Cadmium and Other Metal Levels in Autopsy Samples
from a Cadmium-Polluted Area and Non-polluted Control
Areas in Japan
Chiyo Hayashi
&
Naoko Koizumi
&
Hisahide Nishio
&
Naoru Koizumi
&
Masayuki Ikeda
of cadmium (Cd) and other metals in kidney and liver in
autopsy samples and to compare the levels between those in
an area with heavy Cd exposure and those in no-polluted
areas in Japan. Data on Cd and other metals in kidney
(cortex and medulla) and liver in 95 cases (87 women and
eight men; the exposed) in a Cd-polluted area and 43 cases
(21 women and 22 men; the controls) in non-polluted areas
were cited from 15 previous publications to be summarized
together with six unpublished cases. Cd levels in kidney
cortex and medulla were significantly lower in the exposed
(31.5 and 23.8
μg/g wet tissue as GM, respectively) than in
the controls (82.7 and 36.4
μg/g, respectively), whereas Cd
levels in liver was higher in the exposed (60.2
μg/g) than in
the cortex (29.9
μg/g) and medulla (22.7 μg/g) than
exposed men (55.4 and 38.1
μg/g, respectively) as well as
in cortex of control women (92.9
μg/g). Comparison with
worldwide data other than Japan for non-exposed popula-
tions [19.1, 9.3, and 1.3
μg/g in cortex, medulla, and liver,
respectively, as the inverse variance-weighted averages
(IVWA) of GM values for each of 22 reports] suggests that
the levels for the non-exposed Japanese (123.3, 33.5, and
3.9
μg/g as IVWA) tended to be higher than the levels in
other countries, possibly reflecting high dietary Cd intake in
the past.
Keywords Autopsied samples . Cadmium . Cupper.
Kidney. Lead . Liver. Zinc
Introduction
Cadmium (Cd) is a ubiquitous environmental pollutant,
known to be toxic predominantly affecting proximal tubules
in kidney and bone after long-term exposures [
]. Separate
from occupational Cd exposure, non-occupational expo-
sures occur typically via intake of Cd-polluted foods and
drinking water [
]. In cases of Itai-itai disease (a typical
chronic Cd poisoning) along the Jinzu River basin in Japan,
the toxic effects involved severe damage of renal tubulop-
athy coupled with osteomalacia [
]. Although no exact
report on exposure intensity of the patients was available, a
survey in the basin in 1968 showed that the dietary
exposure among the local population at the time of survey
was about 600
μg/day or even higher [
]. Cd has a long
C. Hayashi
:
H. Nishio
Department of Public Health, Kobe University Graduate School
of Medicine,
Kobe 650-0017, Japan
N. Koizumi
Food Safety Commission, Cabinet Office, Government of Japan,
Tokyo 107-6122, Japan
N. Koizumi
School of Public Policy, George Mason University,
Arlington, VA 22201, USA
M. Ikeda (
*)
Kyoto Industrial Health Association,
67 Nishinokyo-Kitatsuboicho, Nakagyo-ku,
Kyoto 604-8472
( Kyoto, Japan
e-mail: ikeda@hokenkai.jp
Biol Trace Elem Res (2012) 145:10
–22
DOI 10.1007/s12011-011-9155-1
Received: 3 February 2011 / Accepted: 15 July 2011 / Published online: 2 August 2011
# Springer Science+Business Media, LLC 2011
Abstract This study was initiated to examine accumulation
the controls (8.1
μg/g). Exposed women had lower Cd in
biological half-life of 10 or more years [
] to stay long in
the body once absorbed.
Analysis of autopsy tissue samples has been conducted
worldwide since 1970s [
,
], in order to investigate the
extent of accumulation in human body. In Japan in
particular, continuous efforts have been made especially
on those in a Cd-polluted area including Itai-itai disease
victims, and the results of analyses have been reported by
various authors (for details, see the
“
” section). The latest review reports have been
published in 1986 [
] with no follow-up since
then.
It is the purpose of the present study to compile
recent observations. Thus, by citation from 15 previous
publications combined with six unpublished cases, 95
cases from a Cd-polluted area were summarized in the
present report together with 43 cases from areas with no
apparent pollution with Cd, and the extent of accumu-
lation of Cd in kidney cortex, kidney medulla, and liver
was compared between the exposed and non-exposed
cases. Levels of zinc (Zn), lead (Pb), and copper (Cu)
were also reported as the metals of toxicological interest
[
,
–
Materials and Methods
Materials
Data on Cd, Cu, Pb, and Zn in kidney (cortex and
medulla) and liver (right lobe) of autopsied samples of
Itai-itai disease patients and the patients suspected of
the disease in Jinzu River basin [the exposed
—95 cases
(87 women and eight men)] and controls [the controls
—
43 cases (21 women and 22 men)] in non-polluted areas
were cited from 15 previous publications that cover all
of related articles on autopsy cases in Japan till 2007
[
–
]. Findings in six unpublished cases were also
combined together (Table
). It should be noted that the
Itai-itai disease victims were predominantly women (i.e.,
192 women and three men among 195 government-
recognized Itai-itai disease patients and 289 women and
47 men among 336 suspected cases [
]), and as a result,
the autopsy cases were mostly women. The causes of
death of the control group were ischemic heart disease,
cancers (lung, gall bladder, stomach, pancreas, or liver),
brain tumor, and brain thrombosis [
]; the causes of
death were similar also for control cases recorded in later
Table 1 List of databases
References cited
Exposed
Controls
Age range (years) No. of cases
Cd (GM;
μg/g wet tissue)
a
Age (years) No. of cases
Cd (GM;
μg/g wet
tissue)
a
Kidney
Liver
Kidney
Liver
Total Gender
Cortex
Medulla
Total Gender
Cortex Medulla
Kuzuhara et al. [
] 62
–94
44
W37, M7 34.8
26.2
73.3
57
–87
17
W11, M6
87.7
35.5
7.8
Kuzuhara et al. [
] 69
–87
5
W
35.6
27.3
46.5
35
–78
8
W3, M5
95.3
43.6
10.2
Kuzuhara et al. [
] 70
–83
7
W
41.6
27.8
61.8
Kuzuhara et al. [
] 74
–85
7
W
31.2
23.1
63.4
Kuzuhara et al. [
46
–73
3
W2, M2
66.8
31.6
3.6
Kuzuhara et al. [
] 77
–97
6
W
28.3
23.4
34.2
46
–81
14
W5, M9
91.0
36.8
9.3
Kuzuhara et al. [
] 71
–889
3
W
22.3
17.2
43.7
72
1
W
5.7
3.8
22.2
Kuzuhara et al. [
] 82, 87
2
W
22.3, 30.4 11.7, 19.7 34.4,25.2
Kuzuhara et al. [
] 75, 88
2
W
35.9, 40.5 29.3, 25.5 16.5, 30.2
Kuzuhara et al. [
] 84, 79
2
W
9.5, 46.1
11.1, 36.6 117, 69.4
Nogawa et al. [
90
–91
3
W
20.7
14.8
71.1
Nogawa et al. [
87, 87
2
W
11.9, 35.6 8.1, 19.8
40.0, 90.5
Nogawa et al. [
90
1
W
27.0
28.6
120
Nogawa et al. [
83, 88
2
M
30.1, 27.9 25.0, 14.7 76.9, 47.1
Nishio et al. [
95
3
W
22.6
21.1
50.0
Unpublished data
66
–88
6
W
34.5
22.4
43.3
Total
62
–95
95
W87, M8 31.5
23.8
60.2
35
–87
43
W21, M22 82.7
36.4
8.1
W women, M men
a
Individual values are given when a number of cases are two or less
Cadmium and Other Metal Levels in Autopsy Samples
11
years. Of the database, attention was focused to metal
levels in kidney and liver, the two organs of toxicological
importance.
Instrumental Analyses for Metals
As described by Kuzuhara et al. [
], each tissue [fresh and
unfixed (e.g., in formalin), 1
–10 g wet weight] was
mineralized by heating in the presence of 12 N nitric acid
to dryness, and the residue was taken up in 1 N nitric acid.
The final preparation was subjected to instrumental analy-
ses for Cd, Cu, and Pb with a graphite furnace atomic
absorption spectrometer (GFAAS) at 228.8, 324.7, and
283.3 nm, respectively, and for Zn with a flame atomic
absorption spectrometer at 213.8 nm (Hitachi Z-8200, 180-
70 or 180-80, Hitachinaka, Japan). Later cases were treated
also after this protocol.
A bovine liver standard reference material (NIST SRM
1577c) was analyzed for reference. When the material was
analyzed ten times, the accuracy (i.e., the ratio in
percentage of the mean measured values/the certified
values) and the precision (as the coefficients of variation
in percent; given in parentheses) were 95.4% (1.75%) for
Cd, 97.2% (3.29%) for Cu, 94.3% (2.15%) for Pb, and
97.7% (1.49%) for Zn. Thus, the accuracy/precision of the
methods employed was considered satisfactory, and no
adjustment of the measured values was made. For the sake
of better quality control, results of measurements made in a
single laboratory (Department of Public Health, Kobe
University Graduate School of Medicine, Kobe, Japan)
were selectively cited so that all measurements were
conducted by a single analytical chemist (C.H.) in the
laboratory.
Statistical Analysis
A normal distribution was assumed for age. Log-normal
distributions were assumed for metal concentrations in
tissues, by analogy to the cases of the metals in blood [
], in urine [
,
], and in daily food [
,
]. Accordingly,
age was expressed in terms of arithmetic mean and
arithmetic standard deviation (AM±ASD) and metals were
in geometric mean and geometric standard deviation [GM
(GSD)]. In some of publications collected, metal levels
were originally expressed in terms of AM±ASD, and GM
and GSD were estimated by use of the moment method
Element
Group
Parameter
Metal (
μg/g)
Kidney
Liver
Cortex
Medulla
Cd
Exposed
GM
31.5
23.8
60.2
GSD
1.79
1.64
1.94
Controls
GM
82.7
36.4
8.1
GSD
1.99
1.99
2.66
p for difference
↓↓
↓↓
↑↑
Cu
Exposed
GM
1.6
1.4
3.8
GSD
1.49
1.51
1.84
Controls
GM
2.6
2.0
6.1
GSD
1.80
1.52
1.87
p for difference
↓↓
↓↓
↓↓
Pb
Exposed
GM
0.08
0.09
0.27
GSD
1.91
1.87
2.79
Controls
GM
0.09
0.08
0.14
GSD
1.67
1.68
1.69
p for difference
ns
ns
↑↑
Zn
Exposed
GM
30.1
23.2
112.7
GSD
1.37
1.32
1.45
Controls
GM
56.4
34.3
74.5
GSD
1.54
1.51
1.83
p for difference
↓↓
↓↓
↑↑
Table 2 Levels of Cd, Cu, Pb,
and Zn in various organs; com-
parison between the exposed
and the controls
In total, 95 exposed (87 women
and eight men) and 41 controls
(21 women and 21 men) were
studied. Unpaired t test was
applied after log-conversion of
values. Upward and down
arrows show significant increase
or decrease, respectively, in the
exposed as compared with the
levels in the controls (two
arrows for p<0.01). ns for
p>0.10
12
Hayashi et al.
after Sugita and Tsuchiya [
] for uniformity in data
presentation. Thus, inverse variance-weighted average
(IVWA) was calculated as:
Log IVWA
ð
Þ ¼ Σ Log GM
i
½
Þ= Log GSD
i
ð
Þ
2
=Σ½1= Log GSD
i
ð
Þ
2
i ¼ 1 to n
ð
Þ:
Differences in means between the cases and controls
(women and men separately or in combination) were
examined by unpaired t test (after logarithmic conversion)
when a whole of the exposed cases was compared with a
whole of the control cases and by paired t test when 16
exposed cases were matched by age with an equal number
of controls. Simple regression analyses were also applied.
When two regression lines were compared, statistical
significance of the difference in the intercepts, the slopes,
and the correlation coefficients was examined after Ichihara
[
].
Results
Age Distribution of Exposed and Control Groups by Sex
and Combination
When age distributions were compared between the
exposed and controls, the exposed (women and men,
separately and as combined) were significantly (p<0.05)
older than corresponding controls. No significant (p
≧0.05)
difference in age was detected between women and men in
the exposed and also in the controls.
Groups (number of cases)
Parameters
Cd (
μg/g)
Kidney
Liver
Cortex
Medulla
Exposed, total (n=95)
GM
31.5
23.8
60.2
GSD
1.79
1.64
1.94
Max
123
82.4
287
MED
29.3
22.6
58.5
p for difference from total controls
↓↓
↓↓
↑↑
Exposed women (n=87)
GM
29.9
22.7
57.7
GSD
1.75
1.62
1.93
Max
123
82.4
287
MED
28.2
22.4
55.1
p for difference from control women
↓↓
↓↓
↑↑
p for difference from exposed men
↓↓
↓↓
↓
Exposed men (n=8)
GM
55.4
38.1
94.2
GSD
1.61
1.38
1.77
Max
105
65.9
201
MED
57.8
39.9
98.3
p for difference from control men
ns
ns
↑↑
Controls, total (n=43)
GM
82.7
36.4
8.1
GSD
1.99
1.99
2.66
Max
218
111
49.6
MED
86.3
39
8.7
Control women (n=21)
GM
92.9
38.4
11.4
GSD
2.11
2.15
1.99
Max
218
111
49.6
MED
104
43.4
10.7
p for difference from control men
ns
ns
↑
Control men (n=22)
GM
74.1
34.6
5.8
GSD
1.87
1.86
3.02
Max
193
91.6
35.1
MED
75.6
38.7
7.3
Table 3 Comparison of Cd in
kidney and liver between the
exposed and the controls of two
sexes
Arrows (including directions)
are as under Table
. One arrow
for p>0.05, and ns for p>0.1.
Cadmium and Other Metal Levels in Autopsy Samples
13
Metal Levels in Kidney and Liver in Exposed Cases
in Comparison with the Levels in Controls
GM and GSD values for Cd, Cu, Pb, and Zn in kidney
(separately for cortex and medulla) and liver of the exposed
and controls were summarized in Table
, together with
results of comparison between the exposed and the controls.
Cd, Cu, and Zn were substantially (p<0.01) lower in kidney
(both in cortex and in medulla) of the exposed as compared
with the levels in the controls; in case of Cd, the levels in the
cortex of the exposed were less than a half of the controls,
and it was about 65% in the medulla. In contrast, Cd, Zn,
and also Pb in liver of the exposed were much higher (p<
0.01) than the levels for the controls. The behavior of Zn in
the tissues was similar to that of Cd. Trends of changes in Pb
was different from that of Cd in the sense that Pb in kidney
cortex and medulla of the exposed was similar to that of the
controls, although the levels in liver of the exposed was
almost twice as high as the levels of the controls (p<0.01).
Comparison of Cd in Kidney and Liver
Between the Exposed and the Controls
and Between the Two Sexes
Breakdown into two sexes (Table
) showed that exposed
women had lower Cd in both cortex (p < 0.01) and medulla
(p < 0.01) and higher Cd in liver (p < 0.01) than control
women. The reverse was the case for Cd in liver. When
compared with Cd in exposed men, exposed women had
lower Cd (e.g., p < 0.01 in cortex) than exposed men,
although the number of cases of exposed men was as
small as eight. Interestingly, there was no significant
difference (p > 0.05) in Cd in cortex and medulla between
the two groups of the exposed and control men, although
the levels in liver were higher (p < 0.01) in exposed men
than in control men.
Comparison on Cd and Other Metal Levels Between 16
Paired Cases of Women
Further attempts were made to confirm differences in metal
levels between the exposed cases and controls. Because age
distributions were not similar between the exposed and the
controls, age-matched pairs were selected (with an allow-
ance of 2 years) between the two groups. In practice, 16
pairs (13 pairs for women and three pairs for men) were
available (Table
), with no significant difference in age
distribution (p>0.1).
Statistical evaluation showed that Cd was lower in cortex
and higher in liver of the exposed cases as compared with the
levels in controls, whereas no significant difference (p>0.1)
was detected in Cd in medulla. The behavior of Zn was close
Table 4 Comparison of element levels in kidney and liver between 16 age-matched pairs
Groups
Age
Cd (
μg/g)
Cu (
μg/g)
Pb (
μg/g)
Zn (
μg/g)
Kidney
Liver
Kidney
Liver
Kidney
Liver
Kidney
Liver
Parameters
Cortex
Medulla
Cortex
Medulla
Cortex
Medulla
Cortex
Medulla
Exposed
GM
76.1
a
39.3
30.5
62.0
1.8
1.7
4.1
0.10
0.09
0.42
32
26
122
GSD
7.2
a
2.01
1.84
1.93
1.76
1.64
1.90
1.44
1.51
2.93
1.49
1.36
1.42
Min
62
16.9
12.2
16.1
0.7
0.8
1.5
0.06
0.04
0.09
18
17
47
Max
87
123.0
82.4
128.0
9.0
6.5
11.8
0.20
0.21
3.59
82
53
193
MED
75
36.9
29.6
76.9
1.7
1.6
4.1
0.09
0.09
0.41
32
24
129
Controls
GM
75.9
a
93.5
39.6
11.3
2.1
1.7
5.4
0.10
0.08
0.16
53
31
88
GSD
7.0
a
1.71
2.04
2.33
1.48
1.32
1.78
1.78
1.68
1.62
1.63
1.63
1.76
Min
64
27.1
9.6
2.6
0.9
1.1
2.2
0.04
0.04
0.07
22
18
27
Max
87
215.0
111.0
49.6
3.5
3.1
19.8
0.33
0.31
0.38
158
92
200
MED
75
85.6
47.2
14.0
2.3
1.5
5.7
0.10
0.08
0.15
55
27
95
p for difference
ns
b
↓↓
ns
b
↑↑
ns
b
ns
b
ns
b
ns
b
ns
b
↑
↓↓
ns
b
ns
c
Arrows (including directions) and ns are as under Tables
and
; 16 pairs (13 pairs for women and three pairs for men) were compared
a
AM and ASD in case of age
b
ns for p>0.1
c
ns for 0.05<p<0.1
14
Hayashi et al.
to that of Cd in the sense that the levels were lower in kidney
cortex (p<0.01) with no difference in medulla (p>0.1). Cu
and Pb showed no similar behavior with Cd (Table
).
Possible Difference in the Effects of Aging in Cd
Between the Exposed and the Controls
Possible effects of aging on Cd in cortex, medulla, and liver
were examined by regression analysis, taking age as an
independent variable and Cd levels in the tissue a
dependent variable. Only women were selected as sex
difference was detected in Cd in the tissues (Table
), so
that 87 exposed women and 21 control women were
subjected to the analysis. Analyses were made with Cd
levels as measured (i.e., without logarithmic conversion)
and also after logarithmic conversion.
The slopes were negative (i.e., <0) in cases of Cd in
cortex and medulla and positive (i.e., >0) for Cd in liver.
The correlation coefficients were, however, small (|0.3| at
best), and none of them was statistically significant,
irrespective of application of logarithmic conversion. No
significant difference was detected in regression lines
possibly because the correlation was poor with small
correlation coefficients. The regressions are presented in
Fig.
for visual understanding of the cases.
Discussion
The present analysis gave two major findings that Cd in
kidney cortex was lower in the exposed than in the controls
and that Cd in liver of the exposed was higher than that in
the liver of the controls as well as in the cortex of the
exposed. Age-dependent increase in Cd in cortex could not
be confirmed both in the exposed and the controls (Tables
and
; Fig.
] also observed that Cd
in liver was higher than that in kidney cortex among the
autopsy samples from 11 subjects (the two sexes combined)
in Tsushima Island, another Cd-polluted area in Japan,
separate from the current study region of Jinzu River basin.
Unfortunately, no control cases were reported. Neverthe-
less, it should be worthy to note that both Cd in liver
(75.5
μg/g as GM) and in kidney cortex (36.5 μg/g)
reported by Takebayashi et al. [
] were even higher than
the present findings (60.2 and 31.5
μg/g in liver and in
kidney cortex, respectively; Table
).
In reviewing previous publications, some of authors in
1970s reported the Cd levels in dry tissue [
] or dry
ash of the tissue [
,
]. Some others reported Cd in
formalin-fixed tissue samples. Such data were considered to
be inappropriate for comparison with the levels in fresh wet
tissue. Furthermore, only cases with flame AAS, GFAAS,
and inductively coupled mass spectrometry (ICP-MS) as
methods of analyses were in Table
and the
(e.g., the results with other methods such as neutron
activation [
] or X-ray fluorescence [
] were not in the
table to reduce possible difference between the methods
employed). Thus, Cd levels in kidney and liver on a fresh
wet weight basis were available in 27 publications [
] on kidney cortex, kidney medulla, and liver in 48,
5, and 56 groups of subjects who had no occupational or
environmental pollution-induced Cd exposures (Table
;
for details, see
). In addition, Cd in kidney
(without identification of cortex or medulla) was available
in 38 groups. The number of cases in a group was various
from two (for 45
–54-year-old subjects [
] or 30
–39-year-
old women [
]) to 2,659 cases [
]. The inverse
variance-weighted averages of the reported (or estimated)
GM values are shown in the bottom of Table
together
with the minimum and the maximum values. Comparison
with the present findings (GMs) in non-exposed controls (also
cited in the bottom of the table) reveal that the values for cases
in Japan without environmental pollution (i.e., non-exposed
Age (years)
Cd in kidney cortex (µg/g wet tissue)
0
25
50
75
100
125
150
175
200
225
45
50
55
60
65
70
75
80
85
90
95 100
0
25
50
75
100
125
150
175
200
225
45
50
55
60
65
70
75
80
85
90
95 100
A
B
Fig. 1 Poor correlation of Cd in kidney cortex with age. a
Exposed women (n = 87), b Control women (n = 21). The line in the
middle is a calculated regression line, and two dotted curves on both
sides show the 95% confidence interval for the means. Each dot
represents one case. The equation for the regression line in the top
figure of a is Y= 59.1
–0.295× (r=−0.088, p>0.1) and that in the
bottom figure of b is Y= 134.2
–0.360× (r=−0.088, p>0.1)
Cadmium and Other Metal Levels in Autopsy Samples
15
controls) were apparently higher than the levels for popula-
tions in areas other than Japan, irrespective of cortex, medulla,
or liver. Such was also the case even when only adult
populations (selected from [
,
,
]) were compared between those in Japan and
those in other areas. Higher values for Japanese were on line
with previous reports [
,
,
,
] and possibly
associated with high dietary Cd intake for years, especially
in the past [
Age dependency was not evident in the present analysis
both in the exposed and the controls (Table
, Fig.
).
Previously, Tsuchiya et al. [
] observed age-dependent
increase in Cd in kidney cortex up to the age of 60
–
69 years, probably followed by decrease at higher ages.
Nogawa et al. [
] observed age-dependent increase in Cd in
cortex of the non-exposed subjects followed by leveling off
at 50s in men and at 70s in women (two to 17 subjects per
decade of age). According to Lyon et al. [
] with the
largest study number of 2,659 cases, Cd in cortex increased
as a function of age from 10 years of age till 40
–50 years
where leveling off took place, followed by a slight decrease
at the ages over 70s. The regression line by Cikrt et al. [
for Cd in kidney cortex of women appeared to suggest that
the decrease tended to begin earlier in life, e.g., at 40s,
although variation around the line was wide. As the
average ages of people in the present study were 65
(men) to 69 years (women) in the controls and 81 years
(for both sexes) in the exposed (Table
), the lack of
age-dependent increase or moderate decreasing trends
should be taken as in a general agreement with forgoing
studies, understanding that the present observation of lack
of age-dependent increase was obtained at the ages when
the age-dependent increase had reached a plateau to
decline at higher ages.
The observation of higher Cd in liver than in kidney
cortex after high Cd exposure (Table
) was on line with the
paradox that has been reported since early days [
] and
apparently does not agree with the current prevailing
thought in toxicology that toxin will give damage to the
local tissue (e.g., proximal tubules) where it accumulates.
Several possibilities can be postulated for such seemingly
paradoxical findings. For example, dose
–accumulation
relationship may be different after low and high exposure
(e.g., general populations vs. Itai-itai disease patients), most
of Cd that attacked kidney may have leaked out so that the
level at autopsy was low due to cell damage, or
accumulation of Cd to give damage to tubular cells could
be quite topical and high concentration in the tubular cells
would not be detectable (due to dilution with other non-
tubular tissues) when analyzed as cortex. Alternatively,
hepatocytes may be less sensitive (or more tolerable) to Cd
toxicity than tubular cells as Cd in liver may combine with
metallothionein. The mechanism for lower Cd in kidney
cortex in the exposed than in control cases and that for
higher Cd levels in liver than in cortex of the exposed
(Table
) apparently need further studies.
Acknowledgments
The authors are grateful to the administration
and staff of Kyoto Industrial Health association for their interest in and
support to this work.
Conflicts of Interest Statement
The authors declare that they have
no conflicts of interest.
Table 5 Cadmium in the kidney and the liver in autopsy cases; comparison of the present results with results reported in literature
Groups
Cd (GM;
μg/g wet tissue)
Kidney
Liver
Cortex
Medulla
Unspecified
No.
e
AV
f
Min
Max
No.
e
AV
f
Min
Max
No.
e
AV
f
Min
Max
No.
e
AV
f
Min
Max
The present study (controls)
a
43
75.6
5.7
206
43
33.7
3.8
107
0
43
7.3
0.8
48.7
5 reports from Japan
b
18
123.3
3.2
139
1
33.5
33.5
33.5
1
42.6
42.6
42.6
4
3.9
2.2
4.5
Reports from other countries
c
All cases
30
19.1
5.7
133
4
9.3
7.7
35.5
37
17.1
0.2
37.1
52
1.3
0.01
7.0
Adults
d
only
27
18.3
5.7
133
4
9.3
7.7
35.5
36
17.1
0.6
37.1
48
1.4
0.4
7.0
a
Cited from Table
, except for min and max values
b
[
c
[43, 45
–46, 48–56] (for each report, see the
)
d
18 years and over [43, 45
–46, 48–52, 55, 57–59, 61–62, 64–66] (for each report, see the “
”)
e
Number of groups studied (number of individuals in the case of the present study)
f
Inverse variance-weighted average (for details of calculation, see the
section) (geometric mean in the case of the present
study)
16
Hayashi et al.
References
1. International Programme on Chemical Safety (1992) Environ-
mental Health Criteria 134 Cadmium. World Health Organization,
Geneva, p 201
2. Ikeda M, Zhang Z-W, Shimbo S, Watanabe T, Nakatsuka H, Moon
C-S, Matsuda-Inoguchi N, Higashikawa K (2000) Urban popula-
tion exposure to lead and cadmium in east and south-east Asia.
Sci Total Environ 249:373
–384
3. Ikeda M, Zhang Z-W, Shimbo S, Watanabe T, Nakatsuka H, Moon
C-S, Matsuda-Inoguchi N, Higashikawa K (2000) Exposure of
women in general populations to lead via food and air in east and
southeast Asia. Am J Ind Med 38:271
–280
4. Ikeda M, Ezaki T, Tsukahara T, Moriguchi J (2004) Dietary cadmium
intake in polluted and non-polluted areas in Japan in the past and in
the present. Int Arch Occup Environ Health 77:227
–234
5. Kasuya M, Aoshima K, Katoh T, Teranishi H, Horiguchi H,
Kitagawa M, Hagino S (1992) Natural history of Itai-itai disease:
a long-term observation on the clinical and laboratory findings in
patients with Itai-itai disease. In: Cook ME, Hiscock SA, Morrow
H, Volpe RA (eds) Edited Proceedings of the Seventh International
Cadmium Conference, New Orleans. Cadmium Association,
London, pp 180
–192
6. Kitamura S, Sumino K, Kamatani N (1970) Cadmium concen-
trations in livers, kidneys and bones of human bodies. Jpn J Publ
Health 17:177, in Japanese
7. Ishizaki A, Fukushima M, Sakamoto M (1970) On the accumu-
lation of cadmium in the bodies of Itai-itai patients. Jpn J Hyg
25:86, in Japanese
8. Nogawa K, Honda R, Yamada Y, Kido T, Tsuritani I, Ishizaki M,
Yamaya H (1986) Critical concentration of cadmium in kidney
cortex of humans exposed to environmental cadmium. Environ Re
40:251
–260
9. Yoshinaga J, Matsuo N, Imai H, Nakazawa M, Suzuki T, Morita M,
Akagi H (1990) Interrelationship between the concentrations of some
elements in the organs of Japanese with special reference to
selenium-heavy metal relationships. Sci Total Environ 91:127
–140
10. Ikeda M, Ohashi F, Fukui Y, Takada S, Moriguchi J, Ezaki T
(2007) Changes in tubular dysfunction marker levels in parallel
with the levels of copper, rather than cadmium, in urine of middle-
aged women in non-polluted areas. Int Arch Occup Environ
Health 80:171
–183
11. Ikeda M, Ohashi F, Fukui Y, Sakuragi S, Moriguchi J (2010)
Cadmium, chromium, lead, manganese and nickel concentrations
in blood of women in non-polluted areas in Japan, as determined
by inductively coupled plasma-sector field-mass spectrometry. Int
Arch Occup Environ Health 84:139
–150
12. Kuzuhara Y, Minami M, Fujita M, Kitamura S, Shibata T, Hayashi
C, Sumino M (1985) Heavy metals in autopsy samples. Kankyo
Hoken Rep 51:162
–195 (in Japanese)
13. Kuzuhara Y, Kashiwatani H, Fujita M, Kitamura S, Hayashi C,
Koizumi N, Ninomiya R, Inoue Y (1986) Heavy metals in
autopsy samples. Kankyo Hoken Rep 52:270
–283 (in Japanese)
14. Kuzuhara Y, Kitamura S, Hayashi C, Sumino M (1987) Heavy
metals in autopsy samples. Kankyo Hoken Rep 53:344
–347 (in
Japanese)
15. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1988) Heavy
metals in autopsy samples. Kankyo Hoken Rep 54:216
–219 (in
Japanese)
16. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1989) Heavy
metals in autopsy samples. Kankyo Hoken Rep 56(Pt. 2):120
–129
(in Japanese)
17. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1990) Heavy
metals in autopsy samples. Kankyo Hoken Rep 57:107
–120 (in
Japanese)
18. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1991) Heavy
metals in autopsy samples. Kankyo Hoken Rep 58:144
–153 (in
Japanese)
19. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1992) Heavy
metals in autopsy samples. Kankyo Hoken Rep 59(Pt. 1):154
–174
(in Japanese)
20. Kuzuhara Y, Sumino M, Hayashi C, Kitamura S (1993) Heavy
metals in autopsy samples. Kankyo Hoken Rep 60:177
–192 (in
Japanese)
21. Kuzuhara Y, Furusho Y, Sumino M, Hayashi C (1997) Heavy
metals in autopsy samples. Kankyo Hoken Rep 61:243
–262 (in
Japanese)
22. Nogawa K, Nishio H, Kobayashi E, Hayashi C, Lee MJ (2004)
Heavy metal concentrations in organs from autopsies on three
patients with Itai-itai disease who died in 2002. Kankyo Hoken
Rep 69(Pt. 2002):165
–170 (in Japanese with English abstract)
23. Nogawa K, Nishio H, Kobayashi E, Hayashi C, Lee MJ (2005)
Heavy metal concentrations in organs from autopsies on two
patients with Itai-itai disease who died in 2003. Kankyo Hoken
Rep 69(Pt. 2003):95
–100 (in Japanese with English abstract)
24. Nogawa K, Nishio H, Kobayashi E, Hayashi C, Lee MJ (2005)
Heavy metal concentrations in organs from autopsies on a patient
with Itai-itai disease who died in 2004. Reports of studies on Itai-
itai disease and chronic cadmium poisoning, on a consignment
with Ministry of the Environment, pp 129
–133 (in Japanese with
English abstract)
25. Nogawa K, Nishio H, Kobayashi E, Hayashi C, Lee MJ (2006)
Heavy metal concentrations in organs from autopsies on two
patients with Itai-itai disease who died in 2004. Reports of studies
on Itai-itai disease and chronic cadmium poisoning, on a
consignment with Ministry of the Environment, pp 135
–140 (in
Japanese with English abstract)
26. Nishio H, Hayashi C, Lee MJ, Nogawa K, Kobayashi E (2007)
Heavy metal concentrations in organs from autopsies on three
patients with Itai-itai disease who died in 2006. Reports of studies
on Itai-itai disease and chronic cadmium poisoning, on a
consignment with Ministry of the Environment, pp 214
–219 (in
Japanese with English abstract)
27. Toyama Prefecture Department of Public Health (2010) Reports
on Itai-itai disease cases. Toyama Prefecture Department of Public
Health, Toyama
28. Watanabe T, Fujita H, Koizumi A, Chiba K, Miyasaka M, Ikeda M
(1985) Baseline level of blood lead concentration among Japanese
farmers. Arch Environ Health 40:170
–176
29. Ikeda M, Ohashi F, Fukui Y, Sakuragi S, Moriguchi J (2011)
Cadmium, chromium, lead, manganese and nickel concentrations
in blood of women in non-polluted areas in Japan, as determined
by inductively coupled plasma-sector field-mass spectrometry. Int
Arch Occup Environ Health 84:139
–150
30. Watanabe T, Nakatsuka H, Kasahara M, Ikeda M (1987) Urinary
lead levels among farmers in non-polluted areas in Japan. Toxicol
Lett 37:69
–78
31. Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai
H, Okamoto S, Sakurai H, Honda S, Ikeda M (2003) No
clear-cut evidence for cadmium-induced tubular dysfunction
among over 10,000 women in the Japanese general popula-
tion; a nationwide large-scale survey. Int Arch Occup Environ
Health 76:186
–196
32. Sugita M, Tsuchiya K (1995) Estimation of variation among
individuals of biological half-times of cadmium calculated from
accumulation data. Environ Res 68:31
–37
33. Ichihara K (1995) Comparison of two regression slopes, intercepts
and correlation coefficients. In: Statistics for bioscience. Nanko-
do, Tokyo, pp 218
–219, 233 (in Japanese)
34. Takebayashi S, Jimi S, Segawa M, Kiyoshi Y (2000) Cadmium
induces osteomalacia mediated by proximal tubular atrophy and
Cadmium and Other Metal Levels in Autopsy Samples
17
disturbance of phosphate reabsorption. A study of 11 autopsies.
Pathol Res Pract 196:653
–663
35. Syversen TLM, Stray TK, Syversen GB, Ofstad J (1976)
Cadmium and zinc in human liver and kidney. Scand J Clin Lab
Invest 36:251
–256
36. McKenzie JM (1974) Tissue concentration of cadmium, zinc and
copper from autopsy samples. NZ Med J 79:1016
–1019
37. Kayaalti Z, Mergen G, Söylemezo
ğlu T (2010) Effect of metal-
lothionein core promoter region polymorphism on cadmium, zinc
and copper levels in autopsy kidney tissues from a Turkish
population. Toxicol Apll Pharmacol 245:252
–255
38. Morgan JM (1972)
“Normal” lead and cadmium content of human
kidney. Arch Environ Health 24:364
–368
39. Hammer DI, Calocci AV, Hasselblad V, Williams ME, Pinkerson C
(1973) Cadmium and lead in autopsy tissues. J Occup Med
15:956
–963
40. Brune D, Nordberg G, Wester PO (1980) Distribution of 23
elements in the kidney, liver and lungs of workers form a smelter
and refinery in North Sweden exposed to a number of elements
and of a control group. Sci Total Environ 16:13
–35
41. Nilsson U, Schütz A, Skerfving S, Mattsson S (1995) Cadmium in
kidneys in Swedes measured in vivo using X-ray fluorescence
analysis. Int Arch Occup Environ Health 67:405
–411
42. Sumino K, Hayakawa K, Shibata T, Kitamura S (1975) Heavy metals
in normal Japanese tissues. Arch Environ Health 30:487
–494
43. Gross SB, Yeager DW, Middendorf MS (1976) Cadmium in liver,
kidney, and hair of humans, fetal through old age. J Toxicol
Environ Health 2:153
–167
44. Tsuchiya K, Seki Y, Sugita M (1976) Cadmium concentrations in
the organs and tissues of cadavers from accidental death. Keio J
Med 25:83
–90
45. Kowal NE, Johnson DE, Kraemer DF, Pahren HR (1979) Normal
levels of cadmium in diet, urine, blood, and tissues of inhabitants
of the United States. J Toxicol Environ Health 5:995
–1014
46. Casey CE, Guthrie BE, McKenzie JM (1982) Trace elements in
tissues from New Zealanders: a compilation of published data. NZ
Med J 95:768
–771
47. Iwao S, Tsuchiya K, Sugita M (1983) Variation of cadmium
accumulation among Japanese. Arch Environ Health 38:156
–162
48. Salmela SS, Vuori E, Huunan-Seppälä A, Kilpiö JO, Sumuvuori H
(1983) Body burden of cadmium in man at low level of exposure.
Sci Total Environ 27:89
–95
49. Scott R, Aughey E, Fell GS, Quinn MJ (1987) Cadmium concen-
trations in human kidneys from the UK. Hum Toxicol 6:111
–120
50. Cikrt M, Lepsi P, Kasparova L, N
ĕmecĕk R, Blaha K, Nerudova J,
Bittnerova D, Tichy M (1990) The study of exposure to cadmium
in the general population. I. Autopsy studies. Pol J Occup Med
3:177
–184
51. Takács S, Tatár A (1991) Trace elements in the environment and in
human organs: analysis according to domicile and sex. Z Gesamte
Hyg 37(2):53
–55
52. Tiran B, Karpf E, Tiran A (1995) Age dependency of selenium
and cadmium content in human liver, kidney, and thyroid. Arch
Environ Health 50:242
–246
53. Torra M, To-Figueras J, Rodamilan M, Brunet M, Corbella J
(1995) Cadmium and zinc relationships in the liver and kidney of
humans exposed to environmental cadmium. Sci Total Environ
170:53
–57
54. Orlowski C, Piotrowski JK, Subdys JK, Gross A (1998) Urinary
cadmium as indicator of renal cadmium in humans: an autopsy
study. Hum Exp Toxicol 17:302
–306
55. Barregård L, Svalander C, Schütz A, Westberg G, Sällsten G,
Blohmé I, Mölne J, Attman PO, Haglind P (1999) Cadmium,
mercury, and lead in kidney cortex of the general Swedish
population: a study of biopsies from living kidney donors.
Environ Health Perspect 107:867
–871
56. Lyon TDB, Aughey E, Scott R, Fell SG (1999) Cadmium
concentrations in human kidney in the UK: 1978
–1993. J Environ
Monit 1:227
–231
57. Falnoga I, Tusek-Znidaric M, Horvat M, Stegnar P (2000) Mercury,
selenium, and cadmium in human autopsy samples from Idriha
residents and mercury mine workers. Environ Res 84:211
–218
58. García F, Ortega A, Domingo JL, Corbella J (2001) Accumulation
of metals in autopsy tissues of subjects living in Tarragona county.
Spain J Environ Sci Health A36:1767
–1786
59. Yilmaz O (2002) Cadmium and lead levels in human liver and
kidney samples obtained from Brusa Province. Int J Environ
Health Res 12:181
–185
60. Satarug S, Baker JR (2002) Cadmium levels in the lung, liver,
kidney cortex, and urine samples from Australians without
occupational exposure to metals. Arch Environ Health 57:69
–97
61. Lyon TDB, Patriarca M, Howatson AG, Fleming PJ, Blair PS, Fell
GS (2002) Ade dependence of potentially toxic elements (Sb, Cd,
Pb, Ag) in human liver tissue from paediatric subjects. J Environ
Monit 4:1034
–1039
62. Lalor GC, Rattray R, Williams N, Wright P (2004) Cadmium
levels in kidney and liver of Jamaicans at autopsy. West Indian
Med J 53:76
–80
63. Bocio A, Nadal M, Garcia F, Domingo JL (2005) Monitoring
metals in the population living in the vicinity of a hazardous waste
incinerator: concentrations in autopsy tissues. Biol Trace Elem
Res 106:41
–50
64. Johansen P, Mulvad G, Pedersen HS, Hansen JC, Riget F (2006)
Accumulation of cadmium in livers and kidneys in Greenlanders.
Sci Total Environ 372:58
–63
65. Schöpfer J, Drasch G, Schrauzer GN (2010) Selenium and
cadmium levels and ratios in prostates, livers, and kidneys of
nonsmokers and smokers. Biol Trace Elem Res 134:180
–187
66. Baaregård L, Fabricius-Lagging E, Lundh T, Mölne J, Wallin M,
Olausson M, Modigh C, Sallesten G (2010) Cadmium, mercury,
and lead in kidney cortex of living kidney donors: Impact of
different exposure sources. Environ Res 110:47
–54
18
Hayashi et al.
Cadmium
in
the
kidney
and
the
liver
in
autopsy
cases
Y
ear
Authors
Ref.
no.
Location
Methods
Gender
Age
No.
of
cases
Cd
(GM;
μ
g/g
wet
tissue)
Kidney
Liver
Cortex
Medulla
Unsp
’d
GM
GSD
GM
GSD
GM
GSD
GM
GSD
1975
Sumino
et
al.
a
[
]
Japan
Flame
AAS
Mixed
Adults
30
42.57
1.10
4.44
1.29
1976
Gross
et
al.
a
[
]
USA
Flame
AAS
assumedly
Mixed
19
–24
10
12.24
1.26
0.69
1.20
Mixed
25
–34
10
21.13
1.15
1.07
1.17
Mixed
35
–44
6
26.44
1.12
0.70
1.25
Mixed
45
–54
2
37.14
1.06
1.20
1.46
Mixed
55
–64
9
26.12
1.15
1.63
1.20
Mixed
65+
10
18.02
1.16
1.73
1.14
1976
T
suchiya
et
al.
a
[
]
Japan
Flame
AAS
Mixed
0–
9
13
3.25
1.46
Mixed
19
–19
5
24.09
1.38
Mixed
20
–29
38
41.94
1.10
Mixed
30
–39
27
63.73
1.09
Mixed
40
–49
11
74.28
1.15
Mixed
50
–59
6
114.14
1.10
Mixed
60
–69
3
125.09
1.01
Mixed
T
otal
a,g
106
57.74
1.00
1979
Kowal
et
al.
[
]
USA
Flame
AAS
Men
19
–19
33
7.57
1.71
0.70
2.23
Men
20
–29
38
13.53
1.66
0.95
1.79
Men
30
–39
33
21.99
1.76
1.21
1.80
Men
40
–49
28
25.83
1.80
1.19
1.88
Men
50
–59
30
25.37
1.68
1.06
2.17
Men
T
otal
162
16.67
1.65
1.00
1.98
1982
Casey
et
al.
a
[
]
New
Zealand
Flame
AAS
assumedly
Mixed
Adults
39
–42
132.99
1.25
35.46
1.28
6.95
1.37
1983
Iwao
et
al.
a
[
]
Japan
Flame
AAS
Unknown
Smokers
h
24
54.1
1
1.20
4.48
1.17
Unknown
N
on
-s
m
ok
er
s
h
17
36.99
1.23
2.19
1.31
1983
Salmela
et
al.
b
[
]
Finland
Flame
AAS
and
GF
AAS
Mixed
0–
9
3
0.17
1.67
0.01
1.470
Mixed
19
–19
16
1.1
1
1.67
0.81
1.470
Mixed
20
–29
24
3.29
1.67
1.44
1.470
Appendix
Cadmium and Other Metal Levels in Autopsy Samples
19
(continued)
Y
ear
Authors
Ref.
no.
Location
Methods
Gender
Age
No.
of
cases
Cd
(GM;
μ
g/g
wet
tissue)
Kidney
Liver
Cortex
Medulla
Unsp
’d
GM
GSD
GM
GSD
GM
GSD
GM
GSD
Mixed
30
–39
12
5.03
1.67
1.43
1.470
Mixed
40
–49
14
4.94
1.67
1.80
1.470
Mixed
50
–59
7
4.75
1.67
1.38
1.470
Mixed
60
–69
4
3.49
1.67
1.95
1.470
Mixed
70+
6
2.62
1.67
1.47
1.470
1986
Nogawa
et
al.
[
]
Japan
Flame
AAS
Men
50
–59
13
116.0
1.34
Men
60
–69
14
88.6
1.47
Men
70
–79
13
76.0
1.73
Men
80
–89
4
61.5
2.27
W
omen
50
–59
4
139.0
1.17
W
omen
60
–69
13
113.0
1.41
W
omen
70
–79
8
105.0
1.54
W
omen
80
–89
7
88.9
1.61
1987
Scott
et
al.
b
[
]
UK
Flame
AAS
Men
<30
–>90
470
14.7
1.38
7.7
1.26
W
omen
<30
–>90
463
15.8
1.38
7.8
1.26
1990
Cikrt
et
al.
a
[
]
Czechoslovakia
Flame
AAS
Men
50
–64
11
1
20.62
1.2
1.06
2.55
Men
65+
101
12.88
1.3
1.20
1.50
W
omen
50
–64
59
22.14
1.4
1.03
2.24
W
omen
65+
147
11.21
1.3
1.38
1.23
1990
Y
oshinaga
et
al.
a
[
]
Japan
ICP-AES
Mixed
A
v.
42.5
36,40
62.60
1.28
33.53
1.38
3.56
2.31
1991
T
akács
and
T
atár
a,c
[
]
Hungary
GF
AAS
Men
Urban
b
297
10.73
1.29
1.21
1.38
W
omen
Urban
b
234
6.81
1.28
0.89
1.61
Men
Rural
b
287
11.20
1.28
1.19
1.47
W
omen
Rural
b
254
7.42
1.25
0.94
2.00
1995
T
iran
et
al.
d
[
]
Austria
GF
AAS
Mixed
25
–36
7
6.38
1.67
0.62
1.470
Mixed
45
–59
7
5.80
1.67
1.51
1.470
Mixed
61
–69
8
10.04
1.67
0.56
1.470
Mixed
70
–79
8
6.72
1.67
0.78
1.470
Mixed
84
–87
4
8.05
1.67
0.79
1.470
1995
T
orra
et
al.
a
[
]
Spain
GF
AAS
Mixed
18
–80
50
13.54
1.08
7.69
1.12
0.87
1.12
20
Hayashi et al.
(continued)
Y
ear
Authors
Ref.
no.
Location
Methods
Gender
Age
No.
of
cases
Cd
(GM;
μ
g/g
wet
tissue)
Kidney
Liver
Cortex
Medulla
Unsp
’d
GM
GSD
GM
GSD
GM
GSD
GM
GSD
1998
Orlowski
et
al.
a
[
]
Poland
GF
AAS
Mixed
10
–72
39
40.47
1.17
2.17
1.24
1999
Barregård
et
al.
b
[
]
Sweden
ICP-MS
Men
30
–39
3
26
1.38
Men
40
–49
6
19
1.38
Men
50
–59
4
9
1.38
Men
60
–69
5
13
1.38
Men
T
otal
18
15
1.38
W
omen
30
–39
2
16
1.38
W
omen
40
–49
3
19
1.38
W
omen
50
–59
6
23
1.38
W
omen
60
–69
6
15
1.38
W
omen
T
otal
17
18
1.38
1999
L
yon
et
al.
d
[
]
UK
ICP-MS
Mixed
<10
–90+
2,659
16
1.38
2000
Falnoga
et
al.
a
[
]
Slovenia
GF
AAS
Mixed
33
–99
22
5.72
1.49
2001
García
et
al.
a
[
]
Spain
ICP-MS
Men
Adults
57
11.84
1.31
1.04
1.18
W
omen
Adults
21
12.73
1.37
0.59
1.30
2002
Y
ilmaz
a
[
]
T
urkey
GF
AAS
Mixed
11
–30
14
0.61
1.20
0.44
1.34
Mixed
31
–50
18
0.79
1.1
1
0.57
1.12
Mixed
51+
11
0.80
1.19
0.57
1.18
2002
Satarug
et
al.
a
[
]
Australia
ICP-MS
Mixed
1–
60+
61
11.43
1.35
0.72
1.32
2002
L
yon
et
al.
[
]
UK
ICP-MS
Mixed
<6+
147
0.03
1.47
2004
Lalor
et
al.
a
[
]
Jamaica
Flame
AAS
and
GF
AAS
Men
40+
21
31.04
1.17
2.30
1.48
W
omen
40+
18
43.98
1.20
5.52
1.38
2005
Bocio
et
al.
e
[
]
Spain
ICP-MS
Mixed
Unknown
22
14.32
1.38
1.02
1.47
2006
Johansen
et
al.
a
[
]
Greenland
GF
AAS
Mixed
19
–29
5–
9
10.70
1.15
1.12
1.29
Mixed
30
–39
8
17.30
1.03
1.88
1.04
Mixed
40
–49
7–
10
21.77
1.03
1.26
1.36
Mixed
50
–59
14
–16
14.93
1.23
1.61
1.14
Mixed
60
–69
16
–17
13.65
1.16
1.24
1.31
Mixed
70
–79
18
–26
13.74
1.12
2.15
1.22
Mixed
80
–89
6
4.17
1.24
1.30
1.25
Cadmium and Other Metal Levels in Autopsy Samples
21
(continued)
Y
ear
Authors
Ref.
no.
Location
Methods
Gender
Age
No.
of
cases
Cd
(GM;
μ
g/g
wet
tissue)
Kidney
Liver
Cortex
Medulla
Unsp
’d
GM
GSD
GM
GSD
GM
GSD
GM
GSD
Mixed
T
otal
71
–91
13.82
1.16
1.59
1.24
2010
Schöpfer
et
al.
[
]
Germany
GF
AAS
Men
Smokers
h
129
(smokers
+
non-smokers)
27.0
1.668
Men
N
on
-s
m
ok
er
s
h
7.1
1.668
2010
Barregård
et
al.
f
[
]
Sweden
ICP-MS
Mixed
Smokers
h
68
16.7
1.668
Mixed
N
on
-s
m
ok
er
s
h
41
8.30
1.668
Year
year
of
publication,
Flame
AAS
flame
atomic
absorption
spectrometry
,
GF
AAS
graphite
furnace
atomic
absorption
spectrometry
,
ICP-MS
inductively
coupled
mass
spectrometry
,
ICP-AES
inductively
coupled
atomic
emission
spectrometry
,
Mixed
men
and
women
in
combination,
Unsp.
’d
unspecified
with
regard
to
cortex
or
medulla
a
GM
and
GSD
are
estimated
from
AM
and
ASD
by
the
moment
method
(Sugita
and
T
suchiya
[
])
b
Originally
only
GM
values
are
given;
GSD
is
estimated
as
a
grand
average
of
GSD
of
38,
3,
22,
and
4
cases
for
cortex,
medulla,
kidney
unspecified,
and
live
r,
respectively
c
Age
unknown
d
Originally
only
medians
are
given;
GSD
is
estimated
as
described
in
footnote
“b
”
e
Only
AM
is
given
(with
no
ASD).
GM
is
estimated
as
81%
and
75%
of
the
reported
AM;
the
81%
and
75%
are
the
average
GM/AM
ratios
of
other
24
and
37
cases
for
cort
ex
and
liver
,
respectively
f
Biopsy
samples
g
Including
three
cases
of
>70-years-old
subjects
h
Adults
22
Hayashi et al.