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THALLOUS MALONATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Thallous malonate is the malonic acid salt of thallium.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C3-H2-O4.2Tl

Available Forms Sources

    A) FORMS
    1) Thallous malonate is the malonic acid salt of thallium. At the time of this review, no information was found on its chemical-physical properties or commercial uses.
    B) SOURCES
    1) The manufacture of thallium compounds has been banned in the United States since 1984 (ATSDR, 1992). Thallium occurs naturally in the environment and is present in soil at levels up to 0.7 ppm (ATSDR, 1992).
    C) USES
    1) Little information was found on the specific toxic effects of thallous malonate. Of its two components, thallium and malonic acid, thallium is most likely to cause toxicity. Malonic acid is a naturally-occurring metabolite. With an acute oral LD50 of 1.3 g/kg in rats (RTECS , 1995), the malonic acid component should not be toxic at doses which do not produce thallium toxicity.
    2) This review is based on the toxicity of THALLIUM and its salts. Effects attributed specifically to thallous malonate are identified.
    3) As one of the water-soluble salts of thallium, thallous malonate is predicted to be more toxic than the less soluble forms (Saddique & Peterson, 1983).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Little was found on the specific toxic effects of thallous malonate. Thallium is a very toxic element. Symptoms are usually delayed 12 to 24 hours in acute poisoning; the gastrointestinal tract and nervous system most often show the first signs of poisoning.
    B) Central and peripheral neurological effects include headache, paresthesias, delirium, convulsions, dementia and psychosis. Hemolysis and renal damage occur, and alopecia appears in one to three weeks.
    C) Chronic poisoning symptoms may be nonspecific, and thallium intoxication may not be suspected until alopecia or kidney damage occurs. Thallium has cumulative toxicity.
    0.2.3) VITAL SIGNS
    A) Hypertension and fever may be seen.
    0.2.4) HEENT
    A) Hair loss may be seen in one to three weeks. Decreased visual acuity and color vision along with ophthalmoplegia and optic neuritis are common. A bluish line may appear in the gums after three or four weeks, and dental caries are increased.
    0.2.5) CARDIOVASCULAR
    A) Hypertension, dysrhythmias, bradycardia, and tachycardia are seen.
    0.2.6) RESPIRATORY
    A) Death may be caused by respiratory paralysis or pneumonia. Adult respiratory distress syndrome has been seen. Pulmonary edema has been reported following exposure to some thallium compounds.
    0.2.7) NEUROLOGIC
    A) Symptoms during the first days may include paresthesias, myalgias, headache, cranial nerve damage, convulsions, delirium and coma. Peripheral neuropathy, severe pain, and muscle weakness with atrophy is also common. Protracted cases may produce ataxia, choreiform movements, dementia, depression and psychosis. Neurological damage is slow to resolve and may be permanent.
    0.2.8) GASTROINTESTINAL
    A) Gastrointestinal symptoms may range from anorexia, salivation, diarrhea, and stomatitis, to severe paroxysmal abdominal pain, vomiting and hemorrhage.
    0.2.9) HEPATIC
    A) Mild liver damage may occur, but is usually not clinically important.
    0.2.10) GENITOURINARY
    A) Kidney damage is manifested by proteinuria, cylindruria and sometimes oliguria and hematuria.
    0.2.11) ACID-BASE
    A) Mild hypochloremic metabolic acidosis has been reported.
    0.2.12) FLUID-ELECTROLYTE
    A) Hypokalemia has been reported.
    0.2.13) HEMATOLOGIC
    A) Hemolysis and anemia have been reported.
    0.2.14) DERMATOLOGIC
    A) Diaphoresis, dry and scaly skin and eruptions may develop. Black pigmentation of the hair root becomes apparent within four days. Mee's lines appear after two to four weeks.
    0.2.15) MUSCULOSKELETAL
    A) Arthralgia and myalgia are seen.
    0.2.18) PSYCHIATRIC
    A) Anxiety, insomnia, depression, dementia, delirium, psychosis, and permanent neuropsychiatric sequelae have occurred.
    0.2.19) IMMUNOLOGIC
    A) Systemic lupus erythematosus has been associated with exposure to thallium.
    0.2.20) REPRODUCTIVE
    A) No reproductive studies were found for thallous malonate. Thallium crosses the placenta and concentrates in the testes.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) Thallium salts are rapidly absorbed by the oral, inhalation, and dermal route. Thallium acts as a cellular poison by substituting for potassium in some but not all situations.

Laboratory Monitoring

    A) Thallium is excreted in the urine for many weeks following ingestion or dermal exposure. The most reliable test for thallium is a 24-hour urine quantitative assay.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Do NOT induce emesis.
    B) 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.
    C) 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.
    D) Lavage with 1% sodium or potassium iodide may be used in an attempt to form insoluble thallium iodide.
    E) Monitor patient's cardiac, renal and hepatic functions.
    F) Hypocalcemia - may occur and calcium levels should be monitored during the acute phase.
    G) Shock related to hemorrhage via the gastrointestinal tract may require volume and whole blood replacement.
    H) Prussian Blue - Although the therapy of choice in Europe, prussian blue is not commercially available in the USA and has not been approved by the FDA (For dose and schedules, see main Treatment section.) Activated charcoal may be as or more effective.
    I) Contraindications - Therapy with diethylthiocarbamate has been reported as resulting in dangerous redistribution of thallium to the CNS and is contraindicated.
    J) POTASSIUM CHLORIDE - has been reported to enhance elimination with equivocal results; can acutely worsen neurological symptoms.
    K) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    L) 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.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Monitor patient's cardiac, renal and hepatic functions.
    C) Hypocalcemia - may occur and calcium levels should be monitored during the acute phase.
    D) Shock related to hemorrhage via the gastrointestinal tract may require volume and whole blood replacement.
    E) Prussian Blue - Although the therapy of choice in Europe, prussian blue is not commercially available in the US and has not been approved by the FDA (For dose and schedules, see main Treatment section.) Activated charcoal may be as or more effective.
    F) Contraindications - Therapy with diethylthiocarbamate has been reported as resulting in dangerous redistribution of thallium to the CNS and is contraindicated.
    G) POTASSIUM CHLORIDE - has been reported to enhance elimination with equivocal results; can acutely worsen neurological symptoms.
    H) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    I) 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.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    B) Observe patients with eye exposure for the possible development of clinical signs and symptoms and follow treatment recommendations in the DERMAL EXPOSURE section when appropriate.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    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. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Monitor patient's cardiac, renal and hepatic functions.
    3) Hypocalcemia - may occur and calcium levels should be monitored during the acute phase.
    4) Shock related to hemorrhage via the gastrointestinal tract may require volume and whole blood replacement.
    5) Prussian Blue - Although the therapy of choice in Europe, prussian blue is not commercially available in the US and has not been approved by the FDA (For dose and schedules, see main Treatment section.) Activated charcoal may be as or more effective.
    6) Contraindications - Therapy with diethylthiocarbamate has been reported as resulting in dangerous redistribution of thallium to the CNS and is contraindicated.
    7) POTASSIUM CHLORIDE - has been reported to enhance elimination with equivocal results; can acutely worsen neurological symptoms.
    8) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    9) 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).
    a) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    b) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

Range Of Toxicity

    A) The reported adult fatal dose is approximately 1 g of absorbed thallium. The minimum lethal dose is 8 mg/kg of body weight based on animal data. Thallium is a cumulative poison.

Clinical Effects

Summary Of Exposure

    A) Little was found on the specific toxic effects of thallous malonate. Thallium is a very toxic element. Symptoms are usually delayed 12 to 24 hours in acute poisoning; the gastrointestinal tract and nervous system most often show the first signs of poisoning.
    B) Central and peripheral neurological effects include headache, paresthesias, delirium, convulsions, dementia and psychosis. Hemolysis and renal damage occur, and alopecia appears in one to three weeks.
    C) Chronic poisoning symptoms may be nonspecific, and thallium intoxication may not be suspected until alopecia or kidney damage occurs. Thallium has cumulative toxicity.

Vital Signs

    3.3.1) SUMMARY
    A) Hypertension and fever may be seen.
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) FEVER may be seen. It is probably due to brain injury and indicates a poor prognosis (Hayes & Laws, 1991; Clayton & Clayton, 1994).
    3.3.4) BLOOD PRESSURE
    A) WITH POISONING/EXPOSURE
    1) HYPERTENSION - Increased blood pressure may be seen (Wainwright et al, 1988).

Heent

    3.4.1) SUMMARY
    A) Hair loss may be seen in one to three weeks. Decreased visual acuity and color vision along with ophthalmoplegia and optic neuritis are common. A bluish line may appear in the gums after three or four weeks, and dental caries are increased.
    3.4.2) HEAD
    A) WITH POISONING/EXPOSURE
    1) ALOPECIA - Loss of hair begins after the second week following exposure and becomes nearly total in 1 month (HSDB, 1999; (Clayton & Clayton, 1994).
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) SUMMARY - Impaired color vision, decreased visual acuity, and ophthalmoplegia have been described (Anon, 1978; Clayton & Clayton, 1994; Harbison, 1998).
    2) OPTIC NEURITIS - Severe bilateral optic neuritis was reported to occur in 25% of acute thallium poisonings (p 1092; Grant, 1993). Changes in pupillary reflexes and optic atrophy may occur (Sittig, 1991).
    a) Severe bilateral optic neuritis was reported to occur in virtually all chronic poisonings (p 1092).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) GUM LINES - A bluish line in the gums may appear 3 to 4 weeks postingestion (Clayton & Clayton, 1994).
    2) DENTAL CARIES - may become evident several months after exposure to thallium (Moeschlin, 1980).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypertension, dysrhythmias, bradycardia, and tachycardia are seen.
    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Increased blood pressure may be seen (Wainwright et al, 1988) HSDB, 1999).
    B) CONDUCTION DISORDER OF THE HEART
    1) WITH POISONING/EXPOSURE
    a) ECG changes similar to hypokalemia and gradual development of tachycardia due to direct vagal nerve and myocardial damage may be seen (Saddique & Peterson, 1983).
    C) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia and hypotension as well as ventricular and atrial dysrhythmias and myocardial dysfunction have been reported (Roby et al, 1984) HSDB, 1999).
    D) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Tachycardia is frequently present (Cavanagh et al, 1974); (Wainwright et al, 1988; Clayton & Clayton, 1994).

Respiratory

    3.6.1) SUMMARY
    A) Death may be caused by respiratory paralysis or pneumonia. Adult respiratory distress syndrome has been seen. Pulmonary edema has been reported following exposure to some thallium compounds.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH POISONING/EXPOSURE
    a) Death may be caused by respiratory paralysis (Clayton & Clayton, 1994) HSDB, 1999).
    B) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Adult respiratory distress syndrome (ARDS) has been observed (Roby et al, 1984).
    C) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) Pulmonary edema has been reported following exposure to some thallium compounds (HSDB, 1999).

Neurologic

    3.7.1) SUMMARY
    A) Symptoms during the first days may include paresthesias, myalgias, headache, cranial nerve damage, convulsions, delirium and coma. Peripheral neuropathy, severe pain, and muscle weakness with atrophy is also common. Protracted cases may produce ataxia, choreiform movements, dementia, depression and psychosis. Neurological damage is slow to resolve and may be permanent.
    3.7.2) CLINICAL EFFECTS
    A) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) Peripheral neuropathy, primarily of the legs and feet, is among the first symptoms noted (Grunfeld & Hinostroza, 1964).
    B) MUSCLE PAIN
    1) WITH POISONING/EXPOSURE
    a) Muscle weakness and atrophy are seen (Harbison, 1998).
    C) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may be seen occasionally (Moeschlin & Condrau, 1950; Smith & Doherty, 1964).
    D) CRANIAL NERVE DISORDER
    1) WITH POISONING/EXPOSURE
    a) Cranial nerve damage may be noted. Pseudobulbar paralysis with paralysis of ocular muscles, ptosis, amblyopia, and facial paralysis have been noted (Moeschlin, 1980) HSDB, 1999).
    E) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures may be seen occasionally (Moeschlin & Condrau, 1950; Smith & Doherty, 1964; Rambar, 1932) Munch, 1984; (Harbison, 1998) HSDB, 1999).
    F) COMA
    1) WITH POISONING/EXPOSURE
    a) Coma may be seen (Harbison, 1998) HSDB, 1999).
    G) DELIRIUM
    1) WITH POISONING/EXPOSURE
    a) Delirium may be noted (HSDB, 1999).
    H) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Ataxia, choreiform movements, hallucinations, dementia, depression and psychosis may be prominent (Hayes & Laws, 1991; Clayton & Clayton, 1994).
    b) Leg pain, paresthesia of the hands and feet, and a frank peripheral neuropathy, principally in the legs, may occur (HSDB, 1999).
    c) Sequelae, including mental retardation, psychosis, abnormal reflexes, ataxia, and tremor were noted in 26 of 48 children who survived thallium sulfate poisoning (Reed et al, 1963). There are other isolated reports of neurological sequelae lasting more than 30 years (Barnes et al, 1984).
    d) Sequelae one year after a large acute ingestion included flaccid paraparesis, cerebellar ataxia, and mental impairment (Wainwright et al, 1988).

Gastrointestinal

    3.8.1) SUMMARY
    A) Gastrointestinal symptoms may range from anorexia, salivation, diarrhea, and stomatitis, to severe paroxysmal abdominal pain, vomiting and hemorrhage.
    3.8.2) CLINICAL EFFECTS
    A) CONSTIPATION
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal manifestations include initial constipation unresponsive to laxatives (Saddique & Peterson, 1983; Moeschlin, 1980; Wainwright et al, 1988).
    B) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Severe paroxysmal abdominal pain, and vomiting may be seen. Vomitus may be bloody (HSDB, 1999).
    C) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea has been noted. Stools may be bloody (HSDB, 1999).
    D) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia may be seen, as may stomatitis (Hayes & Laws, 1991) HSDB, 1999).
    E) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Excessive salivation may be a symptom (HSDB, 1999).
    F) GASTROINTESTINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal hemorrhage may be noted (Saddique & Peterson, 1983; Harbison, 1998).

Hepatic

    3.9.1) SUMMARY
    A) Mild liver damage may occur, but is usually not clinically important.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) WITH POISONING/EXPOSURE
    a) Liver damage occurs but is not prominent clinically. Fatty infiltration and necrosis of the liver may occur. Mild elevation of SGOT was reported in two patients who snorted thallium sulfate (Insley et al, 1986; Harbison, 1998) HSDB, 1999).

Genitourinary

    3.10.1) SUMMARY
    A) Kidney damage is manifested by proteinuria, cylindruria and sometimes oliguria and hematuria.
    3.10.2) CLINICAL EFFECTS
    A) RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Proteinuria and renal failure may occur (Harbison, 1998).
    B) ALBUMINURIA
    1) WITH POISONING/EXPOSURE
    a) Albuminuria was present in the first week postingestion in 8 of 70 cases (Moeschlin, 1980).

Acid-Base

    3.11.1) SUMMARY
    A) Mild hypochloremic metabolic acidosis has been reported.
    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Mild hypochloremic metabolic acidosis has been reported (Saddique & Peterson, 1983).

Hematologic

    3.13.1) SUMMARY
    A) Hemolysis and anemia have been reported.
    3.13.2) CLINICAL EFFECTS
    A) HEMOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Hemolytic changes have been reported following acute ingestions (Saddique & Peterson, 1983).

Dermatologic

    3.14.1) SUMMARY
    A) Diaphoresis, dry and scaly skin and eruptions may develop. Black pigmentation of the hair root becomes apparent within four days. Mee's lines appear after two to four weeks.
    3.14.2) CLINICAL EFFECTS
    A) ABNORMAL COLOR
    1) WITH POISONING/EXPOSURE
    a) A blue gingival line may be seen (Clayton & Clayton, 1994).
    B) DISORDER OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Anhydrosis, diaphoresis and dry and scaly skin may be noted. Severe acne may result (Moeschlin, 1980). Keratinization, petechiae, and ecchymoses may appear (CHRIS, 1999).
    C) HAIR DISCOLORATION
    1) WITH POISONING/EXPOSURE
    a) Black pigmentation of hair roots may be seen within 4 days (Moeschlin, 1980; Saddique & Peterson, 1983).
    D) MEE'S LINE
    1) WITH POISONING/EXPOSURE
    a) Mee's lines may appear after 2 to 4 weeks (Saddique & Peterson, 1983; Grunfeld & Hinostroza, 1964) HSDB, 1999).

Musculoskeletal

    3.15.1) SUMMARY
    A) Arthralgia and myalgia are seen.
    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) WITH POISONING/EXPOSURE
    a) Alarcon-Segovia et al (1989) reported features of connective tissue disease (arthralgia, polyarthritis) associated with thallium intoxication.
    B) MUSCLE ATROPHY
    1) WITH POISONING/EXPOSURE
    a) Muscle weakness and atrophy are seen (Harbison, 1998).

Immunologic

    3.19.1) SUMMARY
    A) Systemic lupus erythematosus has been associated with exposure to thallium.
    3.19.2) CLINICAL EFFECTS
    A) DRUG-INDUCED LUPUS ERYTHEMATOSUS
    1) WITH POISONING/EXPOSURE
    a) Alarcon-Segovia et al (1989) reported features of connective tissue disease (systemic lupus erythematosus with positive antinuclear antibodies) associated with thallium intoxication.
    b) A systemic lupus erythematosus-like syndrome was also reported in a preschool boy who ingested thallium sulfate (Montoya-Cabrera et al, 1991).

Reproductive

    3.20.1) SUMMARY
    A) No reproductive studies were found for thallous malonate. Thallium crosses the placenta and concentrates in the testes.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) At the time of this review, no human data were available to assess the teratogenic potential of thallous malonate.
    2) Chronic exposure to thallium during the first three months of pregnancy has been reported to cause congenital malformations, and exposures later than three months result in damage to the fetal central nervous system leading to polyneuropathy, anaurosis and cachexia (Schardein, 1993) HSDB, 1999).
    3) Exposure to thallium during the last trimester may cause malformations of the fingernails in newborns (Clayton & Clayton, 1994).
    B) ANIMAL STUDIES
    1) Some thallium salts, such as thallium sulfate, are fetotoxic and teratogenic in animals (RTECS, 1999). Other forms of thallium have not been teratogenic in experimental animals (Schardein, 1993). Impairment of learning was reported in rats after prenatal exposure to thallium (as the sulfate) at doses up to 1.6 mg thallium/kg/day on days 6 to 9 of gestation; no malformations were apparent (Bornhausen & Hagen, 1984).
    3.20.3) EFFECTS IN PREGNANCY
    A) PLACENTAL BARRIER
    1) Thallium crosses the placenta and has induced congenital alopecia from exposure during pregnancy (Moeschlin, 1980).
    B) LACK OF EFFECT
    1) In one retrospective community study, no excess risk for birth defects was found in residents living near an industrial source of thallium dust. Exposures were based on levels of urinary thallium which ranged from 0.6 to 2.2 mcg/L, compared with less than 1 mcg/L for the general population (Dolgner et al, 1983).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS2757-18-8 (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
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.
    B) Other thallium salts are genotoxic at the level of DNA damage, mutations, and chromosome aberrations (ATSDR, 1992).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Thallium is excreted in the urine for many weeks following ingestion or dermal exposure. The most reliable test for thallium is a 24-hour urine quantitative assay.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor liver and renal function tests.
    2) Normal thallium concentrations ranged from 0 to 0.08 mg/L in 320 young urban children (Singh et al, 1975).
    4.1.3) URINE
    A) URINARY LEVELS
    1) The normal limit of urinary thallium is 0.005 mg/L (Baselt, 1988).
    2) Thallium is excreted in the urine for many weeks following ingestion or dermal absorption. In severe intoxications, urinary excretions have been greater than 5 to 10 mg/24 hours (Grunfeld & Hinostroza, 1964) van der Merwe et al, 1972; Pederson et al, 1978; (Koshy & Lovejoy, 1981).
    3) THALLIUM MOBILIZATION TEST - One reported method of diagnosis involves administration of 45 mEq of oral potassium and measuring a 24-hour urine collection (Insley et al, 1986). The value of this test is debatable, since urinary excretion has been reported to be identical before and after potassium administration (Anon, 1978).

Radiographic Studies

    A) ABDOMINAL RADIOGRAPH
    1) Thallium is radiopaque (Grunfeld & Hinostroza, 1964). Abdominal x-ray may be useful in documenting adequate gastric decontamination following acute ingestion.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Thallium is excreted in the urine for many weeks following ingestion or dermal exposure. The most reliable test for thallium is a 24-hour urine quantitative assay.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Do NOT induce emesis.
    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) A lavage fluid of one percent sodium or potassium iodide may be used in an attempt to form insoluble thallium iodide (Morgan, 1989), thus lessening the amount absorbed from the gastrointestinal tract.
    2) 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.
    3) 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.
    4) 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.
    5) 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).
    6) 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 patient's cardiac, renal, and hepatic function closely.
    2) HYPOCALCEMIA - can occur and calcium levels should be monitored during the acute phase.
    B) HEMORRHAGE
    1) SHOCK - directly related to hemorrhage via the gastrointestinal tract, requires volume and whole blood replacement.
    C) PRUSSIAN BLUE
    1) EFFICACY -
    a) Therapy of choice in Europe consists of Prussian Blue, a non-absorbable lattice of potassium ferric ferrocyanide. Prussian Blue is not commercially available in the USA and is not approved by the FDA. Data supporting efficacy come from animal studies or single poorly documented cases (Kamerbeek et al, 1971; Stevens et al, 1974; Schwartz et al, 1988).
    b) Nine people poisoned with thallium tainted food received Prussian Blue (Pai, 1987). Two grams of Prussian Blue were administered orally three times a day for a total duration of six weeks. Symptoms improved and all patients were discharged from the hospital within six weeks. Total body thallium removal was not calculated nor were pretreatment serum or urine thallium levels given. Thus, efficacy in removal could not be documented.
    c) Other works have demonstrated removal of 400 milligrams of thallium out of a total body burden of 17 grams (Hologgitas et al, 1980).
    d) Prussian blue was reported to result in increased fecal excretion of thallium, with approximately 2,000 mg eliminated over 20 days by this route, compared to 820 mg over 46 days in the urine, and 225 mg over 25 days in dialysate. Because of other concomitant therapies, including diethyldithiocarbamate, potassium, hemodialysis, and hemofiltration, the effects of Prussian blue are difficult to assess. Fecal excretion while not receiving therapy was not reported (Wainwright et al, 1988).
    2) DOSE - Administer 250 milligrams/kilogram/day via naso-jejunal tube in 2 to 4 doses. This agent is reported to be devoid of systemic toxicity at this dose.
    3) MECHANISM - The mechanism of action is the release of potassium ion to mobilize intracellular thallium with the absorption of thallium onto the insoluble crystal lattice in the gut. Urinary excretion of thallium during this therapy will fall as a measure of effective binding in the gut.
    4) END-POINT - Therapy is continued until less than 0.5 microgram/24 hours is excreted in the urine. Rebound following cessation of therapy has not been reported, but should be monitored.
    5) PRECAUTION - Additional potassium salts should not be required during this therapy.
    D) CONTRAINDICATED TREATMENT
    1) DIETHYLDITHIOCARBAMATE - Therapy with diethyldithiocarbamate has been reported as resulting in dangerous redistribution of thallium to the CNS and is contraindicated (Kamerbeek et al, 1971a).
    a) Administration of diethyldithiocarbamate was associated with an increase in serum thallium from 800 to 1,350 micrograms/liter in one case. This was accompanied by clinical deterioration (stupor). After the second dose ventilatory failure occurred, and artificial ventilation was required for 3 weeks (Wainwright et al, 1988).
    E) POTASSIUM
    1) POTASSIUM CHLORIDE - therapy has been reported to enhance excretion of thallium. However, it may produce transient worsening of acute neurological symptoms (Roby et al, 1984; Bank et al, 1972; Anon, 1978). Furthermore, there are conflicting reports as to its efficacy in enhancing elimination (Koshy & Lovejoy, 1981).
    F) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    G) 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).

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.
    6.7.2) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor patient's cardiac, renal, and hepatic function closely.
    2) HYPOCALCEMIA - can occur and calcium levels should be monitored during the acute phase.
    B) HEMORRHAGE
    1) SHOCK - due to gastrointestinal tract hemorrhage requires volume and whole blood replacement.
    C) PRUSSIAN BLUE
    1) EFFICACY - Therapy of choice in Europe consists of Prussian Blue, a non-absorbable lattice of potassium ferric ferrocyanide. Prussian Blue is not commercially available in the US and is not approved by the FDA. Data supporting efficacy come from animal studies or single poorly documented cases (Kamerbeek et al, 1971; Stevens et al, 1974; Schwartz et al, 1988).
    a) Nine people poisoned with thallium tainted food received Prussian Blue (Pai, 1987). Two grams of Prussian Blue were administered orally three times a day for a total duration of six weeks. Symptoms improved and all patients were discharged from the hospital within six weeks. Total body thallium removal was not calculated nor were pretreatment serum or urine thallium levels given. Thus, efficacy in removal could not be documented.
    b) Other works have demonstrated removal of 400 milligrams of thallium out of a total body burden of 17 grams (Hologgitas et al, 1980).
    c) Prussian blue was reported to result in increased fecal excretion of thallium, with approximately 2,000 mg eliminated over 20 days by this route, compared to 820 mg over 46 days in the urine, and 225 mg over 25 days in dialysate. Because of other concomitant therapies, including diethyldithiocarbamate, potassium, hemodialysis, and hemofiltration, the effects of Prussian blue are difficult to assess. Fecal excretion while not receiving therapy was not reported (Wainwright et al, 1988).
    2) DOSE - Administer 250 milligrams/kilogram/day via naso-jejunal tube in 2 to 4 doses. This agent is reported to be devoid of systemic toxicity at this dose.
    3) MECHANISM - The mechanism of action is the release of potassium ion to mobilize intracellular thallium with the absorption of thallium onto the insoluble crystal lattice in the gut. Urinary excretion of thallium during this therapy will fall as a measure of effective binding in the gut.
    4) END-POINT - Therapy is continued until less than 0.5 microgram/24 hours is excreted in the urine. Rebound following cessation of therapy has not been reported, but should be monitored.
    5) PRECAUTION - Additional potassium salts should not be required during this therapy.
    D) CONTRAINDICATED TREATMENT
    1) DIETHYLDITHIOCARBAMATE - Therapy with diethyldithiocarbamate may result in dangerous redistribution of thallium to the CNS and is contraindicated (Kamerbeek et al, 1971a).
    a) Administration of diethyldithiocarbamate was associated with an increase in serum thallium from 800 to 1,350 micrograms/liter in one case. This was accompanied by clinical deterioration (stupor). After the second dose ventilatory failure occurred, and artificial ventilation was required for 3 weeks (Wainwright et al, 1988).
    E) POTASSIUM
    1) POTASSIUM CHLORIDE - therapy has been reported to enhance excretion of thallium. However, it may produce transient worsening of acute neurological symptoms (Roby et al, 1984; Bank et al, 1972; Anon, 1978). Furthermore, there are conflicting reports as to its efficacy in enhancing elimination (Koshy & Lovejoy, 1981).
    F) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    G) 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).
    H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

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).
    6.8.2) TREATMENT
    A) OBSERVATION REGIMES
    1) Observe patients with eye exposure for the possible development of clinical signs and symptoms and follow treatment recommendations in the DERMAL EXPOSURE section when appropriate.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor patient's cardiac, renal, and hepatic function closely.
    2) HYPOCALCEMIA - Can occur and calcium levels should be monitored during the acute phase.
    B) HEMORRHAGE
    1) SHOCK - directly related to hemorrhage via the gastrointestinal tract, requires volume and whole blood replacement.
    C) PRUSSIAN BLUE
    1) EFFICACY - Therapy of choice in Europe consists of Prussian Blue, a non-absorbable lattice of potassium ferric ferrocyanide. Prussian Blue is not commercially available in the US and is not approved by the FDA. Data supporting efficacy come from animal studies or single poorly documented cases (Kamerbeek et al, 1971; Stevens et al, 1974; Schwartz et al, 1988).
    a) Nine people poisoned with thallium tainted food received Prussian Blue (Pai, 1987). Two grams of Prussian Blue were administered orally three times a day for a total duration of six weeks. Symptoms improved and all patients were discharged from the hospital within six weeks. Total body thallium removal was not calculated nor were pretreatment serum or urine thallium levels given. Thus, efficacy in removal could not be documented.
    b) Other works have demonstrated removal of 400 milligrams of thallium out of a total body burden of 17 grams (Hologgitas et al, 1980).
    c) Prussian blue was reported to result in increased fecal excretion of thallium, with approximately 2,000 mg eliminated over 20 days by this route, compared to 820 mg over 46 days in the urine, and 225 mg over 25 days in dialysate. Because of other concomitant therapies, including diethyldithiocarbamate, potassium, hemodialysis, and hemofiltration, the effects of Prussian blue are difficult to assess. Fecal excretion while not receiving therapy was not reported (Wainwright et al, 1988).
    2) DOSE - Administer 250 milligrams/kilogram/day via naso-jejunal tube in 2 to 4 doses. This agent is reported to be devoid of systemic toxicity at this dose.
    3) MECHANISM - The mechanism of action is the release of potassium ion to mobilize intracellular thallium with the absorption of thallium onto the insoluble crystal lattice in the gut. Urinary excretion of thallium during this therapy will fall as a measure of effective binding in the gut.
    4) END-POINT - Therapy is continued until less than 0.5 microgram/24 hours is excreted in the urine. Rebound following cessation of therapy has not been reported, but should be monitored.
    5) PRECAUTION - Additional potassium salts should not be required during this therapy.
    D) CONTRAINDICATED TREATMENT
    1) DIETHYLDITHIOCARBAMATE - Therapy with diethyldithiocarbamate has been reported as resulting in dangerous redistribution of thallium to the CNS and is contraindicated (Kamerbeek et al, 1971a).
    a) Administration of diethyldithiocarbamate was associated with an increase in serum thallium from 800 to 1,350 micrograms/liter in one case. This was accompanied by clinical deterioration (stupor). After the second dose ventilatory failure occurred, and artificial ventilation was required for 3 weeks (Wainwright et al, 1988).
    E) POTASSIUM
    1) POTASSIUM CHLORIDE - therapy has been reported to enhance excretion of thallium. However, it may produce transient worsening of acute neurological symptoms (Roby et al, 1984; Bank et al, 1972; Anon, 1978). Furthermore, there are conflicting reports as to its efficacy in enhancing elimination (Koshy & Lovejoy, 1981).
    F) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    G) 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).
    H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EXTRACORPOREAL ELIMINATION
    1) HEMODIALYSIS -
    a) Hemodialysis is indicated in the presence of renal failure (Saddique & Peterson, 1983).
    b) Hemodialysis instituted 12 hours postingestion and performed repeatedly for 200 hours over 10 days removed 143 milligrams of thallium in 120 hours in a patient who had ingested 2 grams of thallium sulfate (1.6 grams thallium); 110 milligrams was excreted in the urine during this time. Although the amount removed was more than twice endogenous clearance, the total amount removed is small and is unlikely to affect clinical outcome (Pedersen et al, 1978).
    c) Hemodialysis for five hours per day over 19 consecutive days, followed by an additional 7-day treatment achieved greater elimination than forced diuresis in a case where approximately 750 mg of thallium sulfate had been ingested (Nogue et al, 1982).
    2) HEMOPERFUSION/HEMODIALYSIS -
    a) Hemoperfusion has been reported to enhance excretion of thallium sulfate. A 32-year-old woman who ingested 100 milligrams of thallium sulfate by history was treated with a combination of hemoperfusion-hemodialysis following classical therapy including Prussian Blue. The clearance rates of the hemoperfusion and hemodialysis were calculated to be 139 and 47 milliliters/minute, respectively. A 4 hour hemoperfusion-hemodialysis treatment resulted in 12 milligrams and 1.2 milligrams thallium eliminated by hemoperfusion and hemodialysis, respectively. Hemoperfusion appeared to enhance elimination of thallium since only 2.3 milligrams was excreted in the urine over a 16 hour collection period (De Backer et al, 1982).
    b) However, other investigators have concluded that hemoperfusion does not affect the time course of thallium intoxications. Twelve hours of hemoperfusion removed 63 milligrams, compared to 300 milligrams eliminated in the urine during forced diuresis in one patient (Heath et al, 1983). In another patient who ingested 8 grams of thallium, 149 milligrams was removed after 4 hours of hemoperfusion-hemodialysis (Aoyama et al, 1986). The amount of thallium removed during a 4 hour period of hemoperfusion ranged from 15 to 84 milligrams in 3 patients (de Groot et al, 1985).
    3) FORCED DIURESIS -
    a) Forced diuresis has proved effective in increasing the elimination rate of thallium (Heath et al, 1983; Thompson, 1981) Nogue et al, 1982). It should be used only in the most severely poisoned patients (Anon, 1987).
    b) Forced diuresis was used successfully, along with hemodialysis and antidote, from days three to seven in a case of ingestion of thallous sulfate (Barckow & Jenss, 1976).

Range Of Toxicity

Summary

    A) The reported adult fatal dose is approximately 1 g of absorbed thallium. The minimum lethal dose is 8 mg/kg of body weight based on animal data. Thallium is a cumulative poison.

Minimum Lethal Exposure

    A) ACUTE
    1) The reported adult minimum lethal dose (MLD) is approximately 1 gram of absorbed thallium (Clayton & Clayton, 1994).
    2) The minimum lethal dose is 8 mg/kg of body weight based on animal data (ACGIH, 1991).
    3) Thallium is a cumulative poison (Sittig, 1991).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The more water-soluble forms (sulfate, acetate, malonate, and carbonate) are more toxic than the less water-soluble forms (sulfide and iodide) (Saddique & Peterson, 1983).
    B) CASE REPORTS
    1) ADULT
    a) Six adults who survived the accidental or intentional ingestion of thallium sulfate, were observed to have blood concentrations of 0.08 to 1.0 milligrams per milliliter within 1 to 30 days after hospital admission (Baselt, 1988).
    b) Ingestion of 650 milligrams of thallium sulfate by four adults has been associated with survival (Grunfeld & Hinostroza, 1964), as has 2 grams of thallium sulfate (Pedersen et al, 1978), 1.3 grams of thallium sulfate (Grunfeld & Hinostroza, 1964), 1 gram of thallium sulfate (15 milligrams/kilogram of thallium) (Richelmi et al, 1980), and 20 grams of thallium iodide (12 grams thallium) (Koshy & Lovejoy, 1981).

Workplace Standards

    A) ACGIH TLV Values for CAS2757-18-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS2757-18-8 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS2757-18-8 :
    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 CAS2757-18-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Reference: RTECS, 1999
    1) LD50- (ORAL)RAT:
    a) 18,800 mcg/kg
    2) LD50- (SKIN)RAT:
    a) 57,700 mcg/kg

Physicochemical

Physical Characteristics

    A) No information was found at the time of this review.

Molecular Weight

    A) 510.79 (Lewis, 1996)

References

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