Derivation of an Aquatic Predicted No-Effect Concentration for the Synthetic Hormone, 17α-Ethinyl Estradiol

Abstract

17α-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 One hundred English language studies published between 1994 and 2007, one as yet unpublished study, and findings published in conference proceedings (in German) were compared to published data quality criteria to identify the most relevant studies for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.

Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model

“…Previous work with several fish species, including the fathead minnow, has documented induction of VTG in male and immature animals by EE2 at water concentrations comparable to those used in this study (for reviews, see U.S. Environmental Protection Agency, 2008;Caldwell et al, 2008). Kang et al (2007) reviewed the effects of BPA on aquatic organisms, and reported induction of VTG in several fish species, including the fathead minnow, at water concentrations similar to or greater than that producing effects in the present study (100 g/L).…”

“…First we evaluated whether a third widely studied model AR antagonist, the anti-neoplastic drug cyproterone acetate (CA; Sonneveld et al, 2005), would block TB-induced tubercle formation in fathead minnows in a manner similar to flutamide and vinclozolin. We also conducted mixture studies with TB and 17␣-ethinylestradiol (EE2) or bisphenol A (BPA) which are considered, respectively, strong and weak ER agonists (Kang et al, 2007;Caldwell et al, 2008). Although tubercle formation in fathead minnows is clearly an AR-mediated phenomenon, it is possible that ER agonists could affect development of tubercles in the fathead minnow (Miles-Richardson et al, 1999).…”

Ecological Risk of Nonylphenol in China Surface Waters Based on Reproductive Fitness

“…The result is 100 or more times less than concentrations (0.13 μg L −1 ) derived from traditional test endpoints with application of assessment factors. 31 …”

Toxicity Reference Values and Tissue Residue Criteria for Protecting Avian Wildlife Exposed to Methylmercury in China

“…SSD is a statistical distribution representing the variation in sensitivity of species to a contaminant, and can be developed by a statistical or empirical distribution function of response for a sample of species ( Posthuma et al 2002 ) . This method has been used to assess risks to aquatic organisms and for deriving water quality criteria (WQC) for protecting aquatic species ( Caldwell et al 2008 ;Hall et al 1998 ;Solomon et al 1996 ;Stephan et al 1985 ) . However, because data on the toxicity of contaminants to wildlife are often insuf fi cient, the SSD approach to assess wildlife risks has not often been applied.…”