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CADMIUM OXIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cadmium oxide is an insoluble metallic oxide used as an electroplating chemical, in the manufacture of cadmium electrodes for storage batteries, a component of silver alloys or solder, in semiconductors, glass and ceramic glazes, as a vermicide, and a catalyst for organic syntheses (EPA, 1985; ITI, 1985).
    1) Cadmium oxide fume is formed from the burning or heating of cadmium in air. The fumes from welding, heat-cutting, brazing, or silver-soldering cadmium-plated or cadmium-containing metals can be lethal even from very short exposures (ACGIH, 1986; Gosselin et al, 1984).
    a) Concentrations of cadmium oxide in the air from silver-soldering operations depended more on the temperature of the flame than on cadmium content of the solder (Mangold & Beckett, 1971).
    2) The bulk material is made by distillation of cadmium metal in a retort and reacting the vapor with air (Sax & Lewis, 1987).
    3) Significant cadmium oxide exposure of up to 0.5 to 2 mcg/day/pack can occur from cigarette smoking (ACGIH, 1986).

Specific Substances

    1) Cadmium oxide
    2) Cadmium fume
    3) Cadmium monoxide
    4) Cadmium oxide fume
    5) NCI-c O2551
    6) NIOSH/RTECS EV 1925000
    7) Molecular Formula: Cd-O
    8) CAS 1306-19-0

Available Forms Sources

    A) SOURCES
    1) Cadmium oxide fume is formed from the burning or heating of cadmium in air; the fumes from welding, heat-cutting, brazing, or silver-soldering cadmium-plated or cadmium-containing metals can be lethal even from very short exposures (ACGIH, 1986; Gosselin et al, 1984).
    2) Concentrations of cadmium oxide in the air from silver-soldering operations depended more on the temperature of the flame than on cadmium content of the solder (Mangold & Beckett, 1971).
    3) The bulk material is made by distillation of cadmium metal in a retort and reacting the vapor with air (Sax & Lewis, 1987).
    4) Significant cadmium oxide exposure of up to 0.5 to 2 mcg/day/pack can occur from cigarette smoking (ACGIH, 1986).
    B) USES
    1) Cadmium oxide is an insoluble metallic oxide used as an electroplating chemical, in the manufacture of cadmium electrodes for storage batteries, a component of silver alloys or solder, in semiconductors, glass and ceramic glazes, as a vermicide, and a catalyst for organic syntheses (EPA, 1985; ITI, 1985).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) ACUTE INHALATION EXPOSURE - Even a single exposure to cadmium oxide fume can cause (after several hours) dry throat, cough, aches and pains, chills, chest pain, breathing difficulty, rales, and potentially fatal non-cardiogenic pulmonary edema. Cadmium oxide is odorless and POISONING FROM THE FUME CAN OCCUR AT CONCENTRATIONS TOO LOW TO CAUSE IRRITATION.
    B) Kidney or liver damage may occur several days later in survivors of acute exposure, and respiratory symptoms may persist for months.
    C) ORAL EXPOSURE - Ingestion can cause severe gastrointestinal distress and vomiting.
    D) CHRONIC EXPOSURES have been associated with severe progressive emphysema, kidney damage (renal tubular dysfunction with proteinuria), osteomalacia, and possible cancer of the respiratory tract and prostate.
    0.2.3) VITAL SIGNS
    A) Dyspnea, hypertension, and shock could occur. Temperature deregulation has occurred in experimental animals exposed to cadmium.
    0.2.4) HEENT
    A) A metallic taste in the mouth is a symptom of acute cadmium oxide poisoning.
    0.2.5) CARDIOVASCULAR
    A) Shock can occur from ingestion of cadmium salts. Hypertension, ECG abnormalities, and dystrophic processes in the myocardium were reported in cadmium workers.
    0.2.6) RESPIRATORY
    A) Inhalation of fresh cadmium oxide fume can produce severe and possibly fatal acute cadmium poisoning. A severe chemical pneumonitis initially resembling influenza may occur. Pulmonary fibrosis was observed in experimental animals but it has not been reported in humans.
    0.2.7) NEUROLOGIC
    A) CNS effects of acute exposures in humans have included delayed parkinsonism.
    B) Headache, severe pain, muscle cramps, dizziness, and rarely seizures, may occur. Cadmium-poisoned experimental animals were hyperactive, had loss of reflexes, spinal ganglion necrosis, sciatic lesions, and showed histological lesions in the central nervous system.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, chills, weakness, and diarrhea may occur after inhalation.
    B) Ingestion of cadmium salts may cause severe nausea, vomiting, diarrhea, abdominal cramps, salivation, liver damage, exhaustion, collapse, shock and death generally within 24 hours. Since cadmium oxide is one of the more insoluble cadmium compounds, its gastrointestinal symptoms may not be as severe as with soluble cadmium salts (e.g., cadmium acetate).
    0.2.9) HEPATIC
    A) Hepatotoxicity with hepatic failure may occur.
    0.2.10) GENITOURINARY
    A) Kidney damage is common from acute industrial exposure. Urinary excretion of cadmium occurs with exposure to cadmium oxide. Renal failure may occur.
    0.2.13) HEMATOLOGIC
    A) Chronic exposure to cadmium has been associated with anemia and eosinophilia.
    0.2.15) MUSCULOSKELETAL
    A) Cadmium may act directly on the bone collagen in rats, causing acceleration of collagen catabolism and demineralization. Chronic exposure to cadmium has been associated with microfractures, osteomalacia, radiologic decreases in bone density, and disturbances in calcium metabolism.
    B) Acute human exposures have resulted in symptoms of arthralgia.
    C) In Japan, a painful osteomalacia with skeletal deformities called "itai-itai byo" (ouch-ouch disease) has been linked with ingestion of cadmium-contaminated shellfish; occurring primarily in postmenopausal multi-parous women.
    0.2.17) METABOLISM
    A) Cadmium is a general metabolic poison and may inhibit zinc-containing enzymes. Cadmium is a potent inhibitor of hepatic microsomal oxidases both in vivo and in vitro. Enzymatic repair was induced in experimental rats exposed to cadmium oxide.
    0.2.18) PSYCHIATRIC
    A) Insomnia and loss of appetite have been reported from exposure to cadmium oxide.
    0.2.20) REPRODUCTIVE
    A) Women occupationally exposed to cadmium had children with lower birth weights. Children of women exposed to cadmium during pregnancy exhibited reduced intellectual/motor skills at 6 years of age. There is some question as to whether these results are the result of lead rather than cadmium since lead occurs commonly with cadmium and causes similar effects. Teratogenic effects were observed in animal experiments.
    0.2.21) CARCINOGENICITY
    A) Cadmium oxide may be an occupational carcinogen and has been linked with prostate and respiratory tract cancer.
    0.2.22) OTHER
    A) Persons with respiratory or kidney disease may be hypersusceptible to cadmium oxide and should be excluded from exposure.

Laboratory Monitoring

    A) Renal damage can be identified by increased urinary levels of beta2-microglobulin, retinol-binding protein, or other low-molecular- weight proteins. Urinary beta2-microglobulin levels greater than 290 mcg/L may indicate kidney damage.
    B) Urinary metallothionein may be a better indicator of body burden.
    C) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) 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.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    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) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    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).

Range Of Toxicity

    A) The lethal inhalation dose of cadmium oxide in humans is 2500 mg/m(3) for 1 minute, 40 to 50 mg/m(3) for 1 hour, or 9 mg/m(3) for 5 hours.

Clinical Effects

Summary Of Exposure

    A) ACUTE INHALATION EXPOSURE - Even a single exposure to cadmium oxide fume can cause (after several hours) dry throat, cough, aches and pains, chills, chest pain, breathing difficulty, rales, and potentially fatal non-cardiogenic pulmonary edema. Cadmium oxide is odorless and POISONING FROM THE FUME CAN OCCUR AT CONCENTRATIONS TOO LOW TO CAUSE IRRITATION.
    B) Kidney or liver damage may occur several days later in survivors of acute exposure, and respiratory symptoms may persist for months.
    C) ORAL EXPOSURE - Ingestion can cause severe gastrointestinal distress and vomiting.
    D) CHRONIC EXPOSURES have been associated with severe progressive emphysema, kidney damage (renal tubular dysfunction with proteinuria), osteomalacia, and possible cancer of the respiratory tract and prostate.

Vital Signs

    3.3.1) SUMMARY
    A) Dyspnea, hypertension, and shock could occur. Temperature deregulation has occurred in experimental animals exposed to cadmium.
    3.3.2) RESPIRATIONS
    A) DYSPNEA - Shortness of breath, chest pain, coughing, and reduced pulmonary function can occur in acute cadmium oxide poisoning (EPA, 1985; Gosselin et al, 1984).
    3.3.3) TEMPERATURE
    A) Fever may occur after inhalation of fumes and is a predominant sign. The development of fever shortly after exposure has been reported in several cases (Okuda et al, 1997; Yates & Goldman, 1990).
    B) ANIMAL STUDIES - Temperature deregulation has occurred in animals exposed to cadmium (IRPTC, 1984).
    3.3.4) BLOOD PRESSURE
    A) HYPERTENSION has been reported in cadmium workers (IRPTC, 1984).
    B) SHOCK can occur from ingestion of cadmium salts (Gosselin et al, 1984).
    3.3.5) PULSE
    A) SHOCK can occur from ingestion of cadmium salts (Gosselin et al, 1984).

Heent

    3.4.1) SUMMARY
    A) A metallic taste in the mouth is a symptom of acute cadmium oxide poisoning.
    3.4.5) NOSE
    A) ANOSMIA - Chronic exposure to cadmium can cause anosmia (loss of the sense of smell) (Louria et al, 1972).
    3.4.6) THROAT
    A) METALLIC TASTE in the mouth is a symptom of acute cadmium oxide poisoning (EPA, 1985; Gosselin et al, 1984).
    B) CHRONIC EXPOSURE to cadmium has been associated with yellow discoloration of teeth (HSDB , 2000; ACGIH, 1986).

Cardiovascular

    3.5.1) SUMMARY
    A) Shock can occur from ingestion of cadmium salts. Hypertension, ECG abnormalities, and dystrophic processes in the myocardium were reported in cadmium workers.
    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) Hypertension was reported in cadmium workers (IRPTC, 1984).
    B) ELECTROCARDIOGRAM ABNORMAL
    1) ECG abnormalities was reported in cadmium workers (IRPTC, 1984).
    C) CARDIOVASCULAR FINDING
    1) Dystrophic processes in the myocardium were reported in cadmium workers (IRPTC, 1984).
    D) HYPOTENSIVE EPISODE
    1) SHOCK can occur from ingestion of cadmium salts (Gosselin et al, 1984).

Respiratory

    3.6.1) SUMMARY
    A) Inhalation of fresh cadmium oxide fume can produce severe and possibly fatal acute cadmium poisoning. A severe chemical pneumonitis initially resembling influenza may occur. Pulmonary fibrosis was observed in experimental animals but it has not been reported in humans.
    3.6.2) CLINICAL EFFECTS
    A) PNEUMONITIS
    1) Inhaling fresh cadmium oxide fume can produce severe and possibly fatal acute cadmium poisoning. A severe chemical pneumonitis initially resembling influenza may occur (Gosselin et al, 1984).
    B) TOXIC EFFECT OF GAS, FUMES AND/OR VAPORS
    1) ACUTE TOXICITY
    a) Early symptoms are throat irritation, metallic taste in the mouth, and headache. These may be delayed by 4 to 8 hours after exposure (Gosselin et al, 1984).
    1) A few hours later, cough, shivering, sweating, and aches and pains develop (Blejer, 1966).
    2) By the end of the day there may be severe weakness, dyspnea, tightness of the chest, wheezing, and burning retrosternal pain and coughing with foamy or bloody sputum and pulmonary rales (EPA, 1985; Beton et al, 1966; Gosselin et al, 1984).
    C) ACUTE LUNG INJURY
    1) Non-cardiogenic pulmonary edema may develop rapidly, with progressive dyspnea, decreased vital capacity and reduced carbon monoxide diffusing capacity. Alveolar metaplasia may be present (Proctor & Hughes, 1978; Beton et al, 1966; ACGIH, 1986). Death may be from asphyxiation due to intense pulmonary edema (Gosselin et al, 1984).
    2) Alternatively the pulmonary edema may be resolved, fever may develop, and cough, chest pain, and dyspnea may persist for one or more weeks followed by late liver or kidney damage (Gosselin et al, 1984).
    3) CASE REPORT - Four days following acute inhalation of cadmium fumes from a soldering process, a 64-year-old man was admitted to the ED with dyspnea. A chest x-ray revealed pulmonary edema, necessitating mechanical ventilation (Okuda et al, 1997).
    4) CASE REPORT - A 35-year-old man developed acute lung injury after exposure to cadmium oxide. He inhaled cadmium fumes after accidentally opening a vat containing molten cadmium. In the three days following the exposure, the patient developed a dry cough and progressive dyspnea. Chest x-ray revealed bilateral hazy lung fields. He continued to be dyspneic and became severely cyanotic. Despite ventilatory support, the patient expired (Panchal & Vaideeswar, 2006).
    D) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 35-year-old man developed acute lung injury after exposure to cadmium oxide. He inhaled cadmium fumes after accidentally opening a vat containing molten cadmium. In the three days following the exposure, the patient developed a dry cough and progressive dyspnea. Chest x-ray revealed bilateral hazy lung fields. He continued to be dyspneic and became severely cyanotic. Despite ventilatory support, the patient expired (Panchal & Vaideeswar, 2006).
    b) CASE REPORT - Four days following acute inhalation of cadmium fumes from a soldering process, a 64-year-old man was admitted to the ED with dyspnea. A chest x-ray revealed pulmonary edema, necessitating mechanical ventilation (Okuda et al, 1997).
    E) FIBROSIS OF LUNG
    1) CASE REPORT - A 49-year-old male welder presented to the ED after working 10 days welding with a 20% cadmium alloy in a confined space with no respirator. Chest x-ray showed bilateral lower zone mottled shadowing. Fibrosing alveolitis due to acute cadmium poisoning was diagnosed. After three weeks of steroid therapy clinical improvement was significant (Yates & Goldman, 1990).
    2) SEQUELAE
    a) CASE REPORT - Progressive pulmonary fibrosis developed as a late result (17 years later) of acute cadmium inhalation in a welder using cadmium silver alloy. A single day exposure resulted in acute cadmium pneumonitis. Acute symptoms resolved, however, some shadowing at the lung bases remained, and 17 years later the patient presented with shortness of breath. Respiratory function tests confirmed a restrictive ventilatory defect (Townshend, 1982).
    F) DEAD
    1) Even a single exposure of a few hours duration may be fatal. While deaths from acute cadmium oxide poisoning are rare, every case in the United States has been from industrial exposures, especially in welders (Blejer, 1966).
    2) Mortality rate from acute cadmium oxide poisoning has been about 20% (ACGIH, 1986).
    G) RESPIRATORY FINDING
    1) In survivors of acute inhalation exposure, respiratory symptoms may persist for several weeks and impairment of pulmonary function for months (Proctor & Hughes, 1978).
    H) EMPHYSEMA
    1) CHRONIC exposure to cadmium oxide has been associated with severe emphysema without chronic bronchitis (Smith et al, 1957; Gosselin et al, 1984; Proctor & Hughes, 1978).
    2) In chronic exposures there were deviations in dynamic respiratory function tests indicating a reduction of reserve potential of the respiratory system (Aleksieva & Dimitrova, 1969).
    3) Further deterioration of respiratory function in cases with emphysema occurred even though there was no further exposure to cadmium oxide (Bonnell et al, 1959; Proctor & Hughes, 1978).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PULMONARY FIBROSIS
    a) DOGS - Pulmonary fibrosis has developed in dogs following acute pulmonary edema and proliferative interstitial pneumonitis, but the fibrosis has not been reported in humans (Gosselin et al, 1984; Proctor & Hughes, 1978).
    b) RATS - Pulmonary fibrosis was induced in rats by cadmium in the drinking water (Gosselin et al, 1984).
    2) INTERSTITIAL PNEUMONIA
    a) RATS developed interstitial thickening, numerous inflammatory cells and cuboidal alveolar epithelial cells (Buckley & Bassett, 1987). Alveolar macrophages decreased at first and then increased, polymorphonuclear and lymphocytic cells appeared in the alveoli, and there was an increase in death rate from exposure to pathogenic bacteria (Bouley, 1977).

Neurologic

    3.7.1) SUMMARY
    A) CNS effects of acute exposures in humans have included delayed parkinsonism.
    B) Headache, severe pain, muscle cramps, dizziness, and rarely seizures, may occur. Cadmium-poisoned experimental animals were hyperactive, had loss of reflexes, spinal ganglion necrosis, sciatic lesions, and showed histological lesions in the central nervous system.
    3.7.2) CLINICAL EFFECTS
    A) EXTRAPYRAMIDAL DISEASE
    1) CASE REPORT - Three months after an acute exposure to cadmium fumes from a soldering process a 64-year-old developed stiffness of his limbs with difficulty in manipulating objects and initiating steps. Six months after the exposure parkinsonism effects were noted, with bradykinesia, stooped posture and cogwheel muscle rigidity.
    a) Antiparkinson drugs were ineffective. MRI revealed cerebral infarctions in the right frontoparietal region and periventricular white matter, but no lesions in the basal ganglia (Okuda et al, 1997).
    B) HEADACHE
    1) Headache can occur in acute cadmium oxide poisoning (EPA, 1985).
    C) SENSE OF SMELL ALTERED
    1) ANOSMIA - Workers chronically exposed to cadmium oxide showed neurological changes involving reduced optical and dermal stimulability, functional changes in the cerebral cortex, and anosmia (loss of smell) (Vorobeva, 1957; O'Donoghue, 1985).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEUROPATHY
    a) Cadmium-poisoned animals were hyperactive, had loss of reflexes, spinal ganglion necrosis, sciatic lesions, and showed histological lesions in the central nervous system (Gosselin et al, 1984; O'Donoghue, 1985).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, chills, weakness, and diarrhea may occur after inhalation.
    B) Ingestion of cadmium salts may cause severe nausea, vomiting, diarrhea, abdominal cramps, salivation, liver damage, exhaustion, collapse, shock and death generally within 24 hours. Since cadmium oxide is one of the more insoluble cadmium compounds, its gastrointestinal symptoms may not be as severe as with soluble cadmium salts (e.g., cadmium acetate).
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) Cadmium compounds are much less lethal by ingestion than if inhaled because they induce vomiting and are not retained. Even so, as little as 10 mg of cadmium salts has produced severe toxic reactions when ingested (Gosselin et al, 1984).
    B) GASTROENTERITIS
    1) Ingestion of cadmium salts may cause severe nausea, vomiting, diarrhea, abdominal cramps, salivation, headache, muscle cramps, dizziness, rare seizures, exhaustion, collapse, shock, and death generally within 24 hours (Gosselin et al, 1984).
    2) Because cadmium oxide is one of the more insoluble cadmium compounds, its gastrointestinal symptoms may not be as severe as with soluble cadmium salts.
    C) CHRONIC POISONING
    1) CHRONIC EXPOSURE to cadmium has produced gastrointestinal symptoms (ACGIH, 1986).

Hepatic

    3.9.1) SUMMARY
    A) Hepatotoxicity with hepatic failure may occur.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Liver damage can occur in acute or chronic cadmium poisoning because the liver contains high levels of metallothionein. Involvement of the liver does not occur as often as with the kidney (Gosselin et al, 1984).
    2) TARGET - The liver is one the primary sites of systemic distribution of cadmium because it contains high levels of metallothionein binding protein (Gosselin et al, 1984).

Genitourinary

    3.10.1) SUMMARY
    A) Kidney damage is common from acute industrial exposure. Urinary excretion of cadmium occurs with exposure to cadmium oxide. Renal failure may occur.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) NEPHROTOXICITY - The kidney is the primary target organ for chronic cadmium toxicity. Kidney damage is common from both acute and chronic industrial exposure (ACGIH, 1986; Gosselin et al, 1984).
    2) BETA2-MICROGLOBULIN - One of the earliest signs is an increase in urinary metallothionein and beta2-microglobulin (ACGIH, 1986).
    B) RENAL TUBULAR DISORDER
    1) FANCONI SYNDROME - Fully developed Fanconi syndrome may occur with continued exposure (ACGIH, 1986).
    C) GLOMERULONEPHRITIS
    1) CHRONIC poisoning has been associated with proteinuria, indicating damage to the renal tubules (Gosselin et al, 1984; Friberg et al, 1986).
    2) GLOMERULAR DAMAGE - Heavy exposure may also cause glomerular damage involving more intense proteinuria with excretion of high molecular-weight plasma proteins, decreased excretion of creatinine, and elevated plasma levels of creatinine and beta2-microglobulin (Gosselin et al, 1984).
    D) ACUTE RENAL CORTICAL NECROSIS
    1) Acute severe cadmium fume poisoning was accompanied by bilateral cortical necrosis of the kidneys in workers (Beton et al, 1966).
    E) KIDNEY FINDING
    1) There may be a latent period of months or years for kidney disease to develop, and further deterioration can occur in the absence of further exposure (ACGIH, 1986).
    2) ACCUMULATION - Because of daily intake in the diet and the extremely long half-life of elimination, cadmium accumulates in the kidney throughout the lifetime (Friberg et al, 1986).
    F) ABNORMAL URINARY PRODUCT
    1) URINARY EXCRETION - Urinary excretion of cadmium occurs with exposure to cadmium oxide. There may be poor correlation between exposure levels and urinary cadmium concentration, as cadmium can damage the kidney itself by complex dynamics and the excretion of cadmium is dependent on the functional state of the kidney (Gosselin et al, 1984; Proctor & Hughes, 1978). Elevated urine cadmium levels may not occur following acute exposures (Friberg et al, 1986).

Hematologic

    3.13.1) SUMMARY
    A) Chronic exposure to cadmium has been associated with anemia and eosinophilia.
    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) CHRONIC exposure to cadmium has been associated with anemia and eosinophilia (ACGIH, 1986).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ANEMIA MICROCYTIC
    a) A microcytic hypochromic anemia refractory to iron therapy was produced in rabbits by cadmium in feeding studies (Gosselin et al, 1984).

Musculoskeletal

    3.15.1) SUMMARY
    A) Cadmium may act directly on the bone collagen in rats, causing acceleration of collagen catabolism and demineralization. Chronic exposure to cadmium has been associated with microfractures, osteomalacia, radiologic decreases in bone density, and disturbances in calcium metabolism.
    B) Acute human exposures have resulted in symptoms of arthralgia.
    C) In Japan, a painful osteomalacia with skeletal deformities called "itai-itai byo" (ouch-ouch disease) has been linked with ingestion of cadmium-contaminated shellfish; occurring primarily in postmenopausal multi-parous women.
    3.15.2) CLINICAL EFFECTS
    A) DISORDER OF BONE
    1) CHRONIC exposure to cadmium has been associated with microfractures, osteomalacia, radiologic decreases in bone density, and disturbances in calcium metabolism (ACGIH, 1986; Gosselin et al, 1984).
    2) In Japan, a painful osteomalacia with skeletal deformities called "itai-itai byo" (ouch-ouch disease) has been linked with ingestion of cadmium-contaminated shellfish (Gosselin et al, 1984; Takebayashi et al, 1987). It has occurred primarily in postmenopausal multi-parous women (Proctor & Hughes, 1978).
    a) Severe pain was associated with induction of skeletal deformities in itai-itai disease (O'Donoghue, 1985).
    B) JOINT PAIN
    1) CASE REPORT - An acute exposure to cadmium oxide fumes from welding resulted in fever and arthralgia in a 49-year-old male (Yates & Goldman, 1990).
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) BONE DISORDER
    a) RATS - Cadmium may act directly on the bone collagen in rats, causing acceleration of collagen catabolism and demineralization (Gosselin et al, 1984).

Reproductive

    3.20.1) SUMMARY
    A) Women occupationally exposed to cadmium had children with lower birth weights. Children of women exposed to cadmium during pregnancy exhibited reduced intellectual/motor skills at 6 years of age. There is some question as to whether these results are the result of lead rather than cadmium since lead occurs commonly with cadmium and causes similar effects. Teratogenic effects were observed in animal experiments.
    3.20.2) TERATOGENICITY
    A) BIRTH WEIGHT SUBNORMAL
    1) LOW BIRTH WEIGHTS - Women occupationally exposed to cadmium did not have increased risk of birth defects but did have children with lower birth weights (Friberg et al, 1984; (IRPTC, 1984).
    B) ANIMAL STUDIES
    1) Other cadmium salts have been teratogenic in animals (IRPTC, 1984).
    2) RATS - Newborn pups showed behavioral effects when female rats were exposed to 23 mcg/m(3) of cadmium oxide for 15 weeks prior to mating and up to 20 days during gestation. Reduced viability and weight gain occurred at 183 mcg/m(3) (RTECS , 1988).
    3.20.3) EFFECTS IN PREGNANCY
    A) BIRTH WEIGHT SUBNORMAL
    1) LOWER BIRTH WEIGHTS - Women occupationally exposed to cadmium did not have increased risk of birth defects but did have children with lower birth weights (Friberg et al, 1984; (IRPTC, 1984).
    B) MENTAL STATUS CHANGES
    1) DECREASED INTELLECTUAL/MOTOR SKILLS - Children of women exposed to cadmium during pregnancy performed more poorly on tests for intellectual and motor skills at 6 years of age than children whose mothers were not exposed (Bonithon-Kopp, 1986). However, in view of the fact that lead occurs commonly with cadmium and that these results are similar to those obtained in children exposed prenatally to lead, it would be important to distinguish between exposure to lead and cadmium in this or any such study.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of cadmium exposure during lactation.
    3.20.5) FERTILITY
    A) FERTILITY DECREASED MALE
    1) TESTES/SPERM DAMAGE - Four workers who died from cadmium-related emphysema had oligospermia. Damage to seminiferous tubules has not been reported in chronically exposed men (Gosselin et al, 1984).
    B) ANIMAL STUDIES
    1) ANIMAL REPRODUCTIVE EFFECTS - Soluble cadmium salts can induce temporary chemical castration by the parenteral route in rats, mice, or calves. This effect can be prevented by administration of zinc (Gosselin et al, 1984; IRPTC, 1984).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS1306-19-0 (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) IARC Classification
    a) Listed as: Cadmium oxide
    b) Carcinogen Rating: 1
    1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    3.21.2) SUMMARY/HUMAN
    A) Cadmium oxide may be an occupational carcinogen and has been linked with prostate and respiratory tract cancer.
    3.21.3) HUMAN STUDIES
    A) SUMMARY
    1) Cadmium oxide may be an occupational carcinogen and has been linked with prostate and respiratory tract cancer (Clayton & Clayton, 1982; Proctor & Hughes, 1978; Oberdorster, 1986).
    B) PULMONARY CARCINOMA
    1) A NIOSH mortality study on cadmium production workers found a statistically significant increase in lung cancer deaths among persons exposed to 2920 mg-days/m(3) cumulative exposure (more than 40 years at 200 mcg/m(3)) (ACGIH, 1986).
    a) Some of these workers may have also been exposed to arsenic, a known human carcinogen (ACGIH, 1986).
    2) A mortality study on 3025 nickel cadmium battery workers exposed to cadmium oxide dust found "some evidence" of increased lung cancer deaths in workers first exposed between 1923 and 1946, especially in the highest exposure group, but "no evidence" for those hired since 1947 (Sorahan, 1987).
    3) A mortality study on 6995 British cadmium workers found significant excess mortality from lung cancer with at least 10 years of low exposure (Armstrong & Kazantzis, 1983).
    4) Some of the epidemiological studies on cadmium workers did not distinguish between different cadmium compounds in the exposures. This has made interpretation of the results controversial (Oberdorster, 1987).
    C) PROSTATE CARCINOMA
    1) Early studies found an association between occupational exposure to cadmium (possibly cadmium oxide) and prostate cancer. A slight but not statistically significant increase in prostate cancer was also seen in a later study of battery workers and cadmium alloy workers (Sittig, 1985).
    D) RENAL CARCINOMA
    1) Renal cancer patients had a 2.5-fold elevated risk from occupational cadmium exposure and an even greater risk from cigarette smoking (Sittig, 1985).
    3.21.4) ANIMAL STUDIES
    A) NEOPLASM
    1) Cadmium oxide has produced mixed results in animal carcinogenicity studies (ACGIH, 1986; Sittig, 1985; IRPTC, 1984; Sanders & Mahaffey, 1984); but was found to be neoplastic by RTECS criteria with tumors at the site of application (RTECS , 1991).
    B) CARCINOMA
    1) MIXED RESULTS - Cadmium oxide has produced mixed results in carcinogenicity studies in animals.
    2) LACK OF CARCINOGENICITY - Intratracheally-instilled cadmium oxide was not carcinogenic in the lung, liver, kidney, or prostate gland of male Fischer rats but did increase the number of tumors in the mammary gland or in rats with three or more tumor types (Sanders & Mahaffey, 1984).
    3) In the NTP Fifth Annual Report on Carcinogens, 1989 cadmium oxide was anticipated to be a carcinogen (RTECS , 1991).
    4) In the NTP Carcinogenesis Studies (Prechronic Studies) 1990, cadmium oxide was 'on test' to determine its carcinogenicity (RTECS , 1991).
    C) PULMONARY CARCINOMA
    1) The dust and fume induced lung cancer in rats at 30 mcg/m(3) for up to 18 months (ACGIH, 1986).
    2) LACK OF CARCINOGENICITY - Intratracheally-instilled cadmium oxide was not carcinogenic in the lung of male Fischer rats but did increase the number of tumors in rats with three or more tumor types (Sanders & Mahaffey, 1984).
    D) SARCOMA
    1) Cadmium oxide caused local sarcomas after subcutaneous injection in rats (Sittig, 1985; IRPTC, 1984).

Genotoxicity

    A) Soluble cadmium salts have been genotoxic in vitro but cadmium oxide is not expected to be strongly genotoxic in vitro since it is insoluble in water (IRPTC, 1984).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Renal damage can be identified by increased urinary levels of beta2-microglobulin, retinol-binding protein, or other low-molecular- weight proteins. Urinary beta2-microglobulin levels greater than 290 mcg/L may indicate kidney damage.
    B) Urinary metallothionein may be a better indicator of body burden.
    C) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Typical normal levels for cadmium in blood are 0.4 to 1 mcg/L for nonsmokers and 1.4 to 4.5 mcg/L for smokers, with a dose-related increase from smoking (ACGIH, 1986).
    2) Cadmium concentrations in blood are believed to be related more to recent than to cumulative exposure (ACGIH, 1986).
    3) Surveillance of persons exposed to cadmium oxide should include urinary beta2-microglobulin, retinol-binding protein, total protein, albumin, protein electrophoresis, certain enzymes, amino acids, glucose, and clearance of creatinine, calcium, and phosphate (ACGIH, 1986).
    4) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.3) URINE
    A) URINARY LEVELS
    1) URINARY BETA2-MICROGLOBULIN >290 mcg/L represents preclinical kidney dysfunction (ACGIH, 1986). Renal damage can be identified by increased urinary levels of beta2-microglobulin, retinol-binding protein, or other low-molecular- weight proteins (Hathaway et al, 1996).
    a) Beta2-microglobulin levels from 203 unexposed men had a mean value of 130 mcg/L. A similar distribution of values was obtained from employees hired after 1950. Elevated levels (>765 mcg/L) were found in 9 individuals of whom 4 were already known to have clinical proteinuria. It should be noted, however, that the unexposed values were among the highest reported (Stewart & Hughes, 1981).
    2) CADMIUM LEVELS - Urinary excretion of cadmium occurs with exposure to cadmium oxide. However, there may be poor correlation between exposure levels and concentration of urinary cadmium, because cadmium can damage the kidney itself by complex dynamics and the excretion of cadmium is dependent on the functional state of the kidney (Gosselin et al, 1984; Proctor & Hughes, 1978).
    a) Urinary levels of cadmium may depend not only on occupational exposure but also on age, cigarette smoking, and contamination of food and water (ACGIH, 1986).
    b) Typical normal levels of urinary cadmium are 0.5 to 1.0 mcg/L, ranging from 0.02 to 4.5 mcg/L (ACGIH, 1986).
    c) The relationship between urinary cadmium levels and occupational exposures is complex and depends on the stage of exposure relative to kidney function (ACGIH, 1986).
    B) OTHER
    1) MEDICAL SURVEILLANCE - Surveillance of persons exposed to cadmium oxide should include urinary beta2-microglobulin, retinol-binding protein, total protein, albumin, protein electrophoresis, certain enzymes, amino acids, glucose, and clearance of creatinine, calcium, and phosphate (ACGIH, 1986).
    2) NAG - Urinary N-acetyl-B-D-glucosaminidase (NAG) also correlates to renal tubular damage from heavy metals; both proteinuria and enzymuria are nonspecific indicators of renal injury (Kosnett, 1990).
    C) URINALYSIS
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Preplacement and annual physical examinations should include examination of the respiratory system with pulmonary function tests (FVC, FEV (1 sec)) (ACGIH, 1986; Proctor & Hughes, 1978).
    b) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Chest X-ray findings after acute inhalation exposures may indicate diffuse pulmonary edema. Later findings are those of bronchopneumonia (proliferative interstitial pneumonitis) (Gosselin et al, 1984).
    2) Medical surveillance of persons exposed chronically should include chest x-rays (ACGIH, 1986; Proctor & Hughes, 1978).
    3) If respiratory tract irritation is present, monitor chest x-ray.

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) AIR - Cadmium oxide can be measured in air as cadmium by the NIOSH analytical method for cadmium (7048) (RTECS , 1988). Atomic absorption spectrometry is a highly sensitive method (IRPTC, 1984).
    2) Cadmium levels in blood can be determined by atomic absorption spectrometry with electron-transfer activation (ACGIH, 1986).

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.

Monitoring

    A) Renal damage can be identified by increased urinary levels of beta2-microglobulin, retinol-binding protein, or other low-molecular- weight proteins. Urinary beta2-microglobulin levels greater than 290 mcg/L may indicate kidney damage.
    B) Urinary metallothionein may be a better indicator of body burden.
    C) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) Do NOT induce emesis.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Do NOT induce vomiting.
    B) GASTRIC LAVAGE
    1) 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.
    2) 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.
    3) 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.
    4) 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).
    5) 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
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) IRRITATION SYMPTOM
    1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.
    C) 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) BRONCHOSPASM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    B) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).
    a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.
    1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).
    3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
    4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.
    C) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    D) OBSERVATION REGIMES
    1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    2) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    3) Long-term follow-up including pulmonary function tests may be required in patients with significant initial pulmonary injury.
    E) 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) 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).

Enhanced Elimination

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

Abstracts

Case Reports

    A) CHRONIC EFFECTS
    1) Four workers who died from cadmium-related emphysema had oligospermia. Damage to the seminiferous tubules has not been seen in chronically-exposed men (Gosselin et al, 1984).
    2) A NIOSH mortality study of cadmium production workers found a statistically significant increase in lung cancer deaths among persons exposed to 2920 mg-days/m(3) cumulative exposure (more than 40 years at 200 mcg/m(3)) (ACGIH, 1986). Some of these workers may have also been exposed to arsenic, a known human carcinogen (ACGIH, 1986).
    3) A mortality study of 3025 nickel cadmium battery workers exposed to cadmium oxide dust found "some evidence" of increased lung cancer deaths in workers first exposed between 1923 and 1946, especially in the highest exposure group, but "no evidence" for those hired since 1947 (Sorahan, 1987).
    4) A mortality study of 6995 British cadmium workers found significant excess mortality from lung cancer with at least 10 years of low exposure (Armstrong & Kazantzis, 1983).
    5) Workers exposed to up to 50 mcg/m(3) for up to 11 years did not have increased beta2-microglobulin in the urine (Stewart & Hughes, 1981).

Range Of Toxicity

Summary

    A) The lethal inhalation dose of cadmium oxide in humans is 2500 mg/m(3) for 1 minute, 40 to 50 mg/m(3) for 1 hour, or 9 mg/m(3) for 5 hours.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) No essential role for cadmium in humans has been shown (Friberg et al, 1986).

Minimum Lethal Exposure

    A) ACUTE
    1) There have been many fatal acute industrial exposures to cadmium oxide. One estimate of a fatal dose in reference to a particular case was not over 2900 minute mg/m(3). Doses considerably less than this caused incapacitation of all workers exposed during the accident (Barrett & Card, 1947).
    2) The lethal inhalation dose of cadmium oxide in humans is 2500 mg/m(3) for 1 minute (EPA, 1985).
    3) Lethal exposure is 40 or 50 mg/m(3) for 1 hour for cadmium oxide dust and for 30 minutes with the fume (EPA, 1985; ACGIH, 1986).
    4) Lethal exposure is 9 mg/m(3) for 5 hours (ACGIH, 1986).
    5) 40 mg/m(3) is considered Immediately Dangerous to Life or Health (EPA, 1985).
    6) There is generally insufficient discomfort in high concentrations to warn the worker of overexposure (EPA, 1985).

Maximum Tolerated Exposure

    A) ACUTE
    1) INHALATION - Because symptoms from acute inhalation are delayed by several hours, the maximum exposure which could be tolerated with no effect is not clear in the literature.
    2) TCLo (INHL) HUMAN - 8630 mcg/m(3)/5h (RTECS , 1991).
    3) PROTEINURIA - The lowest published toxic concentration for changes in the sense of smell and proteinuria is 500 mcg/m(3), intermittently for 5 years (RTECS , 1991).
    4) CARDIOVASCULAR - The lowest published toxic concentration for heart rate changes and elevation of blood pressure is 40 mcg/m(3) (RTECS , 1991).
    5) IDLH - 40 mg/m(3) is considered Immediately Dangerous to Life or Health (EPA, 1985).
    B) CHRONIC
    1) Workers exposed to up to 50 mcg/m(3) for up to 11 years did not have increased beta2-microglobulin in the urine (Stewart & Hughes, 1981).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Tubular-type proteinuria may occur with blood cadmium levels >1 mcg/dL and urine levels >10 mcg/gm creatinine (Gosselin et al, 1984).
    2) ACUTE
    a) Blood cadmium levels of 1.49 micrograms/deciliter were reported in a 64-year-old male following a one hour inhalation exposure to cadmium fumes from a soldering process (Okuda et al, 1997).

Workplace Standards

    A) ACGIH TLV Values for CAS1306-19-0 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS1306-19-0 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Cadmium fume (as Cd)
    2) REL:
    a) TWA: NIOSH REL*:
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    e) Skin Designation: Not Listed
    f) Note(s): See Appendix A; [*Note: The REL applies to all Cadmium compounds (as Cd).]
    3) IDLH:
    a) IDLH: 9 mg Cd/m3 (as Cd)
    b) Note(s): Ca
    1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

    C) Carcinogenicity Ratings for CAS1306-19-0 :
    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): 1 ; Listed as: Cadmium oxide
    a) 1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Cadmium fume (as Cd)
    a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
    5) MAK (DFG, 2002): Category 2 ; Listed as: Cadmium and its compounds (as inhalable dusts/aerosols): Cadmium oxide
    a) Category 2 : Substances that are considered to be carcinogenic for man because sufficient data from long-term animal studies or limited evidence from animal studies substantiated by evidence from epidemiological studies indicate that they can make a significant contribution to cancer risk. Limited data from animal studies can be supported by evidence that the substance causes cancer by a mode of action that is relevant to man and by results of in vitro tests and short-term animal studies.
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS1306-19-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1991
    1) LD50- (ORAL)MOUSE:
    a) 72 mg/kg
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 12 mg/kg
    3) LD50- (ORAL)RAT:
    a) 72/mg/kg
    4) TCLo- (INHALATION)HUMAN:
    a) 8630 mcg/m(3) for 5H
    b) 500 mcg/m(3) for 5Y-I
    c) 40 mcg/m(3)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Cadmium bound to metallothionein is filtered through the renal glomeruli and reabsorbed and released in the tubules. Unbound cadmium stimulates synthesis of new metallothionein which then binds cadmium in the renal tubular cells. If this step does not occur, toxic effects can occur possibly by interference with zinc-containing enzymes (Friberg et al, 1986).
    B) Cadmium interferes with the uptake, distribution and action of zinc, an essential micronutrient (Friberg et al, 1986).
    C) Cadmium pre-treatment can induce synthesis of metallothionein and protect from a subsequent lethal dose of cadmium in animals (Gosselin et al, 1984).
    D) Cadmium may act directly on the bone collagen in rats, causing acceleration of collagen catabolism and demineralization (Gosselin et al, 1984).

Physicochemical

Physical Characteristics

    A) Cadmium oxide is noncombustible, odorless, red or brown crystals or a white or brown amorphous powder (EPA, 1985; ACGIH, 1986).

Molecular Weight

    A) 128.4

Other

    A) ODOR THRESHOLD
    1) Odorless (CHRIS , 2002)

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