Table 2.
Epidemiologic studies investigating occupational exposure to manganese
| Author | Location | Study Design | Participants Age at Motor Assessment | Source of Mn Exposure | Biomarker/Environmental Measures | Covariates | Outcome Measure | Results |
|---|---|---|---|---|---|---|---|---|
| Bouchard et al,58 2007 | Canada | Prospective cohort | Exposed n = 69 Referents n = 68 Mean age 58.1 y |
Mn ferroalloy plant | Dust (mg Mn/m3 years) n = 69 | Age, education, alcohol, and smoking | Motor Scale of the Luria-Nebraska, finger tapping, Dynamometer, 9-hole Hand Steadiness Test | Exposed had poorer scores compared with referents both in the initial and follow-up examinations for the Luria-Nebraska test. Increasing levels of CEI were significantly associated with poorer scores on the Luria Motor Scale and the Hand Steadiness Test |
| Shin et al, 200726 | Korea | Cross-sectional study | 350 workers Age not specified |
Manufacturing factories | Air (mg/m3) n = 121 Blood (μg/dL) n = 121 Duration of work (years) n = 121 CEV n = 121 PI n = 111 |
Age, alanine aminotransferase, and educational level | WHO-NCTB and computerized finger tapping | The proportion of workers with increased signals increased with all the Mn exposure variables. The PI was significantly associated with a correct score of pursuit aiming II tests and finger tapping of the dominant hand |
| Cowan et al,27 2009 | Guizhou, China | Cross sectional study | Smelters n = 26 18–56 y |
Ferroalloy plant | Air (mg/m3) Blood MIR n = 136 Plasma MIR n = 143 Mn concentration in erythrocytes n = 144 |
Age, years of education, sex, income, and years of employment | Groove-type steadiness tester, 9-hole tests, and Purdue Pegboard Coordination Test | Plasma MIR was significantly correlated with pegboard scores. Age-related decline in fine-movement coordination was observed among all study participants regardless of Mn exposure |
| Chang et al,24 2009 | Korea | Cross-sectional study | Welders n = 43 Controls n = 29 40–57 y |
Steel block factory | Air (mg/m3) Blood (μg/dL) n = 72 PI n = 73 |
Age, educational level, alcohol consumption, and smoking | Grooved pegboard, finger-tapping test, CATSYS, hand pronation/supination test | Grooved-pegboard and finger-tapping tests showed significant differences between the 2 groups. Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) |
| Chang et al,32 2010 | Korea | Cross-sectional study | Welders n = 42 Controls n = 26 40–57 y |
Steel block factory | Air (mg/m3) n = 73 Blood (μg/dL) n = 73 Pallidal index n = 73 |
Age, educational level, alcohol consumption, and smoking | Grooved pegboard, finger-tapping test, CATSYS, hand pronation/supination test | Hand pronation/supination and finger-tapping tests were significantly lower among the welders than among the controls |
| Bowler et al,60 2011 | California | Prospective cohort | Welders n = 26 32–65 y |
Mn-containing welding fumes | Blood (μg/L) n = 24 | Age, ethnicity, duration of welding, type of welding, blood Pb, and smoking | UPDRS3 and the CATSYS Tremor system | Rigidity, dominant postural hand tremor, and body sway increased significantly at follow-up |
| Sen et al,88 2011 | United States | Cross-sectional study | Welders n = 7 Controls n = 7 Mean age 48 y |
Not specified | CEI (Mg Mn/m3) n=7 | Age | Grooved pegboard; MRI | The welders scored worse than the controls on the grooved-pegboard test for both dominant and nondominant hand |
| Laohaudomchok et al,30 2011 | United States | Cross-sectional study | Welders n = 46 Mean age 37.4 y |
Welding school | Air (μg/m3) n = 46 |
Age, race, education, income, dietary Mn, and BMI | Neuroskill device and finger tapping | Mn exposure over a work shift was significantly associated with worse stability of handwriting |
| Kim et al,33 2011 | Korea | Cross-sectional study | Welders n = 30 Controls n = 19 40–58 y |
Factory | Air (μg/m3) n = 100 Blood (μg/L) n = 191 |
Age, educational level, smoking status, and alcohol consumption status | Finger-tapping tests and the grooved-pegboard test | Fractional anisotropy and radial diffusivity were significantly associated with grooved-pegboard (dominant and nondominant hand) and finger-tapping (dominant and nondominant hand) test outcomes |
| Racette et al,56 2012 | United States | Prospective cohort | 389 welders 40–58 y |
Factories and shipyards | CEI (Mg Mn/m3) n = 886 | Age at baseline, sex, race, tobacco smoking, alcohol consumption, and occupational pesticide exposure | UPDRS3 | Exposure was most strongly associated with progression of upper limb bradykinesia, upper and lower limb rigidity |
| Wastensson et al,61 2012 | Sweden | Cross-sectional study | Welders n = 17 Referents n = 21 Mean age 69 y |
Shipyard | CEI (mA/m2) n = 17 | Age and smoking habits | The Kløve-Matthews static steadiness test, CATSYS, finger-tapping test, grooved-pegboard test, eurythmokinesimeter, diadochokinesimeter, and Jamar dynamometer | Former welders performed less well than referents in the grooved-pegboard test, and poorer performance was associated with CEI |
| Chang et al,75 2013 | Korea | Cross-sectional study | Welders n = 40 Controls n = 26 40–58 y |
Steel block factory | Air (mg/m3) Blood (μg/dL) n = 66 |
Age, educational level, alcohol consumption, and smoking | MRI, Grooved-pegboard, and finger-tapping test | Significant brain volume reductions were found in welders compared with controls, and these volume reductions are associated with motor deficits |
| Ellingsen et al,28 2014 | Russia | Cross-sectional study | Welders n = 137 Referents n = 137 19–70 y |
Shipyard | Air (μg/m3) n = 130 Blood (μg/L) n = 123 Urine (μg/g) n = 126 |
Age, tobacco smoking, the concentration of carbohydrate-deficient transferrin in serum, self-reported mild head injury, shift work, duration of education, coffee consumption | Finger-tapping, foot-tapping, grooved-pegboard, dynamometer, CATSYS 2000, Kløve-Matthews Static Steadiness and Hand Pronation-Supination tests | Welders had poorer performance on motor tests compared with nonwelder referents |
| Park et al,59 2014 | Quebec, Canada | Cross-sectional study | Referents n = 67 Alloy workers n = 68 Mean age 43.9 y |
Silico-Mn and ferro-Mn production plant | CE (mg/m3) n = 68 | Age and educational level | Luria-Nebraska Neuropsychological Battery–Motor Scale and Finger Tapping | The duration of Mn exposure and Mn as small respirable particulates is strongly associated with the Luria-Nebraska Motor Scale |
| Long et al,29 2014 | Guangxi, China | Cross-sectional study | Smelters n = 9 Controls n = 23 Mean age 39.3 y |
Mn-iron alloy factory | Air (mg/m3) n=9 Blood (mg/L) n = 32 Urine (μg/L) n = 32 |
Age | Purdue pegboard motor testing | Increase in GABA level was significantly associated with the duration of exposure and significant inverse associations between GABA levels and all Purdue Pegboard Test scores in the smelter workers |
| Baker et al,71 2015 | Washington | Prospective cohort | Welders n = 56 Mean age 28 y |
Welding | Air (μg/m3) n = 56 TI-weighted indices n = 17 |
Smoking status, alcohol drinker, prior self-reported loss of consciousness, self-reported respirator use, and age at baseline | Grooved pegboard (Lafayette Instrument Evaluation, West Lafayette, IN), UPDRS3 | There were no associations between cumulative exposure and UPDRS3 score or grooved-pegboard time |
| Lewis et al,69 2016 | Pennsylvania | Cross-sectional study | Welders n = 20 Controls n = 13 Mean age 47.1 y |
Not specified | hW (hours) n = 20 yW (years) n = 20 |
Age, education level, BMI, and respirator use | Maximal voluntary contraction tasks, single-finger ramp tasks, quick force pulse production tasks., UPDRS, and the grooved-pegboard test | There also were no significant differences between welders and controls on the grooved-pegboard test |
| Seo et al,73 2016 | Korea | Cross-sectional study | Welders n = 53 Controls n = 44 40+ y |
Factories for mild steel blocks and shipbuilding | Air (mg/m3) n = 53 Blood (μg/dL) n = 97 |
Age, education level, tobacco use, alcohol consumption, use of medication, medical history, subjective symptoms, job type (type of welding and duration), work history | fMRI, Wisconsin Card-sorting Task, Word-Color Test, Computerized Neuropsychological Test | Blood Mn level was significantly higher in welders than in controls. Reaction time for given tasks were not significantly different between groups even though welders took longer. Based on fMRI images, no specific regions had significant activity in welders while WCST was being completed |
| Al-Lozi et al,57 2017 | United States | Cross-sectional study | Welders n = 82 Nonwelders n = 13 23–66 y |
Welding | Exposure welding metrics (duration, intensity and total exposure) | Work history, cumulative Mn exposure, age, sex, race, ethnicity, medical history, history of head injury, previous exposures, alcohol/tobacco use | Assess cognitive control in response inhibition, working memory, fluency, verbal fluency, letter-number sequencing, Two Black Letter Task, Go-N-Go, Simon Task, Cognitive Control Summary was scored for those completing all 5 tasks, WAIS3- verbal/matrix reasoning | Poorer performance in cognitive control tasks in relation to welding fume exposure. Welders had lower IQ and cognitive control scores |
| Zhang et al,35 2017 | Qingdao City, China | Cross-sectional study | n = 505 19–54 y |
Welding | Work history | Smoking habits, years of work, education level, age | Questionnaires assessing symptoms | Correlation between the highest level of symptom reports with highest level of air Mn measurements. Those with >15 y of welding reported high levels of tremor and motor disabilities |
| Bowler et al,23 2018 | United States | Cross-sectional study | Welders n = 26 Controls n = 17 ≥18 y |
Welding for semitruck manufacture | Air (mg/m3) n = 43 MRI n = 43 |
Age, education, ethnicity, alcohol consumption, smoking habits | Rey-O Copy Trial, Trials B Test, Trails A, Digit Symbol Coding, WAIS3, WHO-AVLT, verbal fluency | Welders scored lower than controls in verbal fluency, Parallel Lines Test, and Digit Symbol Coding. Welders had shorter T1 relaxation times |
| Lee et al,36 2018 | Pennsylvania | Cross-sectional study | Welders n = 43 Controls n = 32 Age not stated |
Welding | Blood (ng/mL) n = 75 | Recent hours welding, lifetime exposure, cumulative exposure inhaled over lifetime | Grooved-pegboard test, UPDRS3, single-finger/multifinger pressing task, MRI | Results of Phonemic Fluency Test suggest that processes associated with phonemic fluency are among some of the earliest changes in welders with low Mn exposure |
| Ma et al,31 2018 | United States | Cross-sectional study | Welders n = 39 Controls n = 22 Mean age 40 y |
Mn fumes | Air (mg/m3) n = 39 | Age | UPDRS3 | High exposure to Mn showed a significant increase of thalamic GABA levels, as well as significantly worse performance in general motor function |
| Wells et al,48 2018 | United States | Cross-sectional study | Workers n = 7 Comparison n = 12 18–62 y |
Trailer manufacturer | Bone Mn (μg/g) n = 19 | Age and occupation | Purdue Pegboard Test | High MnBn was significantly associated with lower manual dexterity based on the Purdue pegboard assembly task |
| Criswell et al,65 2019 | Midwest United States | Cross-sectional study | Mn-exposed welders n = 27 Other Mn-exposed workers n = 12 Nonexposed n = 29 22–69 y |
Welding worksites | CEI n = 68 PI n = 68 |
Sex; age; imaging scan date; current consumption of cigarettes, caffeine or alcohol | UPDRS3 | Cumulative Mn exposure is associated with increased PI. PI was associated with clinical parkinsonism |
| Palzes et al,46 2019 | Zarcero County, Costa Rica | Cross-sectional study | Organic farmers n = 26 Conventional farmers n = 22 18+ y |
Farmers from organic and conventional farms | Hair (μg/g) n = 33 Toenails (μg/g) n = 40 |
Sociodemographic characteristics, work history, medical history, computer literacy, age | Letter retrieving/working memory task, fNIR | Brain activity decreased with every 2-fold increase in nail and hair Mn concentration |
| Rolle-McFarland et al,45 2019 | Zunyi, China | Cross-sectional study | Ferroalloy smelters n = 30 Manufacturing workers n = 30 ≥18 y |
Equipment manufacturing and installation company (control) and ferroalloy smelting facility | Bone (μg/g) n = 60 Fingernail (μg/g) n = 55 Blood (μg/L) n = 60 |
Age, education, drinking status, smoking status | Animal naming, fruit naming, WHO/UCLA Verbal Learning Test (AVLT), UPenn Smell Identification Test | MnBn and MnFn are associated with decreased performance in cognitive function but not smell MnB had no association with cognitive function |
Abbreviations: AVLT, auditory verbal learning test; BMI, body mass index; CEI, Cumulative Exposure Index; CEV, cumulative exposure variable; CATSYS, Coordination Ability Test System; GABA, gamma-aminobutyric acid; Ferro-Mn, ferromanganese; fMRI, functional MRI; fNIR, functional near infrared; IQ, intelligence quotient; hW, hours spent welding in the 90 day period preceding MRI; MnBn, Bone Mn; MnB, Blood Mn; MnFn, Fingernail Mn; NCTB, Neurobehavioral Core Test Battery; PI, pallidal index; UCLA, University of California, Los Angeles; UPDRS, Unified Parkinson Disease Rating Scale; UPenn, University of Pennsylvania; WAIS, Wechsler Adult Intelligence Scale; WHO, World Health Organization; yW, cumulative lifetime years welding.