Pathways and Measuring Exposure To Toxic Substances Morton Lippmann PhD CIH

3 Human Exposure Pathways and Dosimetry

People can be exposed to chemicals in the environment in numerous ways. The chemicals can be inhaled, ingested, or taken up by and through the skin. Effects of concern can take place at the initial epithelial barrier, i.e., the respiratory tract, the gastrointestinal (GI) tract, or the skin, or can occur in other organ systems after penetration and translocation by diffusion or transport by blood, lymph, etc. As illustrated in Fig. 2.1, exposure and dose factors are intermediate steps in a larger continuum ranging from the release of chemicals into an environmental medium to an ultimate health effect in an exposed individual. There are, of course, uncertainties of varying magnitude at each stage. The diagram could also be applied to populations as well as to individuals. In that case, each stage of the figure would include additional variance for the interindividual variability within a population associated with age, sex, ethnicity, size, activity patterns, dietary influences, use of tobacco, drugs, alcohol, etc.

Figure 2.1. Framework for personal exposure assessment and exposure-response (modified from Ref. 1a).

Exposure is a key and complex step in this continuum. The concept of total human exposure developed in recent years is essential to the appreciation of the nature and extent of environmental health hazards associated with ubiquitous chemicals at low levels. It provides a framework for considering and evaluating the contribution to the total insult from dermal uptake, ingestion of food and drinking water, and inhaled doses from potentially important microenvironments such as workplace, home, transportation, recreational sites, etc. More thorough discussions of this key concept have been prepared by Sexton and Ryan (2), Lioy (3), and the National Research Council (4). Guidelines for Exposure Assessment have been formalized by the U.S. Environmental Protection Agency (5).

Figure 2.2 outlines possible approaches for estimating contaminant exposures of populations, as well as individuals, in a conceptual sense, and Fig. 2.3 indicates terminologies used by EPA to describe exposures and their distributions within a population.

Figure 2.2. Possible approaches for analyzing contaminant exposures.
Figure 2.3. EPA guidance on terminology for exposures in the general population.

Toxic chemicals in the environment that reach sensitive tissues in the human body can cause discomfort, loss of function, and changes in structure leading to disease. This section addresses the pathways and transport rates of chemicals from environmental media to critical tissue sites, as well as retention times at those sites. It is designed to provide a conceptual framework as well as brief discussions of (1) the mechanisms for—and some quantitative data on—uptake from the environment; (2) translocation within the body, retention at target sites, and the influence of the physicochemical properties of the chemicals on these factors; (3) the patterns and pathways for exposure of humans to chemicals in environmental media; and (4) the influence of age, sex, size, habits, health status, etc. 3.1 Terminology

An agreed on terminology is critically important when discussing the relationships among toxic chemicals in the environment, exposures to individuals and populations, and human health. Key terms used in this chapter are defined as follows:

Exposure: Contact with external environmental media containing the chemical of interest. For fluid media in contact with the skin or respiratory tract, both concentration and contact time are critical. For ingested material, concentration and amount consumed are important.

Microenvironments: Well-defined locations that can be treated as homogeneous (or well characterized) in the concentrations of a chemical or other stressor.

Deposition: Capture of the chemical at a body surface site on the skin, the respiratory tract, or the GI tract.

Clearance: Translocation from a deposition site to a storage site or depot within the body or elimination from the body.

Retention: Presence of residual material at a deposition site or along a clearance pathway. Dose: The amount of chemical deposited on (applied dose) or translocated to a site on or within the body where toxic effects can take place (delivered dose).

Target tissue: A site within the body where toxic effects lead to damage or disease. Depending on the toxic effects of concern, a target tissue can extend from whole organs to specific cells and to subcellular constituents within cells.

Exposure surrogates or indices: Indirect measures of exposure, such as: (1) concentrations in environmental media at times or places other than those directly encountered; (2) concentrations of the chemical of interest, a metabolite of the chemical, or an enzyme induced by the chemical in circulating or excreted body fluids, generally referred to as a biomarker of exposure; and (3) elevations in body burden measured by external probes.

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