Although manganese (Mn) is an essential trace nutrient, intoxication is caused by chronic, primarily respiratory overexposure. Sources of inorganic manganese exposure include mining, smelting, welding and battery manufacturing. There is a potential link between organic manganese fungicides (Maneb and Mancozeb) and chronic neurologic toxicity. An organic manganese gasoline additive, methylcyclopentadienyl manganese tricarbonyl (MMT) is in limited use in the United States and in wider use elsewhere. Parenteral exposure to inorganic manganese can occur through injection drug use of potassium permanganate-adulterated substances (eg, methcathinone), through manganese-containing total parenteral nutrition, and administration of the manganese-releasing pharmaceutical mangafodipir.

1. The precise mechanism of chronic toxicity is not known. The CNS is the target organ, specifically the globus pallidus within the basal ganglia. Iron deficiency may predispose to CNS toxicity due to competition for blood-brain barrier endothelial transport mechanisms.
2. Pharmacokinetic data in humans are limited. Manganese is well absorbed by inhalation. Metallic inorganic Mn is poorly absorbed from the GI tract of adults, although relative bioavailability is increased in infants and in iron deficiency. The volume of distribution is approximately 1 L/kg, with extensive peripheral distribution including in the liver and kidneys. Excretion is primarily via the bile and may be reduced in persons with impaired hepatic function. Bone can be a major site of long-term storage (estimated 8.5-year half-life).

1. The primary route of exposure for both inorganic and organic Mn is inhalation, and there is evidence that absorption to the CNS directly through the olfactory system may play a role in CNS toxicity. Potassium permanganate ingestion can cause systemic toxicity. MMT can be absorbed across the skin.
2. Workplace exposure limits. The Federal OSHA workplace limit (permissible exposure limit—ceiling [PEL-C]) for inorganic manganese is 5 mg/m³; the California OSHA PEL is 0.2 mg/m³ (respirable fraction) and the ACGIH-recommended workplace exposure limit (threshold limit value-8-hour time-weighted average [TLV-TWA]) is considerably lower at 0.02 mg/m³ (respirable fraction). For MMT, the Federal OSHA PEL-C is 5 mg/m³ and the ACGIH TLV-TWA is 0.2 mg/m³ (skin). The NIOSH air level of manganese considered immediately dangerous to life or health (IDLH) is 500 mg/m³.

Acute high-level manganese inhalation can produce an irritant-type pneumonitis, but this is rare (Gases, Irritant). More typically, toxicity occurs after chronic exposure over months or years. The time course following injection of manganese is considerably shorter. The patient may present with a psychiatric disorder with extreme emotional lability that can be misdiagnosed as schizophrenia or atypical psychosis. Signs of frank neurologic toxicity usually appear later and are largely irreversible. Known as manganism, prominent features include parkinsonism with bradykinesia and poor balance, and a severe gait disturbance with characteristic “cock walk” due to lower extremity dystonia. Ingestion of potassium permanganate can cause severe acute hepatic and renal toxicity and methemoglobinemia. Ingestion of the fungicides Maneb or Mancozeb is associated with acute toxicity attributed to its carbamate structure, although a subacute picture linked to manganese has been reported.

Depends on a thorough occupational, drug abuse, and psychiatric history.

1. Specific levels. Testing of whole blood, serum, or urine may be performed, but the results should be interpreted with caution, as they may not correlate with clinical effects, and only reflect very recent exposures. Whole-blood levels are 20 times higher than levels in serum or plasma, and red blood cell contamination can falsely elevate serum or plasma levels.
   1. Normal serum manganese concentrations are usually less than 1.2 mcg/L.
   2. Elevated urine manganese concentrations (>2 mcg/L) may confirm recent acute exposure. Exposures at the OSHA PEL usually do not raise urinary levels above 8 mcg/L. Chelation challenge does not have a role in diagnosis.
   3. Hair and nail levels are not useful as clinical tests.
2. Other useful laboratory studies include arterial blood gases or oximetry and chest radiography (after acute, heavy, symptomatic inhalation exposure if acute lung injury is suspected). Liver function tests may also be useful. Magnetic resonance imaging (MRI) of the brain may provide more persistent evidence of exposure. Symmetrical enhancement of the globus pallidus on T1-weighted images may be seen up to 6 months after exposure.

1. Emergency and supportive measures
   1. Acute inhalation. Administer supplemental oxygen. Treat bronchospasm and noncardiogenic pulmonary edema if they occur.
   2. Chronic intoxication. Psychiatric and neurologic effects are treated with the usual psychiatric and antiparkinsonian drugs but often respond poorly.
2. Specific drugs and antidotes. Calcium EDTA and other chelators have not been proven effective after chronic neurologic damage has occurred. The efficacy of chelators early after acute exposure has not been demonstrated, but studies in rodents suggest possible benefit.
3. Decontamination
   1. Acute inhalation. Remove the victim from exposure and give supplemental oxygen if available.
   2. Ingestion. Because inorganic metallic manganese is so poorly absorbed from the GI tract, gut decontamination is probably not necessary. For massive ingestions, particularly of organic compounds (eg, Maneb, Mancozeb, or MMT) or of potassium permanganate, gut decontamination may be appropriate but has not been studied.
4. Enhanced elimination. There is no known role for dialysis or hemoperfusion.