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PENTETATE CALCIUM TRISODIUM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Pentetate calcium trisodium (Ca-DTPA), a chelating agent, increases the rates of radiocontaminant elimination by forming stable chelates with metal ions.

Specific Substances

    1) Ca-DTPA
    2) Calcium trisodium DTPA
    3) Calcium trisodium nitrilodiethylenedintrilopenta-acetate
    4) NSC-34249
    5) Pentetate calcium trisodium
    6) Pentetato calcico trisodico
    7) Trisodium calcium diethylenetriaminepentaacetate
    8) Molecular formula: C14-H18-Ca-N3-Na3-O10
    9) CAS 12111-24-9

Available Forms Sources

    A) FORMS
    1) Ca-DTPA is available as a sterile solution in 5 mL single-use clear glass ampoules (1000 mg of Ca-DTPA per ampoule) at a concentration of 200 mg/mL for intravenous use. Each mL has 200 mg of Ca-DTPA (obtained from 158.17 mg pentetic acid, 40.24 mg calcium carbonate and NaOH) in water for injection, USP. If internal contamination is only by inhalation within the preceding 24 hours, patients can receive Ca-DTPA by nebulized inhalation (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).
    B) USES
    1) Pentetate calcium trisodium (Ca-DTPA) is used to treat individuals with known or suspected internal contamination with transuranium ions, specifically plutonium, americium, and/or curium, to increase rates of elimination (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Pentetate calcium trisodium (Ca-DTPA) is used to treat individuals with known or suspected internal contamination with transuranium ions, specifically plutonium, americium, and/or curium, to increase rates of elimination.
    B) PHARMACOLOGY: Pentetate calcium trisodium (Ca-DTPA) increases the rates of radiocontaminant elimination by forming stable chelates with metal ions. The calcium ion is exchanged for ions with higher binding capacity. The radioactive chelates are then excreted into the urine by glomerular filtration.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Chest pain, fever, chills, headache, lightheadedness, dermatitis, pruritus, nausea, vomiting, metallic taste, diarrhea, and Injection site reactions have been reported following therapeutic use of pentetate zinc trisodium (Ca-DTPA). In addition, Ca-DTPA therapy has been associated with trace element deficiency including zinc, magnesium, and manganese depletion. Cough and/or wheezing have been reported in 2 patients who received nebulized Ca-DTPA; one patient had a history of asthma.
    E) WITH POISONING/EXPOSURE
    1) Deaths have been reported in patients with severe hemochromatosis who received up to 4 times the recommended daily dose via intramuscular injection.
    0.2.20) REPRODUCTIVE
    A) Pentetate calcium trisodium (Ca-DTPA) is believed to be teratogenic based on multiple-dose studies in animals. In humans, multiple doses of Ca-DTPA increase the risk of adverse reproductive outcomes. It is recommended that chelation treatment for pregnant women begin and continue with pentetate zinc trisodium (Zn-DTPA). In cases of high internal contamination with radioactive material, the risk of radiation-induced toxicity to the mother and fetus must be weighed against the risk of toxicity with Ca-DTPA therapy.
    B) The US Food and Drug Administration's Pregnancy Category C.

Laboratory Monitoring

    A) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    B) Monitor CBC with differential, renal function, and serum electrolytes (including calcium, zinc, magnesium, and manganese).
    C) Measure the radioactivity in blood, urine, and fecal samples weekly to monitor the radioactive contaminant elimination rate. A baseline estimate of the total body burden of transuranium element should be obtained by whole-body counting and bioassay when possible.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any electrolyte abnormalities, as necessary. NOTE: A patient exposed to radiation requires concomitant monitoring and treatment for radiation toxicity; see RADIATION management, as appropriate.
    C) DECONTAMINATION
    1) Gastrointestinal decontamination is not recommended; administered via the parenteral or inhalational routes.
    D) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary.
    E) ANTIDOTE
    1) None.
    F) HYPERSENSITIVITY REACTION
    1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    G) ENHANCED ELIMINATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of pentetate calcium trisodium from plasma.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: Home exposure is very unlikely to occur. A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients with underlying cardiac abnormalities may require ECG monitoring in addition to electrolyte/fluid analysis. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients with significant gastrointestinal symptoms and persistent electrolyte imbalances likely need to be admitted for further treatment and monitoring.
    4) CONSULT CRITERIA: Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    I) PITFALLS
    1) Appropriate therapy may be delayed due to failure to diagnose radiation exposure.
    J) PHARMACOKINETICS
    1) Absorption: inhalation: approximately 20% absorption from the lungs; oral: Ca-DTPA is poorly absorbed in the gastrointestinal tract. Distribution: extracellular fluid, primarily; Ca-DTPA is rapidly distributed throughout the extracellular space. No significant penetration into erythrocytes or other cells. No accumulation in specific organs has been observed. Metabolism: minimal. Excretion: Ca-DTPA is cleared from the plasma in the first few hours after dosing through urinary excretion by glomerular filtration. By 24 hours after administration, cumulative urinary excretion was more than 99% of the injected dose.
    K) DIFFERENTIAL DIAGNOSIS
    1) Patients with underlying electrolyte imbalance may develop more severe symptoms. If a radiation exposure has occurred, symptoms observed may be related to radiation toxicity.

Range Of Toxicity

    A) TOXICITY: Pentetate calcium trisodium (Ca-DTPA) is usually well-tolerated. Deaths have been reported in 3 patients with severe hemochromatosis who received up to 4 times the recommended daily dose via intramuscular injection. After receiving 14 grams of Ca-DTPA, one patient became comatose and died. The other two patients died after 14 days of daily treatment. Another patient with a less severe case of hemochromatosis did not experience any adverse effects after receiving 30 grams of Ca-DTPA by intravenous injection over 12 days.
    B) THERAPEUTIC DOSES: ADULTS AND ADOLESCENTS: 1 g IV as a single dose initially and then once daily as maintenance dose (only if Zn-DTPA is not available); diluted in 100 to 250 mL D5W, LR or NS; either give by slow IV push over 3 to 4 min or IV infusion. CHILDREN: Less than 12 years: 14 mg/kg IV as a single dose initially and then once daily as maintenance dose (only if Zn-DTPA is not available); MAX: 1 g/day. INHALATION: Diluted to a 1 to 1 ratio with sterile water or NS for nebulization (only if Zn-DTPA is not available).

Clinical Effects

Summary Of Exposure

    A) USES: Pentetate calcium trisodium (Ca-DTPA) is used to treat individuals with known or suspected internal contamination with transuranium ions, specifically plutonium, americium, and/or curium, to increase rates of elimination.
    B) PHARMACOLOGY: Pentetate calcium trisodium (Ca-DTPA) increases the rates of radiocontaminant elimination by forming stable chelates with metal ions. The calcium ion is exchanged for ions with higher binding capacity. The radioactive chelates are then excreted into the urine by glomerular filtration.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Chest pain, fever, chills, headache, lightheadedness, dermatitis, pruritus, nausea, vomiting, metallic taste, diarrhea, and Injection site reactions have been reported following therapeutic use of pentetate zinc trisodium (Ca-DTPA). In addition, Ca-DTPA therapy has been associated with trace element deficiency including zinc, magnesium, and manganese depletion. Cough and/or wheezing have been reported in 2 patients who received nebulized Ca-DTPA; one patient had a history of asthma.
    E) WITH POISONING/EXPOSURE
    1) Deaths have been reported in patients with severe hemochromatosis who received up to 4 times the recommended daily dose via intramuscular injection.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) Fever and chills have been reported with Ca-DTPA treatment (Anon, 2002).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CHEST PAIN
    1) WITH THERAPEUTIC USE
    a) Chest pain has been reported with Ca-DTPA treatment (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FINDING
    1) WITH THERAPEUTIC USE
    a) Cough and/or wheezing have been reported in 2 patients who received nebulized Ca-DTPA; one patient had a history of asthma (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Headache and lightheadedness have been reported with Ca-DTPA treatment (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).
    b) Anosmia was reported in a patient receiving 27 months of therapy with Ca-DTPA (over 123 grams total dose). The loss of smell was possibly related to zinc depletion. Discontinuation of Ca-DTPA resulted in an improvement in the patient's sense of smell (Anon, 2002).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting, metallic taste, and diarrhea have been reported with Ca-DTPA treatment (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005; Anon, 2002).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) WITH THERAPEUTIC USE
    a) Microhematuria has been reported with Ca-DTPA treatment (Brugsch et al, 1965).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Dermatitis and pruritus have been reported with Ca-DTPA treatment (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005; Anon, 2002).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) Allergic reaction has been reported with Ca-DTPA treatment (Prod Info pentetate calcium trisodium IV injection, inhalation solution, 2005).

Reproductive

    3.20.1) SUMMARY
    A) Pentetate calcium trisodium (Ca-DTPA) is believed to be teratogenic based on multiple-dose studies in animals. In humans, multiple doses of Ca-DTPA increase the risk of adverse reproductive outcomes. It is recommended that chelation treatment for pregnant women begin and continue with pentetate zinc trisodium (Zn-DTPA). In cases of high internal contamination with radioactive material, the risk of radiation-induced toxicity to the mother and fetus must be weighed against the risk of toxicity with Ca-DTPA therapy.
    B) The US Food and Drug Administration's Pregnancy Category C.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Ca-DTPA is believed to be teratogenic based on multiple-dose studies in animals and because chelation therapy results in depletion of zinc in the body, which is known to affect DNA and RNA synthesis in humans (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    2) Mouse studies have demonstrated teratogenic and embryocidal effects of multiple doses of Ca-DTPA. Mice received 5 daily injections of Ca-DTPA at doses 2 to 8 times the recommended daily human dose. A higher incidence of gross malformations (eg; exencephaly, spina bifida, and cleft palate) was observed at higher doses, with a higher susceptibility in early and mid gestation. Five daily injections at doses approximately equivalent to the recommended human dose did not produce harmful effects in mice (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    3) A study of 2 pregnant dogs given daily injections of Ca-DTPA demonstrated severe teratogenic effects, especially fetal brain damage. Ca-DTPA was administered from implantation until parturition at a dose approximately 50% of the recommended human dose (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The US Food and Drug Administration's Pregnancy Category C (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    2) Multiple doses of Ca-DTPA increase the risk of adverse reproductive outcomes. It is recommended that chelation treatment for pregnant women begin and continue with pentetate zinc trisodium (Zn-DTPA), if available, except in cases of high internal contamination with radioactive material. In these cases, the risk of radiation-induced toxicity to the mother and fetus must be weighed against the risk of toxicity with Ca-DTPA therapy. Since Ca-DTPA is more effective than Zn-DTPA in the first 24 hours after internal contamination, a single dose of Ca-DTPA with zinc-containing vitamin and mineral supplements may be appropriate initial treatment (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is unknown if Ca-DTPA is excreted in breast milk. However, radiocontaminants are known to be excreted in breast milk. Whether receiving chelation therapy or not, women with suspected or known internal contamination should not breast feed. Precautions should be taken when discarding breast milk (Prod Info Pentetate Calcium Trisodium Injection, 2004).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS12111-24-9 (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

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    B) Monitor CBC with differential, renal function, and serum electrolytes (including calcium, zinc, magnesium, and manganese).
    C) Measure the radioactivity in blood, urine, and fecal samples weekly to monitor the radioactive contaminant elimination rate. A baseline estimate of the total body burden of transuranium element should be obtained by whole-body counting and bioassay when possible.
    4.1.2) SERUM/BLOOD
    A) Monitor CBC with differential, BUN, serum chemistry and electrolytes (including calcium, zinc, magnesium, and manganese) and urinalysis regularly during therapy.
    4.1.4) OTHER
    A) OTHER
    1) Measure the radioactivity in blood, urine, and fecal samples weekly to monitor the radioactive contaminant elimination rate. A baseline estimate of the total body burden of transuranium element should be obtained by whole-body counting and bioassay when possible.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients with significant gastrointestinal symptoms and persistent electrolyte imbalances likely need to be admitted for further treatment and monitoring.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) Home exposure is very unlikely to occur. A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a Poison Center or medical toxicologist for assistance in managing patients with severe toxicity or for whom diagnosis is unclear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients with underlying cardiac abnormalities may require ECG monitoring in addition to electrolyte/fluid analysis. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
    B) Monitor CBC with differential, renal function, and serum electrolytes (including calcium, zinc, magnesium, and manganese).
    C) Measure the radioactivity in blood, urine, and fecal samples weekly to monitor the radioactive contaminant elimination rate. A baseline estimate of the total body burden of transuranium element should be obtained by whole-body counting and bioassay when possible.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is not recommended; administered via the parenteral or inhalational routes.
    6.5.3) TREATMENT
    A) SUPPORT
    1) See the PARENTERAL EXPOSURE treatment section for further information.

Enhanced Elimination

    A) LACK OF INFORMATION
    1) There is no information regarding the effectiveness of hemodialysis or hemoperfusion for the removal of pentetate calcium trisodium from plasma.

Range Of Toxicity

Summary

    A) TOXICITY: Pentetate calcium trisodium (Ca-DTPA) is usually well-tolerated. Deaths have been reported in 3 patients with severe hemochromatosis who received up to 4 times the recommended daily dose via intramuscular injection. After receiving 14 grams of Ca-DTPA, one patient became comatose and died. The other two patients died after 14 days of daily treatment. Another patient with a less severe case of hemochromatosis did not experience any adverse effects after receiving 30 grams of Ca-DTPA by intravenous injection over 12 days.
    B) THERAPEUTIC DOSES: ADULTS AND ADOLESCENTS: 1 g IV as a single dose initially and then once daily as maintenance dose (only if Zn-DTPA is not available); diluted in 100 to 250 mL D5W, LR or NS; either give by slow IV push over 3 to 4 min or IV infusion. CHILDREN: Less than 12 years: 14 mg/kg IV as a single dose initially and then once daily as maintenance dose (only if Zn-DTPA is not available); MAX: 1 g/day. INHALATION: Diluted to a 1 to 1 ratio with sterile water or NS for nebulization (only if Zn-DTPA is not available).

Therapeutic Dose

    7.2.1) ADULT
    A) INTRAVENOUS
    1) Treatment with pentetate calcium trisodium (Ca-DTPA) is most effective within the first 24 hours after internal contamination and should be started as soon as possible after suspected or known contamination. Chelation treatment should be started as soon as possible, even if treatment with Ca-DTPA cannot be started right away. Ca-DTPA is most effective when radiocontaminants are still circulating or are in interstitial fluids. Since radiocontaminants become sequestered in liver and bone, the efficacy decreases with time following internal contamination (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    2) Ca-DTPA intravenous route (1 gram in 5 mL solution either by a slow intravenous push over 3 to 4 minutes or by intravenous infusion diluted in 100 to 250 milliliters of 5% dextrose in water, lactated Ringer's, or normal saline) is recommended. The intravenous route should be used of the route if internal contamination is not known or if multiple routes of internal contamination are likely (Prod Info Pentetate Calcium Trisodium Injection, 2004)
    3) Patients should drink plenty of fluids and void frequently to promote dilution of the chelated radiocontaminant in the urine and reduce radiation exposure directly to the bladder (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    4) Other therapies may be needed (eg; Prussian blue, potassium iodide) if internal contamination with agents other than plutonium, americium, or curium is suspected, or if the radiocontaminant is unknown (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    5) INITIAL DOSE - A single intravenous dose of 1 gram of Ca-DTPA is recommended (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    6) MAINTENANCE DOSE - The day after the initial dose, if additional chelation therapy is needed, it is preferable to switch to pentetate zinc trisodium (Zn-DTPA), if available, due to safety concerns with prolonged Ca-DTPA administration. If Zn-DTPA is not available, treatment with Ca-DTPA may continue, but concomitant zinc supplementation should be given as needed. An intravenous dose of 1 gram of Ca-DTPA once daily is recommended for maintenance treatment (if Zn-DTPA is not available). Ca-DTPA should not be given simultaneously with Zn-DTPA (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    B) INHALATION
    1) If internal contamination is only by inhalation within the preceding 24 hours, patients can receive Ca-DTPA by nebulized inhalation. Dilute Ca-DTPA for nebulization at a 1:1 ratio with sterile water or saline. After nebulization, patients should not swallow any expectorant (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    7.2.2) PEDIATRIC
    A) INTRAVENOUS
    1) ADOLESCENTS -
    a) INITIAL DOSE - An initial single intravenous dose of 1 gram of pentetate calcium trisodium (Ca-DTPA) is recommended (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    b) MAINTENANCE DOSE - The day after the initial dose, if additional chelation therapy is needed, it is preferable to switch to pentetate zinc trisodium (Zn-DTPA), if available, due to safety concerns with prolonged Ca-DTPA administration. If Zn-DTPA is not available, treatment with Ca-DTPA may continue, but concomitant zinc supplementation should be given as needed. An intravenous dose of 1 gram of Ca-DTPA once daily is recommended for maintenance treatment (if Zn-DTPA is not available). Ca-DTPA should not be given simultaneously with Zn-DTPA (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    2) CHILDREN LESS THAN 12 YEARS OF AGE -
    a) INITIAL DOSE - An initial single intravenous dose of 14 milligrams per kilogram, not to exceed 1 gram, of pentetate calcium trisodium (Ca-DTPA) is recommended for children less than 12 years of age (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    b) MAINTENANCE DOSE - The day after the initial dose, if additional chelation therapy is needed, it is preferable to switch to pentetate zinc trisodium (Zn-DTPA), if available, due to safety concerns with prolonged Ca-DTPA administration. If Zn-DTPA is not available, treatment with Ca-DTPA may continue, but concomitant zinc supplementation should be given as needed. In pediatric patients (less than 12 years of age), an intravenous dose of 14 milligrams per kilogram (not to exceed 1 gram per day) of Ca-DTPA once daily is recommended for maintenance treatment (if Zn-DTPA is not available),(Prod Info Pentetate Calcium Trisodium Injection, 2004).
    B) INHALATION
    1) ADOLESCENTS - If internal contamination is only by inhalation within the preceding 24 hours, patients can receive Ca-DTPA by nebulized inhalation. Dilute Ca-DTPA for nebulization at a 1:1 ratio with sterile water or saline. After nebulization, patients should not swallow any expectorant (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    2) CHILDREN LESS THAN 12 YEARS OF AGE - The safety and efficacy of the nebulized route of administration have not been established in children (Prod Info Pentetate Calcium Trisodium Injection, 2004).

Minimum Lethal Exposure

    A) Deaths have been reported in three patients with severe hemochromatosis who received up to 4 times the recommended daily dose via intramuscular injection. After receiving 14 grams of Ca-DTPA, one patient became comatose and died. The other two patients died after 14 days of daily treatment (Prod Info Pentetate Calcium Trisodium Injection, 2004).

Maximum Tolerated Exposure

    A) One patient with a less severe case of hemochromatosis did not experience any adverse effects after receiving 30 grams of Ca-DTPA by intravenous injection over 12 days (Anon, 2004).

Workplace Standards

    A) ACGIH TLV Values for CAS12111-24-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS12111-24-9 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS12111-24-9 :
    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 CAS12111-24-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Ca-DTPA is indicated for the treatment of known or suspected internal contamination with transuranium ions with molecular weight greater than uranium, specifically plutonium, americium, and/or curium, to increase rates of elimination (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    B) Pentetate calcium trisodium (Ca-DTPA) increases the rates of radiocontaminant elimination by forming stable chelates with metal ions. The calcium ion is exchanged for ions with higher binding capacity. The radioactive chelates are then excreted into the urine by glomerular filtration (Prod Info Pentetate Calcium Trisodium Injection, 2004).
    C) Ca-DTPA is most effective when radiocontaminants are still circulating or are in interstitial fluids. Since radiocontaminants become sequestered in liver and bone, the efficacy decreases with time following internal contamination. The day after initial dosing, if additional chelation therapy is needed, it is preferable to switch to pentetate zinc trisodium (Zn-DTPA), if available, due to safety concerns (eg; endogenous essential metal chelation) with prolonged Ca-DTPA administration. If Zn-DTPA is not available, treatment with Ca-DTPA may continue, but concomitant zinc supplementation should be given as needed (Prod Info Pentetate Calcium Trisodium Injection, 2004).

Physicochemical

Physical Characteristics

    A) Ca-DTPA is a clear, colorless, hyperosmolar (1260 mOsmol/kg) solution (Prod Info Pentetate Calcium Trisodium Injection, 2004).

Molecular Weight

    A) 497.4 Daltons (Prod Info Pentetate Calcium Trisodium Injection, 2004)

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
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