Cadmium - Toxicology of Metals - page 457

subjects (46 men and 210 women) requiring observa-
tion. Renal tubular injury is highly prevalent among the
inhabitants of the Cd-polluted Jinzu River basin, with
urinary

IPCS, 1992) suggesting that exposure to Cd can give
rise to adverse effects on the central nervous system
(CNS). Oral exposure of pregnant or lactating rats to
low levels of Cd caused alterations in the brain sero-
tonin levels of their offspring (Andersson et al ., 1997;
Oskarsson et al ., 2004; see also Section 5.2).
A direct toxic effect of Cd on primitive nervous tis-
sue seems possible at early stages of gestation, before
the blood-brain barrier is established (Dencker, 1975).
At later stages of pregnancy and in adult animals, the
blood-brain barrier offers considerable protection of the
CNS from the effects of Cd, as demonstrated in animals
(Sonawane et al ., 1975). One explanation why there is
limited transfer of Cd across the blood-brain barrier
might involve its binding to MT and larger proteins in
blood plasma (see Section 7.9). The reported neurotoxic
effects of Cd during development are, therefore, likely
to be secondary to the interference of Cd toward Zn
metabolism or other factors of importance for the devel-
opment of the CNS (e.g., hormones) and not to a direct
effect of Cd on brain cells. Metallothionein-3 (MT-3)
a form of MT found in the brain is rich in zinc and the
interference of Cd in the placenta with the uptake of Zn
in MT-3, MT-1, or MT-2 in fetal brain tissue seems to be
a possible mechanism for induction of brain damage by

β 2 -mg concentrations in the most heavily Cd-
polluted district exceeding 4 mg/L for 71-74% of those
aged in their 50s and 91-100% of those aged 70 years
or above (Kobayashi, 1981). The rate of prevalence of
Itai-Itai disease in the Jinzu River basin is high, but it is
low in surrounding regions, with a clear regional accu-
mulation found (Figure 8). In addition, rice-Cd concen-
trations correlate highly with the rates of prevalence of
renal injury and Itai-Itai disease (Ogawa et al ., 2004). In
Cd-polluted regions other than the Jinzu River basin,
at least 16 cases resembling Itai-Itai disease have been
reported, with tubular injury prevalent in the inhabit-
ants of each of these Cd-polluted regions as well (Table 7).
One of the criteria for diagnosing Itai-Itai disease is that
the subject is an inhabitant of a Cd-polluted region, but
it does not mean that subjects with the clinical signs of
Itai-Itai disease cannot be found elsewhere.

7.2.9 Cadmium and the Central and Peripheral
Nervous System

There are only limited data from animals and
humans (Friberg et al ., 1986; Jarup et al ., 1998c; WHO/

Sea of Japan

Jinzu River

Kumamo
River

Prevalence of
Itai Itai disease

(per 1,000 subjects)

−

Ida River

− 10
10 − 30
30 − 50
50

−

FIGURE 8 Geographical distribution of Itai-Itai disease in the Jinzu River basin
(Nogawa, K., unpublished).