Regulatory Risk Assessment of Pharmaceuticals in the Environment - Current Practice and Future Priorities.

How can data on the occurrence of pharmaceuticals and personal care products (PPCPs) in the environment and quality of ecosystems exposed to PPCPs be used to determine whether current regulatory risk assessment schemes are effective? This is one of twenty "big questions" concerning PPCPs in the environment posed in a landmark review paper in 2012. Ten years later, we review the developments around this question, focusing on the first P in PPCPs, i.e., pharmaceuticals, or more specifically the active ingredients included in them (active pharmaceutical ingredients; APIs). We illustrate how extensive data on both the occurrence of APIs and ecotoxicological sensitivity of aquatic species to them can be used in a retrospective risk assessment. In the Netherlands, current regulatory risk assessment schemes offer yet insufficient protection against direct ecotoxicological effects from APIs: the toxic pressure exerted by the 39 APIs included in our study exceeds the policy-related protective threshold of 0.05 (the '95%-protection level') in at least 13% of sampled surface waters. In general, anti-inflammatory and antirheumatic products (e.g., diclofenac, ibuprofen) contributed most to the overall toxic pressure, followed by sex hormones and modulators of the genital system (e.g., ethinylestradiol) and psychoanaleptics (e.g., caffeine). We formulated three open questions for future research. The first relates to improving the availability and accessibility of good quality ecotoxicity data on pharmaceuticals for the global scientific, regulatory and general public. The second relates to the adaptation of regulatory risk assessment frameworks for developing regions of the world. The third relates to the integration of effect-based and ecological approaches into regulatory risk assessment practice. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0-0. © 2022 SETAC.