Environmental Health Criteria 214

HUMAN EXPOSURE ASSESSMENT
factors (e.g., smoking) or dietary habits (Perera & Weinstein, 1982;
Droz, 1992). Biological variability can complicate assessment of an
individual's exposure using biological markers. However, the factors
contributing to biological variability influence the internal dose and
may ultimately be informative about potential health effects relating
to exposure. For chemicals with large inter-individual variability in
biological response to exposure, biological monitoring techniques are
more useful for groups than for individuals.
10.3.3 Validation of biological markers
Validation of biological markers of exposure occurs at three
levels.
* The first validation level involves sample collection and
determination of sample stability following collection and during
transport and storage. Sample collection and handling can influence
external contamination both during the sample collection and from
the sample collection material. Stability of the sample prior to
analysis can be affected by chemical degradation, evaporation,
biological activity and interaction between the sample and its
container or with other compounds (Bernard, 1995).
* The next level pertains to the analytical method itself and the
ability to measure the marker accurately and reproducibly at levels
relevant to environmental exposure. Low limits of detection and
high analytical sensitivity (i.e., instrument response) are
critical for evaluation of environmental exposures.
* The third validation level stems from the sensitivity and
specificity of the biological marker itself. The biological marker
must demonstrate that an exposure is occurring or has occurred, and
separate individuals on the basis of their level of exposure
(Hulka, 1991). Components of this level of validation include
understanding the temporal relevance of the marker, identifying
background variability and determining potential confounding
factors (Perera, 1987; Sato, 1993). Temporal relevance is critical
since it relates the timing of exposure to the appearance of a
measurable biological marker and to the duration of time that the
biological marker is measurable following the cessation of
exposure. This includes both toxicokinetic and toxicodynamic
considerations.
Validation occurs in the laboratory, in pilot studies and in
populations (Schulte & Talaska, 1995).
For environmental exposure assessment, chemical-specific markers
of exposure such as blood lead concentrations are preferred. However,
for some chemicals, compound-class specific markers (e.g., PAH-DNA
adducts) or non-specific markers (e.g., acetylcholinesterase
inhibition) may be available. Non-specific markers of contaminants
(i.e., some metabolites or non-chemical specific biological changes)
as indicators of exposure may be more sensitive than external measures
of exposure to predict an individual's total dose (van Welie et al.,
1991; Smith & Suk, 1994). However, since non-specific markers are
neither source- nor chemical-specific, characterization of the
variability in these markers is an important validation component
prior to use in exposure assessment. To date, few biomarkers of
environmental exposure can be utilized to estimate such exposure
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