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ZIRCONIUM

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Zirconium is a grey-white, hard, lustrous solid metal (as flakes, crystals, powder, or platelets) or a bluish-black amorphous powder (Siegers & Sullivan, 1992; ACGIH, 1986; ILO, 1983; Sax & Lewis, 1987; Budavari, 1989; HSDB , 1992). It may also have a gold color (HSDB , 1992).
    B) Zirconium is used in flash bulbs, nuclear reactors, lamp filaments, in steel alloys for surgical instruments, in corrosion-resistant alloys, in laboratory crucibles, in spinnerets for lamp filaments, and in explosive primers (Siegers & Sullivan, 1992; Bismuth et al, 1987; Hathaway et al, 1991; ACGIH, 1986; Sax & Lewis, 1987; Budavari, 1989; Finkel, 1983; HSDB , 1992).
    1) Zirconium is also used in the fabrication of refractory materials, abrasives, reducing agents, porcelain, ceramics, and pigments, as a "getter" in vacuum tubes, as a deoxidizer and scavenger in steel manufacturing, in high-temperature batteries, in pyrotechnics, in metal-to-glass seals, in acid manufacturing plants, and as a textile water repellent and tanning agent (Bismuth et al, 1987; Hathaway et al, 1991; ACGIH, 1986; Sax & Lewis, 1987; Budavari, 1989; Finkel, 1983; HSDB , 1992).
    a) During WWII and afterwards, zirconium was used in tracer bullets and detonators (Finkel, 1983).
    b) Zirconium is used as a pacifier and polishing powder for lens and television tubes, in arc lamps, as a catalyst in organic reactions, as a reflective surface on satellites, and in cigarette lighter flints (as a powder alloyed with lead) (HSDB , 1992).
    C) Various zirconium compounds have been used experimentally in the treatment of plutonium and yttrium poisoning, to prevent deposition or to displace these radionuclides from the skeleton (ILO, 1983; Clayton & Clayton, 1981).
    1) In mice, zirconium citrate reduced the body burden of strontium-90 by about 33% (Zander-Principati & Kuzma, 1964).
    2) In rats, zirconium citrate increased the excretion of plutonium from 1% to 50%, and that of yttrium from 25% to 60% during a 24-hour period (Schubert, 1948).
    D) Commercial grade zirconium contains between 1% and 3% hafnium (HSDB , 1992).
    1) Impurities in zirconium may include chromium, hafnium, iron, niobium, and tin (HSDB , 1992).

Specific Substances

    1) ZIRCONIUM
    2) ZIRCAT
    3) ZIRCONIUM METAL, dry, chemically produced, finer than 270 mesh particle size
    4) ZIRCONIUM, METAL, dry, coiled wire, finished metal sheets smaller than 18 microns
    5) ZIRCONIUM METAL, dry, mechanically produced, finer than 270 mesh particle size
    6) ZIRCONIUM METAL, liquid suspensions
    7) ZIRCONIUM METAL, wet, chemically produced, finer than 270 mesh particle size
    8) ZIRCONIUM METAL, wet, mechanically produced, finer than 270 mesh particle size
    9) ZIRCONIUM METAL POWDER, wetted with not less than 25% water
    10) ZIRCONIUM SCRAP
    11) ZIRCONIUM SHAVINGS
    12) ZIRCONIUM SHEETS
    13) ZIRCONIUM TURNINGS
    14) ZIRCONIUM METAL, DRY
    15) ZIRCONIUM METAL, LIQUID
    16) ZIRCONIUM METAL, LIQUID SUSPENSION
    17) ZIRCONIUM METAL, POWDER, DRY
    18) ZIRCONIUM METAL, POWDER, WET
    19) ZIRCONIUM METAL, WIRE, SHEET, OR STRIPS (SMALLER THAN 18 MICRONS)
    20) ZIRCONIUM POWDER, WET
    21) ZIRCONIUM POWDER, WETTED WITH NOT LESS THAN 25% WATER
    22) ZIRCONIUM SUSPENDED IN A LIQUID (FLAMMABLE)
    23) ZIRCONIUM, BORINGS
    24) ZIRCONIUM, CLIPPINGS
    25) ZIRCONIUM, DRY
    26) ZIRCONIUM, DRY, COILED WIRE, FINISHED METAL SHEETS OR STRIPS
    27) ZIRCONIUM, LIQUID
    28) ZIRCONIUM, SUSPENDED IN A FLAMMABLE LIQUID
    29) ZIRCONIUM, WET
    1.2.1) MOLECULAR FORMULA
    1) Zr

Available Forms Sources

    A) FORMS
    1) Zirconium is a grey-white, hard, lustrous solid metal (as flakes, crystals, powder, or platelets) or a bluish-black amorphous powder (Siegers & Sullivan, 1992; ACGIH, 1986; ILO, 1983; Sax & Lewis, 1987; Budavari, 1989). It may also have a gold color (HSDB , 1992).
    B) SOURCES
    1) Zirconium is found in the minerals zircon, malacon, baddeleyite, and eudialyte (Budavari, 1989). It is frequently found in the rare-earth minerals and in monazite sand (Budavari, 1989).
    2) Zirconium constitutes approximately 0.017% of the lithosphere; its most common ores are zircon (ZrO2) and baddeleyite (ZrSiO4) (ILO, 1983).
    3) Most commercially useful zirconium deposits are found in beach sands or other locations where zirconium containing minerals have been deposited and the rock subjected to the action of water in washing away the lighter rock portions (ILO, 1983; Clayton & Clayton, 1981).
    a) Zirconium containing beach sands are found in Australia, India, Malaya, the Ukraine, and the United States (ILO, 1983).
    b) Baddeleyite is found in Brazil, Italy, India, and Sweden (ILO, 1983).
    c) Zirconium ores have been mined in Australia, Brazil, East Africa, India, Korea, Madagasgar, Nigeria, the Republic of China, Senegal, South Africa, Sri Lanka, the Soviet Union, and the United States (ILO, 1983; Clayton & Clayton, 1981).
    d) In the United States, most zirconium mineral production is from Florida and Georgia (Clayton & Clayton, 1981).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Zirconium has a low order of toxicity. There are no characteristic signs of zirconium poisoning.
    B) Certain ZIRCONIUM SALTS (eg, zirconium tetrachloride) may cause IRRITATION or CAUSTIC INJURY.
    1) If such effects develop following exposure to a zirconium compound, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    C) Dermal exposure to zirconium in topical poison ivy medications and deodorants has caused subcutaneous granulomas, probably due to a hypersensitivity reaction.
    D) Pulmonary abnormalities have NOT been demonstrated in workers with zirconium fume exposure. Prolonged exposure to aerosols of zirconium lactate and sulfate have caused respiratory tract irritation and peribronchial granuloma formation in experimental animals.
    E) Experimental animals exposed to massive doses have developed CNS depression. Two individuals administered 50 milligrams of zirconium malate intravenously developed vertigo.
    F) Zirconium and its compounds are eye irritants.
    0.2.4) HEENT
    A) Zirconium and its compounds are eye irritants.
    0.2.6) RESPIRATORY
    A) Pulmonary abnormalities have NOT been demonstrated in workers with zirconium fume exposure for 1 to 5 years.
    B) Prolonged exposure to aerosols of zirconium lactate and sulfate have caused respiratory tract irritation and peribronchial granuloma formation in experimental animals.
    1) Severe, persistent interstitial pneumonitis has been produced in experimental animals exposed to airborne zirconium concentrations of 5 mg/m(3).
    C) A single worker exposed to both zirconium and hafnium for 7 years developed a granulomatous lung condition.
    0.2.7) NEUROLOGIC
    A) Experimental animals exposed to massive doses have developed CNS depression.
    B) Two individuals administered 50 milligrams of zirconium malate intravenously developed vertigo.
    0.2.8) GASTROINTESTINAL
    A) Ingestion of certain zirconium salts may cause IRRITANT or CAUSTIC EFFECTS.
    1) If such IRRITANT or CAUSTIC EFFECTS occur, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    0.2.13) HEMATOLOGIC
    A) In dogs, inhalation of zirconium tetrachloride mist at a concentration of 6 mg Zr/m(3) for 2 months caused slight decreases in hemoglobin and erythrocyte counts, as well as some increased mortality.
    0.2.14) DERMATOLOGIC
    A) Dermal exposure to zirconium in topical poison ivy medications and deodorants has caused subcutaneous granulomas, probably due to a hypersensitivity reaction.
    B) Certain zirconium salts may cause IRRITANT or CAUSTIC SKIN INJURY.
    1) If such IRRITANT or CAUSTIC EFFECTS occur, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) Small fractions of zirconium were absorbed in female rats by the oral route, and the metal seemed to concentrate in the ovaries and produce hypervascularization.
    C) In one animal study, offspring of pregnant mice who received trace amounts of zirconium had long-lasting behavioral changes.
    D) Zirconium is found in newborn rats.
    E) In rats, zirconium appears in the breast milk.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies on the possible carcinogenic effects of zirconium were found in humans.

Laboratory Monitoring

    A) Recent exposure to zirconium can be monitored by proton-induced x-ray emission of hair samples.
    B) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    C) Monitor the chest x-ray in patients with significant exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Do NOT induce emesis.
    B) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    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) Administration of activated charcoal and cathartic are NOT RECOMMENDED following ingestion of zirconium or its compounds.
    1) Most zirconium compounds are poorly absorbed into the blood stream from the gastrointestinal tract.
    2) There is no evidence that activated charcoal or cathartics are efficacious in decreasing the absorption of ingested zirconium or its compounds.
    3) Activated charcoal could obscure endoscopic findings if irritant or caustic zirconium compounds have been ingested.
    E) Ingestion of certain zirconium salts may cause IRRITANT or CAUSTIC EFFECTS such as burning of the mouth and throat, vomiting, watery or bloody diarrhea, retching, tenesmus, possible gastrointestinal tract bleeding, and systemic effects due to blood and fluid losses.
    1) If such IRRITANT or CAUSTIC EFFECTS occur REFER to the IRRITANTS or ACIDS MEDITEXT(R) MEDICAL MANAGEMENTS for MORE INFORMATION.
    F) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    G) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    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) AVOIDANCE OF FURTHER EXPOSURE - is recommended if pulmonary granulomas develop following zirconium exposure.
    C) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    D) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    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.
    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) AVOIDANCE OF FURTHER EXPOSURE - is recommended if skin granulomas develop following zirconium exposure.
    3) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Range Of Toxicity

    A) TOXIC DOSE: A toxic dose has not been established. Zirconium is of low toxicity by the oral route. ORAL: A woman developed symptoms of parkinsonism and progressive blue-grey discoloration of the skin and nails after chronic inadvertent exposure to zirconium found in a dietary supplement.

Clinical Effects

Summary Of Exposure

    A) Zirconium has a low order of toxicity. There are no characteristic signs of zirconium poisoning.
    B) Certain ZIRCONIUM SALTS (eg, zirconium tetrachloride) may cause IRRITATION or CAUSTIC INJURY.
    1) If such effects develop following exposure to a zirconium compound, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    C) Dermal exposure to zirconium in topical poison ivy medications and deodorants has caused subcutaneous granulomas, probably due to a hypersensitivity reaction.
    D) Pulmonary abnormalities have NOT been demonstrated in workers with zirconium fume exposure. Prolonged exposure to aerosols of zirconium lactate and sulfate have caused respiratory tract irritation and peribronchial granuloma formation in experimental animals.
    E) Experimental animals exposed to massive doses have developed CNS depression. Two individuals administered 50 milligrams of zirconium malate intravenously developed vertigo.
    F) Zirconium and its compounds are eye irritants.

Heent

    3.4.1) SUMMARY
    A) Zirconium and its compounds are eye irritants.
    3.4.3) EYES
    A) IRRITATION - Zirconium and its compounds are eye irritants (HSDB , 1992).

Respiratory

    3.6.1) SUMMARY
    A) Pulmonary abnormalities have NOT been demonstrated in workers with zirconium fume exposure for 1 to 5 years.
    B) Prolonged exposure to aerosols of zirconium lactate and sulfate have caused respiratory tract irritation and peribronchial granuloma formation in experimental animals.
    1) Severe, persistent interstitial pneumonitis has been produced in experimental animals exposed to airborne zirconium concentrations of 5 mg/m(3).
    C) A single worker exposed to both zirconium and hafnium for 7 years developed a granulomatous lung condition.
    3.6.2) CLINICAL EFFECTS
    A) PNEUMONITIS
    1) While acute inhalational zirconium poisoning has not been described in humans, prolonged exposure to aerosols of zirconium lactate and sulfate have caused respiratory tract irritation and peribronchial granuloma formation in experimental animals (Bismuth et al, 1987).
    2) A severe, persistent interstitial pneumonitis has been produced in experimental animals exposed to airborne zirconium concentrations of 5 mg/m(3) (ILO, 1983).
    3) In rats, inhalation of zirconium dioxide caused pulmonary emphysema and enlarged bronchial glands (Mogilevskaya, 1961).
    B) GRANULOMA
    1) A single worker exposed to both zirconium and hafnium for 7 years developed a granulomatous lung condition; however, no other workers in the same facility had evidence of a similar pulmonary injury (ILO, 1983).
    C) LACK OF EFFECT
    1) PULMONARY FUNCTIONS - Pulmonary abnormalities have NOT been demonstrated in workers with zirconium fume exposure for 1 to 5 years (Ellenhorn & Barceloux, 1988; Hathaway et al, 1991; Reed, 1956).

Neurologic

    3.7.1) SUMMARY
    A) Experimental animals exposed to massive doses have developed CNS depression.
    B) Two individuals administered 50 milligrams of zirconium malate intravenously developed vertigo.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Experimental animals exposed to massive doses have developed CNS depression (Bismuth et al, 1987; Hathaway et al, 1991). This effect has not been reported in exposed humans.
    B) DIZZINESS
    1) Two individuals administered 50 milligrams of zirconium malate intravenously developed vertigo (Hathaway et al, 1991).
    C) PARKINSONISM
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 72-year-old woman sought medical care for complaints of tremor and slowness of the body that began about 3 months prior to admission. Her history included taking a silver-containing dietary supplement for more than a year for general health. A neurologic exam demonstrated bilateral resting tremor, rigidity and bradykinesia that was consistent with parkinsonism. A MRI of the brain was negative and a dopamine transporter positron emission tomography was normal. Dopaminergic medications did not produce any clinical improvement. It was also noted that the patient had progressive, widespread blue-grey discoloration of the skin and nails. Laboratory testing for heavy metals was negative. A punch skin biopsy was positive for zirconium; silver was not detected. Her neurologic and dermatologic changes were assumed to be due to systemic zirconium intoxication (Ryu et al, 2014).

Gastrointestinal

    3.8.1) SUMMARY
    A) Ingestion of certain zirconium salts may cause IRRITANT or CAUSTIC EFFECTS.
    1) If such IRRITANT or CAUSTIC EFFECTS occur, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    3.8.2) CLINICAL EFFECTS
    A) CHEMICAL BURN
    1) IRRITANT/CAUSTIC EFFECTS - Ingestion of certain zirconium salts may cause IRRITANT or CAUSTIC EFFECTS such as burning of the mouth and throat, vomiting, watery or bloody diarrhea, retching, tenesmus, possible gastrointestinal tract bleeding, and systemic effects due to blood and fluid losses (HSDB , 1992).
    a) If such IRRITANT or CAUSTIC EFFECTS occur REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.

Hematologic

    3.13.1) SUMMARY
    A) In dogs, inhalation of zirconium tetrachloride mist at a concentration of 6 mg Zr/m(3) for 2 months caused slight decreases in hemoglobin and erythrocyte counts, as well as some increased mortality.
    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) In dogs, inhalation of zirconium tetrachloride mist at a concentration of 6 mg Zr/m(3) for 2 months caused slight decreases in hemoglobin and erythrocyte counts, as well as some increased mortality (Clayton & Clayton, 1981). These effects have not been reported in exposed humans.

Dermatologic

    3.14.1) SUMMARY
    A) Dermal exposure to zirconium in topical poison ivy medications and deodorants has caused subcutaneous granulomas, probably due to a hypersensitivity reaction.
    B) Certain zirconium salts may cause IRRITANT or CAUSTIC SKIN INJURY.
    1) If such IRRITANT or CAUSTIC EFFECTS occur, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    3.14.2) CLINICAL EFFECTS
    A) GRANULOMA
    1) Dermal exposure to zirconium in topical poison ivy medications and deodorants has caused subcutaneous granulomas, probably due to a hypersensitivity reaction (Ellenhorn & Barceloux, 1988; Hathaway et al, 1991; Prior et al, 1957; Shelley & Hurley, 1958).
    2) These skin lesions are red-brown papular eruptions, and have the histologic appearance of giant cell epithelioid granulomas (Bismuth et al, 1987). They may occur as linear streaks of small, indolent, flesh-colored or reddish-brown 1 to 4 millimeter diameter papular eruptions, usually in the domes of the axillae and sparsely at the periphery (Clayton & Clayton, 1981).
    a) Histologically, these lesions are made up of epithelioid cells and Langerhan's giant cells, surrounded by a typical tuberculoid pattern of lymphocytes (Clayton & Clayton, 1981).
    b) Such lesion were associated with use of deodorants containing zirconium salts, particularly sodium zirconium lactate (Clayton & Clayton, 1981).
    3) Rabbits developed granulomas when injected intradermally with zirconium aluminum glycinate and sodium zirconium lactate (Kang et al, 1977; Prior et al, 1957).
    4) Mice injected intradermally with zirconium lactate, sodium zirconium lactate, and zirconyl chloride developed foreign body granulomas (Shelley & Raque, 1971).
    B) SKIN IRRITATION
    1) Exposure to certain ZIRCONIUM SALTS (eg, zirconium tetrachloride), however, may cause IRRITATION or CAUSTIC INJURY. If such effects develop following exposure to a zirconium compound, REFER to the IRRITANTS or ACIDS MEDITEXT MEDICAL MANAGEMENTS for MORE INFORMATION on EVALUATION and TREATMENT.
    C) DISCOLORATION OF SKIN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 72-year-old woman sought medical care for symptoms of parkinsonism and was noted to have progressive, widespread blue-grey discoloration of the skin and nails. Her history included taking a silver-containing dietary supplement for more than a year for general health. She also had prominent bluish discoloration of the face and hands. Other areas included the gums, oral mucosa, extremities, trunk and gastric mucosa. Initially, the skin color changes were presumed to be consistent with silver intoxication, but laboratory analysis was negative for heavy metals. A skin punch biopsy detected small black-brown granules that confirmed the presence of zirconium; silver was not detected. Her neurologic and dermatologic changes were assumed to be due to systemic zirconium intoxication (Ryu et al, 2014).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS7440-67-7 (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 studies on the possible carcinogenic effects of zirconium were found in humans.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) Rats administered 5 ppm of zirconium sulfate in drinking water for the entire lifetime did NOT have an increased incidence of tumors (Hathaway et al, 1991).
    2) Zirconocene was not carcinogenic in rats and mice (Clayton & Clayton, 1981; Kanisawa & Schroeder, 1969).

Genotoxicity

    A) In mouse lymphocytes, zirconium oxychloride stimulates division and enhances the frequency of abnormal metaphases.
    B) Zirconium compounds did not induce sister chromatid exchanges in hamster cells.

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) Small fractions of zirconium were absorbed in female rats by the oral route, and the metal seemed to concentrate in the ovaries and produce hypervascularization.
    C) In one animal study, offspring of pregnant mice who received trace amounts of zirconium had long-lasting behavioral changes.
    D) Zirconium is found in newborn rats.
    E) In rats, zirconium appears in the breast milk.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) OVARIAN DISORDER
    1) Small fractions of zirconium were absorbed in female rats by the oral route, and the metal seemed to concentrate in the ovaries and produce hypervascularization (Delongeas, 1983).
    B) BEHAVIORAL CHANGES
    1) In one animal study, offspring of pregnant mice who received trace amounts of zirconium had long-lasting behavioral changes (Tsujii & Hoshishima, 1979).
    C) PLACENTAL BARRIER
    1) Zirconium is found in newborn rats (Schroeder & Balassa, 1966).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) In rats, zirconium appears in the breast milk (Schroeder & Balassa, 1966).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Recent exposure to zirconium can be monitored by proton-induced x-ray emission of hair samples.
    B) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    C) Monitor the chest x-ray in patients with significant exposure.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    B) CHEST RADIOGRAPH
    1) Monitor the chest x-ray in patients with significant exposure.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Zirconium can be determined by emission spectroscopy, atomic absorption spectroscopy, argon inductively coupled plasma with optical emission spectroscopy, colorimetry, and a combined morin fluorescence and energy dispersive x-ray (EDXA) method (Clayton & Clayton, 1981).
    a) The EDXA method has been used to screen lung specimens for the presence of zirconium from antiperspirants (Clayton & Clayton, 1981).
    b) Recent exposure to zirconium can be monitored by proton-induced x-ray emission of hair samples (Clayton & Wooller, 1985).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

    A) Recent exposure to zirconium can be monitored by proton-induced x-ray emission of hair samples.
    B) This agent may produce abnormalities of the hematopoietic system. Monitor the complete blood count in patients with significant exposure.
    C) Monitor the chest x-ray in patients with significant exposure.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Because of possible irritant or caustic effects with ingestion of some zirconium salts, EMESIS SHOULD NOT BE INDUCED.
    B) GASTRIC LAVAGE
    1) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    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.
    C) ACTIVATED CHARCOAL/CATHARTIC
    1) Administration of activated charcoal and cathartic are NOT RECOMMENDED following ingestion of zirconium or its compounds.
    a) Most zirconium compounds are poorly absorbed into the blood stream from the gastrointestinal tract.
    b) There is no evidence that activated charcoal or cathartics are efficacious in decreasing the absorption of ingested zirconium or its compounds.
    c) Activated charcoal could obscure endoscopic findings if irritant or caustic zirconium compounds have been ingested.
    6.5.3) TREATMENT
    A) IRRITATION SYMPTOM
    1) Ingestion of certain zirconium salts may cause IRRITANT or CAUSTIC EFFECTS such as burning of the mouth and throat, vomiting, watery or bloody diarrhea, retching, tenesmus, possible gastrointestinal tract bleeding, and systemic effects due to blood and fluid losses (HSDB , 1992).
    2) If such IRRITANT or CAUSTIC EFFECTS occur, REFER to the IRRITANTS or ACIDS MEDITEXT(R) MEDICAL MANAGEMENTS for MORE INFORMATION.
    B) OBSERVATION REGIMES
    1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

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) PROCEDURE EDUCATION
    1) AVOIDANCE OF FURTHER EXPOSURE - is recommended if pulmonary granulomas develop following zirconium exposure.
    B) IRRITATION SYMPTOM
    1) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    C) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    D) 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).

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) WOUND GRANULOMA
    1) AVOIDANCE OF FURTHER EXPOSURE - is recommended if skin granulomas develop following zirconium exposure.
    B) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) TOXIC DOSE: A toxic dose has not been established. Zirconium is of low toxicity by the oral route. ORAL: A woman developed symptoms of parkinsonism and progressive blue-grey discoloration of the skin and nails after chronic inadvertent exposure to zirconium found in a dietary supplement.

Minimum Lethal Exposure

    A) SUMMARY
    1) A toxic dose has not been established.

Maximum Tolerated Exposure

    A) CASE REPORT
    1) CASE REPORT: A 72-year-old woman sought medical care for complaints of tremor and slowness of the body that began about 3 months prior to admission. Her history included taking a silver-containing dietary supplement for more than a year for general health. A neurologic exam demonstrated bilateral resting tremor, rigidity and bradykinesia that was consistent with parkinsonism. A MRI of the brain was negative and a dopamine transporter positron emission tomography was normal. Dopaminergic medications did not produce any clinical improvement. It was also noted that the patient had progressive, widespread blue-grey discoloration of the skin and nails. Laboratory testing for heavy metals was negative. A punch skin biopsy was positive for zirconium; silver was not detected. Her neurologic and dermatologic changes were assumed to be due to systemic zirconium intoxication (Ryu et al, 2014).
    B) ANIMAL DATA
    1) Dogs inhaling zirconium tetrachloride mist for 2 months at a concentration of 6 mg/m(3) had slight decreases in hemoglobin and RBC counts, as well as some increased mortality (Hathaway et al, 1991; Clayton & Clayton, 1981).
    2) No detectable effects were noted in experimental animals inhaling zirconium oxide dust for 1 month at a concentration of 75 mg/m(3) (Hathaway et al, 1991) or 11 mg/m(3) for 2 months (Clayton & Clayton, 1981).
    3) Zirconium is of low toxicity by the oral route (Clayton & Clayton, 1981; ACGIH, 1986), with LD50s for zirconium tetrachloride of 1688 mg/kg (rats) and 655 mg/kg (mice), and for zirconium tetrafluoride of 98 mg/kg (rats) (ACGIH, 1986).
    4) Mild toxic effects noted following zirconium tetrachloride inhalation exposure in experimental animals were presumably due to liberated hydrogen chloride (ACGIH, 1986).
    5) Rats tolerate 20% zirconium in the diet for long periods without adverse effects (ILO, 1983). Rats did not develop toxicity when administered zirconium at 5 ppm in drinking water and 2.66 ppm in the solid diet over a lifetime (Clayton & Clayton, 1981).
    6) Pulmonary granulomas have been produced in experimental animals at airborne zirconium lactate concentrations of 0.049 mg/cm(3) (ILO, 1983).
    7) A severe, persistent interstitial pneumonitis has been produced in experimental animals exposed to airborne zirconium concentrations of 5 mg/m(3) (ILO, 1983).
    8) No effects were seen in laboratory animals inhaling zirconium oxide dust or zirconium tetrachloride mist for one year at a concentration of 3.5 mg Zr/m(3) (Clayton & Clayton, 1981).
    a) Inhalation of ZrSiO2 dust for 7.5 months caused the development of shadows on chest x-rays, but no histologic cellular reaction (Clayton & Clayton, 1981).
    9) Guinea pigs exposed to a zirconium process for 2 to 6 months developed no pulmonary abnormalities attributable to the exposure (Clayton & Clayton, 1981).
    10) Guinea pigs, rats, and hamsters exposed to zirconium lactate at an airborne concentration of 15 or 150 mg/m(3) or to 15 mg/m(3) of barium zirconate had poor weight gain, an increase in the zirconium concentration in the lungs, and pathological changes consistent with fibrosis; granulomas were not seen (Brown et al, 1963).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) OCCUPATIONAL
    1) In the lungs of coal miners, zirconium concentrations were 1.0 ppm in a normally-functioning section, 3.8 ppm in a lightly pigmented section, and at 14 ppm in a heavily pigmented section (Clayton & Clayton, 1981). Zirconium was present at 3.6 ppm in the lung of a non-mining male, and 1.5 ppm in a female who resided near mining operations (Clayton & Clayton, 1981).
    a) Pulmonary lymph nodes from miners with lung zirconium concentrations of 1.1 and 2.8 ppm had concentrations of 6.8 and 22 ppm (Clayton & Clayton, 1981).
    2) In two coal miners, blood zirconium levels were 0.3 and 10 mcg/100 grams, and urine levels were 3 and 12 mcg/Liter (Clayton & Clayton, 1981).

Workplace Standards

    A) ACGIH TLV Values for CAS7440-67-7 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Zirconium, and compounds, as Zr
    a) TLV:
    1) TLV-TWA: 5 mg/m(3)
    2) TLV-STEL: 10 mg/m(3)
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Not Listed
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight: 91.22
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS7440-67-7 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Zirconium compounds (as Zr)
    2) REL:
    a) TWA: 5 mg/m(3)
    b) STEL: 10 mg/m(3)
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s): [*Note: The REL applies to all zirconium compounds (as Zr) except Zirconium tetrachloride.]
    3) IDLH:
    a) IDLH: 50 mg Zr/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS7440-67-7 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Zirconium, and compounds, as Zr
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    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 ; Listed as: Zirconium compounds (as Zr)
    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 CAS7440-67-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Zirconium compounds (as Zr)
    2) Table Z-1 for Zirconium compounds (as Zr):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Physicochemical

Physical Characteristics

    A) Zirconium is a grey-white, hard, lustrous solid metal (as flakes, crystals, powder, or platelets) or a bluish-black amorphous powder (Siegers & Sullivan, 1992; ACGIH, 1986; ILO, 1983; Sax & Lewis, 1987; Budavari, 1989). It may also have a gold color (HSDB , 1992).
    B) Gray to gold (amorphous powder) (NIOSH, 1990)
    C) Zirconium may be in the 4+, 3+, or 2+ valence state; the 4+ valence is most common (Clayton & Clayton, 1981).
    D) Zirconium can absorb up to 10 atoms per cent of oxygen or nitrogen (Budavari, 1989).
    E) Zirconium is very slightly radioactive (Lewis, 1992).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 91.22 (Budavari, 1989)

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