IRSST Management of Occupational Manganism: Consensus of an Experts’ Panel

IRSST Management of Occupational Manganism:

Consensus of an Experts’ Panel

Occupational manganism


Pg 25

"Few scientific data are available on the reversibility of the neurotoxic effects associated with  chronic Mn overexposure. The researchers believe that the effects are rather irreversible (Ellenhorn  and Barceloux 1988). However, there is some evidence that recovery may occur when the exposure stops (Smyth et al. 1973). Antiparkinson drugs such as levodopa may be able to reverse some of the neuromuscular signs of manganism (Ejima et al. 1992; Rosenstock et al. 1971), but these drugs have several side effects, and reports indicate that they do not improve the patients’ neurotoxic symptoms (Calne et al. 1994; Chu et al. 1995; Cook et al. 1974; Ellenhorn and Barceloux 1988; Haddad and Winchester 1990; Huang et al. 1989). The ATSDR review (2000) reports that symptoms of manganism can be improved by certain medical treatments, but the improvement is generally temporary and damage to the brain permanent.

Huang et al. (1993, 1998) documented the progression of manganism in five workers chronically exposed to Mn in the ferroalloy sector. Their results show that the disease continues to progress even 10 years after leaving the workplace. Roels et al. (1999) carried out an eight-year longitudinal study on the same cohort as that published in 1992 in order to determine the reversibility of three early neurotoxic effects: hand-eye coordination (HEC), hand steadiness (HS), and simple visual reaction time (SVRT). They concluded that the tests used were reproducible and reliable throughout the study. They also demonstrated that past severity of Mn exposure determined the relative significance of the loss in precision in hand and forearm movement (HEC) in exposed workers as compared to the control group as well as their recovery potential. However, for the two other tests, HS and SVRT, no recovery was noted, suggesting that these conditions are irreversible.

However, when neurological damage is measured, it could be reversible but could also worsen over time, even in the absence of occupational exposure. As a result, it is important to intervene as rapidly as possible, in a phase that is possibly still reversible. Then, any significant additional exposure to manganese or to any other neurotoxic agent could contribute to the acceleration in the progression of the disease."

MORE QUOTES

"...concentration at which no effect (NOAEL) should occur on the CNS or pulmonary system of healthy workers. This level is 0.07 mg Mn/m3 in respirable dust and represents an average exposure level for a healthy worker.

Based on the level of scientific knowledge and for practical reasons, the experts agreed on the  following recommendations for keeping workers with manganism at work or for returning them to work when medical conditions permit: the occupational exposure to manganese should be kept as low as possible and should be accompanied by a ceiling value, a value never to be exceeded of 0.03 mg/m3, measured in respirable dusts. This value is based on the ATSDR established NOAEL. The ATSDR value of 0.07 is divided by 2 and, rather than being an average value for the work shift, it is converted to a ceiling value. Since the ATSDR level has been established for healthy workers, the experts concluded that half this value, 0.03 mg/m3, evaluated in respirable dusts and never to be exceeded should not be detrimental to the health of the confirmed (definite and probable) or suspected (possible) diseased worker and should be applied to all those cases where medical diagnosis is such that the worker is judged capable of returning to or staying at work."

NLM - United States National Library of Medicine - Tox Maps

NLM - United States National Library of Medicine 
Tox Maps Environmental Health E-Maps 
Finding the correct map and related information can be pesky.  Instructions for finding Ashtabula and On-site information from which the information below was taken. 
 Go to:  SEARCH.  Check small box, over search, TRI.  Fill in Ashtabula, Ohio 44004
   Begin Search.
Go to:  Right side of page menu.  Click TRI Facility Details.
A list will appear in the Right menu with links to facilities.  More information is available as you scroll down the page.  
At the bottom of the page you will see:

	All chemicals reported by this facility
	On-site release summary for this facility

  Click these for more information, still.  


Millenium Inorganic Chemicals & A Cristal Company
In this case we are looking at Millenium, which has two facilities exactly contiguous with each other.  Individually, each is a heavy emitter of Manganese.  Together they are really scary. 

This was not an accident. 

Historical summary 1

http://toxmap.nlm.nih.gov/toxmap/main/allChemByFacn.jsp?facn=44004SCMCH2426M&linkback=true

Historical summary 2

http://toxmap.nlm.nih.gov/toxmap/main/allChemByFacn.jsp?facn=44004SCMCH2900M&linkback=true

EPA - Manganese (IRIS) Integrated Risk Information System

Manganese (IRIS) Integrated Risk Information System

http://www.epa.gov/iris/subst/0373.htm

 

Iris Risks

Among the primary effects associated with Mn toxicity from inhalation exposure in humans are signs and symptoms of CNS toxicity. The first medical description of chronic Mn neurotoxicity (manganism) in workers is generally credited to Couper in the 1830s (NAS, 1973). Although the course and degree of Mn intoxication can vary greatly among individuals, manganism is generally considered to consist of two or three phases (Rodier, 1955). The first is the psychiatric aspect, which includes disturbances such as excessive weeping and laughing, sleep disturbance, irritability, apathy, and anorexia. These symptoms can occur independently of the second phase, neurological signs. The latter may include gait disturbances, dysarthria, clumsiness, muscle cramps, tremor, and mask-like facial expression. In addition, there may be a final stage of Mn intoxication involving symptoms of irreversible dystonia and hyperflexion of muscles that may not appear until many years after the onset of exposure (Cotzias et al., 1968). Cotzias et al. (1976) noted a parallel between these stages of symptoms and the biphasic pattern of dopamine levels over time in the Mn-exposed individuals noted above. Indeed, various specific features of Mn toxicity show biphasic patterns in which there is generally first an increase then a decrease in performance (e.g., a notable increase in libido followed by impotence, or excitement followed by somnolence) (Rodier, 1955).

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Nogawa et al. (1973) investigated an association between atmospheric Mn levels and respiratory endpoints in junior high school students. A questionnaire focusing on eye, nose, and throat symptoms and pulmonary function tests were given to students attending junior high schools that were 100 m (enrollment = 1258) and 7 km (enrollment = 648) from a ferromanganese plant. Approximately 97-99% of the students participated. Based on measurements obtained at another time by a government agency, the 5-day average atmospheric Mn level 300 m from the plant was reported to be 0.0067 mg/cu.m.

Significant increases in past history of pneumonia, eye problems, clogged nose, nose colds, throat swelling and soreness, and other symptoms were noted among the students in the school 100 m from the plant. Those living closest to the plant reported more throat symptoms and past history of pneumonia than did students living farther away. Pulmonary function tests revealed statistically significant decreases in maximum expiratory flow, forced vital capacity (FVC), forced expiratory volume at 1 second (FEV-1), and the FVC:FEV- 1 ratio in the students attending the school closer to the plant, with some measures suggesting a relationship between performance and distance of residence from the plant.

Evidence for Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Classification — D; not classifiable as to human carcinogenicity

Basis — Existing studies are inadequate to assess the carcinogenicity of manganese.

__II.A.2. Human Carcinogenicity Data

None.

Welding Rod Dangers - Progression and Recovery

Manganism progression and recovery

FROM:  Welding Rod Dangers

Finding a Cure: The Quest for New Manganism Treatments

Patients in the early stages of manganese poisoning or manganism may be exhausted, weak, depressed, and headachy. Some researchers believe that the disease is reversible at this point, provided the patient is no longer exposed to manganese. These early manganism symptoms look a lot like signs of other conditions. Therefore, if you are a welder with health problems, you should check with your doctor and explain about your manganese exposure. Once more serious signs of manganism appear, such as awkward gait and tremors, it may be too late to stop the progression of the disease. Removing the source of manganese may no longer be helpful.

Doctors have used edetate calcium disodium (EDTA) as a manganism treatment. EDTA is a chelating agent, which means it binds metals into stable cyclic compounds. This is thought to lower their toxic effects and enhance their excretion from the body. One 1957 study used EDTA, caramiphen hydrochloride (an anticonvulsant ), mephenesin (a muscle relaxant), and a vitamin C preparation to treat a miner with motor problems, hallucinations, and other signs of manganese poisoning. He recovered nicely (Arch Neurol. 2000 Apr; 57(4): 597–9; Arch Ind Health. 1957; 16:64–66).

In 1996, a Japanese researcher reported the case of a 55–year old woman with a moving tremor, unsteady gait, high manganese levels in her blood and urine, and an MRI scan consistent with a diagnosis of manganism. She responded well to EDTA, and an MRI scan after this manganism treatment showed a lessening of the brain pattern typical of manganism patients (Rinsho Shinkeigaku, 1996 Jun; 36(6): 780–2). An Italian study, again on only one patient, also showed the value of EDTA in manganism treatment (Neurotoxicology 2000 Oct; 21(5): 863–6).

Chinese researchers reported on two manganism patients who were given sodium para–aminosalicylic acid (PAS sodium), a drug used along with other medications to treat tuberculosis (Br J Ind Med. 1992 Jan; 49(1): 66–9). One manganism patient was considered cured and the other’s symptoms were lessened.

These studies are encouraging, but limited by the small number of patients treated and the lack of control groups. More work needs to be done to see if PAS sodium or EDTA are truly effective and safe manganism treatments. If they prove valuable, even more tests would be necessary to determine proper dosage and to deal with any side effects. Meanwhile, the best way to treat manganism is to recognize it early, before it becomes irreversible, and to remove the patient from the source of manganese exposure.

June 6, 2006 - New Hope for Manganese Toxicity

 From:  Science Now

NewHope for Manganese Toxicity

by Greg Miller on 9 June 2006, 12:00 AM

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 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

Nov. 29, 2011 - NIH grant to help MRI scientist seek answers about manganese toxicity, Parkinson's disease

From:  Purdue University News Service 

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)

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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.

"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.

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, apatterson@purdue.edu

Source: Ulrike Dydak, 765-494-0550, udydak@purdue.edu
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, apattereson@purdue.edu.