Chemistry Reference
In-Depth Information
elements, fractionation and speciation analysis meth-
ods are available (see Chapter 2), and thus important
qualitative information on the exposure may be gained
from such analyses.
On the other hand, concentrations of chemicals in
workplace air are seldom stable but fl uctuate with time
and are different in different locations. The amount of
a chemical that reaches the alveolar region of the res-
piratory tract is directly related to the volume of res-
piration and thus to the workload. Exposure peaks
often coincide with increased workloads caused by,
for example, the malfunctioning of a closed process.
Several chemicals, including some metal compounds,
are absorbed also via the dermal route, and absorption
through the skin is generally not related to the concen-
tration in the air. Even when the exposure takes place
mainly by inhalation, the bulk of the actual absorp-
tion may be through the gastrointestinal tract (notably
aerosols with particle sizes too large to lead to deposi-
tion in the alveolar region). Personal working habits
vary, and individuals may absorb different amounts of
chemicals in apparently similar conditions. Protection
afforded by masks varies, depending on the individual
who wears it and on the condition of the mask. Fur-
thermore, biomarker, in contrast to industrial hygiene
measurements, refl ects the accumulation of the
chemical in the body. Biomarkers of exposure, which
refl ect all this variation in exposure and, at the same
time, exposure from all sources, are thus closer than
industrial hygiene measurement to the toxicologically
important concentration of the chemical at the target
site (Aitio, 1999).
Biomarkers of exposure do not consider interindi-
vidual or intraindividual differences in the toxicody-
namics of the chemical, which are covered in an ideal
case of effect biomarkers (see Section 8). Biomarkers do
not differentiate between sources of exposure and to
decrease the risk from the chemical, it may be neces-
sary to consider (and analyze) separately, from where
the exposure is derived, from work or from for example
hobbies, or environment.
Biomarkers of exposure refl ect the amount of the
chemical in the systemic circulation, and models have
been developed to predict concentrations in other
compartments in the body. However, a major obstacle
in the interpretation of biomonitoring data involves
concentration and effects at the site of entry, such as
the lungs after exposure to particulates containing
metals; concentrations in the urine or even blood of
nickel tell little of the concentrations or the health
risks in the lungs after exposure to soluble or insoluble
nickel. Similarly, irritation, a mainly concentration-
derived effect, is not easily assessed from exposure
biomonitoring data.
8 BIOMARKERS OF EFFECTS
Biomarkers of effects are molecular tools that can
serve to identify changes or effects occurring in the
organism as a result of exposure to any given toxicant.
In the case of exposure to toxic metals, tests relying on
effect biomarkers are usually only used when exces-
sive metal levels are found in exposed populations or
their environment. The combined use of biomarkers of
effects and biomarkers of exposure is also important
for a correct interpretation of the data, because a diag-
nosis of metal intoxication relying on biomarkers can
be made only if the observed effects are, indeed, associ-
ated with an excessive exposure or body burden of the
metal. To be applicable to the diagnosis of intoxication
or to the monitoring of populations at risk, biomarkers
must meet several criteria. First, they must be sensitive
enough to detect effects at a stage when these are still
reversible or at least not yet predictive of further organ
degradation. They must also be specifi c of the target
organ, and if this is not the case, suffi cient information
must be available on the possible confounding factors.
Finally, biomarkers of effects must be measurable in
the least invasive way possible by use of easily acces-
sible biological media such as urine, blood, sputum,
exhaled air, or exhaled breath condensate. Because of
their noninvasiveness, some biomarkers can be used
repeatedly without any major restriction related to
exposure conditions, age, or health status of the exam-
ined subjects. These tests are particularly useful for
monitoring susceptible populations such as children.
Biomarkers meeting all these criteria and applicable
to detect metal toxicity are relatively few, and among
them the number of biomarkers that have undergone a
complete validation are even less numerous.
8.1 Renal Toxicity Biomarkers
Metals, notably cadmium, lead, and mercury, have
been known for a long time to be nephrotoxic, with
numerous reports of tubulointerstitial nephritis pos-
sibly leading to renal failure, in most cases linked to
high occupational or environmental exposures. Early
signs of renal dysfunction have also been found at low
environmental exposure levels, consisting for instance
of an increased urinary loss of tubular enzymes and
proteins. These effects have mainly been described in
adults, but certain reports have also shown them to
occur in children (de Burbure
et al.
, 2003; 2006). The
early recognition of the nephrotoxicity of metals has
led, since the 1960s, to intense research aimed at devel-
oping sensitive screening tests and deriving thresholds
of toxicity. These studies have shown that the acute or
chronic nephrotoxicity of most metals can be detected
