Manganese neurotoxicity: behavioral, pathological, and biochemical effects following various routes of exposure

The human central nervous system is an important target for manganese intoxication, which causes neurological symptoms similar to those of Parkinson's disease. With the increasing use of methylcyclopentadienyl manganese tricarbonyl (MMT) as an octane-improving additive to unleaded gasoline, the prospect of worldwide manganese exposure is once again attracting attention as increases in environmental manganese concentrations have been recorded relative to traffic density. One crucial question is whether a small increase of manganese contamination resulting from the widespread use of MMT could have neurotoxic effects. In this review we concentrate on central nervous system abnormalities and neurobehavioral disturbances. Most experimental animal studies on manganese neurotoxicity have been conducted in nonhuman primates and rodents. Most studies performed in rodents used oral manganese administration and did not assess bioaccumulation or central nervous system changes. The major effect found was transient modification of spontaneous motor activity. Very few inhalation toxicological studies were carried out. As manganese intoxication in humans usually occurs via inhalation, more studies are required using the respiratory route of administration. Given the proven neurotoxic effects of manganese and the prospect of worldwide MMT usage, this metal should be considered a new environmental pollutant having potentially widespread public health consequences.