MANGANESE HEALTH RESEARCH PROGRAM (DoD)

Manganese is a critical metal in many defense and defense-related private sector applications including steel making and fabrication, improved fuel efficiency, welding, and portable power sources (batteries). At the current time, there is much debate concerning the potential adverse health effects of manganese in these and other applications. Due to the significant use of manganese by the Department of Defense, its contractors and its suppliers, the Manganese Health Research Program seeks to use the resources of the federal government, in tandem with manganese researchers and those industries involved with manganese, to determine the exact health effects of manganese, as well as to devise proper safeguard measures for both public and private sector workers.

Humans require manganese as an essential element; however, exposure to high levels of this metal is sometimes associated with adverse health effects, predominantly within the central nervous system. Exposure scenarios vary extensively in relation to geographical location, urban versus rural environment, lifestyles, diet, and occupational setting. Furthermore, exposure may be brief or chronic, it may be to different types of manganese compounds (aerosols or salts of manganese with different physical and/or chemical properties), and it may occur at different life-stages (e.g., in utero, neonatal life, puberty, adult life, or senescence). These factors along with diverse genetic composition likely reflect on differential sensitivity of individuals to manganese exposure. Unraveling these complexities requires a multi-pronged research approach to address multiple questions about the role of manganese as an essential metal, as well as its modulation of disease processes and dysfunction.

The DoD-funded Manganese Health Research Program involves investigators in seven different institutions (in the U.S. and abroad) and consists of fourteen research projects and an administrative core. Building on the existing base, a strategy has been devised to focus the proposal on core projects deemed most needed for the advancement of novel scientific knowledge that will characterize airborne and dietary manganese exposures, its deposition and fate, and its impact on central nervous system function. The objectives of the Manganese Health Research Program are to:

• Define the scope of the contributions of environmental and occupational manganese exposure to health, disease, and dysfunction.
• Identify and investigate factors, such as age, nutritional deficiencies, pre-existing disease, and genetics that make individuals more susceptible to the effects of manganese.
• Develop common exposure assessment protocols and exposure reconstruction methodologies.
• Determine whether manganese plays a role in increasing the relative risk for the development of idiopathic Parkinson’s disease (IPD) in welders.
• Identify biomarkers for the diagnosis of the potential adverse effects of manganese, taking account of other factors such as diet (i.e. iron deficiency).
• Understand the physiological mechanisms that govern manganese accumulation within the brain, with special emphasis on the role of olfactory transport of the metal.
• Provide new modalities for the treatment of excessive manganese exposure (i.e. iron repletion).
• Provide data to health forum regulators on which sound regulatory measures and risk assessment may be based.
• Provide timely research activity awareness services to health professionals and the manganese industry and its workers.
• Support innovative, multidisciplinary research in humans and animal models on the specific cellular, molecular, and physiologic mechanisms by which manganese mediates possible adverse health effects.