Manganese toxicity in humans is a well-recognized occupational hazard for people who inhale manganese dust. The most prominent effect is central nervous system pathology, especially in the extra-pyramidal motor system. The lesions and symptoms are similar to those of Parkinson’s disease (Barceloux, 1999; Keen et al., 1994). Manganese is probably transported into the brain via transferrin (Aschner et al., 1999). These authors hypothesize that the greater vulnerability of the extrapyramidal system (globus pallidus and substantia nigra) for manganese accumulation could be due to the fact that these are areas that are efferent to areas of high transferrin receptor density. These same efferent areas are also regions of high iron content.

Neurotoxicity of orally ingested manganese at relatively low doses is more controversial. However, several lines of evidence suggest this possibility. The data on manganese neurotoxicity are reviewed below.

Elevated Blood Manganese and Neurotoxicity. People with chronic liver disease have neurological pathology and behavioral signs of manganese neurotoxicity, probably because elimination of manganese in bile is impaired (Butterworth et al., 1995; Hauser et al., 1994; Spahr et al., 1996). This impairment results in higher circulating concentrations of manganese, which then has access to the brain via transferrin. Hauser and coworkers (1994) reported whole blood manganese concentrations of 18.8 to 45 μg/L in three patients with chronic liver disease, as compared to a normal range of 4.2 to 14.3 μg/L. Spahr and coworkers (1996) reported blood manganese concentrations of 124.7 nmol/L (6.85 μg/L) in control subjects versus 331.4 nmol/L (18.2 μg/L) in patients with cirrhosis. High concentrations of circulating manganese as a result of total parenteral nutrition have also been associated with manganese toxicity (Keen et al., 1999). Davis and Greger (1992) reported that women who ingested 15 mg/day of supplemental manganese had serum manganese concentrations that increased gradually throughout the 125-day study; significant differences were reported after 25 days of supplementation.

Neurotoxicity in Laboratory Animals. High subchronic or chronic doses of manganese given to animals in food or water result in