Annals of Occupational and Environmental Medicine

Review

Manganese Neurotoxicity: a Focus on Glutamate Transporters: Pratap Karki, Eunsook Lee, Michael Aschner; Ann Occup Environ Med 2013;25:4-4. Published online May 21, 2013; DOI: https://doi.org/10.1186/2052-4374-25-4

Manganese (Mn) is an essential element that is required in trace amount for normal growth, development as well maintenance of proper function and regulation of numerous cellular and biochemical reactions. Yet, excessive Mn brain accumulation upon chronic exposure to occupational or environmental sources of this metal may lead to a neurodegenerative disorder known as manganism, which shares similar symptoms with idiopathic Parkinson’s disease (PD). In recent years, Mn exposure has gained public health interest for two primary reasons: continuous increased usage of Mn in various industries, and experimental findings on its toxicity, linking it to a number of neurological disorders. Since the first report on manganism nearly two centuries ago, there have been substantial advances in the understanding of mechanisms associated with Mn-induced neurotoxicity. This review will briefly highlight various aspects of Mn neurotoxicity with a focus on the role of astrocytic glutamate transporters in triggering its pathophysiology.

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Original Article

The Brain Pathology on Recovery of Brain MRI after Manganese Administration in Rats: Ji Hyeon Jung, Jung Il Kim, Se Young Kim, Min Ho Jung, Soon Sub Choi, Soo Jin Kim, Young Jin Park, Kap Yeol Jung; Korean Journal of Occupational and Environmental Medicine 2010;22(4):371-377. Published online December 31, 2010; DOI: https://doi.org/10.35371/kjoem.2010.22.4.371

Abstract PDF: OBJECTIVES
This study was carried out to investigate the effect on manganese on the brain of Sprague-Dawley rats, with particular focus on changes to anatomical pathology when brain MRI was recovered after manganese administration.
METHODS
There were 15 rats divided into 3 groups of 5 based on dose of manganese: control group, low dose group (10 mg/kg), and high dose group (40 mg/kg). Each dosing group received an injection of normal saline and manganese via the tail vein once a week for 4 weeks. And then, the rats were observed for 12 weeks after stopping manganese administration. Next, each rat underwent a brain MRI and then each was sacrificed. After the rats were killed, the concentrations of blood manganese were measured, and pathologic examinations of the brain were performed.
RESULTS
The signal intensity of basal ganglia on T1-weighted imaging of brain MRI did not differ between dosing groups. However, the ratio of neuron/glial cell in the basal ganglia was decreased in the low- and high-dose groups compared to the control group.
CONCLUSIONS
This study showed that the damage of neuron in basal ganglia might be permanent after signal intensity of basal ganglia on T1-weighted imaging of brain MRI was recovered.

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Original Article

Induction of Inducible Nitric Oxide Synthase Expression by Manganese in C6 Glioma Cells: Gyeong Im Yu, Dong Hyul Lee, In Sung Chung, Mi Young Lee, Dong Hoon Shin; Korean Journal of Occupational and Environmental Medicine 2009;21(3):259-266. Published online September 30, 2009; DOI: https://doi.org/10.35371/kjoem.2009.21.3.259

Abstract PDF: OBJECTIVE: It is well established that manganese neurotoxicity is associated with clinical symptoms similar to those of idiopathic Parkinson's disease. Recent research has shown that the exposure to manganese (MnCl2) leads to induction of iNOS in BV2 microglial cells via iNOS transcriptional up-regulation and activation of both MAPKs and PI3K/Akt signaling pathways. Here, we further investigated the effect and the action mechanism of MnCl2 on iNOS expression in C6 glioma cells.
METHODS
Western blot analyses demonstrated that treatment with MnCl2 at 250 micronmeter was sufficient to induce iNOS at both the protein and mRNA levels in C6 cells.
RESULTS
These studies demonstrated that the induction of iNOS protein and mRNA was visible after 4h- and 2 h-treatment with MnCl2, respectively. MnCl2 treatment led to strong phosphorylation of JNKs and ERKs, members of MAP kinases (MAPKs), and Akt, a PI3-kinase (PI3K) downstream effector, in C6 cells. MnCl2 treatment had no effect on I kappa B-alpha in C6 cells. Notably, pretreatment with LY294002 (a PI3K inhibitor), which inhibited phosphorylation of Akt by MnCl2, caused strong suppression of MnCl2- induced iNOS protein and mRNA expression in C6 cells. Moreover, pretreatment with SP600125 (an inhibitor of JNKs) and PD98050 (an inhibitor of ERKs), which respectively interfered with MnCl2-mediated phosphorylation of JNKs and ERKs, led to the partial suppression of MnCl2-induced iNOS protein. Interestingly, pretreatment with LY294002 inhibited phosphorylation of not only Akt, but also ERKs and JNKs, in response to MnCl2. Moreover, there was an effective suppression of MnCl2-mediated phosphorylation of AKT by SP600125.
CONCLUSION
These results collectively suggest that MnCl2 induces iNOS expression in C6 glioma cells via activation of PI3K/Akt and JNK-ERK MAPK signaling proteins, whose activations seem to be mutually interconnected in response to MnCl2.

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Original Article

The Change of Brain MRI and Pathology According to the Administered Dose of Manganese in Rats: Jae Myeong Lee, Jung Il Kim, Yoon Kou Kim, Min Ho Jung, Soon Sub Choi, Dae Chul Kim, Kap Yeol Jung; Korean Journal of Occupational and Environmental Medicine 2009;21(2):184-191. Published online June 30, 2009; DOI: https://doi.org/10.35371/kjoem.2009.21.2.184

Abstract PDF: OBJECTIVES
This study was carried out to investigate the effect of manganese on the brains of rats, and chronic exposure to manganese is known to induce Parkinsonism in human.
METHODS
The rats were divided into three groups: the first group was a control group that was administrated normal saline, and the second group was subdivided into the low dose group (10 mg/kg) and the high dose group (40 mg/kg) according to the administered dose of manganese. The rats of each group received an injection of normal saline and manganese via a tail vein once a week for 4 weeks. The rats were sacraficed at 4 weeks after the first adminstration of manganese. Brain MR imaging was performed before the rats were killed. After the rats were killed, the concentration of blood manganese was measured, and pathologic examination of the brain was performed in all the groups.
RESULTS
The concentration of blood manganese was increased proportionally to the administered dose. The signal intensity of the basal ganglia on the T1-weighted imaging of brain MRI was increased in accordance with the administered dose. The ratio of neuron/glial cells in the basal ganglia was decreased in the experiment group as compared to that of the control group.
CONCLUSIONS
This study showed that the signal intensity and the damage of neurons in basal ganglia were increased according to the administered dose of manganese in rats.

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Review

Health Effects of Manganese and Some Recent Issues in Manganese Neurotoxicity Research: Yangho Kim; Korean Journal of Occupational and Environmental Medicine 2009;21(1):87-105. Published online March 31, 2009; DOI: https://doi.org/10.35371/kjoem.2009.21.1.87

Abstract PDF

INTRODUCTION: This article reviews the health effects of manganese (Mn) and introduces readers to recent issues in Mn neurotoxicity research.
METHODS
An extensive Medline search that covered publications up to December 2008 was conducted and the relevant papers and their references were evaluated for review.
RESULTS
AND DISCUSSION: Exposure to excess levels of the essential trace element Mn produces cognitive, psychiatric, and motor abnormalities. The lungs and the gastrointestinal tract both absorb Mn, but homeostatic mechanisms limit the absorption of Mn by the gastrointestinal tract. Elimination of Mn occurs primarily by excretion into the bile. Average Mn levels in the blood reflect the total body burden on a group basis, but not on an individual basis. Previous studies have shown that blood Mn contributes to a high pallidal signal in a T1-weighted brain MRI and that the high signal is an effective predictor of neurobehavioral performance. Thus, a high pallidal signal on an MRI may offer clues concerning the target organ dose from Mn exposure in the spectrum of Mn symptomatology. Neuroimaging as well as a clinical evaluation with exposure history is very important in a differential diagnosis that can distinguish manganism from Parkinson disease (PD). Recent research on Mn neurotoxicity has focused on several issues. First, concerns about the interaction between manganism and PD have been raised, but further research is needed. Second, epidemiological studies on non-occupational Mn exposure have suggested that environmentally induced neurotoxicities may have features that are different from the classic features of occupational manganism, but, again, this requires further research. Third, liver cirrhosis could be used as a model of manganism. Finally, functional neuroimaging such as magnetic resonance spectroscopy, functional MRI, or diffusion tensor imaging appears to have promising applications in Mn research.
CONCLUSION
Reviewing the health effects of Mn and recent issues in Mn neurotoxicity research provides us with important suggestions for how to pursue other lines of toxicological research as well as for how best to develop a systematic understanding of Mn symptomatology.

Citations

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Fundamental Study on Adsorption of Manganese in Water using Manganese-oxide coated Sand (MCS) Generated in a Filtration Tank of a Mine Drainage Treatment Facility
Sangwoo Ji, Dong-Wan Cho, Gil-Jae Yim, Jong-Man An, Gi-O An, Jeong-Yun Jang, Young-Wook Cheong
Journal of the Korean Society of Mineral and Energy Resources Engineers.2020; 57(3): 249. CrossRef
A large, nationwide, longitudinal study of central nervous system diseases among Korean workers exposed to manganese
Jin-Ha Yoon, Yeon-Soon Ahn
Parkinsonism & Related Disorders.2015; 21(3): 194. CrossRef
Associations between Airborne Manganese and Blood Manganese in the Korean General Population according to KNHANES 2008-2009
Kyung Sick Jung, Jong Dae Lee, Yong Bae Kim
Journal of Environmental Science International.2013; 22(12): 1589. CrossRef
Occupational Neurological Disorders in Korea
Eun-A Kim, Seong-Kyu Kang
Journal of Korean Medical Science.2010; 25(Suppl): S26. CrossRef

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Original Article

Gene Expression Analysis in Basal Ganglia of Manganese-Exposed Rat Based on cDNA Array: Chae Kwan Lee, Noh Sung Min, Deog Hwan Moon, Jeong Ho Kim, Byung Chul Son, Dae Hwan Kim, Chang Hee Lee, Hwi Dong Kim, Jung Won Kim, Jong Eun Kim, Jin Hong Ahn, Chae Un Lee; Korean Journal of Occupational and Environmental Medicine 2005;17(4):352-364. Published online December 31, 2005; DOI: https://doi.org/10.35371/kjoem.2005.17.4.352

Abstract PDF: OBJECTIVES
This study investigated the gene expression profile in basal ganglia of manganese-exposed rats based on cDNA array analysis.
METHODS
For cDNA array, 25 male Sprague-Dawley rats (250+/-25 g) were intraperitoneally injected with 25 mg/kg B.W./day of MnCl2 (0.3 ml) for 10 days. For dose-related gene expression analysis, rats were intraperitoneally injected with 0.2, 1.0, and 5.0 mg/kg B.W/day of MnCl2 for 10 days. Control rats were injected with an equal volume of saline. RNA samples were extracted from brain tissue and reversetranscribed in the presence of [alpha32P]-dATP. Membrane sets of the Atlas Rat 1.2 array II and Toxicology array 1.2 kit (Clontech, Palo Alto, CA) were hybridized with cDNA probe sets. Northern blot hybridization method was employed to assess the dose-related gene expression.
RESULTS
Fifty-two genes showed significant changes in expression of more than two-fold. Twentyeight were up-regulated and 24 were down-regulated in the manganese-exposed group compared to the control. Among the 52 genes, 28 genes including nuclear factor I-X1 (NF1-X1), neuroligin 2 and 3, mitochondrial stress-70 protein (MTHSP70), neurodegeneration-associated protein 1 (Neurodap1), multidrug resistance protein (MDR), and endoplasmic reticulum stress protein 72 (ERP72), were reported for the first time related to the manganese-induced neurotoxic-metabolism in the rat basal ganglia. According to the dose-related gene expression analyses, MTHSP70, Neurodap1 and ERP72 genes were up-regulated compared to the control even in the group exposed to low manganese dose (0.2 mg/kg B.W./day).
CONCLUSIONS
Twenty-eight genes detected for the first time in this study were closely related to the manganese-induced neurotoxic-metabolism in the rat basal ganglia and further study of these genes can give some more useful information about the manganese metabolism.

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Original Article

Relationship of Biological Indices of Manganese with Pallidal Index on MRI in Liver Cirrhotics: Younghee Choi, Neung Hwa Park, Jung Woo Shin, Hyo Kyung Kim, Sung Ryul Kim, Tae Heum Jeong, Ji Kang Park, Hun Lee, Cheol In Yoo, Choong Ryeol Lee, Ji Ho Lee, Yangho Kim; Korean Journal of Occupational and Environmental Medicine 2004;16(2):129-138. Published online June 30, 2004; DOI: https://doi.org/10.35371/kjoem.2004.16.2.129

Abstract PDF: OBJECTIVES
The objectives of this study were to clarify which biological manganese exposure indices reflect the pallidal signal intensities in magnetic resonance imaging (MRI) in liver cirrhotics.
METHODS
We examined whole blood, plasma, RBC and urinary manganese concentrations, as well as, brain MRI in 22 cirrhotic patients and 10 healthy controls. From MRI scans we calculated the signal intensity of the globus pallidus using the pallidal index (PI), the ratio of the globus pallidus to subcortical frontal white-matter signal intensity in axial T1-weighted MRI planes multiplied by 100. In addition, we studied the relationships between PI and other measurements.
RESULTS
The high signal intensity in the globus pallidus on T1-weighted MRI was observed in 18 (81.8%) patients. There was a significant correlation between whole blood and RBC manganese concentration, and PI on MRI. According to multiple linear regression, whole blood and RBC manganese concentration reflected PI on MRI better the other indices did.
CONCLUSIONS
Whole blood and RBC manganese concentrations could be useful as biological manganese exposure indices that reflect PI on MRI.

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Original Article

Manganese-induced Oxidative Stress in the Corpus Striatum of the Rat Brain: Soo Jin Lee, Soon Oh Hong, Hyun Chul Koh; Korean Journal of Occupational and Environmental Medicine 2002;14(1):23-33. Published online March 31, 2002; DOI: https://doi.org/10.35371/kjoem.2002.14.1.23

Abstract PDF: OBJECTIVES
This study was undertaken to identify the effect of oxidative stress on the pathology of manganese intoxication through an analysis of manganese concentrations, superoxide dismutase (SOD) activities, malondialdehyde (MDA) concentrations, and the compositional changes of fatty acids from the corpus striatum of the rat brain.
METHODS
Ten Sprague-Dawley rats were equally divided into two groups. Five rats in the experimental group were administered MnCl2 intraperitoneally for 4 weeks (4 mg/kg once daily, 5 days per week) and another five rats from the control group were given normal saline. Twenty-four hours after the last injection, the rats were decapitated and, the corpus striatum was isolated from the brain.
RESULTS
In the corpus striatums of the experimental group, manganese concentrations increased significantly by 139 % (p<0.01). The SOD activities decreased significantly by 81 % (p<0.01) and the MDA concentrations increased significantly by 138 % (p<0.01) as compared to the control group. Among fatty acids, total n-6 polyunsaturated fatty acids (PUFAs) increased significantly by 325 % (p<0.01) as compared with the control group. Arachidonic acids (AA) increased by 341 % (p<0.01), and these increases were composed mostly of n-6 polyunsaturated fatty acids (PUFA). Among n-3 PUFAs, with the exception of linolenic acids, eicosapentanoic acid (EPA) decreased significantly by 72 % (p<0.05) and docosahexanoic acids (DHA) decreased by 67 % (p<0.05) as compared with the control group.
CONCLUSIONS
Our results suggest that the oxygen free radicals produced by manganese may cause compositional changes of fatty acids in the corpus striatum of the rat brain. The characteristics of the fatty acids'compositional changes by manganese were a decrease of EPAs and DHAs (n-3 PUFAs), and an increase of AAs (n-6 PUFAs). These changes coupled with the decrease of SOD activity and the increase of MDA, suggest that manganese neurotoxicity is caused by lipid peroxidation mediated with oxygen free radicals, particularly superoxide radicals.

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Original Article

A Study of Relationship between Exposure to Manganese Chloride and Malondialdehyde in Rat Tissues: Chul Jin Moon, Soo Jin Lee, Se Hoon Lee; Korean Journal of Occupational and Environmental Medicine 2000;12(3):338-345. Published online September 30, 2000; DOI: https://doi.org/10.35371/kjoem.2000.12.3.338

Abstract PDF: OBJECTIVES
This research was intended to investigate the relationship between manganese and malodndialdehyde concentration in tissues of rats exposed to maganese chloride.
METHODS
The study groups were 12 manganese treated rats and 9 control rats. Manganese treated rats were given intraperitoneally manganese chloride (Mn, 4 mg/kg) daily for a period of 30 days except Sunday. Control rats were injected 1ml of saline. The plasma manganese concentrations of rats were determined by graphite furnace atomic absorption spectrometry. The tissue manganese concentration was determined by flame atomic absorption spectrometry. Malondialdehyde, the product of lipid peroxidation was determined by ultraviolet-visible spectrophotometry. The plasma malondialdehyde was determined by gas chromatography with mass-detector. Protein concentration was quantified by ultraviolet-visible spectrometry and was used for the compensation of tissue malondialdehyde and manganese concentration.
RESULTS
Manganese concentrations of plasma, brain, liver, and pancreas were very significantly higher in the manganese-treated rats than in the control rats. Malondialdehyde concentration of plasma, brain, and pacrease were significantly higher in the manganese-treated rats than in the control rats. The concentration of malondialdehyde was correlated with manganese levels in plasma, brain and pancreas.
Conclusion
Based on the results obtained as above, it was concluded that the malondialdehyde, product of lipid peroxidation was related to the cell death due to dosing excess manganese.

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Original Article

Assessment of Neurobehavioral Performance among Welders Exposed to Manganese: Nak Jung Sung, Joon Sakong, Jong Hak Chung, Dae Seong Kim, Joong Jung Lee, Jong Tae Park; Korean Journal of Occupational and Environmental Medicine 2000;12(3):327-337. Published online September 30, 2000; DOI: https://doi.org/10.35371/kjoem.2000.12.3.327

Abstract PDF

OBJECTIVES
A cross sectional study was carried out in the welders exposed to manganese and control group. The aim of this study was to assess the adverse effects of manganese on central nervous system of welders.
METHODS
The study group consisted of 49 welders and the reference group, 49 workers matched with welders for age and educational level in automobile manufacturing company. Concentration of manganese in welding hume, in blood, and cumulative exposure index(CEI) were determined for each subject. For each group, computerized neurobehavioral test including Simple Reaction Time, Digit Symbol, Digit Span, and Finger Tapping Speed of Swedish Performance Evaluation System were applied.
RESULTS
Exposure level of manganese in welders were very low(mean CEI 0.069). Welders exposed to manganese had slower response speed, slower motor steadiness, and shorter memory span than control group. But these differences were not statistically significant. The performance of Finger Tapping Speed tended to lower as environmental and biological exposure index got higher. Other neurobehavioral tests were found to have a little association with the exposure indices.
CONCLUSIONS
There was no significant difference of neurobehavioral performance between welders and control group. This study indicates that Finger Tapping Speed measuring motor steadiness might be a one of useful tests for early detection of adverse effects of welding on central nervous system.

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Original Article

Apoptosis Induced by Manganese in Basal Ganglia Primary Neuronal Cell Culture: Morphological Findings: Dong Hoon Shin, Sang Pyo Kim, Young Wook Jung, Jae Hoon Bae, Dae Kyu Song, Won Ki Baek; Korean Journal of Occupational and Environmental Medicine 2000;12(1):41-47. Published online March 31, 2000; DOI: https://doi.org/10.35371/kjoem.2000.12.1.41

Abstract PDF: OBJECTIVES
Manganese is cytotoxic to the central nervous system including basal ganglia. Its toxic mechanism is related to oxidative stress, mediated by toxic free radicals but is specultives. In the present study, we have investigated to manifest apoptosis in manganese-induced cytotoxicity in primary neuronal cell culture of rat basal ganglia.
METHOD
To detect apoptotic neuronal cells were stained by the terminal deoxynu-cleotide(TdT)-mediated dUTP nick end-labelling(TUNEL) method and apoptotic changes in nuclei of neurons were observed by electron microscopy.
RESULTS
We showed that TUNEL immunostain showed brownish signal in the nuclei of apoptotic cells and the proportions of apoptotic cells in Manganese treatment groups were more higher than controls. On transmission electron microscopy, there were chromatine condensation with margination toward nuclear membrane and condensation of cytoplasm in the treated with luM MnC1, for 48 hours in a basal ganglia neurons. Apoptotic bodies were found and consisted of semilunar-like condensed nuclei with relatively intact cytoplasmic organelles.
CONCLUSIONS
Apoptosis appears to be one mechanism in the manganese-induced neuronal cell death. Manganese intoxication is a convenient model for apoptosis study.

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Original Article

Manganese Exposure and its Health Hazards of Welders: Deog Hwan Moon, Byung Chul Son, Dong Mug Kang; Korean Journal of Occupational and Environmental Medicine 1999;11(4):476-491. Published online December 31, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.4.476

Abstract PDF

OBJECTIVES
In order to evaluate the degree of manganese exposure and its health hazards effect on welders in manufacturing industry.
METHODS
The author measured airborne, blood and urine concentrations of manganese and blood chemistry, and also observed clinical symptoms and signs on 60 welders for case an.d 60 non-welders for control working in manufacturing industry by age maching method.
RESULTS
The geometric means of blood and urine concentrations of manganese were 1.13 +/- 1.38 microgram /dI and 2.52 +/- 1.37 microgram /I for Welders group, 1.09 +/- 1.68 microgram /dl and 1.86 +/- 1.34 microgram / I for Non-welders group. Airborne concentration of manganese was 0. 15 +/- 1.66 mg/m3 for exposured group, and the urinary mean concentration of manganese was statistically significant difference between exposured and non-welders group (P < 0.05). Clinical signs in welders group were palmomentle reflex (23.3%), tremor (20.0%) and grabellar sign (5.0%). Symptoms in welders group were fatigue (66.7%), amnesia (66.7%), excessive sweating (51.7%), nervousness (51.7%), general weakness (48. 3%) and arthralgia (46.7%) and so on, and there was statistically significant difference compared to non-welders group (P<0.05). Manganese exposure effects on blood chemistry were not observed. There were statistically significant correlation between manganese concent- ration in blood and urine (r=0. 269), airborne and urine (r=0. 601) and airborne and blood (r=0. 268).
CONCLUSION
The author suggest that further studies are followed to evaluate the health status of welders whose blood and urine manganese concentrations were below normal reference level, and to establish the questionnaire and the diagnostic tools for early detecting the chronic manganese poisioning on welders.

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Kyung Sick Jung, Jong Dae Lee, Yong Bae Kim
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Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature
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Safety and Health at Work.2013; 4(3): 123. CrossRef
Olfactory functions at the intersection between environmental exposure to manganese and Parkinsonism
Silvia Zoni, Giulia Bonetti, Roberto Lucchini
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Exposure-Response Relationship and Risk Assessment for Cognitive Deficits in Early Welding-Induced Manganism
Robert M. Park, Rosemarie M. Bowler, Harry A. Roels
Journal of Occupational & Environmental Medicine.2009; 51(10): 1125. CrossRef
Sequelae of fume exposure in confined space welding: A neurological and neuropsychological case series
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NeuroToxicology.2007; 28(2): 298. CrossRef
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Original Article

Factors Associated with Psychoneurobehavjral Outcomes in Workers Exposed to Manganese: Kyoo Sang Kim, Yangho Kim, Youngwoo Jin, Euna Kim, Jeong Sun Yang, Kwi Ryun Kwon, Jae Woo Kim, Jaehoon Roh, Young Hahn Moon; Korean Journal of Occupational and Environmental Medicine 1999;11(2):213-228. Published online June 30, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.2.213

Abstract PDF

The risk posed to human health by environmental manganese (Mn) exposure is unknown. The purpose of this study is to establish if subclinical effects related to Mn exposure and examine the factors influencing psychoneurobehaviral outcomes of Mn exposed workers. This study involved 121 male workers of welding, alloy furnace, and manufacturing of welding stick. Study investigations include: a questionnaire covering demographic characteristics, job and exposure history and medical symptoms and conditions, monitoring workplace air for personal exposure to respirable and inhalable manganese, analysis of blood and urine samples. psychoneurobehaviral test(neurobehaviral core test battery (NCTB), signal change on magnetic resonance imaging (MRJ) scans, minimental state and neurological examination). The main results of this study were as follows: 1. Preliminary results showed that, with increasing manganese exposure, neurobehaviral performance was poorer and signal change on MRI scans increased. 2. The results of examination revealed significant relations on psychoneurobehaviral out-comes (neurobehaviral performance, signal change on MRI scans, and neurological features). 3. In multiple regression, age and educational status as demographic variables and exposure level were significantly related to 4neurobehaviral test. Also exposure level and serum Mn concentrations were positively relatel to signal change on MRI scans and neurological features affected by Mn on the brain (signal change). 4. Psychoneurobehaviral outcomes from Mn exposure were related to neurobehaviral performance, signal change on MRJ scans, neurological features and profile of mood states (POMS), and influnced positively with age, alcohol and smoking history, and duration of Mn exposure, negatively with educational status. Serum Mn concentrations in combination with brain MRI scans, and perhaps a battery of neurobehaviral tests, appear to be the best way to monitor excessive exposure to Mn. These results are consistent with our knowledge on Mn action on the brain and are similar to the type of neurobehaviral dysfunction. They suggest that there may be age, educational status, and life style (alcohol and drinking history) differences with chronic environmental exposure. These findings suggest further evaluation, particularly on relationships between Mn exposure, aging, and susceptibility factors.

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Associations between Airborne Manganese and Blood Manganese in the Korean General Population according to KNHANES 2008-2009
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Exposure-Response Relationship and Risk Assessment for Cognitive Deficits in Early Welding-Induced Manganism
Robert M. Park, Rosemarie M. Bowler, Harry A. Roels
Journal of Occupational & Environmental Medicine.2009; 51(10): 1125. CrossRef
State-of-the-Science Review: Does Manganese Exposure During Welding Pose a Neurological Risk?
Annette B. Santamaria, Colleen A. Cushing, James M. Antonini, Brent L. Finley, Fionna S. Mowat
Journal of Toxicology and Environmental Health, Part B.2007; 10(6): 417. CrossRef
Issues in neurological risk assessment for occupational exposures: The Bay Bridge welders
Robert M. Park, Rosemarie M. Bowler, Donald E. Eggerth, Emily Diamond, Katie J. Spencer, Donald Smith, Roberto Gwiazda
NeuroToxicology.2006; 27(3): 373. CrossRef
Potential occupational risks for neurodegenerative diseases
Robert M. Park, Paul A. Schulte, Joseph D. Bowman, James T. Walker, Stephen C. Bondy, Michael G. Yost, Jennifer A. Touchstone, Mustafa Dosemeci
American Journal of Industrial Medicine.2005; 48(1): 63. CrossRef

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Original Article

Performance of Neurobehavioral Tests Among Welders Exposed to Manganese: Youngwoo Jin, Yangho Kim, Kyoo Sang Kim, Euna Kim, Young Sook Cho, Yong Chul Shin, Changho Chai, Younghyu Choi, Se Hoon Lee, Young Hahn Moon; Korean Journal of Occupational and Environmental Medicine 1999;11(1):1-12. Published online March 31, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.1.1

Abstract PDF

To study neurobehavioral effects for manganese fume exposure of welders, we administrated questionnaire about subjective symptom, related with manganese exposure. Neurobehavioral Core Test Battery of World Health Qrganization(NCTB) and finger tapping for 98 welders and 29 non-welding workers. We adopted welding duration as a criterion for exposure assessment, because of the lack of the longitudinal valid data and differences in airborne concentrations of manganese in welding types, such as shielded metal arc and CO2 arc welding. Neurologic, musculoskeletal and concentration symptoms were significantly increased by increase of welding duration. Performance of finger tapping preferred hand, Santa Ana dexterity test preferred hand and correct number of pursuit aiming were significantly decreased by increase of welding duration. These results comparable with previous studies that suggest neurobehavioral test, especially motor test, to be an appropriate tool to detect early neurobehavioral abnormalities related with manganeses exposure.

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Thomas Vlasak, Tanja Dujlovic, Alfred Barth
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Derivation of an occupational exposure level for manganese in welding fumes
Lisa A. Bailey, Laura E. Kerper, Julie E. Goodman
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Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature
Robert M. Park
Safety and Health at Work.2013; 4(3): 123. CrossRef
Neuropsychological effects of low-level manganese exposure in welders
Wisanti Laohaudomchok, Xihong Lin, Robert F. Herrick, Shona C. Fang, Jennifer M. Cavallari, Ruth Shrairman, Alexander Landau, David C. Christiani, Marc G. Weisskopf
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Exposure-Response Relationship and Risk Assessment for Cognitive Deficits in Early Welding-Induced Manganism
Robert M. Park, Rosemarie M. Bowler, Harry A. Roels
Journal of Occupational & Environmental Medicine.2009; 51(10): 1125. CrossRef
State-of-the-Science Review: Does Manganese Exposure During Welding Pose a Neurological Risk?
Annette B. Santamaria, Colleen A. Cushing, James M. Antonini, Brent L. Finley, Fionna S. Mowat
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High signal intensity on magnetic resonance imaging as a predictor of neurobehavioral performance of workers exposed to manganese
Yong Chul Shin, Euna Kim, Hae-Kwan Cheong, Sungil Cho, Joon Sakong, Kyoo Sang Kim, Jung Sun Yang, Young-Woo Jin, Seong-Kyu Kang, Yangho Kim
NeuroToxicology.2007; 28(2): 257. CrossRef
Sequelae of fume exposure in confined space welding: A neurological and neuropsychological case series
Rosemarie M. Bowler, Sanae Nakagawa, Marija Drezgic, Harry A. Roels, Robert M. Park, Emily Diamond, Donna Mergler, Maryse Bouchard, Russell P. Bowler, William Koller
NeuroToxicology.2007; 28(2): 298. CrossRef
Issues in neurological risk assessment for occupational exposures: The Bay Bridge welders
Robert M. Park, Rosemarie M. Bowler, Donald E. Eggerth, Emily Diamond, Katie J. Spencer, Donald Smith, Roberto Gwiazda
NeuroToxicology.2006; 27(3): 373. CrossRef

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Original Article

Manganese Concentration in Blood and Urine of Manganese Exposed Welding Workers: Ho Chun Choi, Kangyoon Kim, Sun Hee An, Dae Woo Hyun; Korean Journal of Occupational and Environmental Medicine 1998;10(4):534-547. Published online December 31, 1998; DOI: https://doi.org/10.35371/kjoem.1998.10.4.534

Abstract PDF

Blood and urine samples were taken from 447 welders exposed to manganese containing welding fumes and 127 office workers not exposed to welding fumes as a control. The air samples were analyzed by flame atomic absorption spectrophotometer (Varian 30A, Australia), and blood and urine samples were analyzed by flameless atomic absorption spectrophotometer(Z-8100, Hibachi, Japan). Data were evaluated in accordance with type of industry, smoking habits, and work duration. The results obtained were as follows: 1. The limit of detection(LOD) levels of manganese in blood and urine were 0.11 microgram/100ml of and 0.14 microgram/l, respectively. Our results of manganese concentration were shown within +/-2 standard deviation which was the upper and lower warning limit (UWL or LWL) on quality control chart. 2. The airborne concentrations of manganese in welding workplaces were 0.067 mg/m3 showing differences by type of industry ; 0.017 mg/m3 in automobile assembly and manufacturing industries, 0.084 mg/m3 in steel heavy industries and 0.180 mg/m3 in shipyards. 3. The blood manganese concentrations showed differences by type of industry showing the highest values of 1.70 microgram/100m1 in shipyards, 1.24 microgram/100m1 in automobile assembly and manufacturing industries and 1.11 microgram/100ml in steel heavy industries. Urinary manganese concentration corrected by urinary creatinine concentrations was 0.34 microgram/g creatinine in automobile assembly and manufacturing industries, 0.43 microgram/g creatinine in steel heavy industries and 0.48 microgram/g creatinine in shipyards. There were no difference urinary manganese concentrations by type of industry. 4. The overall blood manganese concentration was 1.26 microgram/100ml, and urinary manganese concentration was 0.35 microgram/g creatinine in welders. In contrast to these values, blood and urinary manganese concentrations were lower in control group showing 0.73 microgram/100m1, and 0.28 microgram/g creatinine, respectively. 5. Smoking habits did not seem to affect on blood and urinary manganese concentrations both in welders and office workers. 6. Blood manganese concentrations were significantly higher in welder who had worked longer than 10 years than in welder who had worked less than 10 years. 7. The blood manganese concentrations were significantly correlated to airborne manganese concentrations(r=0.318, n=64), work duration(r=0.425, n=538), and cumulative exposure indices(CEI) (r=0.354, n=64).

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A Study on the Total, Particle Size-Selective Mass Concentration of Airborne Manganese, and Blood Manganese Concentration of Welders in a Shipbuilding Yard
Jong Su Park, Pan Gyi Kim, Jee Yeon Jeong
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(4): 472. CrossRef
Associations between Airborne Manganese and Blood Manganese in the Korean General Population according to KNHANES 2008-2009
Kyung Sick Jung, Jong Dae Lee, Yong Bae Kim
Journal of Environmental Science International.2013; 22(12): 1589. CrossRef

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Original Article

The Significance of Increased Signal Intensity in MR Imaging among Male Welders: Dong Mug Kang, Ho Chu Park, Hye Sook Son, Jun Han Park, Young Joon Lee; Korean Journal of Occupational and Environmental Medicine 1998;10(1):41-52. Published online February 28, 1998; DOI: https://doi.org/10.35371/kjoem.1998.10.1.41

Abstract PDF

A purpose of present study is to provide basic information evaluating the utility of Magnetic Resonance imaging as a biological marker estimating manganese effects to central nervous system among welders, which is conducted by comparing urinary and blood manganese concentrations and signal intensities of brain MR images between exposed group and non-exposed group, evaluating the objectivity of subjective grading estimated by correlations between Pallidal signal intensity index (P. I) and subjective grades among exposed group, and comparing the difference of signal intensities according to presence of neurologic symptoms, signs and exposure variables among the exposed group. The exposed group is composed of 11 welders complaining severe symptoms or showing neurological signs, and the non-exposed group is composed of 5 patients who admitted a hospital. Urinary manganese concentrations and signal intensities in T1-weighted MR images among exposed group were higher than those of the non-exposed group significantly, which exhibits that increased signal intensities in T1-weighted MR image represent the effect of manganese exposure. P. Is among the exposed group revealed relatively high correlations with subjective grades ( gamma =0.63, p=0.037) , which suggests the objectivity of subjective grade. Signal intensity in globus pallidus was a suitable single variable representing the effect of manganese accumulation in C.N.S system appropriately, which was verified as follows ; Increased signal intensities among the exposed group had the highest frequency and intensity in the globus pallidus, and the P.I. had a relatively high correlation coefficient ( gamma 0.62, p=0.044) with total score of subjective grades. Signal intensity with subjective grading in globus pallidus represented very high correlation gamma =0.97, p=0.00) with total score of subjective grades, and had a similar correlation coefficient with many variables. It is hard to argue that signal intensities are markers representing pathologic change in C.N.S system or can be used as a diagnostic tool for manganese intoxication, because signal intensities had no difference between the exposed group and the non-exposed group according to presence of neurological signs.

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Occupational Neurological Disorders in Korea
Eun-A Kim, Seong-Kyu Kang
Journal of Korean Medical Science.2010; 25(Suppl): S26. CrossRef

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Original Article

A Study on the Manganese Exposure and Health Hazards Among Manganese Manufacturing Workers: Ji Yong Kim, Hyun Sul Lim, Hae Kwan Cheong, Nam Won Paik; Korean Journal of Occupational and Environmental Medicine 1994;6(1):98-112. Published online February 28, 1994; DOI: https://doi.org/10.35371/kjoem.1994.6.1.98

Abstract PDF

To estimate the manganese (Mn, below) exposure of workers in the ferromanganese manufacture factory and to evaluate its health effects, airborne, blood and urine Mn concentration measurements, questionnaire and other neurologic examinations were performed on 80 Mn-handing productive male workers (exposed group), 47 non-Mn-handling productive male workers (internal control group) and 144 productive male workers in other factory (external control group). The results obtained were as follows; The highest airborne Mn fume concentration among the work process was found at charging (0.42 mg/m3), and ferromanganese crushing process (1.14 mg/m3) was the highest in Mn dust. However all of them were below threshold limit value. Mean Mn concentrations in blood and urine of crushing workers were higher than those of other part workers. Among all of them, workers whose urine Mn concentration were exceed normal reference level (10 microgram/l) were 31 (18.5%). There was statistically significant correlation between airborne and urine Mn concentration (r=0.60), and so between airborne and blood Mn concentration (r=0.49), while there was no statistically significant correlation between blood and urine Mn concentration. Mean Mn concentration in airborne (0.60 mg/m3), urine (6.92 microgram/l) and blood (3.16 microgram/dl) in exposed group were significantly higher than those of control groups (p<0.01). Clinical symptoms such as excessive sweating, hypoesthesia, libido change, anosmia, decreased visual acuity and difficulty in writing showed higher positive rate in exposed group. Positive rate of clinical signs such as eye blinking and masked face in exposed group was higher than external control group. However clinical and laboratory findings such as blood pressure, blood chemistry, grip strength in exposed group were not statistically different from those of control groups. The results suggested that further studies were followed to evaluate the workers whose blood Mn concentration were below normal reference level but urine Mn concentrations above normal reference level, and to establish the questionnaire and the diagnostic tools to detect the Mn poisoning workers early.

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A Study on the Total, Particle Size-Selective Mass Concentration of Airborne Manganese, and Blood Manganese Concentration of Welders in a Shipbuilding Yard
Jong Su Park, Pan Gyi Kim, Jee Yeon Jeong
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(4): 472. CrossRef
Neurobehavioral Deficits and Parkinsonism in Occupations with Manganese Exposure: A Review of Methodological Issues in the Epidemiological Literature
Robert M. Park
Safety and Health at Work.2013; 4(3): 123. CrossRef
Exposure-Response Relationship and Risk Assessment for Cognitive Deficits in Early Welding-Induced Manganism
Robert M. Park, Rosemarie M. Bowler, Harry A. Roels
Journal of Occupational & Environmental Medicine.2009; 51(10): 1125. CrossRef
Sequelae of fume exposure in confined space welding: A neurological and neuropsychological case series
Rosemarie M. Bowler, Sanae Nakagawa, Marija Drezgic, Harry A. Roels, Robert M. Park, Emily Diamond, Donna Mergler, Maryse Bouchard, Russell P. Bowler, William Koller
NeuroToxicology.2007; 28(2): 298. CrossRef
State-of-the-Science Review: Does Manganese Exposure During Welding Pose a Neurological Risk?
Annette B. Santamaria, Colleen A. Cushing, James M. Antonini, Brent L. Finley, Fionna S. Mowat
Journal of Toxicology and Environmental Health, Part B.2007; 10(6): 417. CrossRef
Issues in neurological risk assessment for occupational exposures: The Bay Bridge welders
Robert M. Park, Rosemarie M. Bowler, Donald E. Eggerth, Emily Diamond, Katie J. Spencer, Donald Smith, Roberto Gwiazda
NeuroToxicology.2006; 27(3): 373. CrossRef

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