In its review of hormonally active agents in the environment, the National Research Council (NRC 1999) recommended that further investigations of human exposure to natural and anthropogenic hormonally active agents be conducted to determine relative contributions of estrogen equivalents. The NRC (1999, p. 273) further recommended that the biological potency of hormonally active agents must be related to that of endogenous hormones in premenopausal and postmenopausal women and in men. Additional comparisons should be made with pharmacologic estrogens (hormonereplacement therapy and hormonal contraceptives) and phytoestrogens because large segments of the population are exposed to these compounds.In addition, the Endocrine Disruptor Screening and Testing Advisory Committee recommended that the U.S. Environmental Protection Agency (U.S. EPA) screen and potentially test "representative mixtures to which large . . . segments of the population are exposed," including human milk (EDSTAC 1998), which has raised questions regarding whether appropriate methods and data are available for performing such an assessment (LaKind and Berlin 2002).The assessment implied by the recommendations of those scientific bodies would involve using biological mechanistic information coupled with exposure data to assess overall human health risk for a particular mechanism. This concept is not new and has been used, for example, to evaluate risks to dioxin-like chemicals that are presumed or demonstrated to act through an aryl hydrocarbon (Ah) receptor-mediated mechanism (i.e., the toxic equivalents, or TEQ, approach). Similarly, Safe (1995) and NRC (1999) have compared the toxic potency of dietary and environmental estrogenic chemicals, using the concept of estrogen equivalents (EQs) where the substances are presumed to act though an estrogen receptor (ER)-mediated mechanism. On the basis of the EQ approach, Safe (1995) estimated that dietary intake of EQs from naturally occurring estrogenic compounds far exceeds dietary intake of man-made estrogenic compounds.In an extension of this approach, we initially sought to apply methods for estimating relative estrogenic potencies of endogenous and exogenous chemicals to assessing estrogenic risks for the two primary sources of infant nutrition: human milk and infant formulas. Both types of infant nutrition are complex mixtures of chemicals, and both contain an array of substances that have potential estrogenic activity. In combination with information on concentrations of endogenous and exogenous chemicals in these nutrition sources, estrogenic potency estimates would theoretically allow us to evaluate the relative magnitude of hormonal activity from naturally occurring substances compared with hormonal activity from exogenous substances. However, for reasons enumerated in this review, we believe that the current state of scientific understanding does not allow for accurate estimates by such methods. Although we recognize that hormonally active agents encompass a wide range of biochemical mecha...