Manganese - Toxicology of Metals - page 638

their relationship has been extensively investigated.
The addition of manganese to diets depleted of iron
resulted in depressed hemoglobin levels; the addi-
tion of iron to diets prevented the effect of manganese
(Leach and Lilburn, 1978). An increase in the iron con-
tent of milk decreased the whole-body retention of
orally administered 54 Mn in rats by a factor of 10 (Kostial
et al ., 1980). The interdependence between iron and
manganese can be due to the fact that iron and man-
ganese are absorbed by the same transport system in
the gut (Chandra and Tandon, 1973; Diez-Ewald et al .,
1968; Rehnberg et al ., 1982). Both manganese and iron
are bound by transferrin, and these elements compete
for binding protein in the body. Therefore, diets that
are low in iron allow transferrin to bind more manga-
nese. Interaction between iron and manganese occurs
only between non-heme iron and manganese (Davis
et al ., 1992b).
Manganese interactions with other elements (Cd,
Ni, In, Rh, Se) at the level of gastrointestinal absorp-
tion were also observed (Burch et al ., 1975; Doyle and
Pfander, 1975; Jacobs et al ., 1978). Ethanol was shown to
infl uence the transport of manganese in the rat's small
intestine (Schafer et al ., 1974). High dietary intakes
of phosphorus (Wedekind et al ., 1991) and calcium
(Wilgus and Paton, 1939) have been demonstrated
to depress manganese uptake in chicks. More recent
data also confi rm that the absorption of manganese
is related inversely to the level of calcium in the diet
(Lutz et al ., 1993).
Manganese absorption is age dependent. Dorner
et al . (1989) have shown that infants, especially prema-
ture infants, retain a higher proportion of manganese
than adults. Animal studies also support these fi nd-
ings (Kostial et al ., 1978; Rehnberg et al ., 1980; 1982;
1985). Such age-dependent differences in retention of
manganese could also be due to differences in excre-
tory ability (Miller et al . 1975) or to age-related changes
in dietary intake level of iron and manganese (Ballatory
et al ., 1987). Animal studies show that absorption and/
or retention of manganese is higher in neonates but
returns to the level of older animals at approximately
postgestational day 17-18 (Lönnerdal et al ., 1987; Reh-
nberg et al ., 1982). Dorner et al . (1989) do not provide
adequate data to determine when this transition takes
place in human infants. In a recent study published
by Kostial et al . (2004) on regulation of manganese in
perinatally exposed rat pups, it was shown that the
concentration of manganese in perinatally exposed
pups (whose mothers were exposed orally to Mn in
drink—as manganese chloride, dose of 2000 mg/L
Mn, throughout pregnancy and 11 days of lactation)
was 6-8 times higher than in controls, irrespective of
the period and duration of exposure. After cessation

of exposure, the Mn concentration decreased almost
to control levels. These results indicate the existence
of an accurate regulation of Mn accumulation in pups
exposed to Mn during the perinatal period.
There are no studies regarding absorption of man-
ganese after oral exposure to MMT in either humans
or animals.

5.1.3 Dermal Exposure

There is only a case report of a man burned with a hot
acid solution containing 6% manganese. The authors
(Laitung and Mercer, 1983) speculated that manganese
absorption had occurred across the burn area because
the man had slightly elevated urinary manganese lev-
els. Studies reporting systemic effects in animals after
dermal exposure to organic manganese compounds
indicate absorption have occurred (ATSDR, 2000).

5.2 Distribution
Manganese is a normal component of human and
animal tissues and fl uids with highest levels in the liver,
pancreas, and kidney and the lowest levels in bone and
fat. Most tissue concentrations range between 0.1 and
1 g manganese/g wet weight (Tipton and Cook, 1963;

Sumino et al ., 1975).
Absorbed manganese is rapidly eliminated from the
blood and at fi rst concentrates in the liver. Excess metal
may be distributed to other tissues. Manganese is dis-
tributed in the body in constant concentrations, which
are characteristic of the individual tissues and almost
independent of the species (Cotzias, 1958; Underwood,
1971). Generally, organs and tissues do not accumulate
large concentrations of manganese. Minor amounts
go to the brain and bone, as shown in experiments on
mice (Kato, 1963), rats (Dastur et al ., 1969), and mon-
keys (Dastur et al ., 1971). In contrast to many other
trace metals, manganese does not accumulate signifi -
cantly in the lungs with age (Newberne, 1973). Man-
ganese preferentially accumulates in tissues rich in
mitochondria (Maynard and Cotzias, 1955). The brain
has a small amount of manganese, but retention time
is long. Experiments on rats have shown that manga-
nese elimination from the brain is slower than from the
whole body (Dastur et al ., 1969). In monkeys, it was also
shown that elimination from the cerebrum was very
slow; whereas the half-time in whole body was esti-
mated to be 95 days for the slow component, it was not
possible to obtain an estimate for the cerebrum even
after 278 days, indicating an extremely long biological
half-time (Dastur et al ., 1971). In 1999, Aschner wrote a
review on manganese homeostasis in the CNS, focusing
on mechanisms of the transport across the blood-brain

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