Cadmium - Toxicology of Metals - page 463

and 1.5-1.6 g for the lifetime Cd intake. In the studies
performed in the Kakehashi River basin, similar dose-
response relationships were identifi ed between each of
the urinary fi nding positive rates (

rates of 2-4 g/24 hour (Buchet et al ., 1990). In a fol-

low-up study by Hotz et al . (1999), the urinary levels of
Cd were lower, and some subjects who previously had
displayed biomarkers of renal dysfunction presented
normal values, indicating that slight deviations in these
renal biomarkers might be reversible. In Belgium, sta-
tistically signifi cant effects on the urinary excretion of
Clara cell protein 16 (CC16) in women were reported
at very low urinary Cd levels by Bernard et al . (1994).
In the Swedish OSCAR study, which focused on 1021
persons, who were subjected to low-level occupational
or environmental Cd exposure, the a 1 -microglobulin
concentrations were signifi cantly associated with the
urinary Cd concentrations, with tubular proteinuria
found in 10% of subjects exhibiting a urinary Cd con-
centration of 1.0

µ

β 2 -mg, MT, protein,
glucose) and the mean Cd concentration in rice in each
hamlet, with permissible values determined from the
regression lines of dose-response relationships (using
β 2 -mg as an index) of <0.05

g/g (ppm) for rice Cd
concentrations and 1.7-2.1 g for the lifetime Cd intake
(Hochi et al ., 1995; Kido and Nogawa, 1993; Nakashima
et al ., 1997; Nogawa et al ., 1989). In 1997-1998, the mean
Cd concentration in 37,250 rice samples obtained from
the general environment in Japan was 0.06 ppm (mg/
kg), with values exceeding 0.2 ppm (mg/kg) noted in
3.2% of the samples.
Urinary Cd is recognized as a useful index of the
internal dose of Cd (Borjeson et al ., 1997; Kido et al .,
1992, 2004; Nordberg and Nordberg, 1988; Shimbo
et al ., 2000; see also Sections 5.3 and 6.1.2). Investiga-
tions using urinary Cd concentrations as an index of
the internal Cd dose have been undertaken in vari-
ous countries. In the Belgian Cadmibel study, 24-hour
urine samples from 1699 residents of areas polluted
with Cd to various degrees were investigated, with
signifi cant associations detected between the amounts
of urinary Cd excreted and the levels of retinol-bind-
ing protein, NAG,

µ

g/g CR (Alfvén et al ., 2000; Jarup
and Alfvén, 2004; Jarup et al ., 2000). Furthermore, in a
study on 72 subjects living in the vicinity of a Cd fac-
tory, increased NAG excretion was reported at urinary
Cd concentrations of 0.5

µ

g/g CR (Jarup et al ., 1995). It
should be noted that the exposure to Cd among those
living in this area was higher in the past and that the
reported dose-response relationship might be a result
of remaining renal dysfunction caused by such higher
past levels of exposure. Estimates of past exposure
levels in this area were presented by Alfvén (2002).
De Burbure et al . (2006) reported the increased excre-
tion of NAG in children at UCd levels of 0.6-1.3

µ

β 2 -mg, amino acids, and calcium;
urinary fi nding abnormality rates of 10% were found
for each of these parameters at urinary Cd excretion

g/g
CR, but those children lived in areas contaminated by

µ

45

*

40

35

*

*

30

25

*

20

Male
Female

15

*

10

*

5

0

Control 0.00 − 0.09 0.10 − 0.39 0.40 − 0.59 0.60+

Cd concentration in rice (ppm)

FIGURE 9 Prevalence of proteinuria with glucosuria according to sex and Cd concentration in rice (people
living in the same hamlet over 30 years and aged over 50 years). *Signifi cant difference compared with the
prevalence of control group (P<0.05) (Osawa et al ., 2001).