Chemistry Reference
In-Depth Information
and is up-to-date. For example, reference values for
blood lead have changed drastically in many countries
in recent years. A biomarker level above the reference
limit does not tell anything of a possible health hazard;
it simply means that the individual has been exposed
to a greater extent than the reference population.
Reference values are intended to identify exposed
individuals; if biomarker concentrations are available
for several members of a group, a more appropriate
assessment of the exposure situation of the group is
obtained from a statistical comparison of the exposed
group and the reference population.
Quantifi cation of exposure relies on knowledge of
the relationship between the exposure, usually meas-
ured as the time-weighted average concentration of the
chemical in the air, and the concentration at a specifi ed
time of the biomarker in the blood or urine or, in rare
cases, other biological media.
Assessment of health risk from biomonitoring may
be achieved if the relationship between the effects and
the biomarker concentrations is known. This is the case
for lead in blood, cadmium in blood and urine, mercury
in blood and urine, and, to a more limited extent, for
arsenic in urine (see Chapter 19). For these elements, epi-
demiological studies area available, which have studied
the relationship between the biomarker level and long-
term health effects. Such studies are diffi cult to carry out,
and often the study results are not very consistent.
For some chemicals (styrene, carbon disulfi de), an
assessment of health risks may also be obtained indi-
rectly from the relationship between health effects and
external exposure (concentrations in the air) and that
between the biomarker concentration and the concen-
tration in the inhaled air. For metals, however, this
approach so far has not been used successfully for inha-
lation exposures. For oral exposures, however, a good
correlation has been reported between cumulative
intake of cadmium through food and health effects.
The interpretation of results obtained from biomark-
er studies, particularly molecular or “omic”-based
biomarkers, requires correlative validation with other
health outcome parameters such as more standard
clinical chemistry markers and ultrastructural/his-
topathological evaluations for preclinical disease and
ultimately overt clinical manifestations of disease
(Fowler, 1980). These data are essential for interpreting
and defi ning the predictive power of a given biomar-
ker endpoint. Usually, such studies are conducted in
experimental animal model systems, where it is pos-
sible to conduct all the necessary correlative studies
and then extrapolate these fi ndings to exposed human
populations. Such extrapolations are usually possi-
ble because many biomarker systems (e.g., the heme
pathway) are highly conserved across species.
Factors that may complicate interpretation of
biomarker endpoints include species differences in
metabolism of chemical agents, genetic susceptibil-
ity factors, nutritional status, and the presence of
other compensatory molecular systems such as metal-
lothionein induction, stress proteins, and glutathione
synthesis. These protective systems, which are fi nite,
may alter the expected shape of the dose-response
curve for metals/metalloids with regard to biomarker
responses as long as they are able to compensate for
exposure to a given toxic element.
In addition, interpretation of results of biomarker
studies for metals will also be infl uenced, particularly
at low dose levels, by concomitant exposure to com-
binations of toxic elements (Fowler
et al.
, 2004; 2005;
Mahaffey
et al.
, 1981). Interactions between toxic ele-
ments that are frequently additive and may also pro-
duce unexpected alterations in predictive responses to
a given toxic element on an individual basis. Because
humans are frequently exposed to mixtures of toxic ele-
ments (e.g., Superfund sites), it is critical to take such
combined exposures into account for risk assessment
purposes.
Chemically induced adverse health effects or dis-
eases usually are not different from the same disease
induced by other causes, and thus the causal diagnosis
or etiognosis depends on the diagnosis proper plus a
history of exposure considered suffi cient to cause the
disease. In the assessment of the history of exposure,
biomonitoring is probably the best means, because
it provides direct information of the exposure of the
individual.
7.5 Biomarkers of Exposure as a Complement
to Industrial Hygiene Measurements
Biomonitoring of metals is most widely applied in
occupational health and thus has a similar objective as
industrial hygiene measurements (i.e., mostly meas-
urement of the concentration in the air). Although it
is clear that for most chemicals, industrial hygiene
measurements are the best and often the only way of
assessing exposure, the two approaches complement
each other because their scope and performance are
not identical.
Air is a homogeneous and relatively simple matrix,
and therefore, sample preparation is often simple and
straightforward, and analytical methods relatively
easy. When the metal compound is present in the air
at low concentrations, the amount of air collected on
the fi lter may be increased, and thus the sensitivity of
the analysis is improved. Because air measurements
also have a long tradition, established methods exist
for practically every metallic element. For several
