Chemistry Reference
In-Depth Information
The term has more recently been extended to also
include other biomarkers, as will be described. The
term “biomarker” was introduced during the past 20
years into the fi eld of metal toxicology, environmental,
and occupational health (IPCS 1993, 2001, IUPAC 2004;
US NRC, 1989).
A
biomarker
is an indicator signaling an event or
condition in a biological system or sample, giving a
measure of exposure, effect, or susceptibility (IUPAC,
2004).
A
biomarker of exposure
relates exposure to a xenobi-
otic (i.e., a metal or metal compound) to the levels of
this substance, or its metabolite, or of the product of
an interaction between the substance and some target
molecule or cell that can be measured in a compart-
ment within an organism (after IUPAC, 2004, IPCS,
1993).
As seen from this defi nition, biomarkers of expo-
sure include indicators of exposure, internal dose, and
dose/concentration in critical organs, as in the classical
concept of biological monitoring. It also encompasses
measurements of interaction between the substance
and macromolecules (e.g., DNA and protein adducts
and enzyme complexes) as will be discussed in later
sections of this chapter. The concept “biomarker of
exposure” thus includes all aspects of exposure and
internal dose from the contact with the external envi-
ronment through internal dose to the dose at cellular
level and at the molecular target site. The ultimate
measurement of dose (i.e., interaction with target mol-
ecules) is also included.
Biomarkers of exposure are indirectly related to the
occurrence of disease via information about the rela-
tionships between the exposure biomarker (the dose at
the target) and the development of disease. Although
relationships between exposure biomarkers and effects
are indirect, biomarkers of effects or susceptibility
have a direct relationship to the occurrence of disease
or other adverse health effects. Defi nitions of the latter
concepts are as follows:
A
biomarker of effect
is a biomarker that, depending
on its magnitude, can be recognized as associated with
an established or possible health impairment or dis-
ease (IUPAC, 2003; WHO, 1993).
A
biomarker of susceptibility
is a biomarker of an
inherent or acquired ability of an organism to respond
to exposure to a specifi c substance (IPCS, 1993; IUPAC,
2003).
In Figure 1, relationships have been outlined be-
tween exposure and dose, environmental monitoring,
External exposure
and dose
Response - occur-
rence of disease
TK
Occurrence of crit.
effect
Internal dose
TK
Target dose in
susceptible group
Uptake
(dose) in
crit. organ
Target
dose for
crit. effect
BS
Target dose in less
susceptible group
Environmental
monitoring:external
dose
BM: Internal dose
exposure biomarker
e.g., metal conc.
in blood
BM: Exposure
biomarker indicating
Target dose
e.g., metal conc in
crit. organ
BM: Biomarker of susceptibility
indicating individuals with
increased sensitivity of target
molecules or increased target dose
BM: Biomarker
of early (critical)
effect
BM: Biomarker of
disease
FIGURE 1
Relationships between external exposure and dose, environmental monitoring, biological mon-
itoring (BM), and response. The importance of toxicokinetics a (TK) and susceptibility to adverse (critical)
effects (as shown by biomarkers of susceptibility-BS) is indicated.
