Cadmium - Toxicology of Metals - page 447

groups are calculated (Friberg et al ., 1974; Kjellstrom
and Nordberg, 1978). The models for such changes
were amended by Choudhury et al . (2001).
One-compartment models of Cd metabolism in
humans have been used as a basis for such calculations
(Kjellstrom, 1971; Tsuchiya and Sugita, 1971; WHO/
IPCS 1992). By comparing calculated accumulation
curves with empirical data, it was concluded from the
one-compartment models that the whole-body (and
renal cortex) half-life in humans was at least 20 years.
A more elaborate eight-compartment physiologically
based toxicokinetics (PBTK) model has been devel-
oped (Kjellstrom and Nordberg, 1978; Nordberg and
Kjellstrom, 1979); it has also been used by Thun et al .
(1991) for quantitative risk assessment.
The PBTK model takes into account the transfer
between the muscles, liver, and kidneys; the best fi t
of the empirical data was achieved with shorter (8-14
years) half-lives for each compartment (Kjellstrom and
Nordberg, 1978). The multicompartment PBTK model
as amended by Choudhury et al . (2001), which is also
described in Chapter 3, provides good agreement
between the Cd levels in urine generated by the model
and the urine Cd levels measured in a sample of the
population in the United States.
For long-term low-level exposure, toxicity evalua-
tions that use the multicompartment PBTK model do
not differ substantially from evaluations performed
using the one-compartment model. The latter was
used in the risk assessment undertaken by the WHO/
IPCS (1992). The value of the multicompartment
model lies in the possibility of using it to calculate Cd
concentrations in several tissues, including blood and
urine, after both short-term and long-term exposure
(cf. Chapter 3).

ied in animals by the use of radioactive isotopes (cf.
Section 5.2), the low levels occurring in humans have
not made it possible to perform similar studies by use
of chemical analyses. All studies referred to in the fol-
lowing text refer to levels of Cd in whole blood.
In blood, “normal” or reference levels in nonsmok-
ers are below 1 g/L in most countries, whereas con-

siderably higher values, up to 7.6

µ

g/L, have been
found in heavy smokers with the same intake from
food (Friberg and Vahter, 1983; Stoeppler and Brandt,
1978; Ulander and Axelson, 1974). There are great dis-
crepancies in the published data on “normal” or refer-
ence values of Cd in blood, but data with appropriate
quality control from most countries agree with the
levels presented previously (Elinder, 1985b; Friberg
et al ., 1974; Jarup et al ., 1998c; WHO, 1979). Reference
values for nonsmokers in the general population in
Japan in the 1990s are higher (i.e., approximately 2

µ

g/
L (Watanabe et al ., 2000). Although, the relationship to
age is less prominent for blood-Cd than for urine-Cd,
generally somewhat higher levels of Cd in blood are
found among older persons. In Sweden, nonsmoking
men and women with a mean age of 87 years (Nord-
berg et al ., 2000) had Cd concentrations in their blood
of 3.9 nmol/L (0.43

µ

g/L). Previous smokers and
current smokers had levels of 4.4 nmol/L (0.49

µ

µ g/L)

and 7.5 nmol/L (0.83 g/L), respectively. In a study

(Akesson et al ., 2005) of women aged 50-59 years in
Sweden, nonsmokers had a mean blood-Cd level of
0.30

µ

g/L. Among 11-year-old children in Sweden
(Lagerkvist and Lundstrom, 2004), lower values
have been reported: a geometric mean of 0.8 nmol/
L (0.09

µ

g/L). Somewhat higher levels have been
reported in other countries. Children 7-8 years of
age living near a nonferrous metal smelter in Poland
had median levels of Cd in their blood of 0.5

µ

µ g/L,

with a range of 0.3-0.8 µ g/L, and pregnant women

6 BIOLOGICAL MONITORING

had a level of 0.7 g/L

(Osman et al ., 1992). Among 8-9-year-old children
living in an industrialized area of Poland, the median
blood Cd level was 4 nmol Cd/L, with a range of
2-22 nmol/L (Osman et al ., 1994).
Blood Cd can be used as an indicator of exposure
levels, but the alteration after a sudden change of expo-
sure is not as rapid as the alteration of fecal Cd after
a change in daily ingestion. A study of blood Cd in
newly used workers in a cadmium-battery factory
(Kjellstrom and Nordberg, 1978) showed that during
the fi rst months of exposure (50

µ g/L, with a range of 0.4-1.3 µ

6.1 Biomarkers of Exposure
Chapter 4 describes the current terminology. Because
the biomarkers of exposure include biomarkers of the
external and internal doses and the accumulation in
critical organs, the utility of using the Cd content in
blood and urine to indicate these three dose measure-
ments are discussed sequentially under each heading,
immediately after an account of references values for
people in the general population who have not been
subjected to excessive exposure.

g Cd/m 3 air), the
blood Cd increased to levels many times higher than
the initial level; similar fi ndings were reported by
Lauwerys et al . (1979): the half-life was approximately
2.5 months. The workers were studied during their fi rst
year of exposure; after the fourth month of exposure,

µ

6.1.1 Cd in Blood

Cadmium in blood occurs mainly in the blood cells.
Although the binding of Cd in plasma has been stud-