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Influence of particle solubility on the delivery of inhaled manganese to the rat brain: manganese sulfate and manganese tetroxide pharmacokinetics following repeated (14-day) exposure.

Dissolution rate can influence the pulmonary clearance of a metal and thus affect its delivery to the brain and other organs. The goal of this study was to determine the exposure-response relationship for the relatively soluble sulfate (MnSO(4)) and insoluble tetroxide (Mn(3)O(4)) forms of inhaled manganese in adult male CD rats. Rats were exposed 6 h/day for 7 days/week (14 exposures) to either MnSO(4) or Mn(3)O(4) at 0, 0.03, 0.3, or 3 mg Mn/m(3). End-of-exposure olfactory bulb, striatum, cerebellum, bile, lung, liver, femur, serum, and testes (n = 6 rats/concentration/chemical) manganese concentrations and whole-body (54)Mn elimination were then determined. Increased whole-body (54)Mn clearance rates were observed in animals from the high-dose (3 mg Mn/m(3)) MnSO(4) and Mn(3)O(4) exposure groups. Elevated manganese concentrations in the lung were observed following MnSO(4) and Mn(3)O(4) exposure to > or=0.3 mg Mn/m(3). Increased olfactory bulb and femur manganese concentrations were also observed following MnSO(4) exposure at > or=0.3 mg Mn/m(3). Elevated striatal, testes, liver, and bile manganese concentrations were observed following exposure to MnSO(4) at 3 mg Mn/m(3). Elevated olfactory bulb, striatal, femur, and bile manganese concentrations were observed following exposure to Mn(3)O(4) at 3 mg Mn/m(3). Animals exposed to MnSO(4) (3 mg Mn/m(3)) had lower lung and higher olfactory bulb and striatal manganese concentrations compared with levels achieved following similar Mn(3)O(4) exposures. Our results suggest that inhalation exposure to soluble forms of manganese results in higher brain manganese concentrations than those achieved following exposure to an insoluble form of manganese.