Environmental Health Criteria 214

HUMAN EXPOSURE ASSESSMENT
exposures or population exposure distributions from indirect
measurements and other relevant information.
Measures of contaminants in biological material (biomarkers)
afford a direct measure of exposure modified by and integrated over
some time in the past which depends on physiological factors that
control metabolism and excretion. Such measures give no direct
information about the exposure pathways. Examples of the type of
biomarkers measured in human material that can be used for
reconstructing internal dose and their relevance to exposure
assessment are discussed in Chapter 10.
1.5 Linking exposure events and dose events
The schematic framework in Fig. 2 shows how the
interrelationships among significant exposure- and dose-related events
in the paradigm can be conceived.
It is important to keep in mind that, although events along the
continuum are correlated, the relative position of a particular
individual within a distribution may change dramatically from one
event to the next as the agent or its metabolite/derivative moves
through the various stages from exposure concentration to biologically
effective dose.
To make realistic estimates for a specific event (e.g., an
internal dose), it is necessary to have at least one of two types of
information: measurements of the event itself (e.g., internal dose),
or measurements of an earlier (e.g., potential dose) or later (e.g.,
delivered dose) event in the continuum. It is also necessary to
understand the critical intervening mechanisms and processes (e.g.,
pharmacokinetics) that govern the relationship between the event
measured and the event of interest (e.g., internal dose). Unless such
data are on hand, extrapolating from one event to another, moving
either from exposure to dose (downwards in Fig. 2) or from dose to
exposure (upwards in Fig. 2) is problematic.
Suitable data and adequate understanding are seldom, if ever,
available to describe and estimate all of the significant events for
the groups and individuals of interest. Generally speaking,
measurement of exposure concentration and delivered dose (body
burden) is in many cases relatively straightforward, whereas
measurement of potential (administered) dose and internal (absorbed)
dose is usually possible only with substantially greater effort.
Measurement of biologically effective (target) dose may also be
possible in some cases, although it is usually impossible to measure
the applied dose.
This situation presents us with a conundrum. We would like to
have realistic estimates of exposure concentrations of an agent for
all important pathways, and the resulting biologically effective dose.
Typically, however, if relevant data are available at all, they are
related to exposure concentrations for one pathway or route of
exposure. In the few cases where data on dose are also available,
these data usually reflect delivered dose (body burden) rather than
biologically effective dose. Even if suitable measurements of both
exposure concentration and delivered or target dose are on hand, the
absence of pharmacokinetic understanding to relate these measurements
to each other, as well as to other significant events along the
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