An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water

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.Johnson & Johnson Pharmaceutical Research and Development, LLC; Pfizer Inc.; Wyeth Inc

Pharmaceuticals and personal care products in the environment: What are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Centro de Investigaciones del Medioambient

Derivation of an aquatic predicted no-effect concentration for the synthetic hormone, 17α-ethinyl estradiol

17 alpha-Ethinyl estradiol (EE2) is a synthetic estrogen widely used in combination with other steroid hormones in oral contraceptives and in the contraceptive patch. EE2 has been detected in sewage treatment plant effluents in the low nanogram -per-liter range and occasionally in surface waters in the U.S., U.K., Canada, Brazil, Germany, and elsewhere. The mode of action is receptor-mediated, and estrogen receptors exist in mammals and other vertebrates. A large number of studies on the effects of EE2 on aquatic organisms exist. One hundred English language studies published between 1994 and 2007, one as yet unpublished study, and findings published in conference proceedings (in German) were compared to published data quality criteria to identify the most relevant studies for deriving a predicted no-effect concentration (PNEC). Reproduction in fish was identified as the most sensitive end point in aquatic species. A species sensitivity distribution was constructed using no observed effect concentrations (NOECs) for reproductive effects from 39 papers in 26 species, resulting in a median hazardous concentration at which 5% of the species tested are affected (HC5,50) of 0.35 ng/L. After comparing this HC5,50 to all of the laboratory and field-derived toxicity information available for EE2, we recommend using 0.35 ng/L as the PNEC for EE2 in surface water. This PNEC is below 95% of the existing NOECs for effects on reproduction and is also below virtually all of the NOECs for vitellogenin induction in the key fish reproduction studies

Endocrine disruption due to estrogens derived from humans predicted to be low in the majority of U.S. surface waters

In an effort to assess the combined risk estrone (E1), 17β-estradiol (E2), 17α-ethinyl estradiol (EE2), and estriol (E3) pose to aquatic wildlife across United States watersheds, two sets of predicted-no-effect concentrations (PNECs) for significant reproductive effects in fish were compared to predicted environmental concentrations (PECs). One set of PNECs was developed for evaluation of effects following long-term exposures. A second set was derived for short-term exposures. Both sets of PNECs are expressed as a 17β-estradiol equivalent (E2-eq), with 2 and 5 ng/L being considered the most likely levels above which fish reproduction may be harmed following long-term and short-term exposures, respectively. A geographic information system-based water quality model, Pharmaceutical Assessment and Transport Evaluation (PhATE™), was used to compare these PNECs to mean and low flow concentrations of the steroid estrogens across 12 U.S. watersheds. These watersheds represent approximately 19% of the surface area of the 48 North American states, contain 40 million people, and include over 44,000 kilometers of rivers. This analysis determined that only 0.8% of the segments (less than 1.1% of kilometers) of these watersheds would have a mean flow E2-eq concentration exceeding the long-term PNEC of 2.0 ng/L; only 0.5% of the segments (less than 0.8% of kilometers) would have a critical low flow E2-eq exceeding the short-term PNEC of 5 ng/L. Those few river segments where the PNECs were exceeded were effluent dominated, being either headwater streams with a publicly owned treatment works (POTW), or flowing through a highly urbanized environment with one or several POTWs. These results suggest that aquatic species in most U.S. surface waters are not at risk from steroid estrogens that may be present as a result of human releases

Pharmaceuticals and personal care products in the environment: What are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Fil: Boxall, Alistair B. A.. University of York; Reino UnidoFil: Rudd, Murray A.. University of York; Reino UnidoFil: Brooks, Bryan W.. Baylor University; Estados UnidosFil: Caldwell, Daniel J.. Johnson & Johnson; Estados UnidosFil: Choi, Kyungho. Seoul National University; Corea del SurFil: Hickmann, Silke. Umweltbundesamt; AlemaniaFil: Innes, Elizabeth. Health Canada; CanadáFil: Ostapyk, Kim. Health Canada; CanadáFil: Staveley, Jane P.. Exponent; Estados UnidosFil: Verslycke, Tim. Gradient; Estados UnidosFil: Ankley, Gerald T.. United States Environmental Protection Agency; Estados UnidosFil: Beazley, Karen F.. Dalhousie University Halifax; CanadáFil: Belanger, Scott E.. Procter And Gamble; Estados UnidosFil: Berninger, Jason P.. Baylor University; Estados UnidosFil: Carriquiriborde, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Centro de Investigaciones del Medio Ambiente; ArgentinaFil: Coors, Anja. Ect Oekotoxikologie Gmbh; AlemaniaFil: DeLeo, Paul C.. American Cleaning Institute; Estados UnidosFil: Dyer, Scott D.. Procter And Gamble; Estados UnidosFil: Ericson, Jon F.. Pfizer Inc.; Estados UnidosFil: Gagné, François. Environment Canada; CanadáFil: Giesy, John P.. University of Saskatchewan; CanadáFil: Gouin, Todd. Unilever; Reino UnidoFil: Hallstrom, Lars. University of Alberta; CanadáFil: Karlsson, Maja V.. University of York; Reino UnidoFil: Joakim Larsson, D.G.. University of Göteborg; AlemaniaFil: Lazorchak, James M.. United States Environmental Protection Agency; Estados UnidosFil: Mastrocco, Frank. Pfizer Inc.; Estados UnidosFil: McLaughlin, Alison. Health Canada; CanadáFil: McMaster, Mark E.. Environment Canada; CanadáFil: Meyerhoff, Roger D.. Eli Lilly And Company; Estados UnidosFil: Moore, Roberta. Health Canada; CanadáFil: Parrott, Joanne L.. Environment Canada; CanadáFil: Snape, Jason R.. AstraZeneca UK Ltd.; Reino UnidoFil: Murray-Smith, Richard. AstraZeneca UK Ltd.; Reino UnidoFil: Servos, Mark R.. University of Waterloo; CanadáFil: Sibley, Paul K.. University of Guelph; CanadáFil: Straub, Jürg Oliver. F. Hoffmann-La Roche Ltd.; SuizaFil: Szabo, Nora D.. University of Ottawa; CanadáFil: Topp, Edward. Agriculture Et Agroalimentaire Canada; CanadáFil: Tetreault, Gerald R.. University of Waterloo; CanadáFil: Trudeau, Vance L.. University of Ottawa; CanadáFil: Van Der Kraak, Glen. University of Guelph; Canad