Editing Manganese (section)

==Health and safety==
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Manganese is essential for human health, albeit in milligram amounts.<ref name="MnDRI" /> The current maximum safe concentration under U.S. EPA rules is 50&nbsp;μg Mn/L.<ref name="EPA drinking water">{{cite web|title=Drinking Water Contaminants|url=http://water.epa.gov/drink/contaminants/index.cfm|publisher=US EPA|access-date=2 February 2015}}</ref>

===Manganism===
Manganese overexposure is most frequently associated with [[manganism]], a rare neurological disorder associated with excessive manganese ingestion or inhalation. Historically, persons employed in the production or processing of manganese alloys<ref>{{cite book |author1=Brent Furbee |title=Clinical Neurotoxicology |date=2009 |publisher=Elsevier |isbn=9780323052603 |pages=293–301 |url=https://www.sciencedirect.com/science/article/abs/pii/B9780323052603500320 |access-date=5 May 2025 |chapter=Manganese}}</ref><ref>Baselt, R. (2008) ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, pp. 883–886, {{ISBN|0-9626523-7-7}}.</ref><ref>{{cite journal|doi=10.1023/A:1021970120965|date=2002|author=Normandin, Louise|journal=Metabolic Brain Disease |volume=17|pages=375–87|pmid=12602514|last2=Hazell|first2=A. S.|title=Manganese neurotoxicity: an update of pathophysiologic mechanisms |issue=4|s2cid=23679769}}</ref> have been at risk for developing manganism; however, health and safety regulations protect workers in developed nations.<ref name="osha.gov" /> The disorder was first described in 1837 by British academic John Couper, who studied two patients who were manganese grinders.<ref name="Couper 1837 41–42">{{cite journal|last=Couper|first=John|title=On the effects of black oxide of manganese when inhaled into the lungs|journal=Br. Ann. Med. Pharm. Vital Stat. Gen. Sci.|date=1837|volume=1 |pages=41–42}}</ref>

Manganism is a biphasic disorder. In its early stages, an intoxicated person may experience depression, mood swings, compulsive behaviors, and psychosis. Early neurological symptoms give way to late-stage manganism, which resembles [[Parkinson's disease]]. Symptoms include weakness, monotone and slowed speech, an expressionless face, tremor, forward-leaning gait, inability to walk backwards without falling, rigidity, and general problems with dexterity, gait and balance.<ref name="Couper 1837 41–42" /><ref name="Cersosimo 2007 340–346">{{cite journal|last=Cersosimo|first=M. G.|author2=Koller, W.C.|title=The diagnosis of manganese-induced parkinsonism |journal=NeuroToxicology|date=2007|volume=27|pages=340–346|doi=10.1016/j.neuro.2005.10.006|pmid=16325915|issue=3}}</ref> Unlike [[Parkinson's disease]], manganism is not associated with loss of the sense of smell and patients are typically unresponsive to treatment with [[L-DOPA]].<ref>{{cite journal|last=Lu|first=C. S.|author2=Huang, C.C |author3=Chu, N.S. |author4=Calne, D.B. |title=Levodopa failure in chronic manganism|journal=Neurology|date=1994|volume=44|pages=1600–1602|doi=10.1212/WNL.44.9.1600|pmid=7936281|issue=9|s2cid=38040913}}</ref> Symptoms of late-stage manganism become more severe over time even if the source of exposure is removed and brain manganese levels return to normal.<ref name="Cersosimo 2007 340–346" />

Chronic manganese exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities.<ref name="Guilarte2015">{{cite journal | vauthors = Guilarte TR, Gonzales KK | title = Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson's Disease: Environmental and Genetic Evidence | journal = Toxicological Sciences| volume = 146 | issue = 2 | pages = 204–12 | date = August 2015 | pmid = 26220508 | pmc = 4607750 | doi = 10.1093/toxsci/kfv099 | type= Review}}</ref> This condition is not responsive to [[Management of Parkinson's disease|typical therapies used in the treatment of PD]], suggesting an alternative pathway to the typical [[dopamine]]rgic loss within the [[substantia nigra]].<ref name="Guilarte2015" /> Manganese may accumulate in the [[basal ganglia]], leading to the abnormal movements.<ref name="Kwakye2015">{{cite journal | vauthors = Kwakye GF, Paoliello MM, Mukhopadhyay S, Bowman AB, Aschner M | title = Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features | journal = Int J Environ Res Public Health | volume = 12 | issue = 7 | pages = 7519–40 | date = July 2015 | pmid = 26154659 | pmc = 4515672 | doi = 10.3390/ijerph120707519 | type= Review | doi-access = free }}</ref> A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this Parkinsonism-like disease.<ref name="Peres2016">{{cite journal | vauthors = Peres TV, Schettinger MR, Chen P, Carvalho F, Avila DS, Bowman AB, Aschner M | title = Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies | journal = BMC Pharmacology & Toxicology| volume = 17 | issue = 1 | pages = 57 | date = November 2016 | pmid = 27814772 | pmc = 5097420 | doi = 10.1186/s40360-016-0099-0 | type= Review | doi-access = free }}</ref> The [[Lewy body|Lewy bodies]] typical to PD are not seen in Mn-induced parkinsonism.<ref name="Kwakye2015" />

Animal experiments have given the opportunity to examine the consequences of manganese overexposure under controlled conditions. In (non-aggressive) rats, manganese induces mouse-killing behavior.<ref>{{cite journal|last1=Lazrishvili|display-authors=etal|first1=I.|title=Manganese loading induces mouse-killing behaviour in nonaggressive rats|journal= Journal of Biological Physics and Chemistry|date=2016|volume=16|issue=3|pages=137–141 |doi=10.4024/31LA14L.jbpc.16.03}}</ref>

===Toxicity===
Manganese compounds are less toxic than those of other widespread metals, such as [[nickel]] and [[copper]].<ref>{{cite book|pages=31 |title=Manganese|first=Heather|last=Hasan|publisher=The Rosen Publishing Group|date=2008|isbn=978-1-4042-1408-8 |url=https://books.google.com/books?id=nRmpEaudmTYC&pg=PA31}}</ref> However, exposure to manganese dusts and fumes should not exceed the ceiling value of 5&nbsp;mg/m<sup>3</sup> even for short periods because of its toxicity level.<ref>{{cite web|url=http://www.environmentwriter.org/resources/backissues/chemicals/manganese.htm |archive-url=https://web.archive.org/web/20060828211701/http://www.environmentwriter.org/resources/backissues/chemicals/manganese.htm |url-status=dead |archive-date=28 August 2006 |title=Manganese Chemical Background |access-date=30 April 2008 |publisher=Metcalf Institute for Marine and Environmental Reporting University of Rhode Island |date=April 2006 }}</ref> <!--Manganese poses a particular risk for children due to its propensity to bind to CH-7 receptors.{{Clarify|date=September 2011}}--> [[Manganese poisoning]] has been linked to [[impaired motor skills]] and [[cognitive disorder]]s.<ref>{{cite web|url=http://rais.ornl.gov/tox/profiles/mn.html|publisher=Oak Ridge National Laboratory|title=Risk Assessment Information System Toxicity Summary for Manganese|access-date=23 April 2008}}</ref>

===Neurodegenerative diseases===
A protein called [[DMT1]] is the major transporter in manganese absorption from the intestine and may be the major transporter of manganese across the [[blood–brain barrier]]. DMT1 also transports inhaled manganese across the nasal [[epithelium]]. The proposed mechanism for manganese toxicity is that dysregulation leads to [[oxidative stress]], [[mitochondrial dysfunction]], glutamate-mediated [[excitotoxicity]], and aggregation of proteins.<ref>{{Cite journal|last1=Prabhakaran|first1=K.|last2=Ghosh|first2=D.|last3=Chapman|first3=G.D.|last4=Gunasekar|first4=P.G.|date=2008|title=Molecular mechanism of manganese exposure-induced dopaminergic toxicity|journal=Brain Research Bulletin|volume=76|issue=4|pages=361–367|doi=10.1016/j.brainresbull.2008.03.004|pmid=18502311|s2cid=206339744|issn=0361-9230}}</ref>