Although manganese (Mn) is an essential trace nutrient, intoxication is caused by chronic overexposure. Sources of inorganic manganese exposure include mining, metal working, smelting, foundries, and welding. 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 abuse of potassium permanganate–adulterated substances, through manganese-containing total parenteral nutrition, and administration of the manganese-releasing pharmaceutical mangafodipir.
The precise mechanism of chronic toxicity is not known. The CNS is the target organ, specifically regions within the basal ganglia.
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. Bone can be a major site of long-term storage (estimated 8.5-year half-life in humans).
The primary route of exposure is inhalation, but there is evidence that absorption to the CNS 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.
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 to low levels over months or years. The time course following injection of manganese (eg, in contaminated parenteral drug abuse substances) is considerably shorter. The patient may present with a psychiatric disorder that can be misdiagnosed as schizophrenia or atypical psychosis. Signs of neurologic toxicity, such as parkinsonism and other extrapyramidal movement disorders, usually appear later, up to years after any primarily psychiatric presentation. Ingestion of potassium permanganate can cause severe acute hepatic and renal toxicity and methemoglobinemia. Ingestion of Maneb or Mancozeb is associated with acute toxicity attributed to its carbamate structure, although a subacute picture linked to manganese has been reported.
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