Comparative Susceptibility of Children and Adults to Neurological Effects of Inhaled Manganese: A Review of the Published Literature

Overview

Journal Environ Res

Publisher Elsevier

Specialty Environmental Health

Date 2023 Jan 20

PMID 36669586

Authors

Rachel M Shaffer

J Michael Wright

Ila Cote

Thomas F Bateson

Affiliations

Soon will be listed here.

Abstract

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 Outcomes statement focusing on inhalation exposures and neurological outcomes in humans. Screening was performed 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 Brazilian 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.

Citing Articles

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

McBride D, Bhattacharya A, Sucharew H, Brunst K, Barnas M, Cox C Environ Health Perspect. 2024; 132(5):57010.

PMID: 38780454 PMC: 11114102. DOI: 10.1289/EHP13381.

References

Haynes E, Heckel P, Ryan P, Roda S, Leung Y, Sebastian K . Environmental manganese exposure in residents living near a ferromanganese refinery in Southeast Ohio: a pilot study. Neurotoxicology. 2009; 31(5):468-74. PMC: 2891785. DOI: 10.1016/j.neuro.2009.10.011. View

Price P, Keenan R, Swartout J . Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans. Toxicol Appl Pharmacol. 2008; 233(1):64-70. DOI: 10.1016/j.taap.2008.03.026. View

Barton H, Cogliano V, Flowers L, Valcovic L, Setzer R, Woodruff T . Assessing susceptibility from early-life exposure to carcinogens. Environ Health Perspect. 2005; 113(9):1125-33. PMC: 1280390. DOI: 10.1289/ehp.7667. View

Schwartz R, Apgar B, Wien E . Apparent absorption and retention of Ca, Cu, Mg, Mn, and Zn from a diet containing bran. Am J Clin Nutr. 1986; 43(3):444-55. DOI: 10.1093/ajcn/43.3.444. View

Davidsson L, Cederblad A, Lonnerdal B, Sandstrom B . Manganese retention in man: a method for estimating manganese absorption in man. Am J Clin Nutr. 1989; 49(1):170-9. DOI: 10.1093/ajcn/49.1.170. View

Bauer J, Claus Henn B, Austin C, Zoni S, Fedrighi C, Cagna G . Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility. Environ Int. 2017; 108:299-308. PMC: 5679133. DOI: 10.1016/j.envint.2017.08.013. View

Bateson T, Schwartz J . Children's response to air pollutants. J Toxicol Environ Health A. 2007; 71(3):238-43. DOI: 10.1080/15287390701598234. View

Wahlberg K, Kippler M, Alhamdow A, Rahman S, Smith D, Vahter M . Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function. Toxicol Sci. 2015; 149(2):473-83. PMC: 4725612. DOI: 10.1093/toxsci/kfv252. View

Brown L, Schneider J, Lidsky T . Sensory and cognitive functions of the basal ganglia. Curr Opin Neurobiol. 1997; 7(2):157-63. DOI: 10.1016/s0959-4388(97)80003-7. View

10.

Baker M, Simpson C, Sheppard L, Stover B, Morton J, Cocker J . Variance components of short-term biomarkers of manganese exposure in an inception cohort of welding trainees. J Trace Elem Med Biol. 2014; 29:123-9. PMC: 4241381. DOI: 10.1016/j.jtemb.2014.05.004. View

11.

Lewis J, Bench G, Myers O, Tinner B, Staines W, Barr E . Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice. Neurotoxicology. 2004; 26(1):113-23. DOI: 10.1016/j.neuro.2004.06.005. View

12.

Sturaro A, Parvoli G, Doretti L, Allegri G, Costa C . The influence of color, age, and sex on the content of zinc, copper, nickel, manganese, and lead in human hair. Biol Trace Elem Res. 1994; 40(1):1-8. DOI: 10.1007/BF02916815. View

13.

Butler L, Gennings C, Peli M, Borgese L, Placidi D, Zimmerman N . Assessing the contributions of metals in environmental media to exposure biomarkers in a region of ferroalloy industry. J Expo Sci Environ Epidemiol. 2018; 29(5):674-687. PMC: 6472994. DOI: 10.1038/s41370-018-0081-6. View

14.

Reiss B, Simpson C, Baker M, Stover B, Sheppard L, Seixas N . Hair Manganese as an Exposure Biomarker among Welders. Ann Occup Hyg. 2015; 60(2):139-49. PMC: 4834832. DOI: 10.1093/annhyg/mev064. View

15.

Thompson K, Molina R, Donaghey T, Schwob J, Brain J, Wessling-Resnick M . Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB J. 2006; 21(1):223-30. PMC: 2432183. DOI: 10.1096/fj.06-6710com. View

16.

Coetzee D, McGovern P, Rao R, Harnack L, Georgieff M, Stepanov I . Measuring the impact of manganese exposure on children's neurodevelopment: advances and research gaps in biomarker-based approaches. Environ Health. 2016; 15(1):91. PMC: 5004305. DOI: 10.1186/s12940-016-0174-4. View

17.

Haynes E, Sucharew H, Hilbert T, Kuhnell P, Spencer A, Newman N . Impact of air manganese on child neurodevelopment in East Liverpool, Ohio. Neurotoxicology. 2017; 64:94-102. PMC: 5809274. DOI: 10.1016/j.neuro.2017.09.001. View

18.

Davidsson L, Cederblad A, Hagebo E, Lonnerdal B, Sandstrom B . Intrinsic and extrinsic labeling for studies of manganese absorption in humans. J Nutr. 1988; 118(12):1517-21. DOI: 10.1093/jn/118.12.1517. View

19.

Claus Henn B, Austin C, Coull B, Schnaas L, Gennings C, Horton M . Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses. Environ Res. 2017; 161:588-598. PMC: 5965684. DOI: 10.1016/j.envres.2017.12.003. View

20.

Scher D, Goeden H, Klos K . Potential for Manganese-Induced Neurologic Harm to Formula-Fed Infants: A Risk Assessment of Total Oral Exposure. Environ Health Perspect. 2021; 129(4):47011. PMC: 8043326. DOI: 10.1289/EHP7901. View