2006). Intravenous dosing is preferred; however, intramuscular administration may be considered using a 1-g vial of pralidoxime reconstituted with 3 mL of sterile water for injection or 0.9% sodium chloride for injection, producing a solution containing 300 mg/mL (Howland, 2011). An initial intramuscular pralidoxime dose of 1 gram or up to 2 grams in cases of very severe poisoning has also been recommended (Haddad, 1990; S Sweetman , 2002).
    2) CHILD: A loading dose of 20 to 40 mg/kg (maximum: 2 grams/dose) infused over 30 to 60 minutes in 0.9% sodium chloride (Howland, 2006; Schexnayder et al, 1998). Repeat initial bolus dose in 1 hour and then every 3 to 8 hours if muscle weakness or fasciculations persist (continuous infusion preferred). ALTERNATE CHILD: An alternate loading dose of 25 to 50 mg/kg (up to a maximum dose of 2 g), followed via continuous infusion of 10 to 20 mg/kg/hr. In patients with serious cholinergic intoxication, a continuous infusion of 10 to 20 mg/kg/hr up to 500 mg/hr should be considered (Howland, 2006).
    3) Presently, the ideal dose has NOT been established and dosing is likely based on several factors: type of OP agent (ie, diethyl OPs appear to respond more favorably to oximes, while dimethyl OPs seem to respond poorly) which may relate to a variation in the speed of ageing, time since exposure, body load, and pharmacogenetics (Eddleston et al, 2008)
    4) CONTINUOUS INFUSION
    a) A continuous infusion of pralidoxime is generally preferred to intermittent bolus dosing to maintain a target concentration with less variation (Howland, 2011; Eddleston et al, 2008; Roberts & Aaron, 2007; Gallagher et al, 1989; Thompson, 1987). In an open label, randomized study of moderately severe organophosphate poisoned patients treated with high dose continuous infusions required less atropine, were less likely to be intubated and had shorter duration of ventilatory support than patients treated with intermittent bolus doses. HIGH DOSE CONTINUOUS INFUSION: In this study, an initial 2 g bolus (pralidoxime chloride or iodide) was given, followed by 1 g over an hour every hour for 48 hours. Followed by 1 g every 4 hours until the patient could be weaned from mechanical ventilation. The response to therapy was beneficial in patients exposed to either a dimethyl or diethyl organophosphate pesticide (Pawar et al, 2006).
    b) Infusion over a period of several days may be necessary and is generally well tolerated (Namba et al, 1971).
    5) MAXIMUM DOSE
    a) The maximum recommended dose for pralidoxime is 12 grams in 24 hours for adults (S Sweetman , 2002); based on WHO, this dose may be exceeded in severely poisoned adults (Tang et al, 2013).
    6) DURATION OF INTRAVENOUS DOSING
    a) Dosing should be continued for at least 24 hours after cholinergic manifestations have resolved (Howland, 2006). Prolonged administration may be necessary in severe cases, especially in the case of poisoning by lipophilic organophosphates (Wadia & Amin, 1988). Observe patients carefully for recurrent cholinergic manifestations after pralidoxime is discontinued.
    7) ADVERSE EFFECTS
    a) SUMMARY
    1) Minimal toxicity when administered as directed; adverse effects may include: pain at injection site; transient elevations of CPK, SGOT, SGPT; dizziness, blurred vision, diplopia, drowsiness, nausea, tachycardia, hyperventilation, and muscular weakness (Prod Info PROTOPAM(R) CHLORIDE injection, 2006). Rapid injection may produce laryngospasm, muscle rigidity and tachycardia (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
    b) MINIMAL TOXICITY
    1) When administered as directed, pralidoxime has minimal toxicity (Prod Info PROTOPAM(R) CHLORIDE injection, 2006). Up to 40.5 grams have been administered over seven days (26 grams in the first 54 hours) without ill effects (Namba et al, 1971).
    2) One child developed delirium, visual hallucinations, tachycardia, mydriasis, and dry mucous membranes (Farrar et al, 1990). The authors were uncertain if these effects were related to 2-PAM or organophosphate poisoning per se.
    c) NEUROMUSCULAR BLOCKADE
    1) High doses have been reported to cause neuromuscular blockade, but this would not be expected to occur with recommended doses (Grob & Johns, 1958).
    d) VISUAL DISTURBANCES
    1) Oximes have produced visual disturbances (eg, blurred vision, diplopia) (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
    2) Transient increases in intraocular pressure may occur (Ballantyne B, 1987).
    e) ASYSTOLE
    1) Pralidoxime administered intravenously at an infusion rate of 2 grams over 10 minutes was associated with asystole in a single reported case, which occurred about 2 minutes after initiation of the infusion (Scott, 1986). A cause and effect relationship was not established.
    f) WEAKNESS
    1) Mild weakness, blurred vision, dizziness, headache, nausea, and tachycardia may occur if the rate of pralidoxime infusion exceeds 500 milligrams/minute (Jager & Stagg, 1958).
    g) ATROPINE SIDE EFFECTS
    1) Concomitant administration of pralidoxime may enhance the side effects of atropine administration (Hiraki et al, 1958). The signs of atropinization may occur earlier than anticipated when the agents are used together (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
    h) CARDIOVASCULAR
    1) Transient dose-dependent increases in blood pressure have occurred in adults receiving 15 to 30 milligrams/kilogram of 2-PAM (Calesnick et al, 1967). Increases in systolic and diastolic blood pressure have been observed in healthy volunteers given parenteral doses of pralidoxime (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
    2) Electrocardiographic changes and marked hypertension were observed at doses of 45 milligrams/kilogram (Calesnick et al, 1967).
    8) PHARMACOKINETICS
    a) HALF-LIFE: Pralidoxime is relatively short-acting with an estimated half-life of 75 minutes (Prod Info PROTOPAM(R) CHLORIDE injection, 2006). One report found that the effective half-life of pralidoxime chloride was longer in poisoned individuals than in healthy volunteers. This was attributed to a reduced renal blood flow in the poisoned patients (Jovanovic, 1989).
    9) AVAILABLE FORMS
    a) VIALS
    1) Each 20-mL vial contains 1 gram of pralidoxime chloride (Prod Info PROTOPAM(R) Chloride injection, 2010)
    b) SELF-INJECTOR
    1) Each auto-injector contains 600-mg of pralidoxime chloride in 2 mL of a sterile solution containing 20 mg/mL benzyl alcohol, 11.26 mg/mL glycine in water for injection (Prod Info PRALIDOXIME CHLORIDE intramuscular injection, 2003).
    c) CONVERSION FROM AUTOINJECTOR TO IV SOLUTION
    1) In one study, the conversion of intramuscular pralidoxime (from a MARK I Injector) to an IV solution resulted in a stable and sterile solution for up to 28 days. It is suggested that this conversion may be used in a mass casualty situation when additional IV doses of pralidoxime are needed. The following method may be used to transfer the syringe content: (Corvino et al, 2006).
    a) Avoid a shattered glass incident by using a biological safety cabinet.
    b) Double-glove and use a 30 mL empty sterile glass vial.
    c) Sterilize the vial diaphragm with alcohol.
    d) To vent the vial, insert a 1 1/2 inch 21 gauge IV needle bent to 90 degrees.
    e) Obtain the pralidoxime syringe from the kit and place it over the top of the vial diaphragm.
    f) Keep the syringe perpendicular to the vial and grasp the barrel of the syringe and press down firmly until the needle is deployed, and allow the syringe contents to enter into the vial.
    g) Use 5 pralidoxime injectors for one vial, which will be 10 mL in each vial.
    h) A 19 gauge 1.5 inch 5 micro filter needle is used with the 5 or 10 mL syringe to withdraw the pralidoxime solution from the 30 mL vial.
    i) Each vial (10 mL) is used to prepare either 250 mL, 0.9% sodium chloride injection IV bag at 8 mg/mL OR 100 mL, 0.9% sodium chloride injection IV bag to yield a final pralidoxime concentration of 10 mg/mL; 3.33 mL should be added into a 100 mL bag and 6.66 mL should be added into a 250 mL bag.
    d) OTHER SALTS
    1) Pralidoxime mesylate (P2S) in the United Kingdom (UK License holder, Department of Health).
    2) Pralidoxime methisulfate (Contrathion(R)) available in Greece (from IFET), Turkey (from Keymen), Brazil (from Sanofi-Aventis), Italy (from Sanofi-Aventis) and France (from SERB).
    D) SEIZURE
    1) 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).
    2) 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 .
    3) 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).
    4) 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).
    5) 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).
    6) 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).
    E) EXPERIMENTAL THERAPY
    1) CIMETIDINE: Additional studies are needed to determine the clinical significance of these findings.
    2) Cimetidine has been investigated in isolated perfused rat liver and in one human volunteer for its ability to alter the metabolism of carbaryl. Cimetidine prolonged the half-life of carbaryl in this model (Ward et al, 1988).
    a) They did not measure serial cholinesterase levels in the human volunteer, which would have made the study more believable. The exact mechanism of carbaryl metabolism is unknown.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) CLOTHING
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. Rescue personnel and bystanders should avoid direct contact with contaminated skin, clothing, or other objects (Burgess et al, 1999). Since contaminated leather items cannot be decontaminated, they should be discarded (Simpson & Schuman, 2002).

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) ENHANCED ELIMINATION is NOT RECOMMENDED.
    2) Enhanced elimination, especially hemoperfusion, is not indicated or useful (Personal Communication, 1995).

Range Of Toxicity

Summary

    A) TOXICITY: A toxic dose has not been established. Aldicarb is considered the most toxic carbamate. Symptoms developed in patients receiving a dose of 0.0011 to 0.06 milligram/kilogram. The World Health Organization (WHO) has classified aldicarb as pesticide class IA (extremely hazardous). Carbamates are absorbed across the lung, mucous membranes (including gut), and skin. Poisoning depends upon inherent toxicity, dosage, rate of absorption, rate of metabolic breakdown, and prior exposure to other cholinesterase inhibitors. Generally carbamates are less toxic than organophosphates.

Minimum Lethal Exposure

    A) Aldicarb can be fatal if swallowed; at very low exposure levels, it causes reversible cholinesterase inhibition (EPA, 1990; HSDB , 1999).
    B) Aldicarb is the most toxic of the carbamate pesticides; it causes cholinesterase inhibition at very low exposure levels. Unlike other carbamates, aldicarb is extremely toxic by the oral, dermal, and inhalation routes of exposure (EPA Toxicity Category I). When it is applied in solutions of oil or other organic solvents, it is rapidly absorbed through the skin; its skin toxicity is roughly 1000 times that of other carbamates. After ingestion, it is rapidly and almost completely absorbed from the gut. Signs and symptoms of aldicarb poisoning include the sudden onset of diarrhea, nausea and vomiting, abdominal pain, excessive perspiration, blurred vision, headache, muscular fasciculations, temporary paralysis of the extremities, and dyspnea (EPA, 1990) EXTOXNET, 1999; (Hayes, 1982; Hayes & Laws, 1991).
    C) Based on its acute oral toxicity in rats, aldicarb would be in the SUPER TOXIC group of carbamates, with a probable lethal oral dose in humans of less than 5 mg/kg (less than 7 drops for a 150-pound person) (EPA, 1985).

Maximum Tolerated Exposure

    A) PESTICIDE CLASSIFICATION
    1) The World Health Organization (WHO) has classified aldicarb as pesticide class IA (extremely hazardous) (World Health Organization, 2006).
    B) In humans, the primary exposure route is oral, by way of food or water that is contaminated. Aldicarb is excreted in urine, primarily, and is quickly metabolized (EXTOXNET, 1999).
    1) FOOD CONTAMINATION/CALIFORNIA: Illnesses were detected in patients receiving a dose of 0.0011 to 0.06 milligram/kilogram. This amounted to 1/4 to 1 cucumber and 1/2 slice to 5 slices of melon (Goldman et al, 1990).
    2) FOOD CONTAMINATION/CALIFORNIA: Illnesses were detected in patients receiving a dose of 0.0011 to 0.06 milligram/kilogram. This amounted to 1/4 to 1 cucumber and 1/2 slice to 5 slices of melon (Goldman et al, 1990).
    3) FOOD CONTAMINATION/NEBRASKA: Illnesses at doses of 0.025 to 0.041 milligram/kilogram of body weight (Jackson & Goldman, 1986; Goes et al, 1980). Severe poisoning requiring hospital treatment only occurred with exposures to more than 0.01 milligram/kilogram (Goldman et al, 1990).
    4) FOOD CONTAMINATION/LOUISIANA: Of 16 persons who ate an aldicarb-contaminated salad, 14 became ill, with predominantly gastrointestinal and neurological symptoms. It was estimated that a 6 gram portion of the salad contained 272.6 parts per million, or approximately 17 milligrams of aldicarb. Thus, a 70-kg adult would have consumed 0.2 milligrams of aldicarb per kilogram of body weight. All the victims recovered following symptomatic therapy (Anon, 1999).
    5) FOOD CONTAMINATION/GREENHOUSES: Two epidemics of poisoning from eating contaminated cucumbers grown in a hydroponic greenhouse have been recorded (Hayes, 1982b) with victims becoming ill between 1/2 and 12 hours after ingestion. All recovered without treatment.
    6) A woman consumed 0.5-1.0 g of a mint plant growing near a treated rosebush 24 days after the bush was treated with a 10% granular aldicarb formulation. Signs and symptoms of poisoning were maximal 2 hours after onset; after atropine treatment, the patient was resting comfortably three and a half hours after onset (Hayes, 1982).
    7) FAO/WHO estimated that the acceptable daily intake (ADI) of aldicarb is 0-0.005 mg/kg body weight; EPA set the ADI at 0.001 mg/kg body weight (Hayes & Laws, 1991).
    C) Occupational exposure to aldicarb may occur after product handling; most poisonings occur after loading and application. All confirmed occupational overexposures to aldicarb have occurred after improper handling or misuse of the product (EXTOXNET, 1999; (Hayes & Laws, 1991).

Workplace Standards

    A) ACGIH TLV Values for CAS116-06-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS116-06-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS116-06-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): D ; Listed as: Aldicarb
    a) D : Not classifiable as to human carcinogenicity.
    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): 3 ; Listed as: Aldicarb
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    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 CAS116-06-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 300 mcg/kg (RTECS , 1999a)
    B) LD50- (SUBCUTANEOUS)MOUSE:
    1) 250 mcg/kg (RTECS , 1999a)
    C) LD50- (INTRAPERITONEAL)RAT:
    1) 280 mcg/kg (RTECS , 1999a)
    D) LD50- (ORAL)RAT:
    1) 500 mcg/kg (RTECS , 1999a)
    E) LD50- (SKIN)RAT:
    1) 2500 mcg/kg (RTECS , 1999a)
    F) LD50- (SUBCUTANEOUS)RAT:
    1) 666 mcg/kg (RTECS , 1999a)
    G) TCLo- (ORAL)HUMAN:
    1) 28 mg/kg for 10D-I (RTECS , 1999a)

Physicochemical

Physical Characteristics

    A) Aldicarb forms colorless to white crystals which are odorless or have a slightly sulfurous odor (Budavari, 1996; Hartley & Kidd, 1987; Hayes, 1982; Hayes & Laws, 1991; Lewis, 1997) Lewis, 1998; (Verschueren, 1983).

Molecular Weight

    A) 190.27

References

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