Brain Manganese Concentrations in Rats Following Manganese Tetroxide Inhalation Are Unaffected by Dietary Manganese Intake.

Manganese-deficient individuals have decreased manganese elimination. This observation has prompted suggestions that relative manganese deficiency may increase the risk for manganese neurotoxicity following inhalation exposure. The objective of this study was to determine whether dietary manganese intake influences the pharmacokinetics of inhaled manganese tetroxide (Mn3O4). Postnatal day (PND) 10 rats were placed on either a low (2ppm), sufficient (10ppm), or high-normal (100ppm) manganese diet for 2 months. Beginning on PND 77 ± 2, male littermates were exposed 6h per day for 14 consecutive days to 0, 0.042, or 0.42mg Mn3O4/m3. End-of-exposure tissue manganese concentrations and whole-body 54Mn elimination rates were determined. Tissue manganese concentrations were dependent on the dietary intake of manganese, thus confirming that altered hepatic manganese disposition or metabolism occurred. Male rats given 100ppm manganese diet developed increased manganese concentrations in the femur, liver, and bile and had elevated whole-body 54Mn clearance rates when compared to animals given 2ppm manganese diet. Male rats exposed to 0.42mg Mn3O4/m3 had increased manganese concentrations in the olfactory bulb, lung, liver, and bile when compared to air-exposed male rats. A significant interaction between the concentration of inhaled Mn3O4 and dietary manganese level was observed only with the end-of-exposure liver manganese concentration. Our results indicate that animals maintained on either a manganese-deficient or high manganese diet do not appear to be at increased risk for elevated brain manganese concentrations following inhalation exposure to high levels of Mn3O4.