Cadmium - Toxicology of Metals - page 449

TABLE 5 “Best Guess” of Prevalences of Tubular Effects
in the General Population in Different Intervals of
Cadmium in Kidney Cortex, Based on All Available Data
Published Until Mid-1997 (From Jarup et al ., 1998c)

6.1.5 Cd in Kidney and Liver, Measured
In Vivo, Body Burden

Newborn babies are almost free from Cd; the total
body burden is only approximately 1 g (Henke et al .,

1970). A man who is 50 years of age in the United States,
Sweden, or Germany will have a total body burden of
Cd between 10 and 30 mg. These values correspond to
concentrations in the liver of approximately 1-3 mg/kg
weight and in the kidney cortex of 15-50 mg/kg (cor-
responding to approximately 10-30 mg/kg calculated
for a whole kidney). Higher values are found among
smokers than among nonsmokers.
“Normal” or “reference” values in Japan are usu-
ally higher than in other countries (Figure 3). Present-
day values are somewhat lower than those displayed
in Figure 3, because daily intake of Cd has decreased
in Japan during the past two decades as a result of
decreased rice consumption.
In vivo NAA or in vivo X-ray fl uorescence measure-
ments of liver and kidney Cd has made it possible to
measure the correlation between the levels of Cd in the
indicator media and in the critical organ, the kidney
cortex. Roels et al . (1981) found no increase in the blood
Cd with increased body burden. The generally high
blood levels of Cd (5-30

µ

Cadmium in kidney U-Cd Percentage

cortex (mg/kg) ( µ g/g crea) effect

<50 <2.5 0

51-60 2.75 1

61-70 3.25 2

71-80 3.75 3

81-90 4.25 4

91-100 4.75 5

101-110 5.25 6

111-120 5.75 8

121-130 6.25 10

131-140 6.75 12

141-150 7.25 14

151-160 7.75 17

161-170 8.25 20

171-180 8.75 23

181-190 9.25 26

191-200 9.75 30

>200 >10.25 >35

The levels just cited are all from nonoccupation-
ally exposed populations. In a study of female smelter
workers in the UK, Berlin et al . (1992) found a value of
21 ng/g wet weight in placental samples.

g/L) among the workers
studied refl ected their high daily exposures. The levels
of urinary Cd, on the other hand, correlated with the
body burden in workers not exhibiting renal damage
(Figure 6). Ellis et al . (1984) calculated the relationship
between the Cd levels in the kidney or liver measured
with in vivo NAA and the prevalence of renal tubular
dysfunction (see also Section 8). Other studies have not
succeeded in establishing these relationships because
of the lower levels measured and the related larger
proportion of values falling below the detection limit
(for a review, see Jarup et al ., 1998c).

µ

6.1.4 Cd in Hair, Feces, and Other Biological
Materials

For people exposed to Cd almost exclusively from
food, the average daily Cd content in feces is a good
indicator of the daily intake, because the major part
of the ingested Cd passes through the gastrointestinal
tract unabsorbed and reaches the feces (Section 5.1.2);
true fecal excretion is only a fraction of the daily intake
(see Section 5.3).
The average daily fecal Cd (Figure 4) varies with
age in a manner similar to the average daily energy
intake (Kjellstrom et al ., 1978). After a single oral
exposure to Cd-polluted rice, almost 100% of the Cd
was eliminated in the feces within 3 days (Kjellstrom
et al ., 1978). Fecal Cd has been used in several studies
to measure the average daily intake from food in Cd-
polluted areas (for a review, see: Elinder, 1985a) and in
populations exposed to background levels of Cd (for a
review, see Jarup et al ., 1998c).
Cadmium in hair may be used as an indicator of
exposure and of the internal dose in oral Cd-exposure
(Nordberg and Nordberg, 1988). Because Cd levels in
hair are fairly low, there is a risk of external contami-
nation; thus, Cd in hair has not been used signifi cantly
for biological monitoring.

6.2 Biomarkers of Effects
Biomarkers of kidney effects of Cd are well estab-
lished. For glomerular kidney damage, useful biomar-
kers are those of the glomerular fi ltration rate (GFR)
and of albumin in urine (UAlb). For the tubular kidney
effects, crude indicators are glucosuria and aminoaci-
duria. More sensitive indicators are the urinary excre-
tion of RBP, B2M, ProtHC (a 1 -microglobulin), NAG and
its isoenzymes A and B, as well as CC16. Each protein
indicates quite specifi cally where in the tubule the effect
occurs. Metallothionein can also serve as a biomarker of
the effect; Table 6 lists the concentration values of MT.
Section 8.2 of this chapter describes the dose-response
relationships for these effect biomarkers.
As a biomarker of bone effects (i.e., in terms of
osteomalacia and osteoporosis) bone mineral density