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Ethinyl Estradiol and Other Human Pharmaceutical Estrogens in the Aquatic Environment: A Review of Recent Risk Assessment Data

Abstract

Interest in pharmaceuticals in the environment has increased substantially in recent years. Several studies in particular have assessed human and ecological risks from human pharmaceutical estrogens, such as 17α-ethinyl estradiol (EE2). Regulatory action also has increased, with the USA and other countries developing rules to address estrogens and other pharmaceuticals in the environment. Accordingly, the Center for Drug Evaluation and Research at the US Food and Drug Administration has conducted a review and analysis of current data on the long-term ecological exposure and effects of EE2 and other estrogens. The results indicate that mean-flow long-term predicted environmental concentrations (PECs) of EE2 in approximately 99% or more of US surface water segments downstream of wastewater treatment plants are lower than a predicted no-effect concentration (PNEC) for aquatic chronic toxicity of 0.1 ng/L. Exceedances are expected to be primarily in localized, effluent-dominated water segments. The median mean-flow PEC is more than two orders of magnitude lower than this PNEC. Similar results exist for other pharmaceutical estrogens. Data also suggest that the contribution of EE2 more broadly to total estrogenic load in the environment from all sources (including other human pharmaceutical estrogens, endogenous estrogens, natural environmental estrogens, and industrial chemicals), while highly uncertain and variable, appears to be relatively low overall. Additional data and a more comprehensive approach for data collection and analysis for estrogenic substances in the environment, especially in effluent-dominated water segments in sensitive environments, would more fully characterize the risks.

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ACKNOWLEDGMENTS

The authors wish to thank Douglas Throckmorton, Deborah Livornese, Luis Valerio, and Roxane Modares from FDA/CDER for helpful discussions and review. The authors also wish to thank ICF International and IceTech, Inc. staff, in particular Margaret McVey, Arun Varghese, Isaac Warren, Christine Hartman, and Michael Smith, for providing much of the literature, data, and analysis used in this review (under contract no. HHSF223200910010I). Authors are listed according to first author (primary author) and last author (principal investigator) emphasis.

DISCLAIMER

The findings and conclusions in this article have not been formally disseminated by FDA and should not be construed to represent any FDA determination or policy. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

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Guest Editors: James P. Laurenson, Raanan A. Bloom, and Nakissa Sadrieh

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Laurenson, J.P., Bloom, R.A., Page, S. et al. Ethinyl Estradiol and Other Human Pharmaceutical Estrogens in the Aquatic Environment: A Review of Recent Risk Assessment Data. AAPS J 16, 299–310 (2014). https://doi.org/10.1208/s12248-014-9561-3

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KEY WORDS

  • aquatic ecology
  • environmental impact
  • estrogens
  • regulatory science
  • toxicity