embryology and developmental biology, and there is a growing body of literature demonstrating how factors, including internal neural and hormonal events and external sensory events, activate or inhibit gene expression during individual development (see Davidson, 1986, 2001; Gilbert, 2000; Holliday, 1990).

Body Stores

Chemicals in the environment (air, water, dirt, dust, food) move into the body across such biological barriers as skin, lungs, and the gastrointestinal system. Exposure is considered to be contact of the agent with the biological barrier; following exposure, the agent crosses the barrier and is found inside the body (the internal dose). After uptake or absorption across the barrier, chemical agents (including drugs) are distributed throughout the body, metabolized, and eliminated (U.S. Environmental Protection Agency, 2003; Atkinson et al., 2001).

The rate of elimination varies substantially for different agents; some are eliminated in a matter of minutes; others may be found in the body for years following exposure. The amount of chemical/biochemical/vitamin/mineral stored or measured in the body is called the “body stores” or “body burden” of that agent. The committee has adopted the term “body burden” in this report. Body burdens of a chemical or drug represent the amount of cumulative exposure and, in some instances, can be transferred to another individual (e.g., from a mother to the fetus or infant through the placenta or in breast milk).

Body burdens can improve or harm health, based on their biological characteristics and presence during certain periods of development. Maternal body burdens of either lead or polychlorinated biphenyls (PCBs) impair the cognitive function of offspring if present during critical periods during fetal development (Gomaa et al., 2002; Lai et al., 2002). A body burden of lead in the bones of young children has been associated with poor social behavior (Needleman et al., 2002; Wald et al., 2001), poor cognitive performance or development (Lanphear et al., 2003; Rogan and Ware, 2003), and impaired pubertal progression (Selevan et al., 2003). The relative impact of body burdens varies with developmental stage. Relatively lower body burdens of organic mercury will reduce cognitive development in young children more than at older ages (U.S. Environmental Protection Agency, 2000c; National Research Council, 2000).

Some body burdens can have positive impacts on healthy development. For example, maternal body burdens of folate during the early first trimester of pregnancy significantly reduce the risk of a baby with a neural tube defect (Wald et al., 2001). Adolescents with higher levels of folate also have a significantly decreased risk of juvenile hypertension (Kahleova et al., 2002), and adults with high folate stores appear to be at substantially lower risk of cardiovascular disease (Wald, Law, and Morris, 2002). Some body stores that are beneficial at lower levels can become harmful at higher levels: a baby’s appropriate body burdens of iron will improve cognitive outcome, but an inappropriately high body burden of iron



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