ly known genitourinary tract biologic markers, emphasizes the need to identify and evaluate promising technologies to find new markers, and identifies important research opportunities. The report discusses the structure and function of the urinary tract, toxic effects associated with the urinary tract, and their risk factors. Relationships between exposure, susceptibility, and the associated markers are described, and the usefulness of markers in monitoring urinary diseases is discussed. The report presents a rationale, based on epidemiologic studies, for the use of biologic markers in the protection of human health and the extrapolation of data from animals to humans. Currently available biologic markers in the genitourinary tract are discussed throughout the report and summarized in Chapter 4, although exhaustive descriptions of these are readily available elsewhere.

Several characteristics of the normal genitourinary tract increase the risk of damage by toxic chemicals. For example, the total amount of noxious substances delivered to the kidneys can be high, owing to the large amount of blood flowing to them. Furthermore, the capacity of the kidneys to concentrate substances by processes of filtration, reabsorption, and secretion can increase the toxicity of agents that would otherwise not lead to tissue damage. This is particularly important in the bladder, which is routinely exposed to concentrated toxicants. Also important are the mechanisms of biotransformation by which the kidney and bladder epithelium can metabolize xenobiotics and produce substances that might be more toxic than the parent substance.

Biologic markers can be useful in confirming toxic exposures (i.e., biologic markers of exposure), estimating their results (i.e., biologic markers of effect), and identifying persons most likely to be adversely affected if exposures continue (i.e., biologic markers of susceptibility).

Markers of exposure. A biologic marker of exposure is a xenobiotic chemical or its metabolite or a product of interaction between the chemical and some target cell. Markers of exposure most commonly used are the concentrations of such materials in urine, blood, or other body tissue, including hair and nails. Markers of exposure alone give no indication whether an exposure has produced a biologically significant result. The same dose in persons who are susceptible and resistant to a given xenobiotic can have different results. Urine is one source of markers of exposure. High exposures to a toxic substance can result in increased concentrations of the substance or its metabolites in urine. When sufficient pharmacokinetic information is available, urinary markers of exposure can be used to estimate the total exposure of a person to a substance.

Markers of effect. A marker of effect is a measurable cellular, physiologic, or biochemical alteration within an organism caused by interaction with a toxicant. Markers of adverse effect can be biochemical or cellular signals of tissue



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