An assessment of potential exposure and risk from estrogens in drinking water

Abstract

Background: Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans.

Objectives: We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary intake or ADIs.

Methods: We used the Pharmaceutical Assessment and Transport Evaluation (PhATE) model to predict concentrations of estrogens potentially present in drinking water. Predicted drinking water concentrations were combined with default water intake rates to estimate drinking water exposures. Predicted drinking water intakes were compared to dietary intakes and also to ADIs. We present comparisons for individual estrogens as well as combined estrogens.

Results: In the analysis we estimated that a child's exposures to individual prescribed estrogens in drinking water are 730-480,000 times lower (depending upon estrogen type) than exposure to background levels of naturally occurring estrogens in milk. A child's exposure to total estrogens in drinking water (prescribed and naturally occurring) is about 150 times lower than exposure from milk. Adult margins of exposure (MOEs) based on total dietary exposure are about 2 times smaller than those for children. Margins of safety (MOSs) for an adult's exposure to total prescribed estrogens in drinking water vary from about 135 to > 17,000, depending on ADI. MOSs for exposure to total estrogens in drinking water are about 2 times lower than MOSs for prescribed estrogens. Depending on the ADI that is used, MOSs for young children range from 28 to 5,120 for total estrogens (including both prescribed and naturally occurring sources) in drinking water.

Conclusions: The consistently large MOEs and MOSs strongly suggest that prescribed and total estrogens that may potentially be present in drinking water in the United States are not causing adverse effects in U.S. residents, including sensitive subpopulations.

Figure 1

Cumulative distribution (and arithmetic mean) of PECs generated by PhATE for three different categories of estrogens in U.S. drinking water assuming critical low-flow conditions (7Q10). For the endogenous estrogens, the combined concentrations of E1, E2, and E3 were not adjusted for differences in biological activity.

Figure 2

MOEs (equal to the predicted estrogen intake from milk divided by the predicted estrogen intake from drinking water) for a young child. For E1, E2, and E3, MOEs are shown for exposure to prescribed estrogens predicted to be in drinking water and for naturally occurring estrogens predicted to be in drinking water. A single MOE is shown for EE2 because the only source of EE2 in drinking water is assumed to be therapeutic use (i.e., prescribed). MOEs for E1, E2, and E3 are based on the mass-based concentration of each estrogen in drinking water and milk. The EE2 MOE is based on the E2-eq concentration of EE2 in drinking water and of E1, E2, and E3 combined in milk.

Figure 3

MOSs for adult exposure to estrogens via drinking water for the WHO ADI, the TTC, four ADIs derived from OELs, and the four ADIs used to derive the Australian guidelines (EPHC et al. 2008). For the WHO ADI and the TTC, five MOSs are presented corresponding to five categorizations of estrogens predicted to be in drinking water. MOSs for the WHO ADI and TTC are based on estrogen intakes expressed as E2-eq (i.e., are activity adjusted), as are the MOSs for total prescribed and total all sources comparisons to OELs and Australian guidelines, whereas MOSs for the individual estrogens for OEL and Australian guideline comparisons are based on estrogen intakes expressed on a mass basis (i.e., are not activity adjusted because the estrogen-specific ADIs embody differences in activity).