1) Do NOT induce emesis.

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.

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.

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.

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).

1) ALOPECIA - is the predominant sign of chronic ingestion of thallium sulfate (Clayton & Clayton, 1994).

1) Severe bilateral optic neuritis was reported to occur in virtually all chronic poisonings (Bohringer, 1952). Changes in pupillary reflexes and optic atrophy may occur (Sittig, 1991).

1) Increased blood pressure may be seen (Wainwright et al, 1988) HSDB, 1999).

1) ECG changes similar to hypokalemia and gradual development of tachycardia due to direct vagal nerve and myocardial damage may be seen (Saddique & Peterson, 1983; Potes-Gutierrez & Del Real, 1966).
2) Tachycardia persisted as long as six weeks in some cases of ingestion of thallous sulfate (Machtey & Bandmann, 1961).
3) ECG irregularities were produced in rabbits by thallous sulfate. Some of the changes seen were peaked, flat and inverted T waves, ST segment depression, P wave morphology and polarity changes, increased voltage of QRS complexes, prolonged QT interval, sinus tachycardia and dysrhythmia, AV block, and ventricular premature beats (Grunfeld et al, 1963).

1) Bradycardia and hypotension as well as ventricular and atrial dysrhythmias and myocardial dysfunction have been reported (Roby et al, 1984 HSDB, 1999).

1) Tachycardia is frequently present (Cavanagh et al, 1974); (Wainwright et al, 1988; Clayton & Clayton, 1994).

1) Death may be caused by respiratory paralysis (Clayton & Clayton, 1994) HSDB, 1999).

1) Adult respiratory distress syndrome (ARDS) has been observed (Roby et al, 1984).

1) Pulmonary edema may occur from exposure to thallium compounds (HSDB, 1999).

1) Peripheral neuropathy, primarily of the legs and feet, is among the first symptoms noted (Grunfeld & Hinostroza, 1964). Loss of knee and ankle reflexes were seen in one case of thallous sulfate overdose (Curry et al, 1969).

1) Muscle weakness and atrophy are seen (Harbison, 1998).

1) Headache may be seen occasionally (Moeschlin & Condrau, 1950; Smith & Doherty, 1964).

1) 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).

1) Seizures may be seen occasionally (Moeschlin & Condrau, 1950; Smith & Doherty, 1964; Rambar, 1932) Munch, 1984; (Harbison, 1998) HSDB, 1999).

1) Coma may be seen in severe thallium poisoning (Harbison, 1998) HSDB, 1999).

1) Delirium may be noted in severe thallium poisoning (HSDB, 1999).

1) Ataxia, choreiform movements, hallucinations dementia, depression and psychosis may be prominent (Hayes & Laws, 1991; Clayton & Clayton, 1994).
2) 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).
3) Sequelae one year after a large acute ingestion included flaccid paraparesis, cerebellar ataxia, and mental impairment (Wainwright et al, 1988).
4) Structural changes in the nerve or nerve sheath may occur with thallous sulfate (Lewis, 1996).

1) RAPID ONSET - Gastrointestinal symptoms are early signs of thallium poisoning. They may appear within two hours after ingestion (Potes-Gutierrez & Del Real, 1966).

1) Gastrointestinal manifestations include initial constipation unresponsive to laxatives (Saddique & Peterson, 1983; Moeschlin, 1980; Wainwright et al, 1988).

1) Severe paroxysmal abdominal pain, and vomiting may be seen. Vomitus may be bloody (HSDB, 1999).

1) Diarrhea has been noted. Stools may be bloody (HSDB, 1999).

1) Anorexia may be seen, as may stomatitis (Hayes & Laws, 1991) HSDB, 1999).

1) Excessive salivation may be a symptom (HSDB, 1999).

1) Gastrointestinal hemorrhage may be noted (Saddique & Peterson, 1983; Harbison, 1998).

1) 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).

1) Proteinuria and and renal failure may occur (Harbison, 1998).

1) Albuminuria was present in the first week postingestion in 8 of 70 cases (Moeschlin, 1980).

1) Rats and mice given thallous sulfate at 30 to 40 mg/kg showed necrosis of the epithelium of Henle loops, hydropic degeneration, swelling and focal necrosis of the epithelium of proximal convoluted tubules, and stromal edema (Danilewicz et al, 1979).

1) Mild hypochloremic metabolic acidosis has been reported (Saddique & Peterson, 1983).

1) Hemolytic changes have been reported following acute ingestions (Saddique & Peterson, 1983).

1) A blue gingival line may be seen (Clayton & Clayton, 1994).

1) Anhydrosis, diaphoresis and dry and scaly skin may be noted. Severe acne may result (Moeschlin, 1980). Keratinization, petechiae, and ecchymoses may appear (CHRIS , 1999).

1) Black pigmentation of hair roots may be seen within 4 days (Moeschlin, 1980; Saddique & Peterson, 1983).

1) Mee's lines may appear after 2 to 4 weeks (Saddique & Peterson, 1983; Grunfeld & Hinostroza, 1964) HSDB, 1999).

1) Alarcon-Segovia et al (1989) reported features of connective tissue disease (arthralgia, polyarthritis) associated with thallium intoxication.

1) Muscle weakness and atrophy are seen (Harbison, 1998).

1) Clonic jerking of the extremities was seen in one pediatric poisoning with thallium sulfate six days after admission (Mayfield et al, 1983).

1) Alarcon-Segovia et al (1989) reported features of connective tissue disease (systemic lupus erythmatosus with positive antinuclear antibodies) associated with thallium intoxication.
2) A systemic lupus erythematosus-like syndrome was also reported in a preschool boy who ingested thallium sulfate (Montoya-Cabrera et al, 1991).

1) 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 (HSDB, 1999).
2) Exposure to thallium during the last trimester may cause malformations of the fingernails in newborns (Clayton & Clayton, 1994).

1) Thallous sulfate was fetotoxic and induced hydronephrosis and absence of vertebral bodies in fetal rats when given IP at 2.5mg/kg on days 8 to 10, or at 2.5 or 10 mg/kg on days 12 to 14 of gestation (Gibson & Becker, 1970). Thallium sulfate was stated not to be teratogenic in rats (Schardein, 1993).
2) Thallium sulfate induced an achondroplasia-like syndrome in chicks (Hall, 1985). The significance of this finding for human exposures is unknown.

1) Maternal ingestion of thallium sulfate 0.75 mg 60 days before delivery resulted in a neonate with alopecia (Moeschlin, 1980).

1) HUMANS
2) ANIMAL STUDIES

1) Not Listed

1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

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).

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).

1) Do NOT induce emesis.

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

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).
3) PRECAUTIONS:
4) LAVAGE FLUID:
5) COMPLICATIONS:
6) CONTRAINDICATIONS:

1) Monitor patient's cardiac, renal, and hepatic function closely.
2) HYPOCALCEMIA - Can occur and calcium levels should be monitored during the acute phase.

1) SHOCK - Directly related to hemorrhage via the gastrointestinal tract, requires volume and whole blood replacement.

1) EFFICACY -
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.

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).

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).

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).
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).

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

1) Monitor patient's cardiac, renal, and hepatic function closely.
2) HYPOCALCEMIA - Can occur and calcium levels should be monitored during the acute phase.

1) SHOCK - Directly related to hemorrhage via the gastrointestinal tract, requires volume and whole blood replacement.

1) PRUSSIAN BLUE - 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).
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.

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).

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).

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).
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).

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

1) Observe all patients with eye exposure for the possible development of clinical signs and symptoms and follow treatment recommendations in the DERMAL EXPOSURE section where appropriate.

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).

1) Monitor patient's cardiac, renal, and hepatic function closely.
2) HYPOCALCEMIA - can occur and calcium levels should be monitored during the acute phase.

1) SHOCK - Directly related to hemorrhage via the gastrointestinal tract, requires volume and whole blood replacement.

1) PRUSSIAN BLUE - 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).
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.

1) DIETHYLDITHIOCARBAMATE - Therapy with diethyldithiocarbamate may have resulted in dangerous redistribution of thallium to the CNS and is CONTRAINDICATED (Kamerbeek et al, 1971a).

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).

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).
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).

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

a) The reported adult fatal dose is approximately 1 gram of absorbed thallium based on extrapolation from studies in the literature (Clayton & Clayton, 1994).
b) The minimum lethal dose is 8 mg/kg of body weight based on animal data (ACGIH, 1991).
c) Sax & Lewis (1989) has reported the fatal human dose to be about 500 milligrams of thallium.
d) ADULT
e) PEDIATRIC

a) The more water-soluble thallium compounds (sulfate, acetate, malonate, and carbonate) pose a greater toxicity than do the less water-soluble forms (sulfide and iodide) (Saddique & Peterson, 1983).
b) Ingestion of 650 milligrams of thallium sulfate by four adults has been associated with survival, as has 2 grams of thallium sulfate, 1.3 grams of thallium sulfate, 1 gram of thallium sulfate (15 milligrams/kilogram of thallium), and 20 grams of thallium iodide (12 grams thallium) (Grunfeld & Hinostroza, 1964; Koshy & Lovejoy, 1981; Pedersen et al, 1978; Richelmi et al, 1980).

1) LD50- (ORAL)MOUSE:
2) LD50- (SUBCUTANEOUS)MOUSE:
3) LD50- (ORAL)RAT:
4) LD50- (SKIN)RAT: