MANGANISM Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese and first identified in 1837 by James Couper. Chronic exposure to excessive Mn levels can lead to a variety of psychiatric and motor disturbances. Generally, exposure to ambient Mn air concentrations in excess of 5 mg 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 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

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Page 1: Manganese Poisoning


Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese and first identified in 1837 by James Couper. Chronic exposure to excessive Mn levels can lead to a variety of psychiatric and motor disturbances. Generally, exposure to ambient Mn air concentrations in excess of 5 mg 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 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.


Manganese poisoning has been treated successfully with chelation therapy. The current mainstay of manganism treatment is levodopa 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

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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 sometimes remain largely unchanged, raising questions about efficacy of this form of treatment.


Psychiatric illnesses Mental confusion Impaired memory Loss of appetite Mask-like facial expression and monotonous voice Spastic gait Neurological problems


Hair Manganese Levels

Dark hair dyes can contain manganese and thus falsely elevate hair levels. In the case of extremely high manganese levels obtained from scalp hair, pubic hair should be tested as a control.


Because manganese is monitored in public water supplies, high levels of this naturally occurring metal are especially found in wells and private water supplies. The EPA recommends a level of 0.05 PPM in drinking water, based upon taste rather than health. A 2005 analysis based on animal studies suggests that showering in manganese-contaminated water for a decade or more could have permanent effects on the nervous system. The damage may occur even at levels of manganese considered safe by the Environmental Protection Agency, according to researchers from Wake Forest University School of Medicine.

Manganese overload is generally due to industrial pollution. Workers in the manganese processing industry are most at risk. Well water rich in manganese can be the cause of excessive manganese intake and can increase bacterial growth in water.

Manganese poisoning has been found among workers in the battery manufacturing industry. Neurological effects of manganese exposure were evaluated in 92 male workers in a dry alkaline battery factory. The control group was 101 age- and area-matched workers not occupationally exposed to manganese but with similar work schedules and workloads. Workers were exposed an average duration of 5.3 years (range 0.2-17.7 years) to average (geometric mean) concentrations of 215 μg manganese/m3 and 948 μg manganese/m3 in respirable and total dust, respectively.

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Manganese Dust – In September 2010, the Agency for Toxic Substances and Disease Registry published an Addendum to the ATSDR Toxicological Profile for Manganese which stated:

“A [Minimal Risk Level: 0.00004 mg manganese/m3] MRL of 0.04 μg manganese/m3 (manganese in respirable dust)] has been derived for chronic inhalation exposure (365 days or more) to manganese.”

This is a MRL reduction of nearly a factor of 10 from the 2008 Toxic Profile Estimate. “An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse non-cancer health effects over a specified duration of exposure. These substance specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites.”

In 2008, Health Canada determined reference concentrations ranging from 0.05 to 0.08 μg manganese/m3. In this assessment, benchmark dose analyses were conducted on data for neurobehavioral end points from a study of manganese alloy workers by Lucchini et al. (1999). Using the average manganese concentrations in respirable dust over the 5-year period before testing as the dose metric, dose-response data for six tests of fine motor control, two aspects of memory tests, and one test of mental arithmetic were fit to linear models, which were used to calculate benchmark concentration lower confidence limit (BMCL05) values ranging from about 0.019 to 0.0588 mg manganese/m3.


The causes of Manganism have become an active issue in workplace safety 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).

Reports also mention such sources as contaminated drinking water, and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT), which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust, and manganese ethylene-bis-dithiocarbamate (MANEB), a pesticide.

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Manganism victims


Price of manganese madnessBongani Mthethwa | 09 September, 2012 00:03

Simon Miya

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Brian Anderson

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Donnie du Plessis

Life is so hopeless for former Assmang worker Brian Anderson that he has attempted suicide twice.

Anderson, 60, from Prestbury, Pietermaritzburg, was diagnosed with chronic manganism six years ago.

As a result, he was also diagnosed with Parkinson's disease and now suffers from permanent sharp pains on the left side of his body and has difficulty walking.

"I feel hopeless. I feel like I'm in a bottomless pit. I've tried to commit suicide twice. Luckily, I didn't have a firearm to pull it off," he said.

Anderson, who was a factory worker, claimed he was fired by Assmang because of incapacity after 35 years' service. He has since been continually treated by doctors and psychologists.

In 2007, a neuro-psychological assessment concluded that he had permanent concentration and memory problems, as well as depression related to chronic manganism.

He walks with a stick owing to a loss of balance and relies on medication to control his extreme aggression. He and the other injured workers have to foot their own medical bills.

"The specialist told me that it's for life and I'll never come off that medication, and there's no chance of me sleeping without it," he said.

He survives on a monthly pension of R11865 from the Workers Compensation Commission. He is outraged that Assmang has not yet been prosecuted.

His neighbour, Donnie du Plessis, was also diagnosed with manganism in 2006 and was medically boarded in 2008. He worked initially as a production foreman and later as a safety officer. He is also angry that Assmang has so far escaped prosecution.

"This is an injustice to us. My body feels hard and uncomfortable. My wife complains that I've lost interest in life. I'm not worth anything any more. That's how I feel," he said.

Since his diagnosis, Du Plessis, 49, who played club rugby until the age of 35, has become moody, has a low concentration span and suffers from memory loss.

He can't even hold a screwdriver because of the tremors in his hands. "I don't know where the system failed us," said the father of three.

He said his monthly R12000 pension was abruptly stopped by Assmang last month and no explanation was given.

When he made inquiries, he was told that his condition had to be reviewed by a company doctor.

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Simon Miya, 54, from Cato Ridge, who worked as a paste controller at Assmang, was diagnosed with manganese poisoning in 2006 by a Pietermaritzburg neurologist, who advised him not to return to work.

"I was easily forgetful and shaking. I had a sharp headache and loss of balance. I became more aggressive. I didn't know what was happening," said the father of eight.

When Miya broke the news about not returning to work to his wife, Thandi, 48, she suffered a heart attack.

He worked for Assmang for 28 years and told how they used to braai meat on the hot metal at work without "knowing we were exposing ourselves to the danger of manganese poisoning".

"The company knew the dangers of manganese, but they never warned us about it. Now they have completely forgotten about us."

Muziwempi Cebekhulu, 54, a furnace operator from Empangeni in northern KwaZulu-Natal, said he was diagnosed with manganism in June 2007 after working at the factory for 27 years.

Cebekhulu, who was a shop steward and is now a ward councillor, said he was paid R167000 in compensation by Assmang.

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Hazards 104, October -December 2008Docs-for-hire blame anything-but-work for work poisonings

When workers developed the shakes, poor memory and depression working for a South African manganese company, their union knew the job was to blame. The government's compensation body agreed. So why did the company's medics instead suggest the symptoms were caused by alcohol, drugs or Aids?


Hazards issue 104, October-December 2008

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The men move uneasily, with a tell-tale “cock-walk”, a lurching, leaden footed gait. They have

tremors and get confused. And they have something else in common – they shared the same


A team of medical specialists confirmed there were at least 10 cases of debilitated manganese-

related chronic illnesses at the Assmang manganese processing plant in Cato Ridge, South

Africa. The workers knew already their symptoms were caused by their jobs in a grimy

manganese smelter. The 10 had all been certified previously by the Compensation Commissioner

as being permanently disabled as a result of manganism, a Parkinson’s disease-like condition

caused by exposure to excessive levels of manganese.

The company, though, didn’t like what the specialists or the compensation authorities had to say.

So Assmang dumped them “like hot potatoes”, a government inquiry heard in August this year.

Evidence to the long-running Department of Labour inquiry revealed the firm then replaced them

with a new team of doctors that revised the diagnoses to suggest the sick workers might be

suffering from alcohol and drug abuse, Aids, stress, arthritis, diabetes, liver disease, iron

deficiency or carbon monoxide poisoning or idiopathic Parkinson's disease (no specific

identifiable cause) - but not manganism. Another 27 workers, earmarked by doctors as possibly

suffering from manganism, were also “cleared” by the new team of medical doctors and some

were put back to work.

Metal in the blood

Puleng Mminele, the occupational health and safety coordinator with Numsa, the metalworkers’

union representing many of the affected workers at the mining and metal processing giant, is

certain “over-exposure to manganese dust, fumes and its compounds in the workplace” is to

blame for the workers crippling symptoms.

“An independent health and safety consultant, Bernard Winston Randolph, was offered a mask

during a visiting to the company in the last two years but commented that even with this mask he

could feel how his throat became sore and irritated during his visit,” Mminele told Hazards. “He

also spoke of the poor visibility on the factory floor because of the presence of the manganese

dust and fumes.”

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What HSE doesn’t know could hurt you

In 2004, the Health and Safety Executive (HSE) raised concerns about the adequacy of the UK’s control limit for manganese – but the UK standard has remained unchanged. And this occupational exposure limit, HSE believes, could be twice that at which health problems emerge

The UK exposure limit for manganese and its inorganic compounds is 0.5mg per cubic metre . An HSE regulatory impact assessment, however, notes that concentrations at or above half this level, 0.25mg per cubic metre, “can cause neurological changes,” although the changes “would be sub-clinical, and would take place gradually, such that individual workers may remain unaware of their impaired motor co-ordination, or might even consider such changes a result of ageing, rather than of occupational causation."

No-one knows the extent of any manganese problem in the UK. The HSE impact assessment notes “there are no health surveillance data from UK industry directly relating to the effects of exposure to manganese. Nor are there any statistics concerning the numbers of manganese-exposed workers who have changed employment or retired early due to the irreversible neurotoxic effects of manganese. There is no information concerning whether or not manganese-exposed workers might seek medical treatment for health effects caused by exposure to manganese."

With so little data, HSE said “it is not possible to assign any monetary costs to the health benefits” of any new standard “based on standard parameters such as loss of income or costs of medical treatment.” The paper puts the numbers exposed occupationally to manganese in Great Britain at between 65,000 and 90,000.

Maximum exposure limit for manganese and its inorganic compounds: Regulatory Impact Assessment, HSE, 2002 [pdf]

Speaking about his 30 March 2007 occupational hygiene inspection, Randolph said workers in

one process “were surrounded by so much dust and fumes that they were difficult to distinguish

in the haze.” He added: “To date, the mechanical extraction ventilation system is still non-

existent and this must have serious consequences on the employees’ health.”

The Cato Ridge furnace has no roof ventilation in the furnaces, says the union. There are no

medical monitoring systems. And respiratory protection is not up to the job. Tests have

subsequently established several hundred workers have extremely high levels of manganese in

their blood.

In statements ahead of the inquiry, where Numsa has been representing the affected workers for

over a year, “they told how they had never been warned of the dangers of manganese dust.”

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This was not a company with a faultless health and safety record. In the months the inquiry has

been running, Assmang has experienced two explosions, killing seven workers. The most recent,

a furnace blast in February 2008, killed six and triggered another Department of Labour

investigation into Assmang. It emerged the company had ignored a warning from an independent

engineer two days prior to the explosion that serious structural damage to the furnace could

result in a “major explosion which would cause extensive loss of equipment and endanger the

lives of all personnel working around the furnace.”

Destroyed by dust

The union says exposure to manganese has had a devastating effect on Assmang workers. “They

cannot continue working as a result of their physical symptoms. They walk with difficulty, many

of them use walking sticks. They experience tremors and they shake. They have low

concentration spans, and are afflicted with memory loss. At home many have erectile

dysfunction and diminished libido,” Mminele said.

STAND TOGETHER The white Assmang workers affected by manganism have now

joined Numsa, a black-dominated trade union. Their previous union was siding with

management. Photo: Numsa

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DIGGING THE DIRT Assmang opened the Cato Ridge smelter in the 1950s, to process

manganese ore. Its South African mines produce millions of tons of manganese a year.

Photo: Assmang

Numsa says several workers have already died of manganese-related disease. Protesters carried a

coffin into one session of the hearings, shouting “this is where our brothers and sisters end up!”

Their families, too, are suffering. “Their moods swing and they experience depression. This

spills over into spouses and families. Once strong men have been reduced physically and

mentally, they have diminished self-esteem and are now more dependent on their families. This

has a detrimental effect on their marital relationship.”

But the company’s behaviour could make their plight much worse, he said. “Those that are being

compensated by government battle to survive on this money that does not even cover their

medical bills. And the company is challenging this compensation on the grounds that it does not

believe these workers are suffering from manganism.”

In May 2008, as the inquiry was in full swing, a company news release announced: “Assmang

Limited does not believe that any workers at its Cato Ridge plant have manganism,” adding that

it “had fully supported the workers,” pointing out that some of those affected but not yet assessed

for government compensation had been kept on the company payroll.

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The company said “on the basis of later medical evidence the company disputed the original

diagnoses”, adding that it wanted to see all the workers “medically re-examined” and on 19 and

20 May 2008 “a recognised USA specialist neurologist on manganism was contracted and was in

Durban to conduct the examinations.”

Doctoring the evidence

Assmang had already said it doesn’t believe any workers have manganism and it has tried to stop

further cases being assessed for compensation. Ahead of the most recently concluded session,

held in September 2008, Assmang threatened to cut off benefits to those disabled but not yet

receiving government compensation unless they agreed to an examination by the company’s new

team of medical advisers.

So far five sessions of the public hearings have taken place, “with the company showing more

and more intransigence each time,” said Mmineli. When the hearings resumed in November

2008, the company reiterated its demands for new medicals.

The union, though, has no confidence in the experts lined up by the company. Mmineli says in

September 2008 the inquiry heard how independent doctors that had examined the patients “were

sidelined in favour of a company doctor who found no evidence of manganism.”

Dr. Susan Tager, a senior neurologist who heads the movement disorders clinic at Wits

University, was a member of the original Assang expert panel, set up after emergence of

suspected cases of manganese-related chronic disease. She and her colleagues confirmed workers

had developed manganism. In August 2007, however, Tager was among several prominent

neurologists and specialists replaced on Assmang’s expert panel and excluded from conducting

further medical examinations of Assmang patients.

Giving evidence at the September 2008 hearings, she expressed surprise at the conclusion of the

company’s new medical advisers – who said there were no cases of manganism at all at the firm,

instead suggesting the symptoms could be caused by drug and alcohol abuse, Aids, or a range of

other disorders.

Asked at the inquiry about the Assmang patients earmarked in medical tests as “possibly” having

manganism who had been told to return to work, she said she believed it was unethical to send

such a patient back to work and be exposed to further manganese toxins. Among the dead at in

the most recent furnace blast, was one of the workers who had been returned to work.

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Unreasonable tactics

But the company’s attempts to sweep away evidence of disease related to manganese dust and

fume went beyond the use of local medics. The firm is demanding that all the patients are

reassessed by US neurologist Dr. Warren Olanow, to provide a definitive diagnosis. Research by

Numsa suggested he was far from an impartial choice.

Doctoring the evidence

Why was Wits University neurologist Susan Tager “dumped like a hot potato?”, Numsa attorney Richard Spoor asked at a public hearing into the Assmang manganese poisonings. Tager herself was mystified when she and colleagues were dropped last year from Assmang’s expert panel after confirming cases of manganism in the company’s workers. “I don't know. If someone were to tell me, I would be happy to know,” she said.

Tager told the Department of Labour public hearings in September 2008 she stood by her diagnoses and said she did not think it was “advisable” for anyone - even a highly experienced clinician - to revise a diagnosis merely on the basis of reviewing a patient's medical file. She told the inquiry Dr Murray Coombs, a new member of the Assmang panel whose firm, Elixir Corporate Health Solutions, already provided consultancy to Assmang, had rubbished her diagnoses - even though Coombs had not seen or physically examined any of the 10 workers and based his opinion on a review of their medical files.

Numsa’s attorney Richard Spoor told the hearing Coombs had instead suggested that workers might be suffering anything from alcohol and drug abuse to Aids, stress, arthritis, diabetes, liver disease, iron deficiency or Parkinson's disease, but not manganism. Spoor described Dr Coombs as a general practitioner “who to the best of my knowledge has no experience with manganism,” but who still charged Tager “acted in an unscientific manner and drew conclusions which were not possible to make.”

Spoor asked Tager to comment on suggestions from Assmang's new medical advisers that she might have misdiagnosed some of the workers as having manganism when they actually had Parkinson's disease. Tager said the majority of patients visiting her Wits University clinic suffered from Parkinson's, so if anyone were to suggest that she confused these symptoms with manganism, “I would strongly object to anyone who made that allegation.” It is unlikely the other common conditions identified by Coombs, including alcoholism, arthritis and diabetes, would, if present, have been missed by the original medical panel.

Numsa has refused to let Warren Olanow, a US neurologist retained by Assmang to re-examine the workers, anywhere near their sick members. Olanow has made millions in the last three years for providing support for US defence lawyers trying to dismiss manganism cases

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(Hazards 103).

Spin cycle: Product defence – how industry money protects killer chemicals, Hazards 103, July/September 2008

“In manganism-related litigation in the US, Manhattan neurologist Warren Olanow was

identified in court documents this year as this biggest single recipient of industry cash,” said

Mminele. “Two consulting firms linked by the documents to Olanow received almost $2.9m

(about £1.6m) from sources defending manganese-related compensation cases.

“He is a defence favourite in manganese litigation, who has published at least a dozen articles

cited by defence experts in US manganism litigation,” said Mminele [see: Assmang’s kind of


Mizushima Ferroalloys Company Limited and Sumitomo Corporation, Assmang’s partners in a

joint venture at Cato Ridge, are both members of the International Manganese Institute, the

industry body linked to payouts to the defence expert witnesses.

Mminele said the union is “rejecting the company’s calls for a re-examination by Olanow on

medical advice that this would put more stress on the patients and only cause their medical

conditions to further deteriorate.”

The company says it considers the tests very important so the workers can “be properly

diagnosed so that they may be properly treated for their medical conditions,” a claim the union

dismisses as disingenuous and just “feigning care.”

What Assmang wants

According to Numsa’s Puleng Mminele: “Companies will do everything in their power to hire

product defence lawyers and doctors to prove their innocence. Any negative report about the

product is withheld from the public and the workers.”

He accused the company of flouting the law and using job threats to silence critics. “In the latest

hearing, Brian Broekman, the Chief Executive Officer of Assmang, threatened to take his

company to neighbouring countries, where health and safety laws are less onerous.

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“If we are to fight these companies, strong trade unions and international worker solidarity is a

necessity. Some of the affected workers have more than 20 years service with the company.

Their reward for this long service is a debilitating, killing disease.” The union believes “justice

delayed is justice denied”.

But it is not justice for the workers that is to be forefront of the company’s mind. Fighting the

compensation cases is a last ditch attempt to duck responsibility for the ruined lives and evade

prosecution in the courts. By creating doubt about the health effects of inhaling high levels of

toxic fumes, the company’s directors can breathe easy for another day. After all, if Assmang can

manufacture “reasonable doubt” the disease does not exist, its directors can hardly be held

responsible for it.

Assmang’s kind of doctor

Dr Warren Olanow was the expert brought in by Assmang in May 2008

to provide independent medical assessments of the workers previously

identified as confirmed or possible manganism victims. His impartiality,

however, has been questioned. And the NY-based doctor resigned from

his chair at New York’s Mount Sinai Hospital around the time a US

judge disclosed industry payments to medical experts related to

manganese litigation.

Documents submitted to the court revealed the welding industry made over $10 million in

payments to the authors of scientific articles - dwarfing the $500,000 that the plaintiffs had spent.

A breakdown of ‘In camera submission of privileged payments’ identifies almost $1.1m of

“Payments for time spent consulting with Defendants on issues related to welding fume litigation

after Dr Olanow ceased being identified as a testifying witness.”

Other entries making reference to Dr Olanow include:

• No.21: payments received relating to work by Olanow (total, almost $120,000);

• No.24: payments made by Olanow to others named elsewhere in the list as working for


• No.25: Parkinson’s Disease Research Corporation payments for work undertaken by Olanow

(almost $1.7m). In the 15 months from January 2005 to March 2006 alone, 17 payments were

made for work undertaken by Dr Olanow, the smallest being $19,500 and the largest $72,500;

• No.26: payments from the Parkinson’s Institute for work undertaken by authors including

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Olanow, but where Olanow is not identified as a recipient of payments (over $3.3m).

Dr Olanow's biographical page on the Mount Sinai Hospital website makes no reference to his

work for the manganese industry. And a disclosure entry on the faculty webpage of the

Parkinson's Group identifies Dr Olanow only as a consultant to pharmaceutical firms Novartis,

Solvay Pharmaceuticals Inc, Teva Neuroscience, Boehringer Ingelheim and Merck Serono

International SA and gene therapy firm Ceregene Inc.

Welding’s toxic legacy, Center for Public Integrity, June 2008 [pdf]

Mount Sinai Hospital • Parkinson's Group

Search Hazards

Deadly Business. A Hazards special investigation

The decimation of Britain's industrial base was supposed to have one obvious upside - an end to dirty and deadly jobs.

In this 'Deadly business' series, Hazards reveals how a hands off approach to safety regulation means workers continue to die in preventable 'accidents' at work.

Meanwhile, an absence of oversight means old industrial diseases are still affecting millions, and modern jobs are creating a bloodless epidemic of workplace diseases - from 'popcorn lung' to work related suicide.

Hazards Special Investigation

All Deadly Business features

Page 18: Manganese Poisoning

Hazards 104 contents


OCCUPATIONAL HEALTHPathologist challenges Assmang’s denial of manganism among its workers PRINT EMAIL |By: Margie Inggs13th June 2008 TEXT SIZE

Assmang’s argument that its workers are suffering from Parkinson’s disease, and not manganism, was dealt a major blow at the fifth sitting of the Department of Labour inquiry when pathologist Dr Reg Perumal gave evidence after performing a postmortem on the brain of one of the workers who had been diagnosed with manganism.

A neurologist had diagnosed that Freddie Wright was suffering from manganism and this had been confirmed by another specialist, but he died before he could be seen by any other specialists.

Perumal said, however, that he was satisfied that Wright had manganism as the brain lesions associated with Parkinson’s were absent.

“That leaves only one disease – manganism – which undermines Assmang’s case that the workers have Parkinson’s,” said Richard Spoor, the attorney representing the workers. “The

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problem is that the brain cannot be checked for lesions while the patient is still alive, but the theory casts doubt on the diagnosis.”

At the previous sitting, Bryan Broekman, CE of the Assmang ferromanganese factory at Cato Ridge, said in his statement, “It is possible that some or all of the diagnoses of manganism are not correct and that manganism has not been contracted to the degree previously considered, or at all.”

Assmang spokesperson Jan Steenkamp said the company still disputed that Wright had manganism. “The chairperson stopped the cross-examination by our attorney of Dr Perumal, who never saw the patient alive, and, from our point of view, his statement was based on an incorrect evaluation of the probabilities.” Steenkramp had not been diagnosed with manganism in terms of Assmang’s medical surveilance system at the time of his death.

Broekman also pointed out that accredited inspection authorities had indicated that Assmang was generally in compliance with hazardous chemical substance regulations.

In South Africa, the law requires an occupational exposure risk to manganese of less than 5 mg/m3. It is 25 times higher than the American Con-ference of Governmental Industrial Hygienists recommended level of 0,2 mg/m3 but is closer to the UK’s Occupational Safety and Health Administration’s limit of 1 mg/m3. However, the Department of Minerals and Energy uses 1 mg/m3 as its standard for manganese dust.

Assmang has maintained that it is well within acceptable risk levels as, in most cases, its level of manganese dust is below 1 mg/m3.

At the latest sitting, however, occupational hygienists who had been appointed by the company in terms of the law to conduct risk assessments at the plant gave evidence that Assmang had breeched various aspects of the Occupational Health and Safety Act from time to time. According to their reports, no training or information was made available to workers about their safety, the company had not sufficiently dealt with dangerous dust and fumes exposure risks that had been identified, and only poor control measures were in place.

While most of the areas showed reasonably acceptable levels of manganese dust, it was revealed that workers’ safety was compromised in some areas of the factory where significantly high readings were recorded.

During the next sitting, on June 23, two of the accredited inspec- tion authorities will be cross-examined.

Spoor said all the occupational hygienists who had been approved by the company to identify risks and then devise a measuring programme had found a very high risk to workers in the furnances, the crushing plant, the laboratories and around the baghouses.

“The level was well in excess of South African standards and any international standard,” he said.

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“Also, no respiratory programme was in place. No engineering controls to remove the dust were installed and appropriate masks were never provided.”

Spoor claimed that the workers were given paper dust masks and gas masks but said these were only used on a voluntary basis.

“The company never warned workers about the risks to which they were being exposed. The first they heard about the grave dangers posed by manganese was when they saw a television programme on manganism at the Samancor works, at Meyerton, in 2005.

”Broekman pointed out, however, that Assmang had spent R200-million on remedial measures over the last 12 years and had board approval for further projects totalling R150-million. However, Harold Gayze, one of the occupational hygienists appointed by the company to identify risks at the plant, said these measures would have improved dust control but would not have captured the fumes.

According to the evidence led by the occupational hygienists, it is very difficult to separate manganese dust and fumes – the smaller, solid particles which are much more dangerous – and Assmang decided to ignore the fume level despite the massive releases at the furnaces and baghouses, the areas around which all ten employees confirmed to be suffering from manganism were working.

Steenkamp told Business Report last week that the company would continue to pay benefits to workers diagnosed by its medical panel as suffering from manganism – a movement disorder resembling Parkinson’s disease and characaterised by impaired muscle tone – but would not accept claims from workers with manganese toxicity, a condition that may include a much broader spectrum of symptoms, including neurological and cognitive changes, such as reduced concentration, diminished libido, agitation, irritability and emotional instability.

According to a report tabled by Broekman, these features are nonspecific and it is not possible to know that they are caused by manganese intoxication and are not a result of other organic and psychological disorders.

“Similarly, no neuropsychologic abnormalities are known to be specific for manganism,” Broekman reported.

Spoor said basing a diagnosis purely on whether a patient’s movement disorder fitted the medical panel’s definition was rather like trying to identify an elephant from its toe rather than by standing back and looking at the whole animal.

“People suffering from manganese poisoning turn violent if their medication stops, yet Assmang is withdrawing its medical assistance from employees deemed to have manganese toxicity.”

Edited by: Martin Zhuwakinyu

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Everyone is exposed to small levels of manganese (Mn), which is found in food and many types of rocks and then enters the air, soil and water. The human body contains approximately ten milligrams of manganese, most of which is found in the liver, bones, and kidneys. The Required Daily Amount for adults of both genders is 2.5-5.0 mg. But, at higher levels, manganese is toxic to the central nervous system and can cause learning and coordination disabilities, behavioral changes and a condition that is similar to Parkinson's disease.

Manganese is often considered a nutrient which is necessary for normal body functions as follows:

• Normal skeletal growth and development

• Essential for glucose utilization

• Lipid synthesis and lipid metabolism

• Cholesterol metabolism

• Pancreatic function and development

• Prevention of sterility

• Important for protein and nucleic acid metabolism

• Activates enzyme functions

• Involved in thyroid hormone synthesis

Manganism research

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NIH grant to help MRI scientist seek answers about manganese toxicity, Parkinson's disease

November 29, 2011

Ulrike Dydak, a Purdue assistant professor of health sciences who specializes in medical imaging of neurodegenerative diseases, received more than $2 million through an Outstanding New Environmental Scientist Award (ONES) from the National Institute of Environmental Health Sciences. The five-year grant will help fund noninvasive neuroimaging techniques using magnetic resonance imaging to study manganese toxicity and lead to a better understanding of the neural system and the mechanism of this condition, which has similarities to Parkinson's disease. (Purdue University photo/Andrew Hancock)

WEST LAFAYETTE, Ind. - People exposed to manganese in occupational settings such as welding may not see signs for years that the element is toxic to their nervous systems, but new medical imaging techniques being developed and tested by a Purdue University professor could help reveal toxicity before symptoms appear that indicate irreversible brain damage.

Ulrike Dydak, an assistant professor of health sciences who specializes in medical imaging of neurodegenerative diseases, received more than $2 million through an Outstanding New Environmental Scientist Award (ONES) from the National Institute of Environmental Health Sciences, which is part of the National Institutes of Health.

This career award is meant to provide a foundation for outstanding scientists who are in the early, formative stages of their careers in environmental health research. It was given to seven scientists nationally this year to help them launch research programs that focus on human disease and the influence of the environment.

The five-year grant will help fund Dydak's noninvasive neuroimaging techniques using magnetic resonance imaging, known as MRI, to study manganese toxicity. The work could lead to a better understanding of the neural system and the mechanism of manganese toxicity, which has similarities to Parkinson's disease.

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"Patients with manganese intoxication - also known as manganism and manganese-induced Parkinsonism - as well as patients with idiopathic Parkinson's disease, have motor control issues, tremors and problems walking," Dydak said. "However, the patients with manganism don't respond to the medication used to manage Parkinson's disease symptoms because the two conditions have a different mechanism. Early diagnosis is crucial for prevention, and our goal is to see if we can identify pre-symptomatic biomarkers through new imaging techniques to create a diagnostic tool and also learn more about the disease so patients can better manage it."

Those who are mostly affected by manganese intoxication work in welding or smelting in the steel industry. There also is low-level exposure from gasoline as well as the environment of steel plants. Manganese is an element that is essential to neurological function, but too much is toxic and can cause irreversible brain damage. It also has been found recently that low amounts of manganese exposure can affect cognitive functions, such as short-term memory or reaction time.

"So far, most studies on the toxicity of manganese and other metals are performed in animal models," she said. "If we can improve medical imaging to observe specific changes in living human brain chemistry and observe these changes over the long run, it will help create a better understanding of this neurodegenerative disease and help people by improving diagnostic and therapeutic tools."

Imaging techniques that can better reveal the levels and interactions of amino acids, neurotransmitters and other physiological aspects of the brain also would be of interest to those researching other neurodegenerative diseases and in fields such as psychiatry and speech, language and hearing sciences.

Dydak has studied welders in China, where until recently the amount of manganese exposure was less regulated. Dydak will use the grant to continue developing imaging software and to observe study participants for the long term. She also will be able to study U.S. welders.

"Since it is not known at what levels of exposure manganese starts to have adverse effects, it also is important to study our local welders, even if they work under well-regulated exposure conditions," Dydak said.

Dydak has shown in previous studies that manganese exposure is related to an increase of the brain's main inhibitory neurotransmitter, gamma-aminobutyric acid, known as GABA. The increase occurs in a region of the brain responsible for movement. She also found that young, healthy workers exposed to manganese daily in the workplace had double the levels of GABA than control subjects. The increase in GABA was accompanied by a decrease in levels of N-acetylaspartate, which indicates decreased neural function. Her findings were published in the February 2011 Environmental Health Perspectives journal.

In the upcoming study, the brain chemistry and health of 48 workers with high and low exposure levels will be compared to 24 people who aren't exposed, 15 manganism patients, and 24 patients with Parkinson's disease not related to manganese exposure.

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While the study's human component focuses on noninvasive diagnostic tools by MRI, the animal component will focus on new imaging options in positron emission tomography (PET) scans to learn more about brain chemistry. In this part of the study, Dydak will focus on changes of dopamine, which helps the brain regulate movement.

"In Parkinson's disease, it is known that the dopamine system is compromised," she said. "Using PET imaging and novel MRI techniques at the same time allows us to pick up and analyze changes between dopamine and GABA."

Dydak is working with the Guangxi Medical University in Nanning, China, and Indiana University School of Medicine. She is based in Purdue's School of Health Sciences, and her imaging lab is at the Indiana Institute for Biomedical Imaging Sciences at IU's School of Medicine, where she has a joint appointment.

Her interdisciplinary collaborators on this project are Wei Zheng, professor of toxicology and head of Purdue's School of Health Sciences; Frank Rosenthal, Purdue associate professor of occupational and environmental health sciences; Yueming Jiang, professor of toxicology at Guangxi Medical University; S. Elizabeth Zauber, assistant professor of neurology at Indiana University School of Medicine; Karmen Yoder, assistant professor of radiology and imaging sciences at Indiana University School of Medicine.

Writer: Amy Patterson Neubert, 765-494-9723, [email protected]

Source: Ulrike Dydak, 765-494-0550, [email protected]

Note to Journalists: Ulrike Dydak is pronounced Ul-REEK-a DYE-deck. Journalists interested in a copy of the related February 2011 article from Environmental Health Perspectives can contact Amy Patterson Neubert at 765-494-9723, [email protected].

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New Hope for Manganese Toxicity

byGreg Miller on 9 June 2006, 12:00 AM| Permanent Link| 0 Comments

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Off target. In a still from a video shot in 1987, the manganism patient misses the tip of her nose.

Credit: Wei Zheng

A chemical cousin of aspirin may help treat neurological problems caused by exposure to high

levels of manganese metal, according to a dramatic case study in this month's Journal of

Occupational and Environmental Medicine. If the results hold up in larger trials, the drug could

provide the first effective treatment for thousands of workers exposed to high levels of

manganese through mining, steel production, and other occupations.

Neurological problems associated with high-level manganese exposure have been noted since the

1800s. Exposed workers often exhibit tremors, rigidity, and coordination problems strikingly

similar to those observed in Parkinson's disease. (A debate simmers about whether long-term

exposure to low manganese levels can cause similar problems--see Science, 21 May 2003). Yet

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Parkinson's drugs such as levodopa have little effect in people with manganism; the same goes

for compounds that help the body rid itself of manganese.

That's why the new findings are so promising, says Wei Zheng of Purdue University in West

Lafayette, Indiana. He and colleagues in Italy and China have followed the case of a Chinese

woman who worked for 19 years at a manganese milling facility. She was hospitalized several

times in the 1980s. In videos taken in 1987, her movements are unsteady and halting, and she

struggles to touch a finger to the tip of her nose and perform other simple tasks. Then, over 3

months, she received an experimental treatment of 15 intravenous infusions of para-

aminosalicylic acid (PAS), a relative of aspirin that is used to treat tuberculosis. Nearly all of her

symptoms disappeared and she has remained healthy ever since, Zheng and colleagues report.

"The video speaks for itself," Zheng says. He adds that he and colleagues have tried PAS in 85

additional patients in China. The drug seems to help about two-thirds of them, he says, but so far

those results have only appeared in Chinese-language journals.

It's not clear how PAS works, Zheng says, but one possibility is that it sops up manganese and

clears the metal from the brain more effectively than the drugs that have been tried previously.

Or it may have anti-inflammatory properties that protect neurons.

"The results are very impressive," says Michael Aschner, a neurotoxicologist at Vanderbilt

University in Nashville, Tennessee. Even so, Aschner cautions that large-scale trials will be

needed to determine whether PAS is an effective treatment for manganism.

Related sites

Zheng's Web site, with videos of the patient WEBSITE INACTIVE

Information about Parkinson's disease from NINDS

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Image of the day: Ypk9 and Manganism

Posted by feww on February 2, 2009

Link Between Parkinson’s Disease Genes and Manganese Poisoning

The Yeast PARK9 protein (Ypk9) is localized to the vacuole membrane. Shown are yeast cells expressing Ypk9 fused to the green fluorescent protein. Credit: Alessandra Chesi, Ph.D., University of Pennsylvania.

Yeast PARK9 gene (YPK9) helps protect cells from manganese toxicity. Yeast cells missing the YPK9 gene (ypk9) grow normally under standard conditions (- Mn2+) but are much more sensitive to manganese (+ Mn2+) than wild-type (WT) cells. Credit: Alessandra Chesi, Ph.D., University of Pennsylvania School of Medicine

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