ORIGINAL ARTICLE

Neuromotor function in ship welders after cessationof manganese exposure

Gunilla Wastensson • Gerd Sallsten •

Rita Bast-Pettersen • Lars Barregard

Received: 14 May 2011 / Accepted: 11 October 2011 / Published online: 29 October 2011

� Springer-Verlag 2011

Abstract

Purpose The aim of the present study was to investigate

whether previous long-term exposure to manganese (Mn)

via inhalation of welding fumes can cause persistent

impairment in neuromotor function even long after cessa-

tion of exposure.

Methods Quantitative tests of tremor, motor speed,

manual dexterity, diadochokinesis, eye-hand coordination

and postural stability were administered to 17 retired ship

welders (mean age 69 years), with mean exposure time

28 years. The welders’ exposure had ceased on average

18 years before the study. A cumulative exposure index

(CEI) was calculated for each of the former welders. The

welders were compared with 21 referents from the same

shipyards (mean age was 66 years).

Results Former welders performed less well than referents

in the grooved pegboard test, and poorer performance was

associated with CEI. The performance in most of the other

neurobehavioral tests was similar between groups, but the

welders tended to perform slightly better than the referents in

tests demanding hand steadiness. The latter finding may be

due to a training effect from their former working tasks or

selection bias into or out of this occupation.

Conclusions In the present study of welders with previ-

ous welding fume exposure, former welders and referents

performed similarly in most of the neurobehavioral tests.

Previous adverse effects on the neuromotor system might

have ceased, and decreased neuromotor function due to

normal aging processes in both groups might have dis-

guised any slight effect of previous Mn exposure. The

poorer performance in the grooved pegboard test among

welders may indicate an adverse effect on motor function

of long-term exposure to Mn, but this finding has to be

confirmed by other studies.

Keywords Manganese � Welding � Previous exposure �Neuromotor function � Tremor � Neurobehavioral methods

Introduction

Manganese (Mn) is an essential trace element for humans,

required for several functions such as energy metabolism,

nervous system function, and protection from damage due

to free radicals. It occurs naturally in rocks, soil, and water,

but the main source of exposure in the general population is

dietary (Santamaria and Sulsky 2010; Saric and Lucchini

2007). Occupational exposure to Mn occurs mostly via

inhalation of Mn fumes or Mn-containing dust (Saric and

Lucchini 2007). With long-term exposure, Mn accumulates

in the brain, predominantly in the globus pallidus and

midbrain (Kim et al. 1999). Long-term exposure to high

levels of airborne Mn ([1 mg/m3) may cause manganism

(Santamaria and Sulsky 2010), a rare and debilitating

neurological disease. The clinical features of manganism

include psychiatric disturbances, and motor function

impairments similar to those seen in Parkinson’s disease,

such as bradykinesia and rigidity (Calne et al. 1994).

Manganism and Parkinson’s disease are, however, two

separate diseases; neuropathological studies have shown

G. Wastensson (&) � G. Sallsten � L. Barregard

Department of Occupational and Environmental Medicine,

Sahlgrenska University Hospital and Academy,

University of Gothenburg, P.O. Box 414,

405 30 Gothenburg, Sweden

e-mail: gunilla.wastensson@amm.gu.se

R. Bast-Pettersen

National Institute of Occupational Health,

P.O. Box 8149 Dep, 0033 Oslo, Norway

123

Int Arch Occup Environ Health (2012) 85:703–713

DOI 10.1007/s00420-011-0716-6

selective damage to the globus pallidus in manganism, but

not to the substantia nigra pars compacta, in contrast to PD

(Perl and Olanow 2007). Typical features in manganism

are gait disturbances, such as the characteristic ‘‘cock

walk’’, and a tendency to fall backwards. Potentially

adverse effects on the central nervous system (CNS), such

as mood changes and impairment in neuromotor function

and cognition, have been described even at lower exposure

levels (Santamaria et al. 2007; Saric and Lucchini 2007).

High signal intensity, mainly in the globus pallidus area, in

T1-weighted images obtained by magnetic resonance

imaging (MRI) is a biomarker of Mn exposure (Dietz et al.

2001; Kim 2006; Zheng et al. 2011), but is not necessarily

associated with manganism or other neuropathological

changes in the brain (Kim 2006).

Numerous studies of workers exposed to Mn have

revealed poorer performance and/or associations between

performance and exposure in neuromotor tests evaluating

motor speed, eye-hand coordination, manual dexterity, and

rapid alternating movements (Bast-Pettersen et al. 2004;

Beuter et al. 1994; Bouchard et al. 2007; Bowler et al.

2003, 2006, 2007; Chang et al. 2009; Chia et al. 1993;

Ellingsen et al. 2008; Hochberg et al. 1996; Hua and Huang

1991; Iregren 1990; Lucchini et al. 1995, 1997, 1999;

Mergler et al. 1994; Roels et al. 1987, 1992, 1999; Sjogren

et al. 1996; Wennberg et al. 1991). Impairment in hand

steadiness and alterations in tremor parameters are also

common findings (Bast-Pettersen et al. 2004; Bowler et al.

2007; Chang et al. 2009; Crump and Rousseau 1999;

Hochberg et al. 1996; Lucchini et al. 1999; Mergler et al.

1994; Roels et al. 1987, 1992, 1999). However, some

studies are essentially negative (Gibbs et al. 1999; Myers

et al. 2003a, b). It is still unclear whether some of these

effects may persist even long after cessation of exposure

(Beuter et al. 1994; Bouchard et al. 2007; Hochberg et al.

1996; Roels et al. 1999).

Depending on the type of metal being welded, the

majority of welders are exposed to Mn during the welding

process, and this is reflected by an increased MRI signal

intensity in the globus pallidus, which is present in about

75% of asymptomatic welders (Kim et al. 1999). Subtle

effects on the CNS have been reported at 0.1–0.3 mg/m3,

an exposure level which is common in welding, but rela-

tively few studies have been performed among welders

(Bowler et al. 2003, 2006, 2007; Chang et al. 2009;

Ellingsen et al. 2008; Sjogren et al. 1996). The neurobe-

havioral effects reported in welders with current Mn

exposure include alterations in tremor parameters (Bowler

et al. 2007; Chang et al. 2009) and reduced performance in

tests of manual dexterity, motor speed, and coordination

(Bowler et al. 2003, 2007; Chang et al. 2009; Ellingsen

et al. 2008; Sjogren et al. 1996). While most studies have

focused on workers with ongoing exposure, to our

knowledge there are only two existing studies of welders

with previous Mn exposure, both reporting impairment

mainly in motor speed and manual dexterity (Bowler et al.

2006; Ellingsen et al. 2008). Both studies examined

workers a relatively short time (a few years) after cessation

of exposure. The question remains of whether a slight

negative effect on the CNS due to manganese exposure will

persist many years after cessation of exposure. Another

question is what kind of long-term neurobehavioral effects

can be expected, whether these may be impaired motor

speed, impaired manual dexterity, or tremor.

Traditionally, signs of neurological abnormalities are

evaluated with qualitative methods such as clinical rating

scales of tremor severity. However, these clinical tests may

be insufficiently sensitive to detect subclinical changes in

neuromotor function (Notermans et al. 1994). There are

several test batteries available for quantitative assessment

of tremor, motor speed, fine manual dexterity, postural

stability, and eye-hand coordination; these tests are known

to detect early signs of impairment in neuromotor function

(Meyer-Baron et al. 2009).

The aim of this study was to clarify whether previous

Mn exposure may cause persistent impairment in neuro-

motor function even long after cessation of exposure.

Methods

Subjects

The subjects were drawn from an original cohort of ship-

yard workers. We obtained lists of all former full-time ship

welders aged 75 or under (n = 47). The reference popu-

lation consisted of all filers and electricians in the same age

category (n = 51). All subjects were men. Seven of the

welders were deceased, nine had emigrated or moved to

other parts of Sweden, and two were not found in the

national registry, leaving 29 potential participants. In the

referent group, nine were deceased, four had emigrated or

moved to other parts of Sweden, and one was not found in

the national population registries. Thus, 66 subjects (29

former welders and 37 referents) were contacted by tele-

phone and invited to participate in the study. Three of the

former ship welders were not included because of current

exposure to welding fumes. Of the remaining 63 subjects

(26 ? 37), 19 former welders (73%) and 26 referents

(70%) agreed to participate in the study. Exclusion criteria

were known or suspected alcohol abuse (alcohol con-

sumption [300 g/week), diabetes mellitus, and other dis-

eases that might affect neuromotor function but are not

known to be related to Mn exposure. Exclusions were

conducted by one of the authors (LB), who was blinded

with respect to the subject’s exposure status and test

704 Int Arch Occup Environ Health (2012) 85:703–713

123

performance. Among former welders, one was excluded

due to alcohol abuse and one due to diabetes mellitus. Five

referents were excluded due to diabetes mellitus (2),

alcohol abuse and diabetes mellitus (1), stroke (1), or hy-

pothyreosis (1). The background characteristics of the

remaining 17 former welders and 21 referents are given in

Table 1.

Exposure assessment

Each subject completed a questionnaire about work in

different occupations over the years. All of the welders had

worked in the shipyard industry for the majority of their

working lives. The total number of years exposed to

welding fumes ranged from 14 to 45 years (Table 1). Five

former welders had started welding work around 1950,

nine in the 1960s, and the remaining three at the beginning

of the 1970s. Most of them had stopped working as welders

in the 1980s or at the beginning of the 1990s. On average,

the time since cessation of welding was 18 years (range

3–27). No airborne measurement data were available, since

the industry closed down at the beginning of the 1990s. In

the 1980s, investigations of lung dust loads of magnetite

(Fe3O4) were performed with the non-invasive magneto-

pneumography technique among welders in this industry

(Hogstedt et al. 1995). A relatively high correlation

(r = 0.83) has been shown between airborne manganese

and iron exposure among welders (Flynn and Susi 2010),

and iron load in the lungs might therefore reflect manga-

nese exposure. For all welders in this investigation, we had

two values of the magnetic moment (mA m2) from the

years 1980 and 1983, respectively. To calculate a cumu-

lative exposure index (CEI) for each individual, we used

the average value of the magnetic moment and multiplied it

by the exposure time up to 1984. Since we estimated that

the exposure would have decreased over time, we used half

of this average for the years after 1984. The CEI ranged

from 135 to 10,470 mA m2 9 years (median: 615) and

was used to classify the former welders into a high-expo-

sure group (n = 10, median CEI 2015, CEI range

476–10470) and a low-exposure group (n = 7, median CEI

195, CEI range 135–235). The exposure assessment,

including the exposure classification, was performed by

one of the authors (GS), who was blinded with respect to

the subject’s test performance. The welder with the lowest

CEI had an average magnetic moment of 7.3 mA m2. The

same dataset contained measurements for 14 electricians,

none of whom had an average magnetic moment above this

figure, as well as measurements for 17 filers, including 4

(24%) with a value slightly above 7 mA m2 (the highest

was 12 mA m2). A significant correlation was found

between years of exposure and CEI (rs = 0.79).

Questionnaires and clinical examinations

All subjects were examined at the Department of Occu-

pational and Environmental Medicine, Sahlgrenska Uni-

versity Hospital, after having given written informed

consent. First, each subject was asked to complete a

questionnaire about previous and current diseases, medi-

cation, and self-reported current alcohol and tobacco con-

sumption. Additional information concerning the subject’s

state of health was collected at a brief interview. Blood

samples were collected by venous puncture and assayed for

hemoglobin, hematocrit and red blood cell indices,

C-reactive protein, liver function tests (aspartate amino-

transferase, alanine aminotransferase, gamma-glutamyl

transpeptidase), methylmalonate, glucose, and thyroid

function tests (TSH and free T4). The clinical examination

included tests of sensory function, deep tendon reflexes,

gait, motor strength and tone, tremor (including the finger-

nose test), diadochokinesis, and the knee–heel test and

Table 1 Background and exposure characteristics of 17 formerly Mn-exposed welders and 21 referents

Welders (n = 17) Referents (n = 21)

Mean (min, max) Median (Q1, Q3) Mean (min, max) Median (Q1, Q3)

Age (years) 68.9 (59, 76) 71.0 (63, 74) 66.1 (59, 75) 64 (62, 71)

Body mass index 26.1 (20.1, 32.4) 25.2 (24.5, 27.4) 26.5 (20.7, 32.4) 25.9 (25.0, 28.0)

Current smokers, % (n) 12 (2) – 10 (2) –

Current nicotine users, % (n) 18 (3) – 19 (4) –

Self-reported alcohol consumption, g/week 56.4 (0, 268) 41 (13, 59) 67.8 (0, 165) 67 (20, 99)

Self-reported use of medication, % (n) 41 (7) – 38 (8) –

Self-reported hypertension, % (n) 29 (5) – 29 (6) –

Years of exposure 28.1 (14, 45) 26 (22, 36) – –

Years since cessation of welding 18 (3, 27) 18 (14, 23) – –

CEI (cumulative exposure index)a 1,695 (135, 10,470) 615 (201, 2,152) – –

a The cumulative exposure index (mA m2 9 years) is based on estimated lung dust load of magnetite; see the ‘‘Methods’’ section

Int Arch Occup Environ Health (2012) 85:703–713 705

123

Romberg’s test. All clinical tests were assessed as normal

or abnormal, except for tremors (rest, postural, and kinetic

tremors), which were graded as absent, slight (barely

noticeable), or moderate (obvious, noticeable tremor,

but \2 cm excursions). The study was approved by the

Ethics Committee of the University of Gothenburg.

Motor tests

The quantitative tests of neuromotor function were con-

ducted by one of the authors (GW) immediately after the

clinical evaluation. The subjects were asked to wear pre-

scription glasses where relevant, and their near vision was

checked before testing began. They were tested either in

the morning or in the afternoon; the percentages of for-

merly Mn-exposed subjects and referents tested at different

times of day were similar. The sequence of motor tests was

the same for all subjects throughout the study and lasted for

about 1 h in all.

Hand steadiness/hand tremor

The Kløve-Matthews static steadiness test (Matthews and

Kløve 1964) consists of a stylus-and-hole apparatus. In this

test, the subject was asked to hold the stylus for 15 s in

successively smaller holes without it touching the sides and

without any arm support. Both hands were tested, begin-

ning with the dominant hand. The cumulative number and

duration of contacts between stylus and base plate for each

hand were used for the statistical analyses.

The Tremor Pen of the CATSYS system (Danish

Product Development Ltd 2000; Despres et al. 2000) was

used to measure postural tremor. The subject was asked to

hold a light stylus containing a biaxial microaccelerometer

as one would hold an ordinary pen. The stylus was held

with the elbow joint bent at a right angle, at approximately

10 cm in front of the navel and free from body contact or

any obstacles. Tremor was recorded over 16.4 s in each

hand. Fourier transformation was used to determine the

power distribution normalized across a frequency band

varying from 0.9 to 15 Hz. Four measures calculated by the

CATSYS software were used: tremor intensity, center

frequency, frequency dispersion, and harmonic index.

Postural sway

The CATSYS postural sway test (Danish Product Devel-

opment Ltd 2000; Despres et al. 2000) consists of a plat-

form with three orthogonal strain-gauge devices. The

subjects were asked to stand erect on the platform with

their feet 1 cm apart and arms hanging loosely at their

sides. Postural sway was measured twice, over 60 s each

time, first with eyes open and then with eyes closed. The

outcome variables calculated for each condition were mean

sway, transversal sway, sagittal sway, sway area, sway

intensity, and sway velocity.

Tests of motor speed and coordination

Using the manual version of the finger tapping test

(Lafayette Instrument Company), the subject was asked to

press a tapping key with the index finger as fast as possible

during 10 s (Reitan and Wolfson 1985). The median

number of four trials for each hand was used for the sta-

tistical analyses (Bast-Pettersen et al. 2004).

The grooved pegboard test (Matthews and Kløve 1964)

is a test of motor speed and manual dexterity. The subject

was asked to insert 25 pegs with a ridge along one side on

a board with a set of 5 9 5 slotted holes angled in dif-

ferent directions, as fast as possible. The time of com-

pletion (in seconds) for each hand was used for further

calculations.

Quantitative assessment of rapid pointing movements

(eurythmokinesimetry)

The eurythmokinesimeter (EKM) measures rapid and pre-

cise proximo-distal movements in a pointing task (Beuter

et al. 1999a; Wastensson et al. 2008). It is composed of one

distal and one proximal target, each divided into three

electrically isolated concentric areas, and a pointer. The

subject was asked to sit down in front of the apparatus and

hold the pointer like a pen. Before starting the test, the

subject was instructed to alternately touch the center of

each target, as precisely and quickly as possible, beginning

with the proximal target. Each recording lasted 30 s and

was repeated twice with both hands, with a 15-s pause

between each recording. The recordings were transformed

to nine calculated measures, used to characterize the per-

formance (Beuter et al. 1999a). For the statistical analyses,

four values (two trials and two targets) were obtained for

each characteristic and averaged to a mean for each hand.

Quantitative assessment of alternating movements

of the forearms (diadochokinesimetry)

The diadochokinesimeter measures the performance of

rapid alternating movements of the forearms (Beuter et al.

1994, 1999b; Wastensson et al. 2008). The subject was

asked to sit down in front of the testing apparatus and

firmly hold two soft spheres, one in each hand. The spheres

were fixed to flexible rods mounted on a rod and connected

to optical encoders by bendable joints. The subject was

instructed to hold the spheres so that the palms of the hands

were facing each other and then execute alternating

movements of the forearms as fast as possible. Each

706 Int Arch Occup Environ Health (2012) 85:703–713

123

recording lasted 5 s and was repeated twice, with a 15-s

pause between each trial. Six measures used to describe

the performance were calculated as described elsewhere

(Beuter et al. 1999b). The mean for each hand over the two

trials for each characteristic was used for the statistical

analyses.

Grip strength

The JAMAR dynamometer (Mathiowetz et al. 1985) was

used to measure grip strength. The subject was seated, and

instructed to hold the dynamometer in the palm of the hand

and squeeze the stirrup with the fingers as hard as possible.

The amount of pressure in kg was recorded three times for

each hand, and the mean value of the three trials was

calculated.

Statistics

Wilcoxon’s rank-sum test, the chi-squared test, and

Fischer’s exact test were used for group comparisons.

Spearman’s correlation coefficients were used to evaluate

associations between the outcome variables in the quanti-

tative tests, exposure (years of exposure and CEI), and

potential confounders (age and smoking). Multiple linear

regression analysis was used to examine associations

between the outcome variables in the quantitative tests and

exposure (years of exposure or CEI) adjusted for potential

confounders (age, smoking habits). The exposure indices

(years of exposure or CEI) were included separately in the

model as continuous variables. p-values of \0.05 (for

two-tailed tests) were considered statistically significant.

Statistics were calculated with version 9.1 of the SAS

statistical package.

Results

Former welders tended to have slightly more kinetic tremor

at clinical examination compared to the referent group

(47% vs. 29%), but slightly less postural tremor (12% vs.

19%). The prevalence of hyporeflexia was 24% versus

24%, impaired sensation was found in 24% versus 14%,

and impaired sense of vibration was found in 6% versus

14%. Diadochokinesis, knee-heel test, gait, and Romberg’s

test were assessed as normal in all subjects.

In comparison with referents, the former welders had

poorer motor speed and poorer manual dexterity in the

dominant hand (p = 0.04), as evaluated with the grooved

pegboard test (Table 2). Motor speed, as assessed with the

finger tapping test, did not differ between the groups. There

were no group differences in postural forearm tremor as

evaluated with the Tremor Pen of the CATSYS system,

except for a tendency toward a lower tremor frequency

among former welders (Table 3). Conversely, former

welders tended to perform slightly better than their refer-

ents in the static steadiness test (Table 2). Likewise, former

welders tended to have a slightly more precise performance

(dominant hand) than their referents in the eye-hand

coordination test, as measured by the EKM system

(Table 4). As shown in Table 5, no significant group dif-

ferences were found in any of the characteristics used to

describe the performance of rapid alternating movements

in the forearms (diadochokinesimetry). There were no

significant differences between former welders and refer-

ents in the postural sway test (Table 6); the results were

similar between groups irrespective of the recording con-

dition used (eyes open or blindfolded).

As a second step, the test results of a subgroup of former

welders with [30 years of exposure to welding fumes

(n = 7) were compared to those of a subgroup of referents

of similar age (referents [ 61 years old, n = 17). The test

results of the high-exposure group (n = 10) were also

compared to those of this referent subgroup. The results

were, however, similar to those comparing all former

welders and referents as described above (results not shown

in table).

Multiple regression analyses performed on the entire

group (n = 38), taking age and smoking habits into

account, showed an association between exposure status

(being a former welder) and poorer performance in the

grooved pegboard test (p = 0.09) in the dominant hand. A

similar association was found between number of years of

exposure and poorer performance in the grooved pegboard

test (p = 0.06). Moreover, a significant association was

found between CEI and impaired performance in the

grooved pegboard test (p = 0.03) in the dominant hand,

taking age and smoking habits into account. The associa-

tion did not reach significance in the former-welder group

alone (n = 17).

Significant associations between exposure and better

precision (p = 0.04) and less imprecision (p = 0.01) in the

dominant hand in the EKM test were found in the multiple

regression analyses adjusted for age and smoking habits.

Likewise, working many years as a welder was associated

with better precision (p = 0.05) and less imprecision

(p = 0.02) in the dominant hand. Multiple regression

analyses performed in the former-welder group alone

(n = 17) showed no significant associations between the

exposure indices and the results from any of the quantita-

tive tests except for postural sway; CEI was significantly

associated with poorer performance in transversal sway

with eyes open, and with mean sway, transversal sway,

sagittal sway, and sway area when blindfolded. All these

associations disappeared, however, when a single outlier in

the postural sway test was removed.

Int Arch Occup Environ Health (2012) 85:703–713 707

123

Discussion

The aim of this study was to assess effects of previous Mn

exposure. To our knowledge, there is no other similar study

that has incorporated such a long time period since cessa-

tion of exposure. Overall, former welders performed sim-

ilarly to the reference population in most tests of

neuromotor function, except for a test of motor speed and

manual dexterity. The findings and limitations of the study

are discussed below.

Discussion of findings

Former welders performed less well in the grooved pegboard

test in the dominant hand compared with their referents, and

this finding was supported by an association between the test

result and estimated cumulative Mn exposure. Several

studies of workers with current Mn exposure have shown

decreased performance in fine motor function (Bowler et al.

2003; Chang et al. 2009; Chia et al. 1993; Sjogren et al.

1996), some of them also using the grooved pegboard test

(Bowler et al. 2003; Chang et al. 2009). Mn accumulation in

the brain is reflected by high signal intensity in the basal

ganglia, mainly the globus pallidus area, in T1-weighted

images MRI (Dietz et al. 2001; Kim 2006; Kim et al. 2007),

and high signal intensity on MRI is associated with decreased

performance in neurobehavioral tests (Kim et al. 2007). High

pallidal index on MRI has been reported to be associated with

decrement in fine motor function (Shin et al. 2007) and

poorer dominant hand performance in the grooved pegboard

test (Chang et al. 2009). MRI cannot, however, be used when

assessing Mn exposure many years after cessation of expo-

sure (Zheng et al. 2011). The same is true for blood and urine

Mn (Zheng et al. 2011). Our finding that impairment in

Table 2 Results from tests of motor function and hand steadiness

Characteristicsa Welders (n = 17) Referents (n = 21) p valueb

Mean SD Mean SD

Grip strength, dominant hand 45.7 9.6 45.3 7.4 0.74

Grip strength, non-dominant hand 42.7 9.4 44.7 8.5 0.42

Finger tapping, dominant hand 43.9 7.4 41.9 5.8 0.41

Finger tapping, non-dominant hand 39.0 5.4 39.1 4.1 0.97

Grooved pegboard, dominant hand (s) 85.9 16.5 76.0 11.0 0.04

Grooved pegboard, non-dominant hand (s) 95.3 20.8 90.1 16.5 0.40

Static steadiness test, number, dominant hand 146.6 128.9 159.3 79.8 0.35

Static steadiness test, number, non-dominant hand 183.0 156.6 215.0 156.8 0.32

Static steadiness test, duration (s), dominant hand 7.0 4.2 9.70 8.22 0.30

Static steadiness test, duration (s), non-dominant hand 8.0 4.9 9.52 5.29 0.44

a Non-dominant hand, welders, n = 16; referents, n = 19b Wilcoxon’s rank-sum test

Table 3 Results from measurement of postural tremor with the CATSYS system

Characteristicsa Welders (n = 17) Referents (n = 21) p valueb

Mean SD Mean SD

Dominant hand

Tremor intensity (m/s2) 0.129 0.07 0.136 0.05 0.33

Harmonic index 0.924 0.03 0.912 0.04 0.61

Center frequency (Hz) 6.50 0.86 7.04 1.22 0.06

Frequency dispersion (Hz) 2.59 0.82 3.03 0.76 0.11

Non-dominant hand

Tremor intensity (m/s2) 0.133 0.08 0.140 0.05 0.20

Harmonic index 0.921 0.03 0.898 0.04 0.21

Center frequency (Hz) 6.98 1.27 7.78 1.64 0.09

Frequency dispersion (Hz) 2.95 1.18 3.41 0.95 0.19

a Non-dominant hand, welders, n = 16; referents, n = 19b Wilcoxon’s rank-sum test

708 Int Arch Occup Environ Health (2012) 85:703–713

123

manual dexterity, as assessed by the grooved pegboard test,

may remain after cessation of exposure is supported by other

studies on former welders (Bowler et al. 2006; Ellingsen

et al. 2008).

Impaired performance in the finger tapping test is a

common finding in workers exposed to Mn (Bowler et al.

2003, 2006; Chang et al. 2009; Chia et al. 1993; Ellingsen

et al. 2008; Iregren 1990; Lucchini et al. 1999; Shin et al.

2007). Reduced finger tapping speed has been reported

among welders with previous exposure (Bowler et al. 2006;

Ellingsen et al. 2008), but this result was not supported by

the present study. However, our results are in accordance

with those of Bouchard et al. (2007), who reported normal

performance in finger tapping among former Mn alloy

workers, 14 years after cessation of exposure.

Some studies have reported alterations in tremor

parameters among Mn-exposed subjects using the CAT-

SYS system (Bast-Pettersen et al. 2004; Bowler et al. 2007;

Chang et al. 2009; Lucchini et al. 1999), whereas others are

in agreement with the present study in finding no such

alterations (Ellingsen et al. 2008; Kim et al. 2007). Tremor

naturally fluctuates over time, and so a negative finding

might be explained by too short a recording time, such as

the 8.2 s, which is the default time set by the CATSYS

system. Thus, a longer testing time has been recommended

(Bast-Pettersen and Ellingsen 2005), and we used a

recording time of 16.4 s in the present study. Furthermore,

the CATSYS system (which measures acceleration) has

been shown to be less effective than the static steadiness

test (which measures displacement) in discriminating

between Mn-exposed subjects and referents (Bast-Pettersen

and Ellingsen 2005). Several studies on Mn-exposed

workers using a hole tremormeter have shown alterations

in hand tremor (Bast-Pettersen et al. 2004; Crump and

Rousseau 1999; Hochberg et al. 1996; Mergler et al. 1994;

Roels et al. 1987, 1992). An 8-year follow-up study of the

cohort of dry-alkaline workers initially examined by Roels

et al. in 1987 revealed that hand steadiness was still

impaired, indicating irreversible effects despite decreased

exposure (Roels et al. 1999). However, in the present

study, former welders tended to perform better than the

referents in the static steadiness test, contrasting with their

poorer results in the grooved pegboard test. Similar find-

ings have been demonstrated in other welding studies

Table 4 Results of measurement of rapid pointing movements, using the eurythmokinesimeter

Characteristicsa Group comparisons p valueb

Welders (n = 17) Referents (n = 21)

Mean SD Mean SD

Dominant hand

Speed (mm/s) 0.96 0.26 0.92 0.20 0.91

Precision 0.68 0.21 0.56 0.19 0.07

Imprecision 0.40 0.22 0.53 0.19 0.06

Unsureness 1.21 0.27 1.35 0.53 0.26

Tremor 0.14 0.22 0.25 0.46 0.52

Transit duration 0.89 0.18 0.88 0.19 0.45

Contact duration 0.22 0.15 0.28 0.18 0.28

Fitts’ Law constant 0.15 0.03 0.15 0.03 0.80

Irregularity 0.12 0.06 0.16 0.11 0.31

Non-dominant handc

Speed (mm/s) 0.90 0.24 0.87 0.20 0.73

Precision 0.51 0.13 0.50 0.20 0.71

Imprecision 0.60 0.16 0.58 0.19 0.86

Unsureness 1.47 0.60 1.42 0.42 0.96

Tremor 0.34 0.44 0.32 0.36 0.99

Transit duration 0.93 0.16 0.90 0.20 0.73

Contact duration 0.27 0.25 0.32 0.17 0.07

Fitts’ Law constant 0.16 0.03 0.16 0.03 0.59

Irregularity 0.17 0.16 0.17 0.09 0.37

a Mean of four recordingsb Wilcoxon’s rank-sum testc Non-dominant hand, welders, n = 16; referents, n = 19

Int Arch Occup Environ Health (2012) 85:703–713 709

123

(Bast-Pettersen et al. 2000; Ellingsen et al. 2008). Conse-

quently, our finding is probably due to selection bias out of

or into the occupation of a welder and/or a training effect

from former working tasks.

Impairment in eye-hand coordination following Mn

exposure has been described by some authors (Hochberg

et al. 1996; Roels et al. 1987, 1992), and an improvement

in eye-hand coordination following decreasing Mn expo-

sure was reported in a follow-up study of the workers

originally examined by Roels et al. in 1987 (Roels et al.

1999). However, other studies report negative results (Bast-

Pettersen et al. 2004; Iregren 1990; Sjogren et al. 1996).

Table 5 Results of measurement of rapid alternating movements, using a diadochokinesimeter

Characteristicsa Group comparisons p valueb

Welders (n = 17) Referents (n = 20)

Mean SD Mean SD

Dominant hand

Duration 3.31 0.53 3.63 0.86 0.29

Range 275.25 57.20 279.53 69.86 0.76

Velocity 84.50 16.11 79.55 18.21 0.60

Smoothness (910-2) 0.84 0.59 1.44 1.68 0.82

Sharpness 0.55 0.05 0.53 0.07 0.62

Maximum slope 7.57 1.33 7.37 1.58 0.65

Non-dominant handc

Duration 3.83 0.82 3.83 0.82 0.89

Range 290.42 59.76 288.32 72.02 0.92

Velocity 78.17 17.19 77.42 19.12 0.87

Smoothness (910-2) 0.66 0.54 0.58 0.40 0.76

Sharpness 0.53 0.06 0.53 0.05 0.75

Maximum slope 7.25 1.35 7.21 1.58 0.94

a Mean of two recordingsb Wilcoxon’s rank-sum testc Non-dominant hand, welders, n = 16; referents, n = 19

Table 6 Results from the postural sway test

Characteristicsa Welders (n = 15) Referents (n = 21) p valueb

Mean SD Mean SD

Eyes open

Mean sway 6.84 1.84 6.49 2.16 0.64

Transversal sway 3.84 1.49 3.96 1.34 0.58

Sagittal sway 4.74 1.82 4.30 1.89 0.43

Sway area 404.7 191.9 398.4 261.0 0.90

Sway intensity 5.42 1.65 5.02 1.62 0.63

Sway velocity 12.3 2.77 12.4 3.20 0.94

Blindfolded

Mean sway 7.64 2.05 8.35 3.05 0.44

Transversal sway 4.36 1.38 5.26 2.17 0.11

Sagittal sway 5.30 1.68 5.34 2.06 0.97

Sway area 684.2 376.7 847.5 645.3 0.44

Intensity 7.05 1.42 7.89 2.92 0.59

Sway velocity 21.3 7.56 22.5 7.18 0.64

a Missing values in two out of 17 welders and also in one out of 21 referents in the blindfolded conditionb Wilcoxon’s rank-sum test

710 Int Arch Occup Environ Health (2012) 85:703–713

123

The eye-hand coordination test, as measured by the EKM

system, is supposed to be similar to the finger-nose test, a

clinical test of kinetic tremor. The former welders tended to

perform better than the referents in the eye-hand coordi-

nation test, but less well in the finger-nose test. The dis-

crepancy in results between these tests is probably due to a

training effect from former working tasks; the EKM system

has similarities with welding, whereas the finger-nose test

does not.

Impaired ability to perform rapid alternating movement

in the forearms (dysdiadochokinesis) may be an early sign

of dysfunction in the extrapyramidal system and has been

indicated in some studies on Mn-exposed workers (Beuter

et al. 1994; Wennberg et al. 1991). No significant differ-

ences between former welders and referents were found in

the present study, in accordance with the results from a

study by Sjogren et al. (1996).

A tendency to fall backwards when displaced is a typical

feature in manganism. We found associations between CEI

and several outcome variables in the postural sway test, but

all associations were due to the same outlier, a former

welder with the highest CEI (10,470 mA m2 9 years).

Impairment in postural stability has been indicated among

Mn-exposed workers (Bowler et al. 2007; Chia et al. 1995;

Ellingsen et al. 2008; Kim et al. 2007), mostly using the

CATSYS system (Bowler et al. 2007; Ellingsen et al. 2008;

Kim et al. 2007), while Chang et al. (2009) found no such

effect of Mn exposure.

Aspects of validity

All subjects included in the present study were former

blue-collar workers from the same shipyards. The partici-

pation rates were relatively high, and the groups were

comparable with respect to background characteristics,

health status, and lifestyle behavior, although the former

welders were on average 2.8 years older. All subjects were

asymptomatic; those with diseases or other conditions that

might affect performance on the tests were excluded. The

results from the blood tests (see ‘‘Methods’’ section) were

within normal limits in all subjects included in the present

study. Moreover, subjects older than 75 years were not

included in the study due to an increased risk of neurode-

generative diseases at older age. Nevertheless, our partic-

ipants were quite old, and a decrement in neuromotor

function due to normal aging processes in both groups

might have disguised a slight effect caused by previous Mn

exposure. However, previous adverse effects on the neu-

romotor system might have ceased.

A common difficulty in welding studies is to distinguish

whether the observed effects are due to current or previous

Mn exposure. Thus, welders with current exposure were

not included in the present study. However, due to these

exclusions together with restrictions in the inclusion cri-

teria, the number of eligible participants was relatively few.

Post hoc power calculations show that the power is

acceptable for finger tapping, grooved pegboard, Fitts’ Law

constant (EKM), and velocity (diadochokinesimeter); 80%

power (two-tailed alpha = 0.05) to show differences of

11–20%. For tremor intensity, as measured by the CAT-

SYS system, the interindividual variability is larger and the

power more limited. The statistical power is clearly

insufficient to demonstrate group differences regarding the

prevalence of abnormalities in the clinical neurological

examination (i.e. kinetic tremor).

Welding requires optimal hand steadiness and manual

dexterity, making it difficult to find an appropriate referent

group for welders. Even aside from selection bias, working

many years as a welder probably carries a considerable

training effect. Thus, one problem in welding studies is that

adverse neuromotor effects due to Mn exposure might be

underestimated. We chose electricians and filers as refer-

ents, as they were considered to have had the most similar

working demands in the past, with respect to fine motor

function.

The exposure assessment was based on number of years

of welding, and most of the exposure time was from

welding in the shipyard industry. No airborne measurement

data were available, since the industry closed down at the

beginning of the 1990s. However, measurements from

shipyards in Sweden and in other countries have shown

manganese levels of about 0.1–0.3 mg/m3 (Chang et al.

2009; Ellingsen et al. 2008; Fored et al. 2006; Jarvisalo

et al. 1992). We used results from measurements of iron

load in the lungs to calculate a CEI for each welder. These

measurements were performed at the beginning of the

1980s, at which point all of the welders had been welding

for many years (mean 18 years, range 9–33 years) and thus

had probably reached steady state (Kalliomaki et al. 1983).

We assumed that the exposure at the beginning of the

1980s was relatively similar to the exposure in the 1970s.

From the mid-1980s, improvements such as better general

ventilation and local exhaust ventilation led to a reduction

in exposure. Local exhaust ventilation was associated with

a 31% decrease in manganese levels in welders in one

study (Flynn and Susi 2010). We tried to take improve-

ments in ventilation into account when estimating the CEI.

There was a high contrast in CEI between the high-expo-

sure and low-exposure welding groups (a factor of 10

between the average CEIs). However, a possible effect of

Mn among the welders with the highest exposure will be

difficult to show due to the small number of subjects.

Our referents, especially the filers, might have been

exposed to some welding fumes as well, but at much lower

levels. The exposure to welding fumes among the electri-

cians in this study was considered negligible. Their low

Int Arch Occup Environ Health (2012) 85:703–713 711

123

exposure levels were also supported by available exposure

data for 14 electricians and 17 filers from the departments

where the referents were recruited, as reported in the

‘‘Methods’’ section. However, we cannot disregard that a

small but possible effect of Mn exposure may be under-

estimated when comparing our referents to the former

welders.

None of the study participants lived in the vicinity of

industrial Mn emissions or had high Mn levels in drinking

water. Thus, environmental sources of Mn exposure should

not have contributed to further Mn exposure.

Concluding remarks

In the present study of welders with previous welding fume

exposure, former welders and referents performed similarly

in most of the neurobehavioral tests. The welders had long

exposure times, and previous exposure was documented on

an individual basis. However, former welders performed less

well than the referents in the grooved pegboard test, and there

was an association between performance in this test and

estimated cumulative Mn exposure. The observation that

former welders tended to perform better than their referents

in tests demanding hand steadiness is probably explained by

a training effect from previous working tasks, or selection

bias. These findings contrast with the poorer performance in

the grooved pegboard test among welders and may suggest a

remaining effect of long-term Mn exposure, but this finding

has to be confirmed by other studies.

Acknowledgments The authors would like to thank the participants

in this study, as well as Annika Claesson and Kristina Wass for

helpful assistance in the collection of blood samples, and Gunnel

Garsell for skillful administrative assistance. The Swedish Council for

Working Life and Social Research provided financial support for this

study.

Conflict of interest The authors declare that they have no conflict

of interest.

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