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Background: The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned., Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing., Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity. Possible links between these factors and the ecotoxicity data for effects on, growth, mortality and/or reproduction, were evaluated. The environmental risks were then assessed based on a combined analysis of drug toxicity and predicted environmental concentrations based on European patient consumption data., Results: For most (88%) of the of 975 approved small molecule drugs targeting human proteins a complete set of regulatory compliant ecotoxicity data in the public domain was lacking, highlighting the need for both intelligent approaches to prioritize legacy human drugs for a tailored environmental risk assessment and a transparent database that captures environmental data. We show that presence/absence of drug-target orthologues are predictive of susceptible species for the more potent drugs. Drugs that target the endocrine system represent the highest potency and greatest risk. However, for most drugs (>80%) with a full set of ecotoxicity data, risk quotients assuming worst-case exposure assessments were below one in all European countries indicating low environmental risks for the endpoints assessed., Conclusion: We believe that the presented analysis can guide improvements to current testing procedures, and provide valuable approaches for prioritising legacy drugs (i.e. those registered before 2006) for further ecotoxicity testing. For drugs where effects of possible concern (e.g. behaviour) are not captured in regulatory tests, additional mechanistic testing may be required to provide the highest confidence for avoiding environmental impacts., (Copyright © 2019. Published by Elsevier Ltd.)

Many urban European streams are recovering from industrial, mining, and sewage pollution during the 20th century. However, associated recolonization by clean water organisms can potentially result in exposure to legacy or novel toxic pollutants that persist in the environment. Between 2008 and 2010, we sampled eggs of a river passerine, the Eurasian dipper (Cinclus cinclus), from 33 rivers in South Wales and the English borders (UK) which varied in catchment land use from rural to highly urbanized. Dipper egg δ(15)N and δ(13)C stable isotopes were enriched from urban rivers while δ(34)S was strongly depleted, effectively discriminating their urban or rural origins at thresholds of 10% urban land cover or 1000 people/km(2). Concentrations of total polychlorinated biphenyls (PCBs) and polybrominated biphenyl ethers (PBDEs) were positively related to urban land cover and human population density while legacy organochlorine pesticides such as p,p'-DDE, lindane, and hexachlorobenzene were found in higher concentrations at rural sites. Levels of PBDEs in urban dipper eggs (range of 136-9299 ng/g lw) were among the highest ever reported in passerines, and some egg contaminants were at or approaching levels sufficient for adverse effects on avian development. With the exception of dieldrin, our data shows PCBs and other organochlorine pesticides have remained stable or increased in the past 20 years in dipper eggs, despite discontinued use.