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Manganism
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<h2 id="signs-and-symptoms">Signs and symptoms</h2> <p>Chronic exposure to excessive manganese levels can lead to a variety of psychiatric and motor disturbances, termed manganism. Generally, exposure to ambient manganese air concentrations in excess of 5 mg/m3 can lead to manganese-induced symptoms.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> </p><p>In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> Upon protracted exposure symptoms are more prominent and resemble those of <a href="/facts/Idiopathic/YIVAonwA">idiopathic</a> <a href="/facts/Parkinson%27s_disease/xpekKj6x">Parkinson's disease</a>, as which it is often misdiagnosed, although there are particular differences in both the symptoms; for example, the nature of the tremors, response to drugs such as <a href="/facts/L-DOPA/4R7qahlh">levodopa</a>, and affected portion of the <a href="/facts/Basal_ganglia/d9mbF6p3">basal ganglia</a>. Symptoms are also similar to <a href="/facts/Lou_Gehrig%27s_disease/9fIXnNL4">Lou Gehrig's disease</a> and <a href="/facts/Multiple_sclerosis/vghXl0IQ">multiple sclerosis</a>. </p> <h2 id="causes">Causes</h2> <h3>Welding</h3> <p>Manganism has become an active issue in <a href="/facts/Occupational_safety_and_health/ko1IeS92">workplace safety</a> as it has been the subject of numerous <a href="/facts/Product_liability/q4bgKPBU">product liability</a> lawsuits against manufacturers of <a href="/facts/Arc_welding/SFDgoY2g">arc welding</a> supplies. In these lawsuits, <a href="/facts/Welders/LnIAvDw2">welders</a> have accused the manufacturers of failing to provide adequate warning that their products could cause welding fumes to contain dangerously high manganese concentrations that could lead welders to develop manganism. Companies employing welders are also being sued, for what colloquially is known as "welders' disease." However, studies fail to show any link between employment as a welder and manganism (or other neurological problems).[<i>need quotation to verify</i>]<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p> <h3>Illicit methcathinone manufacturing</h3> <p>Manganism is also documented in reports of illicit <a href="/facts/Methcathinone/tF4VcbcI">methcathinone</a> manufacturing.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> This is due to manganese being a byproduct of methcathinone synthesis if <a href="/facts/Potassium_permanganate/nyjjuDlo">potassium permanganate</a> is used as an oxidiser.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic <a href="/facts/Dysarthria/UQFqqkvH">dysarthria</a>. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by <a href="/facts/Freebase_(chemistry)/bLMkVbTk">free-base</a> methods from <a href="/facts/Cocaine/rdQP4zwF">cocaine</a> using manganese <a href="/facts/Carbonate/FES1QHkN">carbonate</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h3>Drinking water, fuel additive, Maneb, paint and steelmaking</h3> <p>Reports also mention such sources as contaminated drinking water,<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> and fuel additive <a href="/facts/Methylcyclopentadienyl_manganese_tricarbonyl/d4gzqKFA">methylcyclopentadienyl manganese tricarbonyl</a> (MMT),<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> which on <a href="/facts/Combustion/ohQoWj8z">combustion</a> becomes partially converted into manganese <a href="/facts/Phosphate/FDGVCxUG">phosphates</a> and <a href="/facts/Sulfate/yuWVxsUf">sulfate</a> that go airborne with the exhaust,<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> and <a href="/facts/Manganese_ethylene-bis-dithiocarbamate/XznNToWX">manganese ethylene-bis-dithiocarbamate</a> (<a href="/facts/Maneb/XznNToWX">Maneb</a>), a pesticide.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> It is found in large quantities in <a href="/facts/Paint/Q176AsIG">paint</a> and <a href="/facts/Steelmaking/95arHmry">steelmaking processes</a>. </p><p>And in very rare cases it can be caused by a defect of the gene <a href="/facts/SLC30A10/wDhU9nck">SLC30A10</a>. </p> <h2 id="pathophysiology">Pathophysiology</h2> <p>Manganese may affect <a href="/facts/Liver/Rtp4Fk2b">liver</a> function, but the threshold of acute toxicity is very high. On the other hand, more than 95 percent of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> The exact <a href="/facts/Neurotoxic/FrgTICfX">neurotoxic</a> mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with <a href="/facts/Iron/QK1JYy8E">iron</a>,<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a><a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a><a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a><a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> <a href="/facts/Zinc/80b1qgk3">zinc</a>,<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> <a href="/facts/Aluminum/7wmR8jYE">aluminum</a>,<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> and <a href="/facts/Copper/I8PEE8oX">copper</a>.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> Based on a number of studies, disturbed iron <a href="/facts/Metabolism/WxDrm8k5">metabolism</a> could underlie the neurotoxic action of manganese.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Manganese displaces Iron in the <a href="/facts/COQ7/WuFAuPot">COQ7</a> hydroxylase enzyme required for <a href="/facts/Coenzyme_Q10/xoeh3R3e">coenzyme Q10</a> synthesis. Supplying CoQ6 (the yeast version of CoQ10) to yeast cells bathed in manganese solution restored mitochondrial function and survival.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a><a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> </p><p>It participates in <a href="/facts/Fenton_reaction/gTBzVprG">Fenton reactions</a> and could thus induce <a href="/facts/Oxidative_damage/HX7dfUUb">oxidative damage</a>, a hypothesis corroborated by the evidence from studies of affected welders.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> A study of the exposed workers showed that they have significantly fewer children.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> This may indicate that long-term accumulation of manganese affects <a href="/facts/Fertility/5S7Xull5">fertility</a>. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> </p> <h2 id="diagnosis">Diagnosis</h2> <h2 id="treatment">Treatment</h2> <p>The current mainstay of manganism treatment is <a href="/facts/Levodopa/4R7qahlh">levodopa</a> and <a href="/facts/Chelation/4G79sXBB">chelation</a> with <a href="/facts/EDTA/XvHgKQyD">EDTA</a>. Both have limited and at best transient efficacy. Replenishing the deficit of <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> with levodopa has been shown to initially improve <a href="/facts/Extrapyramidal_symptom/5d3lLrto">extrapyramidal symptoms</a>,<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a><a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> but the response to treatment goes down after 2 or 3 years,<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> with worsening condition of the same patients noted even after 10 years since last exposure to manganese.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> Enhanced excretion of manganese prompted by <a href="/facts/Chelation_therapy/BtIB1o8I">chelation therapy</a> brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a><a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> </p><p>Increased <a href="/facts/Ferroportin/cmRIBMjv">ferroportin</a> protein expression in human embryonic kidney (<a href="/facts/HEK_293_cells/Xq6NaTq1">HEK293</a>) cells is associated with decreased intracellular manganese concentration and attenuated cytotoxicity, characterized by the reversal of manganese-reduced <a href="/facts/Glutamate/7oXbNcvu">glutamate</a> uptake and diminished <a href="/facts/Lactate_dehydrogenase/FGuLGcXe">lactate dehydrogenase</a> (LDH) leakage.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h2 id="epidemiology">Epidemiology</h2> <p>The <a href="/facts/Red_River_Delta/w8kwK01e">Red River Delta</a> near <a href="/facts/Hanoi/0W2xfMQN">Hanoi</a> has high levels of manganese and <a href="/facts/Arsenic/k1c4f44D">arsenic</a> in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, <a href="/facts/Selenium/k975NApC">selenium</a>, and <a href="/facts/Barium/IkL09XHQ">barium</a>.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Alpha_synuclein/rMau6thf">Alpha synuclein</a></li> <li><a href="/facts/Asphalt_(disambiguation)/yAdleMvL">Asphalt (disambiguation)</a></li> <li><a href="/facts/Concrete/K6whGVNx">Concrete</a></li> <li><a href="/facts/Joss_paper/jA6c3VCx">Joss paper</a></li> <li><a href="/facts/Parkinsonism/orfkyX69">Parkinsonism</a></li> <li><a href="/facts/Particulates/RleGr5E6">Particulates</a></li> <li><a href="/facts/Slag/LD3qEAlV">Slag</a></li> <li><a href="/facts/Slag_cement/R1LMnaqW">Slag cement</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Evans, Garrett R.; Masullo, Lawrence N. (2024). <a href="https://www.ncbi.nlm.nih.gov/books/NBK560903/">"Manganese Toxicity"</a>. <i>StatPearls</i>. StatPearls Publishing. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/32809738">32809738</a>.</li></ul> <ul><li>Lucchini, Roberto; Tieu, Kim (30 July 2023). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452806">"Manganese-Induced Parkinsonism: Evidence from Epidemiological and Experimental Studies"</a>. <i>Biomolecules</i>. 13 (8): 1190. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3390%2Fbiom13081190">10.3390/biom13081190</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452806">10452806</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/37627255">37627255</a>. Acute high dose exposure typically causes manganism and the globus pallidus is the primary target. Chronic, low-level exposure extends Mn deposition and toxicity to other brain regions, including the substantia nigra. When combined with other PD-linked gene products such as α-synuclein, parkin, DJ-1, and ATP13A2, it is likely that Mn contributes to the onset and progression of idiopathic PD ... therefore, it is imperative to control this modifiable factor and eliminate all possible causes of overexposure and long-term absorption of low doses.</li> <li><a href="https://web.archive.org/web/20051124185457/http://www.bio.unipd.it/~zatta/metals/mangan.htm">Lucchini et al., "Metals and Neurodegeneration"</a> — Research paper on <a href="/facts/Heavy_metals/Cblmy8qI">heavy metals</a> poisoning</li> <li>Antonini, James M. (2003). "Health Effects of Welding". <i>Critical Reviews in Toxicology</i>. 33 (1): 61–103. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1080%2F713611032">10.1080/713611032</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12585507">12585507</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:26661513">26661513</a>. — Critical review including manganese discussion from National Institute for Occupational Safety and Health (<a href="/facts/NIOSH/5WjdDNMN">NIOSH</a>)</li> <li><a href="http://www.ibew.org/articles/03journal/030708/p8.htm">"Welding and Manganese Poisoning"</a>. Safety Corner. <i>IBEW Journal</i>. July–August 2003. p. 8.</li> <li><a href="http://www.aws.org/duke_study/index.html">AWS Study on Welding and Exposure to Manganese</a>[<i>permanent dead link</i>] — Report of an independent study commissioned by the American Welding Society</li> <li><a href="https://web.archive.org/web/20060616005310/http://www.welding-rod-litigation.com/">Welding Fume Product Liability</a> — Viewpoint of plaintiffs on welding rod litigation</li> <li><a href="http://www.weldinginfonetwork.com/">Welding Rod Litigation Information Network</a> — Viewpoint of defense on welding rod litigation</li> <li>Serfozo, Norbert; Lazaridis, Mihalis (December 2023). <a href="https://doi.org/10.1007%2Fs41810-023-00192-7">"Estimation of Particle Emission Rates and Calculation of Human Dose from Arc Welding and Cutting of Stainless Steel in a Simulated Confined Workspace"</a>. <i>Aerosol Science and Engineering</i>. 7 (4): 474–487. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2023AerSE...7..474S">2023AerSE...7..474S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs41810-023-00192-7">10.1007/s41810-023-00192-7</a>.</li> <li><a href="https://www.desmoinesregister.com/story/news/2019/01/08/iowa-steel-slag-dust-gravel-roads-children-health-risk-muscatine-county-ssab-americas/2475282002/">Steel slag used on rural Iowa roads could be harming children, report shows</a></li></ul> <h2 id="external-links">External links</h2> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Silva Avila, Daiana; Luiz Puntel, Robson; Aschner, Michael (2013). "Chapter 7. Manganese in Health and Disease". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (ed.). Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. Vol. 13. Springer. pp. 199–227. doi:10.1007/978-94-007-7500-8_7. ISBN 978-94-007-7499-5. PMC 6589086. PMID 24470093. <a href="978-94-007-7499-5" target="_blank">978-94-007-7499-5</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Couper, J. (1837). "Sur les effets du peroxide de manganèse". Journal de chimie médicale, de pharmacie et de toxicologie. 3: 223–5. <a href="https://books.google.com/books?id=WpQ3AAAAMAAJ&pg=PA233" target="_blank">https://books.google.com/books?id=WpQ3AAAAMAAJ&pg=PA233</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Yin, Zhaobao; Jiang, Haiyan; Lee, Eun-Sook Y.; Ni, Mingwei; Erikson, Keith M.; Milatovic, Dejan; Bowman, Aaron B.; Aschner, Michael (2010). "Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation" (PDF). Journal of Neurochemistry. 112 (5): 1190–8. doi:10.1111/j.1471-4159.2009.06534.x. PMC 2819584. PMID 20002294. <a href="http://libres.uncg.edu/ir/uncg/f/K_Erickson_Ferroportin_2009.pdf" target="_blank">http://libres.uncg.edu/ir/uncg/f/K_Erickson_Ferroportin_2009.pdf</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Roth JA (2006). "Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination". Biol. Res. 39 (1): 45–57. doi:10.4067/S0716-97602006000100006. PMID 16629164. <a href="https://doi.org/10.4067%2FS0716-97602006000100006" target="_blank">https://doi.org/10.4067%2FS0716-97602006000100006</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Fryzek JP, Hansen J, Cohen S, Bonde JP, Llambias MT, Kolstad HA, Skytthe A, Lipworth L, Blot WJ, Olsen JH (May 2005). "A cohort study of Parkinson's disease and other neurodegenerative disorders in Danish welders" (PDF). Journal of Occupational and Environmental Medicine. 47 (5): 466–72. doi:10.1097/01.jom.0000161730.25913.bf. PMID 15891525. S2CID 29870690. <a href="http://www.weldinginfonetwork.com/studies/05_05_Danish_JOEM.pdf" target="_blank">http://www.weldinginfonetwork.com/studies/05_05_Danish_JOEM.pdf</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Fored, C M; Fryzek, JP; Brandt, L; Nise, G; Sjögren, B; McLaughlin, JK; Blot, WJ; Ekbom, A (2006). "Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders". Occupational and Environmental Medicine. 63 (2): 135–40. doi:10.1136/oem.2005.022921. PMC 2078076. PMID 16421393. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2078076" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2078076</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Marsh GM, Gula MJ (October 2006). "Employment as a welder and Parkinson disease among heavy equipment manufacturing workers". Journal of Occupational and Environmental Medicine. 48 (10): 1031–46. doi:10.1097/01.jom.0000232547.74802.d8. PMID 17033503. S2CID 1355456. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>de Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE (June 2007). "Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse". Arch. Neurol. 64 (6): 886–9. doi:10.1001/archneur.64.6.886. PMID 17562938. <a href="/wiki/Arch._Neurol." target="_blank">/wiki/Arch._Neurol.</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Sanotsky, Y., Lesyk, R., Fedoryshyn, L., Komnatska, I., Matviyenko, Y. and Fahn, S. (June 2007). "Manganic encephalopathy due to "ephedrone" abuse". Movement Disorders. 22 (9): 1337–1343. doi:10.1002/mds.21378. PMID 17566121. S2CID 11564105.{{cite journal}}: CS1 maint: multiple names: authors list (link) <a href="/wiki/Movement_Disorders_(journal)" target="_blank">/wiki/Movement_Disorders_(journal)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Ensing, J. G. (1985). "Bazooka: Cocaine-Base and Manganese Carbonate". Journal of Analytical Toxicology. 9 (1): 45–46. doi:10.1093/jat/9.1.45. PMID 3981975. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Kondakis, Xenophon G.; Makris, Nicolas; Leotsinidis, Michael; Prinou, Mary; Papapetropoulos, Theodore (1989). "Possible Health Effects of High Manganese Concentration in Drinking Water". Archives of Environmental Health. 44 (3): 175–178. doi:10.1080/00039896.1989.9935883. PMID 2751354. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Hudnell, HK (1999). "Effects from environmental manganese exposures: A review of the evidence from non-occupational exposure studies". Neurotoxicology. 20 (2–3): 379–397. PMID 10385898. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Lynam, DR; Roos, JW; Pfeifer, GD; Fort, BF; Pullin, TG (1999). "Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline". Neurotoxicology. 20 (2–3): 145–150. PMID 10385878. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AR, 1997. <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Lynam, D.R.; Pfeifer, G.D.; Fort, B.F.; Gelbcke, A.A. (1990). "Environmental assessment of MMT™ fuel additive". Science of the Total Environment. 93: 107–114. 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