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 (MnSO4) and insoluble tetroxide (Mn3O4) forms of inhaled manganese in adult male CD rats. Rats were exposed 6 h/day for 7 days/week (14 exposures) to either MnSO4 or Mn3O4 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 Mn-54 elimination were then determined. Increased whole-body Mn-54 clearance rates were observed in animals from the high-dose (3 mg Mn/m3) MnSO4 and Mn3O4 exposure groups. Elevated manganese concentrations in the lung were observed following MnSO4 and Mn3O4 exposure to greater than or equal to0.3 mg Mn/m(3). Increased olfactory bulb and femur manganese concentrations were also observed following MnSO4 exposure at greater than or equal to0.3 mg Mn/m(3). Elevated striatal, testes, liver, and bile manganese concentrations were observed following exposure to MnSO4 at 3 mg Mn/m(3). Elevated olfactory bulb, striatal, femur, and bile manganese concentrations were observed following exposure to Mn3O4 at 3 mg Mn/m(3). Animals exposed to MnSO4 (3 mg Mn/m(3)) had lower lung and higher olfactory bulb and striatal manganese concentrations compared with levels achieved following similar Mn3O4 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. (C) 2001 Academic Press.