Tissue Manganese Concentrations in Young Male Rhesus Monkeys following Subchronic Manganese Sulfate Inhalation

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Abstract
High-dose human exposure to manganese results in manganese accumulation in the basal ganglia and dopaminergic neuropathology. Occupational manganese neurotoxicity is most frequently linked with manganese oxide inhalation; however, exposure to other forms of manganese may lead to higher body burdens. The objective of this study was to determine tissue manganese concentrations in rhesus monkeys following subchronic (6 h/day, 5 days/week) manganese sulfate (MnSO4) inhalation. A group of monkeys were exposed to either air or MnSO4 (0.06, 0.3, or 1.5 mg Mn/m3) for 65 exposure days before tissue analysis. Additional monkeys were exposed to MnSO4 at 1.5 mg Mn/m3 for 15 or 33 exposure days and evaluated immediately thereafter or for 65 exposure days followed by a 45- or 90-day delay before evaluation. Tissue manganese concentrations depended upon the aerosol concentration, exposure duration, and tissue. Monkeys exposed to MnSO4 at ≥ 0.06 mg Mn/m3 for 65 exposure days or to MnSO4 at 1.5 mg Mn/m3 for ≥ 15 exposure days developed increased manganese concentrations in the olfactory epithelium, olfactory bulb, olfactory cortex, globus pallidus, putamen, and cerebellum. The olfactory epithelium, olfactory bulb, globus pallidus, caudate, putamen, pituitary gland, and bile developed the greatest relative increase in manganese concentration following MnSO4 exposure. Tissue manganese concentrations returned to levels observed in the air-exposed animals by 90 days after the end of the subchronic MnSO4 exposure. These results provide an improved understanding of MnSO4 exposure conditions that lead to increased concentrations of manganese within the nonhuman primate brain and other tissues.