Abstract
BACKGROUND AND AIM: Manganese (Mn) is an essential nutrient but a neurotoxicant at elevated concentrations. Inhalation exposure can bypass homeostatic regulations and enter the brain. The U.S. EPA’s 1993 inhalation reference concentration and ATSDR’s 2011 minimal risk level are based on neurological outcomes in adults. To understand whether more recent data could provide information on potential lifestage-based variations in susceptibility, we compared sensitivities to neurotoxicity in children and adults using Mn biomarker data. METHODS: We developed a literature search strategy and a Population, Exposures, Comparators, and Outcomes statement. The search covered 2011-2020, with supplemental backwards reference searching. Screening was performed using SWIFT and DistillerSR. Paired studies were identified based on concordant Mn source, biomarker, and outcome. Comparisons were made based on slope of the observed dose-response (children:adults). RESULTS:We identified five studies evaluating seven pairings of hair Mn and neurological outcomes in child and adult populations with environmental Mn inhalation exposure. Two Brazilian studies of children (ages 6-12) and one of adults reported effects on IQ; effects in both comparisons were stronger in children (203% and 121%). A paired study of children and adults in Ohio reported effects on five metrics of postural sway; children exhibited both stronger and weaker effects compared to adults (175% to 69%). CONCLUSIONS:Preliminary results from a small database of well-matched studies suggest that variability in neurological effects by lifestage is less than 10-fold. This conclusion should be interpreted with caution, given the limited available paired studies. Future work will consider the impact of study quality on these conclusions. Additional studies on Mn-exposed children with direct measurement of air concentrations would provide further understanding of the toxicity of inhaled Mn among susceptible lifestages. *The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. KEYWORDS: Children's environmental health, Heavy metals, Risk assessment, Neurodevelopmental outcomes
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