Environmental Health Criteria 214

HUMAN EXPOSURE ASSESSMENT
possess all these characteristics. However, the use of biological
markers for exposure assessment is increasing.
Biological markers represent one type of monitoring approach
available for environmental exposure assessment. Validation of
biomarkers is a complex process that should include determination of:
specificity of the available biological marker, exposure-related
toxicokinetics and toxicodynamics, dose-response relationship,
biological variation associated with the marker, route of exposure and
type of health effect associated with exposure. In addition,
validation should consider behavioural factors that influence
exposure, participant acceptance, feasibility and cost-effectiveness
(Verberk, 1995), as well as biological variability and specificity
within a human population of interest, and generation of baseline or
normative data for the biological marker. These issues are addressed
later in the chapter.
Collection of samples from humans involves important ethical
issues. Ethical concerns may limit the extent of investigations of
chemically exposed individuals and populations (IPCS, 1993). Ensuring
confidentiality both for subjects and for the obtained individual
results is imperative (Schulte, 1992). Subjects have the right to know
the implications of their participation, the analyses to be performed,
the nature of the sampling procedure, the use of the data collected
and the possible ramifications of positive findings. Knowledge of
previous exposure or genetic predisposition may have adverse
implications for an individual; for example, individuals may be denied
health insurance on the basis of presumed future risk. Since
biological markers are a relatively new tool, interpretation of
results and subsequent health implications is difficult. For many
biological markers, little information is available to interpret the
result for the subject; this may lead to concern on the part of the
individual. For example, knowledge of the presence of pesticides in
breast milk may lead an individual to avoid breast-feeding without
consideration of its advantages (Vandenberg, 1991; Sim & McNeil,
1992).
10.3.1 Toxicokinetics and toxicodynamics
Toxicokinetics describes the absorption, distribution, metabolism
and excretion of a contaminant. Understanding the toxicokinetics and
toxicodynamics of the agent is critical for development and use of a
biological marker of exposure (Sampson et al., 1994). This information
predicts the location and form of the chemical or its metabolite and
identifies sources of biological variability in the population (Droz &
Wu, 1991; Droz, 1992, 1993). Toxicokinetic modelling may be used to
estimate the optimal time for sampling (Saltzman, 1988; Droz & Wu,
1991; Droz, 1993). Differing kinetics determine whether the biological
marker reflects recent exposure, historic exposure, or an integrated
measure of exposure over time (Bernard, 1995).
The utility of biological markers for assessing exposure can be
evaluated on the basis of timing of sampling relative to the exposure
and the biological half-life of the chemical. The parameter which best
describes the toxicokinetic behaviour of a chemical in biological
systems is the elimination half-life, which reflects both the
affinity of the chemical for the biological medium and the efficiency
of the processes of elimination (Bernard, 1995). For samples taken
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