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Veterans and Agent Orange: Update 2006
in biologic specimens. Table 5-1 provides a guide to exposure monitoring and assessment methods used in selected epidemiologic studies of the health effects of the herbicides applied in Vietnam by US military forces and TCDD.
Exposure assessments based on measurements of an environmental contaminant provide estimates of the amount of the contaminant that contacts a body barrier over a defined period. Exposure can occur through inhalation, skin contact, and ingestion. Exposure also can be assessed by measuring the compounds of interest—or their metabolites—in human tissues. Such biologic markers of exposure integrate absorption from all routes, and their interpretation is usually complex. Knowledge of pharmacokinetics is essential for linking measurements at the time of sampling with past exposures.
Quantitative assessments based on environmental or biologic samples are not always available for epidemiologic studies, so investigators often rely on a mixture of qualitative and quantitative information to derive estimates (Armstrong et al., 1994; Checkoway et al., 2004). The most basic approach compares members of a presumably exposed group with the general population or with a non-exposed group. This method of classification offers simplicity and ease of interpretation.
A more refined method assigns each study subject to an exposure category, such as high, medium, and low exposure. Disease risk for each group is calculated separately and compared with a reference or non-exposed group. This method can identify the presence or absence of a dose–response trend. In some cases, more detailed information is available for quantitative exposure estimates, and these can be used to construct what are sometimes called exposure metrics. These metrics integrate quantitative estimates of exposure intensity (such as chemical concentration in air or extent of skin contact) with exposure duration to produce an estimate of cumulative exposure.
The temporal relationship between exposure and disease is complex and often difficult to define in epidemiologic investigations. Many diseases do not appear immediately following exposure. In the case of cancer, for example, the disease may not appear for many years after the exposure. The time between a defined exposure period and the occurrence of disease is often referred to as a latency period (IOM, 2004). Exposures can be brief (sometimes referred to as acute exposures) or protracted (sometimes referred to as chronic exposures). At one extreme the exposure can be the result of a single insult, as in an accidental poisoning. At the other extreme, an individual exposed to a chemical that is stored in the body may continue to experience “internal exposure” for years, even if exposure from the environment has ceased. Defining the proper time frame for duration of exposure represents a challenge in the assessment of exposure for epidemiologic studies.
Occupational-exposure studies use work histories, job titles, and workplace measurements of contaminant concentration; this information is often combined to create a job–exposure matrix (JEM) wherein a quantitative exposure estimate is assigned to each job or task, and the time spent on each job or task is calculated.