Exposure Assessment for Endocrine Disruptors: Some Considerations in the Design of Studies
Rice, Carol, Birnbaum, Linda S., Cogliano, James, Mahaffey, Kathryn, Needham, Larry, Rogan, Walter J., vom Saal, Frederick S., Environmental Health Perspectives
In studies designed to evaluate exposure--response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data. A number of issues that must be considered in study design are summarized here. Key words: developing child, endocrine disruptors, environmental epidemiology, exposure assessment. Environ Health Perspect 111:1683-1690 (2003). doi: 10.1289/ehp.5798 available via http://dx.doi.org/ [Online 18 March 2003]
The assessment of human exposure to environmental chemicals requires an understanding of the source of the chemical, its transport and environmental fate, and subsequent routes of entry into the body. Once an exposure occurs, it is necessary to have data on its absorption, distribution, metabolism, and elimination. This is a complex undertaking for any environmental chemical and for any potentially exposed population. It is especially challenging in the evaluation of exposures to children at various stages of their development. The activity of the endocrine system is vital throughout all stages of human life, but it is particularly critical during the stages of greatest human development--in utero, during infancy, early childhood, and puberty.
Exogenous chemicals such as endocrine disruptors are of special interest because they mimic, block, or in some way alter the activity of endogenous chemicals that are synthesized by the endocrine system (National Research Council 1999). The endocrine system as used here refers to all compounds involved in communicating information that are secreted by cells. These compounds can have autocrine effects (on the same cell), paracrine effects (on cells nearby), and classic endocrine effects (secretion is into the blood stream, potentially exposing all cells to the compound) (National Research Council 1999). The class of endocrine disruptors about which we know the most are those that mimic or block endogenous estrogens. Examples of synthetic chemicals with reported estrogenic activity are listed in Table 1.
Dietary exposures to some potential endocrine disruptors have been quantified for adults. For example, phytoestrogen consumption (expressed as total bioflavoids) is estimated at 1 g/day, whereas 100 g of wheat germ with 2 ppm zearalenone provides 200 [micro]g/day (National Research Council 1999). The estimated exposure to dichlorodiphenyltrichloroethane (DDT) from all dietary sources in the general U.S. population is 0.01 [micro]g/day, and estimated exposure to polychlorinated biphenyls (PCBs) is 0.002 [micro]g/day (National Research Council 1999). However, exposures to environmental contaminants may vary among countries; for example, in areas where DDT is still used extensively, breast milk may be a significant source of DDT exposure for an infant (Kashyap et al. 1991).
Akland et al. (2000) have modeled the various factors influencing dietary exposures of young children. However, at different human developmental stages, not only do the diets vary but also the primary route of human exposure may vary; for example, Hubal et al. (2000) described the challenge of assessing children's residential exposure to pesticides.
In addition to dietary sources, other aspects of exposure assessment that should be considered in developing a research initiative include timing or age at exposure; the rate of exposure (frequency and duration); qualitative versus quantitative assessment; sample collection and storage; sample analysis; and exposures assessed to test hypotheses and those to generate additional hypotheses. …