Quantification and Mapping of Manganese Deposition and Associated Histopathological Correlates in the Lungs of Deceased Mineworkers in South Africa

Abstract

Background Occupational manganese exposure is a known health risk for mineworkers in South Africa, where inhalation of manganese dust may lead to neurological health effects. Manganese is a widely used industrial metal, with South Africa being a major global supplier. Many mineworkers in South Africa are chronically exposed to manganese- containing dust through occupational activities. While the neurotoxic effects of manganese are well established, its respiratory impacts remain poorly understood. This study aimed to address the gap by quantifying and mapping manganese deposition in lung tissues, assessing related histopathological differences, and examining their correlation with manganese deposition findings in the brains of deceased mineworkers in South Africa, thereby providing insights into the effects of manganese exposure. Methods This cross-sectional study included 16 manganese-exposed mine workers who had worked in mines in the Northern Cape province and 48 platinum (manganese- unexposed mine workers from the Northwest province of South Africa. The data sources were the National Institute for Occupational Health’s Pathology Automation (PATHAUT) database and Medical Bureau for Occupational Diseases (MBOD) records. Primary data collection involved quantifying manganese concentrations and assessing lung tissue, as well as histopathology and neuropathology databases. Manganese concentrations in the lungs were measured using Multi Collector Inductively Coupled Plasma Mass Spectrometry (MC-ICP-MS). Histopathological analysis used H&E, MT, PAS, and Reticulin stains. The correlation between lung and brain manganese deposition was analysed. Descriptive statistics were used to summarize manganese concentrations. Correlation analyses, including t-tests, Analysis of Variance, Tukey's Post Hoc test, Pearson correlation coefficient (r) test, Locally Weighted Scatterplot Smoothing (LOWESS), Linear Regression Model, and Generalized Additive Model (GAM) tests were conducted to assess the relationship between manganese levels in the lungs and brain tissues. v Results All lung tissues showed detectable levels of manganese, confirming chronic inhalational exposure among the study participants. Mapping of manganese deposition revealed non-uniform distributions, with increased concentrations in the upper and lower lobe regions of the lungs, areas that are anatomically predisposed to particle deposition due to lower perfusion and clearance. Histopathological evaluation did not reveal any specific inflammation or fibrosis attributable to manganese exposure, although several samples exhibited pathology related to pneumonia or infectious diseases. Many samples were poorly preserved, which limited the ability to fully interpret subtle histological differences. Correlation analyses showed no significant relationship between manganese concentrations in the lung and brain tissues, suggesting that manganese retention in these organs may be influenced by distinct uptake mechanisms, individual metabolic variability, and duration since last exposure. Conclusion These study findings provide novel evidence of manganese accumulation and anatomical deposition patterns in the lungs of deceased mineworkers in South Africa, but there were no histopathological differences specifically linked to manganese. The lack of a significant association supports the null hypothesis and underscores the complex, non-linear toxicokinetics of manganese, suggesting that its distribution is influenced by factors beyond direct occupational exposure.