Extending the environmental risk assessment for oseltamivir (Tamiflu ® ) under pandemic use conditions to the coastal marine compartment Thomas H. Hutchinson a , Amanda Beesley a , Patricia E. Frickers a , James W. Readman a , Jenny P. Shaw a , Jürg Oliver Straub b, ⁎ a Plymouth Marine Laboratory, Prospect Place, The Hoe, UK–Plymouth PL1 3DH, United Kingdom b F. Hoffmann-La Roche Ltd, Corporate Safety, Health and Environmental Protection Department, CSE 49/2.033, CH–4070 Basle, Switzerland abstract article info Article history: Received 5 February 2009 Accepted 2 April 2009 Available online 23 April 2009 Keywords: Ecotoxicology Environmental fate Environmental risk assessment Marine Tamiflu Oseltamivir Pandemic In case of an avian-influenza-derived human flu pandemic, an inordinately high use of medicines over several weeks is predicted, in particular for the recommended influenza antiviral oseltamivir (Tamiflu). While the risk of oseltamivir to sewage works and freshwater bodies has already been assessed, the fact that a large percentage of the human population worldwide lives relatively close to the sea raises concern for its environmental compatibility in coastal marine waters. The potential risk of high oseltamivir use to the marine compartment is assessed in this publication, based on the 2003 European Community Technical Guidance Document (TGD) for risk assessment. Subchronic embryo–larval ecotoxicity tests with three marine invertebrates (Pomatoceros triqueter, Annelida; Mytilus edulis, Mollusca; Paracentrotus lividus, Echinodermata) and chronic growth inhibition tests with two different groups of marine microalgae (Isochrysis galbana, Haptophyta; Skeletonema costatum, Heterokontophyta) were performed with the active substance oseltamivir carboxylic acid to derive a dependable marine predicted no-effect concentration (PNEC). This was compared to a predicted environmental concentration (PEC) for oseltamivir in coastal waters, based on the worst-case freshwater PEC. The PEC/PNEC risk characterisation ratio for the marine compartment is well below 1, which in the terminology of the TGD signifies no immediate concern. Further, while oseltamivir may be persistent (P), it is not bioaccumulative (B) nor highly ecotoxic (T) and therefore not a PBT substance. In conclusion, even a high pandemic use of oseltamivir would not lead to a significant risk for the marine compartment, in confirmation of the risk assessment for sewage works and freshwaters. © 2009 Elsevier Ltd. All rights reserved. 1. Introduction Human active pharmaceutical ingredients (APIs) are released to the environment after administration, metabolism (full, partial or none, depending on the API) and excretion (Kümmerer, 2008). Human excretions including residual APIs will normally be treated in a sewage treatment plant before being released into the receiving waters, in most cases a river or lake. An environmental risk assess- ment (ERA) has been requested for new human medicinal products in the European Community since 1993 (Straub, 2002). Depending on the maximum daily dose and various properties of the API, a risk characterisation for sewage works bacteria, surface water organisms, sediment, groundwater, bioaccumulation or soils may become necessary for such an ERA, as detailed by the 2006 ERA guideline issued by the European Medicines Agency (EMEA, 2006). The environmental safety of the influenza anti-viral API oseltami- vir (Tamiflu ® ) was questioned by Singer et al. (2007), particularly under the assumption of a human influenza pandemic triggered by avian H5N1 (haemagglutinin type 5–neuraminidase type 1) influenza viruses. Widespread usage of oseltamivir, for both treatment and prophylaxis, would lead to exceptionally high concentrations in surface waters that may be sustained over several weeks. A recent ERA for oseltamivir, based on those very high predicted environ- mental concentrations (PECs) and on predicted no-effect concentra- tions (PNECs) derived from chronic ecotoxicity tests, concluded in no evident risk to sewage works and surface waters from the use of oseltamivir, even under pandemic conditions (Straub, in press). Briefly, based on (sub)chronic ecotoxicity tests with algae, daphnia and fish, applying an assessment factor of 10 as per the European Community Technical Guidance Document for Risk Assessment (TGD, 2003), a PNEC of 100 μg/l was determined for oseltamivir as excreted (Straub, in press). This was compared to the worst-case pandemic PEC of 98.1 μg/l for the River Lee catchment in southeastern England, Environment International 35 (2009) 931–936 ⁎ Corresponding author. Tel.: +41 616 885 781; fax: +41 616 881 920. E-mail address: juerg.straub@roche.com (J.O. Straub). 0160-4120/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.envint.2009.04.001 Contents lists available at ScienceDirect Environment International journal homepage: www.elsevier.com/locate/envint