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INTRODUCTION

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Biological markers, or biomarkers, are indicators of events occurring in a biological system. While exposure refers to contact between a substance and the surface of the human body via inhalation, ingestion, or dermal contact, biomarkers provide information about the activity of a substance once it is absorbed. Whether the agent of interest is the original substance to which the individual was exposed or a metabolite, biological monitoring can provide useful information about exposure, early health effects, and susceptibility. Figure 22-1 presents a conceptual model for exposure-related disease.

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Figure 22-1.

Conceptual model for exposure-related disease.

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Biological monitoring is typically conducted by analyzing biological materials such as blood, urine, hair, breath, milk, and saliva, whereas other options such as lung tissue, liver tissue, adipose tissue, and bone are considerably more invasive and rarely available. The usefulness of different materials strongly depends on the compound of interest.

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BIOMARKERS OF EXPOSURE

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Biomarkers provide exposure measurements that are potentially more biologically relevant than personal exposure measurements. Personal exposure represents the total amount of a substance that is available for absorption, but only a portion of the total passes across the skin, gastrointestinal tract, and/or respiratory tract. Internal dose is the amount of a substance that has been absorbed and is, therefore, available to undergo metabolism, transport, storage, or elimination. Similarly, only a portion of the internal dose is eventually transported to the critical target site. Biologically effective dose represents the amount of a substance or metabolite that reaches the site of toxic action and could, therefore, result in an adverse effect.

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One of the key advantages associated with using biomarkers to assess exposure is that measurements of internal dose and biologically effective dose integrate personal exposures over multiple exposure routes (inhalation, ingestion, and dermal contact). Additionally, exposures often vary widely over time such that repeated personal measurements (e.g., air samples) would be necessary to characterize average long-term exposure; however, a single biological measurement can often provide information about average long-term exposure, while also incorporating individual-specific differences in metabolism or other biological processes that may also affect dose.

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A common example of a biomarker of internal dose is the measurement of alcohol in either exhaled breath or blood to determine the amount of alcohol an individual has consumed. Ethanol affects the central nervous system such that most individuals begin to show measurable signs of mental impairment at approximately 0.05% blood alcohol concentration, and motor function continues to deteriorate with increasing concentrations. Additionally, ethanol is volatile and transfers from blood to the alveolar air sacs such that ethanol is also detectable in exhaled breath in proportion to the concentration in blood. Accordingly, the measurement of ethanol in exhaled breath provides a useful and easily obtained measure of internal dose.

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A common example of a biomarker ...

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