Manganese - Toxicology of Metals - page 646

of the close interconnection between the target area of
manganese toxicity, which is represented by the globus
pallidus and the substantia nigra, where the degen-
eration of dopaminergic neurons takes place (Weiss,
2006).
In the development of manganism, individual
susceptibility has been discussed, because poisoning
was found in young people after only a few months
of exposure, whereas in many workers with more than
20 years of exposure, no adverse neurological effect
was observed (Mena et al ., 1969; Tanaka and Lieben,
1969). Typically, the clinical effects of high-level inhala-
tion exposure to manganese do not become apparent
until exposure has occurred for several years. Studies
have been initiated with multigene arrays encoding
for >1000 genes to detect and categorize changes in
gene expression caused by manganese (Aschner, 2002).
Such toxicogenomic studies could help to explain the
observed differences in susceptibility to neurotoxic
effects of manganese.
More recent studies to estimate the impact of occu-
pational exposure to manganese on neurological health
have used a number of sensitive tests designed to detect
early signs of neuropsychological and neuromotor def-
icit in the absence of symptoms (Iregren, 1999).
In descriptions of neurotoxic effects of manganese,
data on manganese levels in air were not regularly
reported in the older literature. Time-weighted aver-
ages of current exposure are reported more frequently,
without clear dose-response relationships that were
shown on the contrary when exposure was expressed
with cumulative exposure indices (Lucchini et al .,
1995; 1999; Roels et al ., 1987; 1992). Manganese levels
reported to lead to early signs of nervous system tox-
icity after inhalation exposure range from 0.027-1 mg
Mn/m 3 (Chia et al ., 1993; 1995; Iregren, 1990; Lucchini
et al ., 1995; 1997; 1999; Mergler et al ., 1994; Roels et al .,
1987; 1992; Wennberg et al ., 1991). On the other hand,
overt manganism has been observed at exposure lev-
els ranging from 2-22 mg Mn/m 3 (Rodier, 1955; Šaric
et al ., 1977; Schuler et al ., 1957; Tanaka and Lieben,
1969). According to WHO (1981), clinical manifestation
of manganese intoxication can also occur at 1 mg/m 3
in susceptible individuals.
Roels et al . (1987) detected early preclinical neuro-
logical effects (alterations in simple reaction time, audio
verbal short-term memory capacity, and hand tremor)
in workers exposed to 0.97 mg manganese (median con-
centration in total dust)/m 3 , for a group average of 7.1
years. Similarly, Iregren (1990) used neurobehavioral
tests (simple reaction time, digit span, fi nger tapping,
verbal ability, hand dexterity, and fi nger dexterity tests
from Swedish Performance evaluation system [SPES])
to study adverse effects in 30 male workers from two

different manganese foundries exposed to an estimated
median concentration of 0.14 mg manganese (in total
dust)/m 3 as MnO 2 for 1-35 years. The exposed work-
ers had below-average scores on a number of the tests,
such as reaction time and fi nger tapping compared
with matched controls. Similar results were reported
in a more recent study by Roels et al . (1992), as well as
in a study by Mergler et al . (1994). In Mergler et al. 's
study, the exposed workers also differed signifi cantly
from the controls in cognitive fl exibility and emo-
tional state. They also exhibited signifi cantly greater
levels of tension, fatigue, and confusion, as well as a
signifi cantly lower olfactory threshold than controls.
Environmental levels of manganese in this study were
measured at 0.014-11.48 mg/m 3 , whereas manganese
levels in respirable fraction were 0.001-1.273 mg/m 3 ,
and mean duration of exposure was 16.7 years.
The epidemiological studies by Lucchini et al . (1995;
1997; 1999) that used similar neurobehavioral tests
have shown similar fi ndings on neurobehavioral and
motor function. These studies have also shown dose-
effect relationships with cumulative exposure indices.
An 8-year follow-up study by Roels et al . (1999) showed
a normalization of performance at the “Eye hand
coordination test” after a decrease of exposure levels,
only for the workers with average annual exposure of
0.4 mg/m 3 of Mn in total dust. No improvement was
observed for hand stability and simple visual reaction
time for the workers with average annual exposure
of 0.6 and 2 mg/m 3 . In a study by Gibbs et al . (1999),
hand steadiness was also analyzed using Movemap
steady, Movemap square, and tremor meter. Although
technically sophisticated Movemap test has not been
observed to discriminate between exposure groups
any better than the other neurobehavioral methods
(Iregren, 1999).
Mergler and Baldwin (1997) pointed out that
although outcomes from individual studies using neu-
rophysiologic and neurobehavioral tests in the absence
of clinical manifestation can vary, they collectively
show a pattern of slowing motor functions, increased
tremor, reduced response speed, enhanced olfactory
sense, possible memory and intellectual defi cits, and
mood changes. Several studies suggest the existence of
dose-effect relationships.
An increased frequency of parkinsonian distur-
bances has been recently shown in case-control studies
on large groups of welders (Racette et al ., 2005b). The
estimated prevalence of parkinsonism among active
male welders age 40-69 was 977-1336 cases/100,000
population and was signifi cantly higher than age-
standardized data for the general population (prev-
alence ratio, 10.19, 95% confi dence interval [CI],
4.43-23.43). The parkinsonian features in welders seem