Nickel toxicity


  • Nickel is a white, lustrous metal
  • Has extensive industrial and occupational uses, especially in the production of metal alloys
  • Elemental nickel, as well as nickel oxide and sulfate compound exposures, are common during the incineration, smelting, and refining of metal ores
  • Nickel carbonyl exposures occur during nickel refining and petroleum processing.

Clinical Features

Distinction should be made between non-carbonyl nickel and nickel carbonyl, Ni(CO)4, exposures

Non-carbonyl nickel

  • Most commonly presents with contact dermatitis
  • Nickel is not antigenic but acts as a hapten by binding to larger proteins, inducing conformational changes and resulting in non-self antigen recognition (type IV delayed hypersensivity immune reaction)
  • Widespread allergic dermatitis (non-contact) may occur when non-carbonyl nickel is ingested or inhaled
  • Severe exposures may result in interstitial lung disease and acute tubular necrosis

Nickel carbonyl

  • Most toxic form of nickel
  • Commonly described as having a musty or sooty odor
  • Does not cause carbon monoxide toxicity despite the in vivo liberation of CO
  • Symptoms may be rapid or delayed; however, most serious toxicities occur within 2 days of exposure
  • Shortness of breath, headache, dizziness, and vague symptoms are generally first reported, these may progress to acute respiratory distress, myocarditis, seizures, cerebral edema, and death
  • Deaths typically result from interstitial pneumonitis or cerebral edema and typically occur within 2 weeks of exposure
  • Sequelae include a prolonged neurasthenic syndrome

Nickel contact dermatitis

  • Basal cell carcinoma
  • Other type IV delayed hypersensitivity immune reactions

Differential Diagnosis

Nickel Carbonyl Differential

Nickel carbonyl exposures should be considered in all relevant occupational or industrial exposures presenting with significant pulmonary, cardiac, or neurological findings. Other occupational and toxicological exposures that should be considered.

  • Manganese
  • Cadmium
  • Elemental mercury
  • Vanadium pentoxide
  • Zinc chloride
  • Dinitrophenol / pentachlorophenol
  • Massive type II pyrethroid exposure
  • Organophosphates / carbamates
  • Hydrocarbon aspiration

Heavy metal toxicity


Diagnostics should be directed based on symptoms. Non-carbonyl nickel exposures are typically benign and limited to skin complaints; these may require no further work up. Nickel carbonyl exposures require more intensive evaluations including but not limited to:

  • Arterial blood gas analysis, CXR in the setting of shortness of breath
  • EKG
  • Liver enzymes
  • Serum electrolytes, including serum creatinine
  • Non-contrast CT head in the setting of significant neurological findings to rule out cerebral edema

Nickel concentrations

May be obtained from the urine, blood, and serum

  • Always collect in metal-free, acid-washed container
  • Average serum [Ni] = 0.3 mcg/L

Urine nickel concentrations are preferentially obtained over 8 hours

  • upper limit of normal = 5 mcg/L
  • < 100 mcg/L = mild nickel toxicity
  • 100 - 500 mcg/L = moderate toxicity
  • > 500 mcg/L = severe poisoning


  • As with all toxicological exposures, primary efforts after patient stabilization should be directed at decontamination to prevent further exposure.
  • Supportive care should be directed at airway support. This may include supplemental oxygen, nebulized bronchodilators, and corticosteroids.
  • Hemodialysis is ineffective due to high protein binding


  • If severe poisoning from nickel carbonyl is suspected give 1 gram diethyldithiocarbamate (DDC) in divided doses (not available in the United States)
  • There is limited evidence for the use of disulfiram in the treatment of nickel carbonyl. No established dosing exists; however, disulfiram is metabolized to two molecules of DDC. Contact your local toxicologist for further guidance in the use of chelators. It is important to note that chelation with disulfiram in the setting of nickel carbonyl is not standard of care.


Non-carbonyl nickel

Symptomatic care and discharge is acceptable in those with nickel contact dermitis. Educate on the need to avoid jewelry containing nickel. Minor respiratory symptoms may be dispositioned similar to others with reactive airway disease Significant respiratory symptoms should be admitted for observation

Nickel carbonyl

Admit all known or suspected nickel carbonyl exposures due to the potential for delayed pulmonary injury and ARDS

See Also