Nasal Toxicity of Manganese Sulfate and Manganese Phosphate in Young Male Rats Following Subchronic (13-Week) Inhalation Exposure

Abstract

Growing evidence suggests that nasal deposition and transport along the olfactory nerve represents a route by which inhaled manganese and certain other metals are delivered to the rodent brain. The toxicological significance of olfactory transport of manganese remains poorly defined. In rats, repeated intranasal instillation of manganese chloride results in injury to the olfactory epithelium and neurotoxicity as evidenced by increased glial fibrillary acidic protein (GFAP) concentrations in olfactory bulb astrocytes. The purpose of the present study was to further characterize the nasal toxicity of manganese sulfate (MnSO₄) and manganese phosphate (as hureaulite) in young adult male rats following subchronic (90-day) exposure to air, MnSO₄ (0.01, 0.1, and 0.5 mg Mn/m³), or hureaulite (0.1 mg Mn/m³). Nasal pathology, brain GFAP levels, and brain manganese concentrations were assessed immediately following the end of the 90-day exposure and 45 days thereafter. Elevated end-of-exposure olfactory bulb, striatum, and cerebellum manganese concentrations were observed following MnSO₄ exposure to ≥0.01, ≥0.1, and 0.5 mg Mn/m³, respectively. Exposure to MnSO₄ or hureaulite did not affect olfactory bulb, cerebellar, or striatal GFAP concentrations. Exposure to MnSO₄ (0.5 mg Mn/m³) was also associated with reversible inflammation within the nasal respiratory epithelium, while the olfactory epithelium was unaffected by manganese inhalation. These results confirm that high-dose manganese inhalation can result in nasal toxicity (irritation) and increased delivery of manganese to the brain; however, we could not confirm that manganese inhalation would result in altered brain GFAP concentrations.