Comparative susceptibility of children and adults to neurological effects of inhaled manganese: A review of the published literature*

Background: Manganese (Mn) is neurotoxic in adults and children. Current assessments are based on the more extensive adult epidemiological data, but the potential for greater childhood susceptibility remains a concern. To better understand potential lifestage-based variations, we compared susceptibilities to neurotoxicity in children and adults using Mn biomarker data. Methods: We developed a literature search strategy based on a Population, Exposures, Comparators, and Out-comes statement focusing on inhalation exposures and neurological outcomes in humans. Screening was per-formed using DistillerSR. Hair biomarker studies were selected for evaluation because studies with air measurements were unavailable or considered inadequate for children. Studies were paired based on concordant Mn source, biomarker, and outcome. Comparisons were made based on reported dose-response slopes (children vs. adults). Study evaluation was conducted to understand the confidence in our comparisons. Results: We identified five studies evaluating seven pairings of hair Mn and neurological outcomes (cognition and motor effects) in children and adults matched on sources of environmental Mn inhalation exposure. Two Bra-zilian studies of children and one of adults reported intelligent quotient (IQ) effects; effects in both comparisons were stronger in children (1.21 to 2.03-fold difference). In paired analyses of children and adults from the United States, children exhibited both stronger and weaker effects compared to adults (0.37 to 1.75-fold differences) on postural sway metrics. Conclusion: There is limited information on the comparative susceptibility of children and adults to inhaled Mn. We report that children may be 0.37 to 2.03 times as susceptible as adults to neurotoxic effects of Mn, thereby providing a quantitative estimate for some aspects of lifestage variation. Due to the limited number of paired studies available in the literature, this quantitative estimate should be interpreted with caution. Our analyses do not account for other sources of inter-individual variation. Additional studies of Mn-exposed children with direct air concentration measurements would improve the evidence base.

Automated summary

This study compares the susceptibility to manganese neurotoxicity in children and adults using biomarker data. The results show that children may be more susceptible to neurotoxic effects of manganese compared to adults. However, due to the limited number of studies available, further research is needed to support the comparison between children and adults.