Manganese - Toxicology of Metals - page 648

after treatment with CaNa 2 EDTA, good clinical, bio-
logical, and neurological results were obtained by
timely removal from exposure and chelating therapy
(Herrero Hernandez et al ., 2006).
Sodium paraaminosalicylic acid (PAS) has also been
observed as effective in treating manganese-induced
clinical manifestations in severe cases (Jiang et al .,
2006).

of manganese action on the lungs. However, it has
to be taken into consideration that an infl ammatory
response is not unique to manganese-containing
particles but is characteristic of nearly all inhalable
particulate matter (EPA, 1984).

6.4.2 Human Studies of Lung Impairment

An increased morbidity and mortality rate from
pneumonia has been found among workers exposed
to manganese dusts (Baader, 1937; Dervillée et al .,
1966; Heine, 1943; Lloyd Davies, 1946; Lloyd Dav-
ies and Harding, 1949; Rodier, 1955; Van Beukering,
1966; Wassermann and Mihail, 1961). The association
between exposure to manganese and a higher rate of
pneumonia was fi rst suspected by Brezina (1921), who
reported that 5 of 10 workers in an Italian pyrolusite
mill died of croupous pneumonia within 27 months.
Clinically, manganese pneumonia has been charac-
terized as an acute alveolar infl ammation with marked
dyspnea. A typical fi nding was that antibiotics were
often without effect (Rodier, 1955). Manganese con-
centrations in air had not been reported in most of the
earlier studies, but Rodier (1955) found that concentra-
tions reached 800 mg/m 3 or more in some parts of a
mine. An increased incidence of pneumonia, as well as
bronchitis, was found in workers exposed to manga-
nese concentrations of 0.39-16.35 mg/m 3 in a factory
producing manganese alloys (Šaric et al ., 1977). In this
study, smoking habits were taken into account.
However, in a number of published articles describ-
ing manganism in exposed workers, there was no
report of lung disease (Flinn et al ., 1940; Schuler et al .,
1957; Smith et al ., 1973; Suzuki et al ., 1960). Some of the
quoted reports had quantitative environmental data,
and examinations or records were such that one would
predict that the presence of excess pulmonary disease
would have been detected.
Studies on populations living in the vicinity of
manganese-emitting plants have also indicated that
manganese exposure might affect the respiratory
system. Elstad (1939) noted an eightfold increase in the
mortality from pneumonia and a fourfold increase in
pneumonia morbidity rate in the general population
living near a ferromanganese plant in Norway. Pro-
duction had started in 1923, but in 1931, air concen-
trations of manganese were only measured once and
reported to be 46

6.4 Effect on the Lungs
6.4.1 Mode of Action

Acute or intermediate exposure to excess manganese
affects the respiratory system. Inhalation exposure to
high concentrations of manganese dusts (manganese
dioxide and manganese tetroxide) can cause an infl am-
matory response in the lung (chemical pneumonitis).
But exposure to manganese in nonsoluble form, such
as MnO 2 , may also be harmful for the lung at low expo-
sure levels. As quoted in the WHO Regional Offi ce for
Europe document (2001), an increase in pneumonia inci-
dence has been registered in rats exposed to 43-139

µ g

manganese/m 3 as MnO 2 (mean MMAD = 0.76 g;

mean standard geometric deviation (Sg) = 2.28) for
2 weeks (Shiotsuka 1984), pulmonary congestion
in monkeys exposed to 0.7 or 3.0 manganese/m 3 as
MnO 2 (80% < 1

µ

m) for 5 months (Nishiyama et al .
1975), pulmonary emphysema in monkeys exposed to
0.7-3.0 mg manganese/m 3 as MnO 2 (80% < 1

µ

m) for 10
months (Suzuki et al . 1978), bronchiolar lesions in rats
and hamsters exposed to 0.117 mg manganese/m 3 as
Mn 3 O 4 (0.29

µ

m) for 56 days (Moore et al . 1975). Never-
theless, no signifi cant pulmonary effects were detected
in some other studies of rats and monkeys exposed
to as much as 1.15 mg manganese/m 3 as Mn 3 O 4 for 9
months (Urlich et al ., 1979a,b) and rabbits exposed to
as much as 3.9 mg manganese/m 3 as MnCl 2 for 4-6
weeks (Camner et al ., 1985).
Laboratory animal studies have also shown that
inhaled manganese may increase susceptibility to
infectious agents such as Streptococcus pyogenes in mice
(Adkins et al ., 1980), Enterobacter cloacae in guinea
pigs (Bergström, 1977), Klebssiella pneumonia in mice
(Maigetter et al ., 1976), and Streptococcus haemolyti-
cus in mice (Lloyd Davies, 1946). Suffi cient evidence
indicates that exposure to manganese has cytotoxic
effects, including a depressive effect on the number
and phagocytic capacity of alveolar macrophages
(Fisher and Škreb, 1980; Graham et al ., 1975; Shan-
ker et al ., 1976; Škreb et al ., 1980; Waters et al ., 1975).
Thus, toxicological fi ndings in experimental animals
and in vitro studies have supported human studies and
corroborated the assumption about the mechanism

µ

g/m 3 3 km from the plant. The time
of sampling was not stated. It was also reported that
the incidence of pneumonia followed the production
of manganese alloys in the plant. Analysis of lung
tissues from 11 persons who died from pneumonia
showed manganese concentrations of 0.35-1.63

µ

µ g/kg

wet weight.