A fish full life-cycle (FFLC) study was conducted for 17α-ethinylestradiol (EE₂) using the fathead minnow, Pimephales promelas. Newly fertilized embryos (<24 h old) were exposed to five concentrations of EE₂ (0.2, 1.0, 4.0, 16, and 64 ng/L nominal) in continuous flow-through conditions for 305 d at 25 ± 1°C. Exposure concentrations were verified by ¹⁴C-EE₂ radiochemistry, supported by radioimmunoassay, and mean measured values were ≥70% of nominal. For the F₀ adult phase until 301 d posthatch, the no-observed-effect concentrations (NOECs) for growth, survival, and reproduction (as egg production) were all ≥ 1.0 ng/L. The NOEC values for F₁ embryo hatching success and larval survival (at 28 d posthatch) were both ≥ 1.0 ng/L. While statistically detectable changes in F₁ growth were evident at 0.2 ng/L, these were not considered to be biologically significant when compared with historical control data. Male fish exposed to EE₂ at 4.0 ng/L failed to develop normal secondary sexual characteristics; on the other hand, assumed females exposed to this level of EE₂ were able to breed when paired with males that had not been exposed to EE₂. Histology of F₀ control, 0.2-, and 1-ng/L exposed fish at 56 d posthatch indicated an approximate female-to-male (F:M) sex ratio of 50:50 (with no ovatestes observed in the control), while fish exposed to EE₂ at 4.0 ng/L for 56 d posthatch had a F: M sex ratio of 84:5 (with ovatestes in 11% of fish). After 172 d posthatch, no testicular tissue was observed in any fish exposed to EE₂ at 4.0 ng/L. At the same time point, plasma vitellogenin levels were significantly higher in fish exposed to EE₂ at 16 ng/L. A lack of sexual differentiation occurred in males at concentrations ≥4.0 ng/L. Taking into account these data, the overall no-observed-adverse-effect concentration was considered to be 1.0 ng/L.

There has been a significant investment in research to define exposures and potential hazards of pharmaceuticals in freshwater and terrestrial ecosystems. A substantial number of integrated environmental risk assessments have been developed in Europe, North America and many other regions for these situations. In contrast, comparatively few empirical studies have been conducted for human and veterinary pharmaceuticals that are likely to enter coastal and marine ecosystems. This is a critical knowledge gap given the significant increase in coastal human populations around the globe and the growth of coastal megacities, together with the increasing importance of coastal aquaculture around the world. There is increasing evidence that pharmaceuticals are present and are impacting on marine and coastal environments. This paper reviews the sources, impacts and concentrations of pharmaceuticals in marine and coastal environments to identify knowledge gaps and suggests focused case studies as a priority for future research.

Biomarkers are currently best used as mechanistic “signposts” rather than as “traffic lights” in the environmental risk assessment of endocrine-disrupting chemicals (EDCs). In field studies, biomarkers of exposure [e.g., ...

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 (HC_5,50) of 0.35 ng/L. After comparing this HC_5,50 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.