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EDETATE DISODIUM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Edetate disodium is a chelating agent for emergency lowering of serum calcium in selected cases of hypercalcemia.

Specific Substances

    1) Acetic acid, (ethylenedinitrilo)tetra-, disodium salt
    2) Molecular Formula: C10-H14-N2-O8.2Na
    1.2.1) MOLECULAR FORMULA
    1) C10-H14-N2-O8.2Na (RTECS, 2006)

Available Forms Sources

    A) FORMS
    1) Edetate disodium is available as a sterile, nonpyrogenic, concentrated solution for injection. Each mL contains 150 mg of anhydrous edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).
    B) USES
    1) Edetate disodium is NOT a first-line agent for any indication. It is approved for the use in the emergency treatment of severe hypercalcemia and in the treatment of dysrhythmias secondary to digitalis toxicity (Prod Info ENDRATE(R) IV injection, 2004). It has largely been replaced for these uses by safer, more effective, agents.
    2) Fatal hypocalcemia has developed when patients being treated for heavy metal poisoning received edetate disodium instead of calcium edetate disodium (Centers for Disease Control, 2006).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) COMMON: Orthostatic hypotension, circumoral paresthesia, abdominal pain, diarrhea, nausea, stomach cramps, vomiting, headache, and numbness. SEVERE: Hypocalcemia, nephrotoxicity, injection site reactions, thrombophlebitis, and scaling eczema.
    B) WITH POISONING/EXPOSURE
    1) Fatal hypocalcemia has developed when patients being treated for heavy metal poisoning received edetate disodium instead of calcium edetate disodium. Nephrotoxicity may develop and appears to be dose related.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Transient drop in blood pressure has been reported with therapeutic use.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Transient decrease in blood pressure have been observed with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Cardiac dysrhythmias resulting from hypocalcemia occurred shortly after edetate disodium infusion.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) Nephrotoxicity is a common adverse effect of edetate disodium, and appears to be dose-related.
    0.2.12) FLUID-ELECTROLYTE
    A) Fatal hypocalcemia has developed when patients being treated for heavy metal poisoning received edetate disodium instead of calcium edetate disodium.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Injection site reactions have been reported with therapeutic use of edetate disodium.
    0.2.20) REPRODUCTIVE
    A) Edetate disodium is classified as FDA pregnancy category C.
    B) There are no data on the use of edetate disodium in pregnant women. The effects, if any, on the developing fetus are unknown. Until more data are available, edetate disodium should not be used unless clearly necessary or for the treatment of a life-threatening condition.
    0.2.21) CARCINOGENICITY
    A) Data are insufficient and conflicting on the carcinogenic and mutagenic potential of edetate disodium.

Laboratory Monitoring

    A) Serum calcium, potassium, and magnesium should be monitored closely. Monitor patient for clinical evidence of hypocalcemia: perioral tingling, Chvosteck sign, Trousseau sign, muscle spasms, numbness, tetany.
    B) Serial ECGs and continuous cardiac monitoring is recommended.
    C) Monitor renal function: BUN, serum creatinine, urine output, and urinalysis.
    D) Monitor blood sugar in insulin dependent diabetic patients.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) SUPPORT
    1) Treatment is symptomatic and supportive. Focus should be on evaluating the patient for clinical, laboratory and ECG evidence of hypocalcemia and instituting aggressive calcium replacement therapy.
    B) DECONTAMINATION
    1) Acute toxicity would be expected to follow rapid intravenous administration; gastrointestinal decontamination is generally not necessary.
    C) HYPOCALCEMIA
    1) Hypocalcemia may develop abruptly. Aggressive calcium replacement should be instituted in patients with clinical or ECG manifestations of hypocalcemia even if laboratory confirmation of hypocalcemia is still pending. Administer 10 mL to 20 mL of 10% calcium chloride or calcium gluconate (initial bolus) IV over 10 to 15 minutes. More rapid administration may be necessary in patients with dysrhythmias. Repeat bolus or a maintenance infusion is often necessary.
    D) HYPOTENSION
    1) Administer IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Central venous pressure monitoring may be indicated to guide fluid therapy.
    E) HYPOMAGNESEMIA
    1) Correct known and suspected hypomagnesemia with intravenous magnesium sulfate. DOSE: ADULT: MILD hypomagnesemia, 1 to 2 g (magnesium sulfate 50% solution; 8.12 mEq) IV infusion, may be repeated as needed. SEVERE hypomagnesemia, up to 5 g (40 mEq) in 1 L of D5W or NS by slow IV infusion over 3 hours. INTRAMUSCULAR: IM route may be used if IV access cannot be obtained. For mild hypomagnesemia 1 g (magnesium sulfate 50% solution; 8.12 mEq) IM every 6 hours for 4 doses. For severe hypomagnesemia 250 mg/kg (magnesium sulfate 50% solution) may be given IM within a period of 4 hours. PEDIATRIC: 25 to 50 mg/kg IV infusion over 30 to 60 minutes; repeat dose as necessary; max 2 g/dose. Monitor serum magnesium.
    F) FLUID/ELECTROLYTE BALANCE
    1) Maintain good urine output (3 to 6 milliliters/kilogram/hour) with intravenous fluids.

Range Of Toxicity

    A) The range of toxicity for edetate disodium has not been established.
    B) Toxicity is dependent on both total dosage and rate of administration, and the serum calcium. A 2-year-old girl died 4 hours after receiving 300 mg of edetate disodium over 4 hours. A 5-year-old boy died shortly after receiving 990 mg of IV edetate disodium over 5 to 10 minutes. A 53-year-old woman died shortly after receiving 1500 mg of edetate disodium over 10 to 15 minutes.
    1) All of these patients were being treated for heavy metal poisoning, and were given edetate disodium in error instead of calcium disodium edetate. The fact that they were not hypercalcemic prior to edetate disodium therapy likely placed them at greater risk for severe toxicity.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) COMMON: Orthostatic hypotension, circumoral paresthesia, abdominal pain, diarrhea, nausea, stomach cramps, vomiting, headache, and numbness. SEVERE: Hypocalcemia, nephrotoxicity, injection site reactions, thrombophlebitis, and scaling eczema.
    B) WITH POISONING/EXPOSURE
    1) Fatal hypocalcemia has developed when patients being treated for heavy metal poisoning received edetate disodium instead of calcium edetate disodium. Nephrotoxicity may develop and appears to be dose related.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Transient drop in blood pressure has been reported with therapeutic use.
    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) Transient drop in blood pressure has been reported with therapeutic use (Prod Info ENDRATE(R) IV injection, 2004).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Transient decrease in blood pressure have been observed with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Cardiac dysrhythmias resulting from hypocalcemia occurred shortly after edetate disodium infusion.
    3.5.2) CLINICAL EFFECTS
    A) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT ADULT - A 53-year-old woman who was being treated for presumed heavy metal poisoning became pulseless and unconscious approximately 10 to 15 minutes after receiving 1500 mg of edetate disodium by intravenous push (instead of calcium edetate disodium). Attempts at resuscitation were unsuccessful, and the cause of death was determined to be cardiac dysrhythmia resulting from hypocalcemia (Brown et al, 2006).
    b) CASE REPORT CHILD - A 5-year-old boy received 990 mg of edetate disodium IV over 10 to 15 minutes instead of calcium disodium edetate. He became limp and pulseless and resuscitation attempts were unsuccessful. The cause of death was determined to be anoxic brain injury secondary to hypocalcemia-induced diffuse subendocardial necrosis(Brown et al, 2006) .
    c) CASE REPORT CHILD - A 2-year-old girl with lead poisoning received 300 mg intravenous edetate disodium over 4 hours instead of calcium edetate disodium. One hour after the start of the infusion she was hypocalcemic (serum calcium 5.2 mg/dL, normal 8.5 to 10.5 mg/dL). Three hours after start of the infusion she became pulseless and apneic. She remained hypocalcemic (serum calcium < 5.0 mg/dL) despite repeated doses of calcium chloride, and resuscitation attempts were unsuccessful (Brown et al, 2006).
    B) VASCULITIS
    1) WITH THERAPEUTIC USE
    a) There is one anecdotal case report of severe vasculitis and cardiac tamponade in a patient treated with edetate disodium (Peterson, 1983).
    C) ELECTROCARDIOGRAM ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Inverted T waves were noted with therapeutic use (Gilman et al, 1990a).
    D) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Transient drops in systolic and diastolic blood pressure have been reported with therapeutic use of edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).
    b) Transient decreases in blood pressure, ranging from 5 to 20 mmHg, occurred in over one half of patients in one study (Seven, 1960).
    c) Moderate (asymptomatic drop in systolic pressure of 30 mmHg) and severe (symptomatic drop of 30 mmHg or more) decreases in blood pressure were observed in 23 and 2 patients, respectively, given infusions of 3 grams over 3 hours (Meltzer et al, 1961).
    E) THROMBOPHLEBITIS
    1) WITH THERAPEUTIC USE
    a) Thrombophlebitis has been reported with use of edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Reported adverse effects include dose-related fatigue, myalgia, numbness, and frontal headache (Prod Info ENDRATE(R) IV injection, 2004; Seven, 1960). These reactions occurred after infusions of high doses of combinations of edetate disodium and calcium edetate disodium formerly used to treat patients with Wilson's disease, usually 3 grams or more over a 24-hour period. Initial symptoms of digital and perioral numbness, tingling, yawning, nasal congestion, and prolonged sneezing occurred toward the end of an infusion, and were followed by abrupt onset of fever and chills. Four to 8 hours after infusion, malaise, fatigue, severe myalgia, periarticular muscle and joint pain, frontal headache, anorexia, nausea, urinary frequency, and thirst were noted. The fever persisted for 12 to 18 hours, with other symptoms subsiding gradually (Seven, 1960).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH THERAPEUTIC USE
    a) Reported adverse reactions include anorexia, nausea, and occasionally vomiting, abdominal pain, and diarrhea (Prod Info ENDRATE(R) IV injection, 2004; Meltzer et al, 1961; Seven, 1960).

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nephrotoxicity is a common adverse effect of edetate disodium, and appears to be dose-related.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) WITH THERAPEUTIC USE
    a) Nephrotoxicity is a common adverse effect of edetate disodium, and appears to be dose-related. Fatal renal failure has been reported in 2 children, aged 1 year and 4.5 years, treated with 125 mg/kg/day for 3 days and 130 mg/kg/day for 7 days, respectively (Reuber & Bradley, 1960; Dudley et al, 1955). It has also been reported in an adult who received 9.5 grams in 60 minutes, and in 2 adults who received more than 5 g/day for the treatment of hypercalcemia (Seven, 1960). No evidence of nephrotoxicity was reported in 81 patients receiving a total of 2000 infusions of 3 grams over 3 hours (Meltzer et al, 1961).
    b) Nephrotoxicity and damage to the reticuloendothelial system with possible hemorrhage have been reported in cases of excessive dosing of edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) WITH THERAPEUTIC USE
    a) Anemia was reported in a patient with Wilson's disease treated chronically with a combination of calcium disodium EDTA and disodium EDTA. After a total dose of 72 grams had been given, anemia was noted, which resolved after discontinuation of the chelators (Seven, 1960).
    B) PSEUDOTHROMBOCYTOPENIA
    1) WITH THERAPEUTIC USE
    a) Edetate disodium has caused platelet aggregation in vitro. This reaction is termed pseudothrombocytopenia and occurs in approximately 1.9% of hospitalized patients and in 0.09% of outpatients (Payne, 1985; Payne & Pierre, 1984). The mechanism of this reaction is not totally clear, but appears to involve platelet specific antibodies in the presence of EDTA (Payne & Pierre, 1984).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Injection site reactions have been reported with therapeutic use of edetate disodium.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Dermatitis has been reported following chronic therapy with disodium EDTA. The lesions appear initially on the nasal cheek folds as erythematous macular lesions, which become papular and scaling and progress to the corners of the mouth, chin, forehead, trunk, or extremities. The lesions resemble vitamin B6 deficiency, but have been reported in patients receiving adequate dietary vitamin supplementation. Exfoliative dermatitis of the scrotum responded to vitamin replacement while continuing EDTA therapy in 2 cases. The lesions disappear after discontinuation of therapy, usually within 6 days (Seven, 1960).
    B) INJECTION SITE PAIN
    1) WITH THERAPEUTIC USE
    a) Intramuscular administration of edetate disodium causes local tissue pain that is partially alleviated by an admixture of procaine (Spencer, 1960a). Intravenous injection resulted in burning at the injection site or along the course of the vein in 4.9% of 2000 infusions; thrombophlebitis was reported in 1 of 81 patients (Meltzer et al, 1961).
    C) CIRCUMORAL PARESTHESIA
    1) WITH THERAPEUTIC USE
    1) Circumoral paresthesia has been reported (Prod Info ENDRATE(R) IV injection, 2004).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) Chills and fever, followed by severe myalgia, have been reported (Gilman et al, 1990a).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPERURICEMIA
    1) WITH THERAPEUTIC USE
    a) Hyperuricemia has been reported in patients administered edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).

Reproductive

    3.20.1) SUMMARY
    A) Edetate disodium is classified as FDA pregnancy category C.
    B) There are no data on the use of edetate disodium in pregnant women. The effects, if any, on the developing fetus are unknown. Until more data are available, edetate disodium should not be used unless clearly necessary or for the treatment of a life-threatening condition.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Edetate disodium is classified as FDA pregnancy category C (Prod Info ENDRATE(R) IV injection, 2004).
    2) There are no data on the use of edetate disodium in pregnant women. The effects, if any, on the developing fetus are unknown. Until more data are available, edetate disodium should not be used unless clearly necessary or for the treatment of a life-threatening condition (Prod Info ENDRATE(R) IV injection, 2004).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) No reports describing the use of edetate disodium during human lactation are available and the effects on the nursing infant from exposure to the drug in milk are unknown (Prod Info ENDRATE(R) IV injection, 2004). Until more data is available, lactating women should avoid breastfeeding while receiving edetate disodium.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS17421-79-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) Data are insufficient and conflicting on the carcinogenic and mutagenic potential of edetate disodium.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) Data are insufficient and conflicting on the carcinogenic and mutagenic potential of edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).

Genotoxicity

    A) Data are insufficient and conflicting on the carcinogenic and mutagenic potential of edetate disodium.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Serum calcium, potassium, and magnesium should be monitored closely. Monitor patient for clinical evidence of hypocalcemia: perioral tingling, Chvosteck sign, Trousseau sign, muscle spasms, numbness, tetany.
    B) Serial ECGs and continuous cardiac monitoring is recommended.
    C) Monitor renal function: BUN, serum creatinine, urine output, and urinalysis.
    D) Monitor blood sugar in insulin dependent diabetic patients.
    4.1.2) SERUM/BLOOD
    A) Serum calcium, potassium, and magnesium should be monitored closely (Prod Info ENDRATE(R) IV injection, 2004).
    B) Monitor renal function: BUN, serum creatinine, urine output, and urinalysis (Prod Info ENDRATE(R) IV injection, 2004).
    C) Monitor blood sugar in insulin dependent diabetic patients. Edetate disodium has been shown to lower blood sugar in these patients (Prod Info ENDRATE(R) IV injection, 2004).
    4.1.4) OTHER
    A) OTHER
    1) Monitor patient for clinical evidence of hypocalcemia: perioral numbness and tingling, Chvosteck sign, Trousseau sign, muscle spasms, numbness, tetany.
    a) Chvosteck sign: Tap briskly over the facial nerve about 2 cm anterior to the tragus. Progressively more severe hypocalcemia causes first twitching at the angle of the mouth, then by the nose, the eye and finally the facial muscles.
    b) Trousseau sign: Inflation of a blood pressure cuff above the systolic pressure causes carpal spasm in patients with hypocalcemia.

Methods

    A) OXALATE METHOD
    1) SERUM CALCIUM - in the presence of edetate disodium, the oxalate method for determination of serum calcium tends to give falsely low readings. Acidification of the sample is recommended if this method is used. Less interference will occur if the sample is drawn immediately before administration of edetate disodium (Prod Info ENDRATE(R) IV injection, 2004).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Serum calcium, potassium, and magnesium should be monitored closely. Monitor patient for clinical evidence of hypocalcemia: perioral tingling, Chvosteck sign, Trousseau sign, muscle spasms, numbness, tetany.
    B) Serial ECGs and continuous cardiac monitoring is recommended.
    C) Monitor renal function: BUN, serum creatinine, urine output, and urinalysis.
    D) Monitor blood sugar in insulin dependent diabetic patients.

Range Of Toxicity

Summary

    A) The range of toxicity for edetate disodium has not been established.
    B) Toxicity is dependent on both total dosage and rate of administration, and the serum calcium. A 2-year-old girl died 4 hours after receiving 300 mg of edetate disodium over 4 hours. A 5-year-old boy died shortly after receiving 990 mg of IV edetate disodium over 5 to 10 minutes. A 53-year-old woman died shortly after receiving 1500 mg of edetate disodium over 10 to 15 minutes.
    1) All of these patients were being treated for heavy metal poisoning, and were given edetate disodium in error instead of calcium disodium edetate. The fact that they were not hypercalcemic prior to edetate disodium therapy likely placed them at greater risk for severe toxicity.

Therapeutic Dose

    7.2.1) ADULT
    A) BLACK BOX WARNING
    1) The use of this drug in any patient is recommended only when the severity of the clinical condition justifies the aggressive measures associated with this therapy (Prod Info ENDRATE(R) IV injection, 2004).
    B) The usual adult dose of edetate disodium is 50 milligrams/kilogram/day, up to a maximum dose of 3 grams/day, infused over 3 hours or more, daily for 5 days, followed by a 2-day interruption. Repeat courses may be given if necessary, up to a total of 15 doses (Prod Info ENDRATE(R) IV injection, 2004).
    C) Rapid infusion of edetate disodium or a high serum concentration of edetate disodium may cause a precipitous drop in serum calcium concentration, which may result in hypocalcemic tetany, seizures, severe cardiac dysrhythmias, and death (Prod Info ENDRATE(R) IV injection, 2004).
    7.2.2) PEDIATRIC
    A) Edetate disodium is not FDA approved for pediatric use.
    B) WARNING
    1) Edetate disodium is NOT recommended in pediatric patients and is NOT a treatment for lead poisoning. There have been reports of deaths due to inadvertent use in both pediatric (for lead chelation therapy) and adult patients (for heavy metal chelation therapy). Edetate disodium is indicated only for emergency treatment of hypercalcemia or control of ventricular dysrhythmias associated with digitalis toxicity, and should only be used if the clinical condition justifies the dangers inherently associated with edetate disodium (Na(2)EDTA) therapy (CDC, 2006; Prod Info ENDRATE(R) IV injection, 2004). It has largely been replaced by less toxic alternatives.

Minimum Lethal Exposure

    A) Several patients being treated for heavy metal poisoning have been given edetate disodium in error instead of calcium disodium edetate, resulting in fatal hypocalcemia. The fact that they were not hypercalcemic prior to edetate disodium therapy likely placed them at greater risk for severe toxicity.
    B) CASE REPORT - A 2-year-old girl died 4 hours after receiving 300 mg of edetate disodium over 4 hours (given by mistake instead of calcium disodium edetate). Her serum calcium fell below 5 mg/dL (normal range: 8.5-10.5 mg/dL) (Brown et al, 2006).
    C) CASE REPORT - A 5-year-old boy died shortly after receiving 990 mg of IV edetate disodium over 5 to 10 minutes (instead of calcium disodium edetate for metal chelation) (Brown et al, 2006).
    D) CASE REPORT - A 53-year-old woman died shortly after receiving 1500 mg of IV edetate disodium given over 10 to 15 minutes (instead of calcium disodium edetate for metal chelation) . The cause of death was determined to be cardiac dysrhythmia resulting from hypocalcemia (Brown et al, 2006).

Workplace Standards

    A) ACGIH TLV Values for CAS17421-79-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS17421-79-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS17421-79-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS17421-79-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)RAT:
    1) 2 to 3.7 gram/kg (RTECS, 2006)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Edetate disodium forms a soluble chelate with calcium, resulting in a rapid decrease in plasma calcium concentrations (Gilman et al, 1990; Prod Info ENDRATE(R) IV injection, 2004).

Toxicologic Mechanism

    A) Edetate disodium forms soluble complexes with calcium in the blood, which can produce a lowering of serum calcium concentrations and a mobilization of extracirculatory calcium stores, especially from bone, during slow intravenous infusion. Symptomatic hypocalcemia can occur with either therapeutic or acute exposure.
    B) HUMAN
    1) Edetate disodium forms soluble complexes with calcium in the blood, which are filtered by the glomeruli and not reabsorbed by the renal tubules (Anon, 1986). Chelation with calcium produces a lowering of serum calcium concentrations and a mobilization of extracirculatory calcium stores, especially from bone, during slow intravenous infusion (Prod Info ENDRATE(R) IV injection, 2004). Theoretically, 1 gram of edetate disodium will chelate 120 mg of calcium (McEvoy, 1986). Hypocalcemic tetany, seizures, severe cardiac dysrhythmias, and respiratory arrest may occur with a rapid decrease in serum calcium concentrations.

Physicochemical

Physical Characteristics

    A) Edetate disodium for injection is a sterile, nonpyrogenic, concentrated solution in water (Prod Info ENDRATE(R) IV injection, 2004).

Molecular Weight

    A) 336.24 (RTECS, 2006)

References

General Bibliography

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