Cadmium - Toxicology of Metals - page 441

respiratory route: 7-40% (and possibly even more) of the
Cd inhaled (Boisset et al ., 1978; Friberg et al ., 1974). Parti-
cles of larger size and particles with very low solubility
will probably be in the lower part of this range, whereas
particles with high solubility and smaller diameters will
be in the upper part (Nordberg, et al ., 1985b).

explained by recent fi ndings, in human enterocytes,
of a close correlation between the expression of the
divalent metal transporter 1 (DMT-1) and Cd absorp-
tion (Tallkvist et al ., 2001). DMT-1 transports Cd and Fe
in a competitive manner, and such competition most
probably explains the interaction between Fe and Cd
in gastrointestinal absorption (Zalups and Ahmad,
2003). Because low iron stores (low serum ferritin) are
common among women of fertile age, it is reasonable,
when considering data on entire populations, to assume
a higher gastrointestinal absorption in women than in
men. Choudhury et al . (2001) assumed an absorption
of 5% in men and 10% in women by use of a toxicoki-
netics model; they found good agreement between the
calculated urine values and those measured by the
NHANES program in the United States (cf. Chapter
3). Thus, 5% for men and 10% for women seems to be
the most reasonable estimate of average gastrointesti-
nal absorption in Western populations. Higher uptake
rates (i.e., 37 or 47% for the two different subgroups)
were reported in a balance study in young female Japa-
nese volunteers given an experimental diet for 20 days
with only 50% of the recommended dietary allowance
of iron. Serum iron and serum ferritin levels decreased
during the study; more than 50% of the volunteers had
serum ferritin levels <20

5.1.2 Ingestion

In several reports in which the fate of a single oral
dose of radioactive Cd was followed in rats, mice, and
monkeys, between 1 and 6% of the dose was taken up
(review by Nordberg, et al ., 1985b). The importance of
the general diet composition, including a decreased
uptake when the fi ber content was increased, and similar
effects of adequate zinc and iron intake compared with
defi ciency, has been demonstrated in animals (Andersen
et al ., 2004; Chaney et al ., 2004). The absorption in humans
is higher. Five volunteers given a single dose of radioac-
tive Cd by mouth showed an average absorption of 6%
(Rahola et al ., 1972), with a range between 4.7 and 7.0%.
In another similar study of 14 volunteers (McLellan et al .,
1978), the average absorption, 2-6 weeks after dosing,
was 4.6% (SD ± 4.0%); uptake was higher in women than
in men. Vanderpool and Reeves (2001) gave 14 women
a sunfl ower kernel preparation labeled with the stable
isotope 11 3 Cd; the fractional absorption was calculated
to be 10.6 ± 4.4% through repeated fecal determinations
during a 21-day period.
Animal experiments have demonstrated that a low
intake of iron, zinc, calcium, or protein may increase
the degree of absorption considerably (Andersen et al .,
2004; Chaney et al ., 2004; Nordberg, et al ., 1985b). Pre-
treatment of animals with Cd may also increase subse-
quent absorption (Nordberg, et al ., 1985b). Cadmium
bound to metallothionein may be taken up from the
gastrointestinal tract partly in intact form and enter the
circulation (Cherian et al ., 1978). There is evidence (for
a review, see Jarup et al ., 1998c) that Cd is, to a large
extent, bound to metallothionein in the gastrointestinal
mucosa. Low maternal iron stores and a high intake of
fi ber (with a relatively high Cd content) increased the
accumulation of Cd in the placenta of Swedish women
(Moberg-Wing et al ., 1992). The increased intake of Cd
in food with higher dietary fi ber content (or other die-
tary components not studied) may have counteracted
the probable protective effect of the fi ber (cf. the animal
data described previously).
In humans, the absorption in persons (mainly
women) with low body iron stores (serum ferritin
values <20

µ g/L at the end of the study

(Kikuchi et al ., 2003).

5.2 Transport and Distribution
5.2.1 Systemic Transport

After absorption from the lungs or the gut, Cd is
transported through the blood to other parts of the
body. Cadmium in blood is found mainly in the blood
cells (Friberg, 1952; Nordberg, G. et al ., 1985b), where
it is bound to a high-molecular-weight fraction and
a low-molecular-weight fraction (Nordberg, et al .,
1971b). Further studies (Garty et al ., 1981; Nordberg,
1978) have demonstrated that the latter fraction is sim-
ilar to metallothionein, a protein that also binds Cd in
plasma (Nordberg, et al ., 1971b) and plays an impor-
tant role in the transport of Cd in animals and humans
(Nordberg, 1972; Nordberg and Nordberg, 2000). Cad-
mium may also possibly be bound in small amounts
to low-molecular-weight SH-rich compounds, such as
glutathione and cysteine (Zalups and Ahmad, 2003),
although evidence for such binding in the plasma of
mammals is limited; the main transporting protein for
Cd into the kidneys is most probably metallothionein
(Nordberg and Nordberg, 2000).
Metallothionein has a molecular weight of approxi-
mately 6000-7000 g/mol. Up to 11% of its weight can
consist of cadmium, zinc, or copper atoms bound by
several sulfhydryl groups (Elinder and Nordberg,

g/L) was on average four times higher
than that in subjects with normal stores (Flanagan
et al ., 1978); more recent studies have confi rmed these
observations (for a review, see: Jarup et al ., 1998c). The
higher uptake in women with low iron stores may be

µ