Environmental Risk Assessment for the Active Pharmaceutical Ingredient Mycophenolic Acid in European Surface Waters

Abstract

An environmental risk assessment is presented for mycophenolic acid (MPA), an immunosuppressive pharmaceutical used for prevention of organ rejection, and its prodrug mycophenolate mofetil (MPM). Mycophenolic acid will not significantly adsorb to activated sludge. In activated sludge, 14C‐MPA attained >80% degradation, supporting an older environmental fate test with the same compound. Based on n‐octanol/water distribution coefficient (log DOW) values of 2.28, 0.48, and ≤–1.54 at pH 5, 7, and 9, respectively, MPA is not expected to bioaccumulate. Sales amounts of MPA+MPM in Europe were used to derive predicted environmental concentrations (PECs) in surface waters; PECs were refined by including expected biodegradation in sewage treatment, average drinking water use, and average dilution of the effluents in the receiving waters per country. In addition, the exposure to pharmaceuticals in the environment (ePiE) model was run for 4 European catchments. The PECs were complemented with 110 measured environmental concentrations (MECs), ranging from below the limit of quantitation (<0.001 µg/L) to 0.656 µg/L. Predicted no‐effect concentrations (PNECs) were derived from chronic tests with cyanobacteria, green algae, daphnids, and fish. The comparison of PECs and MECs with the PNECs resulted in a differentiated environmental risk assessment in which the risk ratio of PEC/PNEC or MEC/PNEC was <1 in most cases (mostly >90%), meaning no significant risk, but a potential risk to aquatic organisms in generally <10% of instances. Because this assessment reveals a partial risk, the following questions must be asked: How much risk is acceptable? and Through which measures can this risk be reduced? These questions are all the more important in view of limited alternatives for MPM and MPA and the serious consequences of not using them. Environ Toxicol Chem 2019;38:2259–2278. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Occurrence of Pharmaceutically Active Compounds and Potential Ecological Risks in Wastewater from Hospitals and Receiving Waters in Sri Lanka

“…To evaluate the adverse ecological effects of PACs on the aquatic ecosystem, the environmental risks posed by the target compounds to the most sensitive aquatic species were assessed based on risk quotients (RQs). The RQ was calculated from the predicted environmental concentration (PEC) and the predicted no‐effect concentration (PNEC; Ministry of the Environment, Government of Japan, 2018; Straub et al, 2019) using Equations (2) and (3). In some studies, the PEC was calculated by applying a dilution factor that was estimated by freshwater availability and domestic sewage discharge (Keller et al, 2014).…”

Evidence for Specific Receptor-Mediated Toxicity of Pharmaceuticals in Aquatic Organisms Derived from Acute and Chronic Standard Endpoints

“…In addition to the experimental results for the APIs we tested, more data were compiled from the pharmaceutical industry, namely, those made publicly available through the platform (iPiEsum 2020) that has been developed within the research project ipiE (Intelligence‐led Assessment of Pharmaceuticals in the Environment 2020), funded by the Innovative Medicines Initiative. We also compiled data from the literature (Vestel et al 2016; Straub et al 2019). These data repositories are publicly accessible; therefore, the compiled individual ecotoxicity data are not presented in the Supplemental Data.…”

Chemotherapeutic drugs in Lebanese surface waters: estimation of population exposure and identification of high-risk drugs

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