Manganism
Encyclopedia
Manganism or manganese poison
ing is a toxic condition resulting from chronic exposure to manganese
and first identified in 1837 by James Couper.
In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors. Upon protracted exposure symptoms are more prominent and resemble those of idiopathic
Parkinson's disease
, which it is often misdiagnosed as, although there are particular differences in both the symptoms (nature of tremors, for example), response to drugs such as levodopa, and affected portion of the basal ganglia
. Symptoms are also similar to Lou Gehrig's disease
and multiple sclerosis
.
as it has been the subject of numerous product liability
lawsuits against manufacturers of arc welding
supplies. In these lawsuits, welders 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).
Manganism is also documented in reports of illicit methcathinone
manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate
is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base
methods from cocaine
using manganese carbonate
.
Reports also mention such sources as contaminated drinking water, and fuel additive methylcyclopentadienyl manganese tricarbonyl
(MMT), which on combustion
becomes partially converted into manganese phosphate
s and sulfate
that go airborne with the exhaust, and manganese ethylene-bis-dithiocarbamate (MANEB
), a pesticide.
function, but the threshold of acute toxicity is very high. On the other hand, more than 95% of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma. The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron
, zinc
, aluminum, and copper
. Based on a number of studies, disturbed iron metabolism
could underlie the neurotoxic action of manganese.
It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders. A study of the exposed workers showed that they have significantly fewer children. This may indicate that long-term accumulation
of manganese affects fertility
. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls. Manganism mimics Schizophrenia. It is found in large quantities in paint and steelmaking.
and chelation
with EDTA
. Both have limited and at best transient efficacy. Replenishing the deficit of dopamine
with levodopa has been shown to initially improve extrapyramidal symptoms, but the response to treatment goes down after 2 or 3 years, with worsening condition of the same patients noted even after 10 years since last exposure to manganese. Enhanced excretion of manganese prompted by chelation therapy brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.
Increased ferroportin
protein expression in human embryonic kidney (HEK293) cells is associated with decreased intracellular Mn concentration and attenuated cytotoxicity, characterized by the reversal of Mn-reduced glutamate uptake and diminished lactate dehydrogenase
(LDH) leakage.
near Hanoi
has high levels of manganese or arsenic
in the water, approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium and barium and published in the Proceedings of the National Academy of Sciences
.
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
ing is a toxic condition resulting from chronic exposure to manganese
Manganese
Manganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...
and first identified in 1837 by James Couper.
Presentation
Chronic exposure to excessive Mn levels can lead to a variety of psychiatric and motor disturbances, termed manganism. Generally, exposure to ambient Mn air concentrations in excess of 5 μg Mn/m3 can lead to Mn-induced symptoms.In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors. Upon protracted exposure symptoms are more prominent and resemble those of idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, which it is often misdiagnosed as, although there are particular differences in both the symptoms (nature of tremors, for example), response to drugs such as levodopa, and affected portion of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
. Symptoms are also similar to Lou Gehrig's disease
Motor neurone disease
The motor neurone diseases are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body. They are generally progressive in nature, and can cause...
and multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.
Causes
Manganism has become an active issue in workplace safetyOccupational safety and health
Occupational safety and health is a cross-disciplinary area concerned with protecting the safety, health and welfare of people engaged in work or employment. The goal of all occupational safety and health programs is to foster a safe work environment...
as it has been the subject of numerous product liability
Product liability
Product liability is the area of law in which manufacturers, distributors, suppliers, retailers, and others who make products available to the public are held responsible for the injuries those products cause...
lawsuits against manufacturers of arc welding
Arc welding
Arc welding is a type of welding that uses a welding power supply to create an electric arc between an electrode and the base material to melt the metals at the welding point. They can use either direct or alternating current, and consumable or non-consumable electrodes...
supplies. In these lawsuits, welders 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).
Manganism is also documented in reports of illicit methcathinone
Methcathinone
Methcathinone , is a psychoactive stimulant, sometimes used as a recreational drug and considered addictive. It is usually snorted, but can be smoked, injected, or taken orally...
manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base
Freebase (chemistry)
Freebase or free base refers to the pure basic form of an amine, as opposed to its salt form. The amine is usually an alkaloid natural product. Free base is commonly used in organic chemistry and pharmaceuticals to describe the unprotonated amine form of a compound.Most alkaloids are unstable in...
methods from cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
using manganese carbonate
Carbonate
In chemistry, a carbonate is a salt of carbonic acid, characterized by the presence of the carbonate ion, . The name may also mean an ester of carbonic acid, an organic compound containing the carbonate group C2....
.
Reports also mention such sources as contaminated drinking water, and fuel additive methylcyclopentadienyl manganese tricarbonyl
Methylcyclopentadienyl manganese tricarbonyl
Methylcyclopentadienyl manganese tricarbonyl is an organomanganese compound with the formula Mn3. Marketed initially in 1958 as a supplement to the gasoline additive tetraethyl lead to increase the fuel's octane rating, MMT was later used in unleaded gasoline...
(MMT), which on combustion
Combustion
Combustion or burning is the sequence of exothermic chemical reactions between a fuel and an oxidant accompanied by the production of heat and conversion of chemical species. The release of heat can result in the production of light in the form of either glowing or a flame...
becomes partially converted into manganese phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
s and sulfate
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
that go airborne with the exhaust, and manganese ethylene-bis-dithiocarbamate (MANEB
Maneb
Maneb is a foliate fungicide and is a polymeric complex of manganese with the ethylene bis anionic ligand. It was included in a biocide ban proposed by the Swedish Chemicals Agency and approved by the European Parliament on January 13, 2009....
), a pesticide.
Pathological mechanisms
Manganese may affect liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
function, but the threshold of acute toxicity is very high. On the other hand, more than 95% of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma. The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, aluminum, and copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
. Based on a number of studies, disturbed iron metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
could underlie the neurotoxic action of manganese.
It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders. A study of the exposed workers showed that they have significantly fewer children. This may indicate that long-term accumulation
Accumulation
Accumulation may refer to:* Accumulation: None, a 2002 lo-fi album* Capital accumulation, the gathering of objects of value* Glacier ice accumulation, an element in the glacier mass balance formula...
of manganese affects fertility
Fertility
Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...
. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls. Manganism mimics Schizophrenia. It is found in large quantities in paint and steelmaking.
Treatment
The current mainstay of manganism treatment is levodopaLevodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
and chelation
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
with EDTA
EDTA
Ethylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
. Both have limited and at best transient efficacy. Replenishing the deficit of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
with levodopa has been shown to initially improve extrapyramidal symptoms, but the response to treatment goes down after 2 or 3 years, with worsening condition of the same patients noted even after 10 years since last exposure to manganese. Enhanced excretion of manganese prompted by chelation therapy brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.
Increased ferroportin
Ferroportin
Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of it. It is found on the surface of cells that store or transport iron, including:*Enterocytes in the duodenum*Hepatocytes...
protein expression in human embryonic kidney (HEK293) cells is associated with decreased intracellular Mn concentration and attenuated cytotoxicity, characterized by the reversal of Mn-reduced glutamate uptake and diminished lactate dehydrogenase
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
(LDH) leakage.
Locations
The Red River DeltaRed River Delta
The Red River Delta is the flat plain formed by the Red River and its distributaries joining in the Thai Binh River in northern Vietnam. The delta measuring some 15,000 square km is well protected by a network of dikes. It is an agriculturally rich area and densely populated...
near Hanoi
Hanoi
Hanoi , is the capital of Vietnam and the country's second largest city. Its population in 2009 was estimated at 2.6 million for urban districts, 6.5 million for the metropolitan jurisdiction. From 1010 until 1802, it was the most important political centre of Vietnam...
has high levels of manganese or arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
in the water, approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium and barium and published in the Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences...
.
External references
- Lucchini et al., "Metals and Neurodegeneration" - Research paper on heavy metalsHeavy metalsA heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...
poisoning - Antonini., "Health Effects of Welding" - Critical review including manganese discussion from National Institute of Occupational Safety and Health (NIOSH)
- Welding and Manganese Poisoning - Safety Corner column in IBEW Journal regarding manganese and welding.
- AWS Study on Welding and Exposure to Manganese - Report of an independent study commissioned by the American Welding Society
- Welding Fume Product Liability - Viewpoint of plaintiffs on welding rod litigation
- Welding Rod Litigation Information Network - Viewpoint of defense on welding rod litigation