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South African Manganese EnvironmentaL NeuroToxic Effects Research (SMELTER)

Award Number: R01ES035388
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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South African Manganese EnvironmentaL NeuroToxic Effects Research (SMELTER) - Manganese (Mn) is a well-established neurotoxicant that likely induces neurodegeneration through inflammatory pathways. Millions of people worldwide experience high levels of environmental Mn from point source emissions or associated fugitive dust. In the first five years of the SMELTER (South African Manganese EnvironmentaL NeuroToxic Effects Research) study, we assembled a cohort of >800 African residents, including >700 exposed to Mn emissions from one of the world’s largest Mn smelters in Meyerton, South Africa. We developed and validated study assessment tools in the appropriate languages, measured environmental Mn in Meyerton and a comparable non-exposed reference community (Ethembalethu), examined participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3), and evaluated participants using targeted cognitive and mood assessments. We demonstrated that Meyerton residents had markedly poorer performance in these outcomes as compared to Ethembalethu residents. These neurological health effects were associated with concentrations ~100-200 ng/m3 of Mn as particulate matter (PM) <2.5 ìm in diameter (PM2.5-Mn), a level consistent with other point sources throughout the world. In this proposal, we will build on these accomplishments by investigating whether Mn exposure is also associated with progression of the observed motor and cognitive health effects in this same cohort and to estimate longitudinal, in addition to cross-sectional, associations. We successfully employed this approach in our studies of Mn-exposed welders in the U.S. in whom longitudinal studies were required to show dose-response effects. To better characterize Mn exposure and mechanism of neurotoxicity, we will incorporate brain magnetic resonance imaging (MRI), including sequences designed to assess neuroinflammation. We will also expand our air monitoring to explore the contribution of PM size on motor, cognitive, and non-motor health outcomes, as well as neuroinflammation as assessed by brain MRI. Finally, we will implement a dissemination plan to inform community and national stakeholders of study results. Our overarching hypothesis is that environmental Mn exposure two orders of magnitude below contemporary occupational exposure is associated with progression of both parkinsonism and cognitive dysfunction and that neuroinflammation mediates the relationship between environmental Mn exposure and clinical neurotoxicity. We further hypothesize that particle sizes <1ìm (i.e., the more inspirable particles within PM2.5) will be more strongly associated with clinical outcomes than larger sizes. Accomplishing these aims will inform international environmental Mn regulations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $585,217 )
2025	2025	DIGNITY HEALTH	185 BERRY ST STE 200	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	000	2	8/7/2025	NON-COMPETING CONTINUATION	$401,669
2025	2025	DIGNITY HEALTH	185 BERRY ST STE 200	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	001	2	8/16/2025	SUPPLEMENT FOR EXPANSION	$183,548
														Subtotal = $585,217

Issue Date FY: 2024 ( Subtotal = $585,531 )
2024	2024	DIGNITY HEALTH	350 W THOMAS RD	PHOENIX	AZ	85013	MARICOPA	USA	Environmental Health	000	1	8/30/2024	NEW	$601,159
2024	2024	DIGNITY HEALTH	350 W THOMAS RD	PHOENIX	AZ	85013	MARICOPA	USA	Environmental Health	001	1	9/4/2024	NEW	-$15,628
														Subtotal = $585,531

Grand Total All Awards = $1,170,748

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South African Manganese EnvironmentaL NeuroToxic Effects Research (SMELTER)

Award Number: R01ES035388

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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