Environmental Health Criteria 214
Environmental Health Criteria 214
Environmental Health Criteria 214
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HUMAN EXPOSURE ASSESSMENT<br />
exposures or population exposure distributions from indirect<br />
measurements and other relevant information.<br />
Measures of contaminants in biological material (biomarkers)<br />
afford a direct measure of exposure modified by and integrated over<br />
some time in the past which depends on physiological factors that<br />
control metabolism and excretion. Such measures give no direct<br />
information about the exposure pathways. Examples of the type of<br />
biomarkers measured in human material that can be used for<br />
reconstructing internal dose and their relevance to exposure<br />
assessment are discussed in Chapter 10.<br />
1.5 Linking exposure events and dose events<br />
The schematic framework in Fig. 2 shows how the<br />
interrelationships among significant exposure- and dose-related events<br />
in the paradigm can be conceived.<br />
It is important to keep in mind that, although events along the<br />
continuum are correlated, the relative position of a particular<br />
individual within a distribution may change dramatically from one<br />
event to the next as the agent or its metabolite/derivative moves<br />
through the various stages from exposure concentration to biologically<br />
effective dose.<br />
To make realistic estimates for a specific event (e.g., an<br />
internal dose), it is necessary to have at least one of two types of<br />
information: measurements of the event itself (e.g., internal dose),<br />
or measurements of an earlier (e.g., potential dose) or later (e.g.,<br />
delivered dose) event in the continuum. It is also necessary to<br />
understand the critical intervening mechanisms and processes (e.g.,<br />
pharmacokinetics) that govern the relationship between the event<br />
measured and the event of interest (e.g., internal dose). Unless such<br />
data are on hand, extrapolating from one event to another, moving<br />
either from exposure to dose (downwards in Fig. 2) or from dose to<br />
exposure (upwards in Fig. 2) is problematic.<br />
Suitable data and adequate understanding are seldom, if ever,<br />
available to describe and estimate all of the significant events for<br />
the groups and individuals of interest. Generally speaking,<br />
measurement of exposure concentration and delivered dose (body<br />
burden) is in many cases relatively straightforward, whereas<br />
measurement of potential (administered) dose and internal (absorbed)<br />
dose is usually possible only with substantially greater effort.<br />
Measurement of biologically effective (target) dose may also be<br />
possible in some cases, although it is usually impossible to measure<br />
the applied dose.<br />
This situation presents us with a conundrum. We would like to<br />
have realistic estimates of exposure concentrations of an agent for<br />
all important pathways, and the resulting biologically effective dose.<br />
Typically, however, if relevant data are available at all, they are<br />
related to exposure concentrations for one pathway or route of<br />
exposure. In the few cases where data on dose are also available,<br />
these data usually reflect delivered dose (body burden) rather than<br />
biologically effective dose. Even if suitable measurements of both<br />
exposure concentration and delivered or target dose are on hand, the<br />
absence of pharmacokinetic understanding to relate these measurements<br />
to each other, as well as to other significant events along the<br />
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