Abstract
BackgroundNeurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation.MethodsSubchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test.ResultsAnimals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure.ConclusionHigh-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m3) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.
Highlights
Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese
Animals exposed to MnSO4 at ≥0.3 mg Mn/m3 for 65 exposure days developed increased lung manganese concentrations
Animals exposed to MnSO4 at ≥0.06 mg Mn/m3 for 65 exposure days developed increased olfactory epithelium manganese concentrations
Summary
Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. There is growing evidence to suggest that a wide variety of respirable particles can induce lung injury under certain exposure conditions Clinical recognition of this hazard originally stemmed from occupational studies examining workplace exposure to metals, asbestos, silica, coal, and other biologically active particles [1,2]. There is strong epidemiologic evidence for significant associations between respiratory morbidity, including exacerbations of asthma and mortality, with exposure to relatively low ambient particulate matter concentrations [3,4]. This association has contributed to the adoption of more stringent ambient air quality standards for respirable particulate matter by the United States Environmental Protection Agency and other health organizations. Significant occupational manganese exposure (≥0.2 mg Mn/m3) can occur in some workers involved in ferroalloy production, iron and steel foundries, and welding [9]
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