Manganese Toxicity Upon Overexposure: a Decade in Review

Current environmental health reports

Volumn 2, Issue 3, 2015, Pages 315-328

  O’Neal, Stefanie L ^a   Zheng, Wei ^a  

^a PURDUE UNIVERSITY   (United States)

Author keywords

Biomarker; Environment; Manganese; Parkinsonism; Toxicity

Indexed keywords

BIOLOGICAL MARKER; MANGANESE;

ABSORPTION; ADULT; ADVERSE EFFECTS; BLOOD; ENVIRONMENTAL EXPOSURE; EXPOSURE; FEMALE; HALF LIFE TIME; HUMAN; INFANT; INFANT MORTALITY; MALE; NEWBORN; RISK ASSESSMENT;

ABSORPTION, PHYSIOLOGICAL; ADULT; BIOMARKERS; ENVIRONMENTAL EXPOSURE; FEMALE; HALF-LIFE; HUMANS; INFANT; INFANT MORTALITY; INFANT, NEWBORN; INHALATION EXPOSURE; MALE; MANGANESE; RISK ASSESSMENT;

EID: 84994003348     PISSN: None     EISSN: 21965412     Source Type: Journal    
DOI: 10.1007/s40572-015-0056-x     Document Type: Review

References (136)

1. Nadaska G, Lesny J, Michalik I. Environmental aspect of manganese chemistry. 2012;1–16. http://heja.szif.hu/ENV/ENV_100702-A/env100702a.pdf
2. Aschner M, Vrana KE, Zheng W. Manganese uptake and distribution in the central nervous system (CNS). Neurotoxicology. 1999;20:173–80.
3. Post JE. Manganese oxide minerals: crystal structures and economic and environmental significance. Proc Natl Acad Sci U S A. 1999;96:3447–54.
4. Aschner M, Guilarte TR, Schneider JS, Zheng W. Manganese: recent advances in understanding its transport and neurotoxicity. Toxicol Appl Pharmacol. 2007;221:131–47.
5. Guilarte TR. Manganese and Parkinson’s disease: a critical review and new findings. Environ Health Perspect. 2010;118(8):1071–80.
6. Crossgrove JS, Zheng W. Manganese toxicity upon overexposure. NMR Biomed. 2004;17:544–53.
7. Cowan DM, Fan Q, Zou Y, Shi X, Chen J, Aschner M, et al. Manganese exposure among smelting workers: blood manganese-iron ratio as a novel tool for manganese exposure assessment. Biomarkers. 2009;14:3–16.
8. Cowan DM, Zheng W, Zou Y, Shi X, Chen J, Rosenthal FS, et al. Manganese exposure among smelting workers: relationship between blood manganese-iron ratio and early onset neurobehavioral alterations. NeuroToxicology. 2009;30:1214–22.
9. Dydak U, Jiang YM, Long LL, Zhu H, Chen J, Li WM, et al. In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese. Environ Health Perspect. 2011;2:219–24.
10. Alessio L, Apostoli P, Ferioli A, Lombardi S. Interference of manganese on neuroendocrinal system in exposed workers. Preliminary report. Biol Trace Elem Res. 1989;21:249–53.
11. Mutti A, Bergamaschi E, Alinovi R, Lucchini R, Vettori MV, Franchini I. Serum prolactin in subjects occupationally exposed to manganese. Ann Clin Lab Sci. 1996;26(1):10–7.
12. Lucchini R, Zimmerman N. Lifetime cumulative exposure as a threat for neurodegeneration: need for prevention strategies on a global scale. NeuroToxicology. 2009;30:1144–8.
13. Rahil-Khazen R, Bolann BJ, Myking A, Ulvik RJ. Multi-element analysis of trace element levels in human autopsy tissues by using inductively coupled atomic emission spectrometry technique (ICP-AES). J Trace Elem Med Biol. 2002;16(1):15–25.
14. Liu YZ, Byrne P, Wang HY, Koltick D, Zheng W, Nie L. A compact DD neutron generator-based NAA system to quantify manganese (Mn) in bone in vivo. Physiol Meas. 2014;35:1899–911.
15. ATSDR (2012). Toxicological profile for manganese. September 2012. http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=102&tid=23
16. Zhang LL, Lu L, Pan YJ, Ding CG, Xu DY, Huang CF, et al. Baseline blood levels of manganese, lead, cadmium, copper, and zinc in residents of Beijing suburb. Environ Res. 2015;140:10–7.
17. Au C, Benedetto A, Aschner M. Manganese transport in eukaryotes: the role of DMT1. Neurotoxicology. 2008;29:569–76.
18. Aschner M, Gannon M. Manganese (Mn) transport across the rat blood-brain barrier: saturable and transferrin-dependent transport mechanisms. Brain Res Bull. 1994;33(3):345–9.
19. Zheng W. Blood-CSF barrier in iron regulation and manganese-induced Parkinsonism. In: Zheng W, Chodobski A, editors. The blood-cerebrospinal barrier. New York: CRC Press; 2005. p. 413–36.
20. Crossgrove JS, Allen DD, Bukaveckas BL, Rhineheimer SS, Yokel RA. Manganese distribution across the blood-brain barrier. I. Evidence for carrier-mediated influx of manganese citrate as well as manganese and manganese transferrin. NeuroToxicology. 2003;24(1):3–13.
21. He L, Girijashanker K, Dalton TP, Reed J, Li H, Soleimani M, et al. ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family: characterization of transporter properties. Mol Pharmacol. 2006;70(1):171–80.
22. Fujishiro H, Yano Y, Takada Y, Tanihara M, Himeno S. Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics. 2012;4(7):700–8.
23. Lucaciu CM, Dragu C, Copaescu L, Morariu VV. Manganese transport through human erythrocyte membranes. EPR Study Biochim Biophys Acta. 1997;1328(2):90–8.
24. Kannurpatti SS, Joshi PG, Joshi NB. Calcium sequestering ability of mitochondria modulates influx of calcium through glutamate receptor channel. Neurochem Res. 2000;25(12):1527–36.
25. Crossgrove JS, Yokel RA. Manganese distribution across the blood-brain barrier. IV. Evidence for brain influx through store-operated calcium channels. NeuroToxicology. 2005;26:297–307.
26. DeWitt MR, Chen P, Aschner M. Manganese efflux in Parkinsonism: insights from newly characterized SLC30A10 mutations. Biochem Biophys Res Commun. 2013;432(1):1–4.
27. Madejczyk MS, Ballatori N. The iron transporter ferroportin can also function as a manganese exporter. Biochim Biophys Acta. 2012;1818(3):651–7.
28. Kobayashi K, Kuroda J, Shibata N, Hasegawa T, Seko Y, Satoh M, et al. Induction of metallothionein by manganese is completely dependent on interleukin-6 production. J Pharmacol Exp Ther. 2007;320(2):721–7.
29. Wang X, Li GJ, Zheng W. Upregulation of DMT1 expression in choroidal epithelia of the blood-CSF barrier following manganese exposure in vitro. Brain Res. 2006;30:1–10.
30. Gibbons RA, Dixon SN, Hallis K, Russell AM, Sansom BF, Symonds HW. Manganese metabolism in cows and goats. Biochim Biophys Acta (BBA) Gen Subj. 1976;444(1):1–10.
31. Sheng Y, Butler GE, Schumacher M, Cascio D, Cabelli DE, Valentine JS. Six-coordinate manganese (3+) in catalysis by yeast manganese superoxide dismutase. Proc Natl Acad Sci U S A. 2012;109(36):14314–9.
32. Harris WR, Chen Y. Electron paramagnetic resonance and difference ultraviolet studies of Mn2+ binding to serum transferrin. J Inorg Biochem. 1994;54(1):1–19.
33. Reaney SH, Kwik-Uribe CL, Smith DR. Manganese oxidation state and its implications for toxicity. Chem Res Toxicol. 2002;15(9):1119–26.
34. Michalke B, Fernsebner K. New insights into manganese toxicity and speciation. J Trace Elem Med Biol. 2014;28:106–16.
35. Yokel RA. Manganese flux across the blood brain barrier. NeuroMolecular Med. 2009;11:297–310.
36. Chua AC, Morgan EH. Manganese metabolism is impaired in the Belgrade laboratory rat. J Comp Physiol B. 1997;167(5):361–9.
37. Sikk K, Haldre S, Aquilonius S-M, Taba P. Manganese-induced Parkinsonism due to ephedrone abuse. Parkinson’s Disease. 2011;1–8.
38. Leavens TL, Rao D, Anderson ME, Dorman DC. Evaluating transport of manganese from olfactory mucosa to striatum by pharmacokinetic modeling. Toxicol Sci. 2007;97:265–78.
39. Jiang YM, Mo XA, Du FQ, Fu X, Zhu XY, Gao HY, et al. Effective treatment of manganese-induced occupational parkinsonism with PAS-Na: a case of 17-year follow-up study. J Occup Environ Med. 2006;48:644–9.
40. Korczynski RE. Occupational health concerns in the welding industry. Appl Occup Environ Hyg. 2000;15:936–45.
41. Lucchini RG, Dorman DC, Elder A, Veronesi B. Neurological impacts from inhalation of pollutants and the nose-brain connection. NeuroToxicology. 2012;33:838–41.
42. Zoni S, Bonetti G, Lucchini R. Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism. J Trace Elem Med Biol. 2012;26:179–82.
43. Kanayama Y, Tsuji T, Enomoto S, Amano R. Multitracer screening: brain delivery of trace elements by eight different administration methods. Biometals. 2005;18:553–65.
44. U.S. EPA. Manganese. EPA integrated risk information system 7439-96-5. Washington, D.C.: Environmental Protection Agency; 1995.
45. Kondakis XG, Makris N, Leotsinidis M, Prinou M, Papapetropoulos T. Possible health effects of high manganese concentration in drinking water. Arch Environ Health. 1989;44(3):175–8.
46. Frisbie SH, Ortega R, Maynard DM, Sarkar B. The concentrations of arsenic and other toxic elements in Bangladesh’s drinking water. Environ Health Perspect. 2002;110(11):1147–53.
47. Khan K, Wasserman GA, Liu X, Ahmed E, Parvez F, Slavkovich V, et al. Manganese exposure from drinking water and children’s academic achievement. Neurotoxicology. 2012;33:91–7.
48. Khan K, Factor-Litvak P, Wasserman GA, Liu X, Ahmed E, Parvez F, et al. Manganese exposure from drinking water and children’s classroom behavior in Bangladesh. Environ Health Perspect. 2013;119:1501–6.
49. Bouchard M, Laforest F, Vandelac L, Bellinger D, Mergler D. Hair manganese and hyperactive behaviors: pilot study of school-age children exposed through tap water. Environ Health Perspect. 2007;115:122–7.
50. Bouchard MF, Sauve S, Barbeau B, Legrand M, Brodeur ME, Bouffard T, et al. Intellectual impairment in school-age children exposed to manganese from drinking water. Environ Health Perspect. 2011;119:138–43.
51. Lucchini RG, Guazzetti S, Zoni S, Donna F, Peter S, Zacco A, et al. Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferromanganese emission. NeuroToxicology. 2012;33:687–96.
52. DeSimone LA, Hamilton PA, Gilliom RJ. The quality of our nation’s waters—quality of water from domestic wells in principal aquifers of the United States, 1991–2004—overview of major findings. U.S. Geological Survey Circular 1332. 2009; p48.
53. Tran TT, Chowanadisai W, Crinella FM, Chicz-DeMet A, Lönnerdal B. Effect of high dietary manganese intake of neonatal rats on tissue mineral accumulation, striatal dopamine levels, and neurodevelopmental status. NeuroToxicology. 2002;23:635–43.
54. Stastny D, Vogel RS, Picciano MF. Manganese intake and serum manganese intake of human milk-fed and formula-fed infants. Am J Clin Nutr. 1984;39:872–8.
55. Collipp PJ, Chen SY, Maitinsky S. Manganese in infant formulas and learning disability. Ann Nutr Metab. 1983;27:488–94.
56. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Asp Med. 2005;26:353–62.
57. Tuschl K, Mills PB, Clayton PT. Manganese and the brain. Int Rev Neurobiol. 2013;110:277–312.
58. Subramanian KS, Meranger JC. Graphite furnace atomic absorption spectrometry with nitric acid deproteinization for determination of manganese in human plasma. 1985;57(13):2478–81.
59. Krebs N, Langkammer C, Goessler W, Ropele S, Fazekas F, Yen K, et al. Assessment of trace elements in human brain using inductively coupled plasma mass spectrometry. J Trace Elem Med Biol. 2014;28(1):1–7.
60. Schmitt C, Strazielle N, Richaud P, Bouron A, Ghersi-Egea JF. Active transport at the blood-CSF barrier contributes to manganese influx in the brain. J Neurochem. 2011;117:747–56.
61. Jiang YM, Zheng W, Long LL, Zhao WJ, Li XG, Mo XA, et al. Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: search for biomarkers of manganese exposure. NeuroToxicology. 2007;28:126–35.
62. Robison G, Zakharova T, Fu S, Jiang W, Fulper R, Barrea R, et al. X-ray fluorescence imaging: a new tool for studying manganese neurotoxicity. PLoS ONE. 2012;7:e48899.
63. Robison G, Zakharova T, Fu S, Jiang W, Fulper R, Barrea R, et al. X-ray fluorescence imaging of the hippocampal formation after manganese exposure. Metallomics. 2013;5:1554–65.
64. Pejovic-Milic A, Aslam, Chettle DR, Oudyk J, Pysklywec MW, Haines T. Bone manganese as a biomarker of manganese exposure: a feasibility study. Am J Ind Med. 2009;52:742–750.
65. Schroeder HA, Balassa JJ, Tipton IH. Essential trace metals in man: manganese. A study in homeostasis. J Chronic Dis. 1966;19:545–71.
66. O’Neal S, Hong L, Fu S, Jiang W, Jones A, Nie LH, et al. Manganese accumulation in bone following chronic exposure in rats: steady-state concentration and half-life in bone. Toxicol Lett. 2014;229:90–100. A detailed report on Mn accumulation and calculation leading to define the half-life of Mn in bone.
67. Chen JY, Tsao G, Zhao Q, Zheng W. Differential cytotoxicity of Mn (II) and Mn (III): special reference to mitochondrial [Fe-S] containing enzymes. Toxicol Appl Pharmacol. 2001;175:160–8.
68. Jiang Y, Zheng W. Cardiovascular toxicities upon manganese exposure. Cardiovasc Toxicol. 2005;5:345–54.
69. Zheng W, Ren S, Graziano JH. Manganese inhibits mitochondrial aconitase: a mechanism of manganese neurotoxicity. Brain Res. 1998;799:334–42.
70. Morello M, Canini A, Mattioli P, Sorge RP, Alimonti A, Bocca B, et al. Sub-cellular localization of manganese in the basal ganglia of normal and manganese-treated rats an electron spectroscopy imaging and electron energy-loss spectroscopy study. NeuroToxicology. 2008;29:60–72.
71. Kalia K, Jiang W, Zheng W. Manganese accumulates primarily in nuclei of cultured brain cells. NeuroToxicology. 2008;29:466–70.
72. Klaassen CD. Biliary excretion of metals. Drug Metab Rev. 1976;5(2):165–96.
73. Zhu J, Gale EM, Atanasova I, Rietz TA, Caravan P. Hexameric Mn (II) dendrimer as MRI contrast agent. Chemistry. 2014;20:14507–13.
74. Marchal G, Ni Y, Zhang X, Yu J, Lodemann KP, Baert AL. Mn-DPDP enhanced MRI in experimental bile duct obstruction. J Comput Assist Tomogr. 1993;17:290–6.
75. Bellusci M, La Barbera A, Padella F, Mancuso M, Pasquo A, Grollino MG, et al. Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process. Int J Nanomedicine. 2014;9:1919–29.
76. Omokhodion FO, Howard JM. Trace elements in the sweat of acclimatized persons. Clin Chim Acta. 1994;231(1):23–8.
77. Grunecker B, Kltwasser SF, Zappe AC, Bedenk BT, Bicker Y, Spoormaker VI, et al. Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese-enhanced MRI. NMR Biomed. 2013;26:542–56.
78. Sengupta P. A scientific review of age determination for a laboratory rat: how old is it in comparison with human age? Biomed Int. 2011;2:81–9.
79. Couper J. On the effects of black oxide of manganese when inhaled into the lungs. Br Ann Med Pharm Vital Stat Gen Sci. 1837;1:41–2.
80. Keen CL, Lönnerdal B. Toxicity of essential and beneficial metal ions. Manganese. In: Berthon G, editor. Handbook of metal-ligand interactions in biological fluids. New York: Marcel Dekker, Inc; 1995. p. 683–8.
81. Huang CC, Chu NS, Lu CS, Wang JD, Tsai JL, Tseng JL, et al. Chronic manganese intoxication. Arch Neurol. 1989;46:1104–6.
82. Lu L, Zhang LL, Li GJ, Guo W, Liang W, Zheng W. Serum concentrations of manganese and iron as the potential biomarkers for manganese exposure in welders. NeuroToxicology. 2005;26(2):257–65.
83. Ono K, Komai K, Yamada M. Myoclonic involuntary movement associated with chronic manganese poisoning. J Neurol Sci. 2002;199:93–6.
84. Bowler RM, Gocheva V, Harris M, Ngo L, Abdelouahab N, Wilkinson J, et al. Prospective study on neurotoxic effects in manganese-exposed bridge construction welders. NeuroToxicology. 2011;32(5):596–605.
85. Wang JD, Huang CC, Hwang YH, Chiang JR, Lin JM, Chen JS. Manganese induced parkinsonism: an outbreak due to an un-repaired ventilation control system in a ferromanganese smelter. Br J Ind Med. 1989;46:856–9.
86. Racette BA, Criswell SR, Lundin JI, Hobson A, Seixas N, Kotzbauer PT, et al. Increased risk of parkinsonism associated with welding exposure. NeuroToxicology. 2012;33(5):1356–61.
87. Wang DX, Zhou WM, Wang SZ, Zheng W. Occupational exposure to manganese in welders and associated neurodegenerative diseases in China. Toxicol Sci. 1998;42(suppl):24.
88. Frumkin H, Solomon G. Manganese in the U.S. gasoline supply. Am J Ind Med. 1997;31:107–15.
89. Lytle CM, Smith BN, McKinnon CZ. Manganese accumulation along Utah roadways: a possible indication of motor vehicle exhaust pollution. Sci Total Environ. 1995;162:105–9.
90. Racette BA, McGee-Minnich L, Moerlein SM, Mink JW, Videen TO, Perlmutter JS. Welding-related Parkinsonism, clinical features, treatment, and pathophysiology. Neurology. 2001;56:8–13.
91. Racette BA, Tabbal SD, Jennings D, Good L, Perlmutter JS, Evanoff B. Prevalence of Parkinsonism and relationship to exposure in a large sample of Alabama welders. Neurology. 2005;64:230–5.
92. Rutchik JS, Zheng W, Jiang YM, Mo XE. How does an occupational neurologist assess welders and steelworkers for a manganese-induced movement disorder? An international team’s experiences in Guangxi, China, part I. J Occup Environ Med. 2012;54(11):1432–4.
93. Rutchik JS, Zheng W, Jiang YM, Mo XE. How does an occupational neurologist assess welders and steelworkers for a manganese-induced movement disorder? An international team’s experiences in Guangxi, China, part II. J Occup Environ Med. 2012;54(12):1562–4.
94. Gwiazda R, Lucchini R, Smith D. Adequacy and consistency of animal studies to evaluate the neurotoxicity of chronic low-level manganese exposure in humans. J Toxicol Environ Health A. 2007;70(7):594–605.
95. Racette BA, Aschner M, Guilarte TR, Dydak U, Criswell SR, Zheng W. Pathophysiology of manganese-associated neurotoxicity. NeuroToxicology. 2012;33:881–6. A thorough review on clinical aspects of Mn neurotoxicity by prominent researchers in this field.
96. O’Neal SL, Lee J-W, Zheng W, Cannon JR. Subacute manganese exposure in rats is a neurochemical model of early manganese toxicity. NeuroToxicology. 2014;44:303–13.
97. Vorhees CV, Graham DL, Amo-Kroohs RM, Braun AA, Grace CE, Schaefer TL, et al. Effects of developmental manganese, stress, and the combination of both on monoamines, growth, and corticosterone. Toxicol Rep. 2015;1:1046–61.
98. Long Z, Li XR, Xu J, Edden RA, Qin WP, Long LL, et al. Thalamic GABA predicts fine motor performance in manganese-exposed smelter workers. PLoS ONE. 2014;9:e88220.
99. Pushkar Y, Robison GA, Sullivan G, Fu SX, Kohne M, Jiang W, et al. Aging results in copper accumulations in subventricular astrocytes. Aging Cell. 2013;12:823–32.
100. Fu S, O’Neal S, Hong L, Jiang W, Zheng W. Elevated adult neurogenesis in brain subventricular zone following in vivo manganese exposure: roles of copper and DMT1. Toxicol Sci. 2015;143:482–98. The first report describing roles of altered metal homeostasis in adult neurogenesis after Mn exposure.
101. Kikuchihara Y, Abe H, Tanaka T, Kato M, Wang L, Ikarashi Y, et al. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice. Toxicology. 2015;331:24–34.
102. Charash B, Placek E, Sos TA, Kligfield P. Dose-related effects of manganese on the canine electrocardiogram. J Electrocardiol. 1982;15:149–52.
103. Vander EL, Colet JM, Muller RN. Spectroscopic and metabolic effects of MnCl2 and MnDPDP on the isolated and perfused rat heart. Investig Radiol. 1997;32:581–8.
104. Spangler AH, Spangler JG. Groundwater manganese and infant mortality rate by county in North Carolina: an ecological analysis. EcoHealth. 2009;6:596–600.
105. Hafeman D, Factor-Litvak P, Cheng Z, van Geen A, Ahsan H. Association between manganese exposure through drinking water and infant mortality in Bangladesh. Environ Health Perspect. 2007;115(7):1107–12.
106. Long LL, Li XR, Huang ZK, Jian YM, Fu SX, Zheng W. Relationship between changes in brain MRI and 1H-MRS, severity of chronic liver damage, and recovery after liver transplantation. Exp Biol Med. 2009;234:1075–85.
107. Squitti R, Gorgone G, Panetta V, Lucchini R, Bucossi S, Albini E, et al. Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants. J Neural Transm. 2009;116:1281–7.
108. Cahill DF, Bercegeay MS, Haggerty RC, Gerding JE, Gray LE. Age-related retention and distribution of ingested Mn3O4 in the rat. Toxicol Appl Pharmacol. 1980;53:83–91.
109. Oulhote Y, Mergler D, Bouchard MF. Sex- and age-differences in blood manganese levels in the U.S. general population: national health and nutritional examination survey 2011-2012. Environ Health. 2014;13:87.
110. Mena I, Horiuchi K, Burke K, Cotzias GC. Chronic manganese poisoning. Individual susceptibility and absorption of iron. Neurology. 1969;19:1000–6.
111. Lee JW, Lee CK, Moon CS, Choi IJ, Lee KJ, Yi SM, et al. Korea national survey for environmental pollutants in the human body 2008: heavy metals in the blood or urine of the Korean population. Int J Hyg Environ Health. 2012;215:449–57.
112. Bocca B, Madeddu R, Asara Y, Tolu P, Marchal JA, Forte G. Assessment of reference ranges for blood Cu, Mn, Se and Zn in a selected Italian population. J Trace Elem Med Biol. 2011;25:19–26.
113. Clark NA, Teschke K, Rideout K, Copes R. Trace element levels in adults from the west coast of Canada and associations with age, gender, diet, activities, and levels of other trace elements. Chemosphere. 2007;70:155–64.
114. Chung SE, Cheong HK, Ha EH, Kim BN, Ha M, Kim Y, Hong YC, Park H, Oh SY. Maternal blood manganese and early neurodevelopment: the mothers and children’s environmental health (MOCEH) study. Environ Health Perspect. 2015.
115. Yazbeck C, Moreau T, Sahuquillo J, Takser L, Huel G. Effect of maternal manganese blood levels on erythrocyte calcium-pump activity in newborns. Sci Total Environ. 2006;354:28–34.
116. Vigeh M, Yokoyama K, Ramezanzadeh F, Dahaghin M, Sakai T, Morita Y, et al. Lead and other trace metals in preeclampsia: a case-control study in Tehran. Iran Environ Res. 2006;100:268–75.
117. Leyva-Illades D, Chen P, Zogzas CE, Hutchens S, Mercado JM, Swaim CD, et al. SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. J Neurosci. 2014;34(42):14079–95.
118. Baker MG, Simpson CD, Sheppard L, Stover B, Morton J, Cocker J, et al. Variance components of short-term biomarkers of manganese exposure in an inception cohort of welding trainees. J Trace Elem Med Biol. 2015;29:123–9.
119. Wang DX, Du XQ, Zheng W. Alteration of saliva and serum concentrations of manganese, copper, zinc, cadmium and lead among career welders. Toxicol Lett. 2008;176:40–7.
120. Smith D, Gwiazda R, Bowler R, Roels H, Park R, Taicher C, et al. Biomarkers of Mn exposure in humans. Am J Ind Med. 2007;50:801–11.
121. Laohaudomchok W, Lin X, Herrick RF, Fang SC, Cavallari JM, Christiani DC, et al. Toenail, blood and urine as biomarkers of manganese exposure. J Occup Environ Med. 2011;53(5):506–10.
122. Riojas-Rodriguez H, Solis-Vivanco R, Schilmann A, Montes S, Rodriguez S, Rios C, et al. Intellectual function in Mexican children living in a mining area and environmentally exposed to manganese. Environ Health Perspect. 2010;118(10):1465–70.
123. Menezes-Filho JA, Paes CR, Pontes AM, Moreira JC, Sarcinelli PN, Mergler D. High levels of hair manganese in children living in the vicinity of a ferro-manganese alloy production plant. Neurotoxicology. 2009;30(6):1207–13.
124. Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environ Sci Technol. 2013;47(3):1629–37.
125. Sriram K, Lin GX, Jefferson AM, Roberts JR, Andrews RN, Kashon ML, et al. Manganese accumulation in nail clippings as a biomarker of welding fume exposure and neurotoxicity. Toxicology. 2012;291(1–3):73–82.
126. Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, et al. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environ Sci Technol. 2012;46(9):5118–25.
127. Ericson JE, Crinella FM, Clarke-Stewart KA, Allhusen VD, Chan T, Robertson RT. Prenatal manganese levels linked to childhood behavioral disinhibition. Neurotoxicol Teratol. 2007;29(2):181–7.
128. Zheng W, Fu SX, Dydak U, Cowan DM. Biomarkers of manganese intoxication. NeuroToxicology. 2011;32(1):1–8. A thorough review on existing and proposed biomarkers of Mn intoxication.
129. Zheng W, Kim H, Zhao Q. Comparative toxicokinetics of manganese chloride and methylcyclopentadienyl manganese tricarbonyl in male Sprague-Dawley rats. Toxicol Sci. 2000;54:295–301.
130. Viana GF, de Carvalho CF, Nunes LS, Rodrigues JL, Ribeiro NS, de Almeida DA, et al. Noninvasive biomarkers of manganese exposure and neuropsychological effects in environmentally exposed adults in Brazil. Toxicol Lett. 2014;231(2):169–78.
131. Grashow R, Zhang J, Fang SC, Weisskopf MG, Christiani DC, Cavallari JM. Toenail metal concentration as a biomarker of occupational welding fume exposure. J Occup Environ Hyg. 2014;11(6):397–405.
132. Liu Y, Koltic D, Byrne P, Wang H, Zheng W, Nie LH. Development of a transportable neutron activation analysis system to quantify manganese in bone in vivo: feasibility and methodology. Physiol Meas. 2013;34:1593–609.
133. Zheng W, Jiang YM, Zhang YS, Jiang W, Wang X, Cowan DM. Chelation therapy of manganese intoxication by para-aminosalicylic acid (PAS) in Sprague-Dawley rats. NeuroToxicology. 2009;30:240–8.
134. Yoon H, Kim DS, Lee GH, Kim JY, Kim DH, Kim KW, et al. Protective effects of sodium para-amino salicylate on manganese-induced neuronal death: the involvement of reactive oxygen species. J Pharm Pharmacol. 2009;61:1563–9.
135. Hong L, Jiang W, Zheng W, Zeng S. HPLC analysis of para-aminosalicylic acid and its metabolite in plasma, cerebrospinal fluid and brain tissues. J Pharm Biomed Anal. 2011;54:1101–9.
136. Hong L, Xu C, O’Neal S, Bi HC, Huang M, Zheng W, et al. Roles of P-glycoprotein and multidrug resistance protein in transporting para-aminosalicylic acid and its N-acetylated metabolite in mice brain. Acta Pharmacol Sin. 2014;35(12):1577–85.