environmental epidemiological studies. Assessment of long-term
exposure is normally based on surrogate measures of exposure,
such as a limited number of air or biomarker concentrations. In
environmental epidemiology, biological monitoring is theoretically
advantageous, first, because it reflects differences in uptake
and kinetics between individuals and second, because it accounts
for all possible routes of exposure, for example, inhalation,
ingestion, and dermal contact, and thus reduces the need to
monitor all environmental sources separately.1 The biological halflife
of a biomarker has been shown to affect the exposure
variability, with slower elimination leading to decreased variability,
and so information on the variability of the potential biomarkers
must be taken into consideration when selecting the least biased
measure and when designing a study.2 Two major components
of variability are the variation within individuals (i.e., the variation
between different samples from the same individual), and the
variation between individuals (in terms of average levels).
Variability could also be introduced in the sampling procedure
and analytical method; this will be included in the withinindividual
variance, although the analytical variability is generally
small.3
In the case of cadmium (Cd), the main route of exposure for
environmentally exposed individuals is through the diet. For
smokers, tobacco use is also an important route of exposure.4–6
After ingestion or inhalation, 3–5% of the Cd in diet and 10–50%
of the inhaled Cd is absorbed, bound to proteins in the blood,
and eventually accumulated in the body, mainly in the kidneys,
with a biological half-life of 20–40 years.4–7 Gastrointestinal Cd
absorption is also dependent on iron status and so young women
with low iron stores might have increased Cd absorption.8
Absorbed Cd is excreted in urine and faeces, and urinary Cd
(U-Cd) is widely used as a biomarker to assess the long-term
exposure or body burden of Cd.5 Although Cd has a long
biological half-life in the human body, and the long-term level in
an individual is therefore thought to be stable, there is still
variability within individuals when U-Cd is measured repeatedly.
This variability is induced by factors, such as natural physiological
variations, the choice of sampling strategy (e.g. time of the day),
and the method used to adjust the U-Cd concentrations for
diuresis. In a study population, there is also variability in U-Cd
excretion between individuals, induced by factors such as level of
exposure and differences in absorption.
Theoretically, 24 h urine (U24) samples represent the average
U-Cd excretion more reliably than spot urine samples. However,
U24 sampling is laborious, and incomplete or contaminated
samples might pose a problem. A common alternative is to use
overnight spot urine (UON) samples (first morning), as a high
correlation has been shown between Cd in U24 and UON
samples.9,10 In large epidemiological studies or in reanalysis of
samples from existing biobanks, UON samples could be difficult to
obtain, and spot urine samples taken at any time of the day may
have to be used.
1Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital and Academy, University of Gothenburg