title: An evaluation of the OECD 308 water/sediment systems for investigating the biodegradation of pharmaceuticals.
abstract: In recent times, trace levels of pharmaceuticals detected in wastewater effluents and surface waters have raised the level of attention around the ultimate fate and the potential persistence of pharmaceuticals in the environment. We have seen the European Agency for the Evaluation of Medicines (EMEA) recently include more rigorous environmental fate testing in European Union (EU) Environmental Risk Assessment (ERA) guidance to assess the ultimate fate in water/sediment systems. Yet to date, there is little data available that covers the fate of pharmaceuticals in the water/sediment compartment, and little that assess whether current aerobic and anaerobic methods are appropriate for pharmaceuticals. In this study, the biodegradation profiles of 3 Pfizer products were investigated following the latest ERA guidance and its recommendation for OECD 308 water/sediment biodegradation testing. Experiments included 14C-labeled exemestane, azithromycin, and varenicline representing neutral and cationic pharmaceuticals with average K(oc) values of 3704, 49 400, and 10 483 respectively. Specific HPLC/radioactive monitoring (RAM) methods were used to profile water and sediment samples for biotransformation products. Binding to sediment, as "non-extractables", was considerable for all three pharmaceuticals, though most notable for the cationic pharmaceuticals varenicline and azithromycin ranging from 52% to 94% at study termination, respectively. In general, for all 3 pharmaceuticals studied, the anaerobic conditions demonstrated less biotransformation and mineralization than the aerobic; though their biotransformation profile (number of metabolites) and amount bound to sediment were similar. Based on these findings and our current understanding of anaerobic biodegradation, we would recommend a tiered approach to the OECD 308 water/ sediment test: with default testing just for aerobic conditions; and then if needed, anaerobic testing only for those compounds potentially amenable to typical anaerobic processes. We suggest that as a simulation test would be better suited in later tier testing under EU ERA guidance. Inherent biodegradation or die-away tests seem better suited to derive biodegradation rate constants for subsequent environmental modeling of water and sediment compartments.
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism, Environmental Sciences, Pfizer Global Research & Development, MS 8118A-2026, Groton, Connecticut 06340, USA. jon.f.ericson@pfizer.com
authors.forename: Jon F
authors.initials: JF
authors.lastname: Ericson
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D000730:Androstadienes / Q000737:chemistry / Q000378:metabolism; D017963:Azithromycin / Q000737:chemistry / Q000378:metabolism; D001552:Benzazepines / Q000737:chemistry / Q000378:metabolism; D001673:Biodegradation, Environmental; D002247:Carbon Isotopes; D005060:Europe; D019015:Geologic Sediments / Q000737:chemistry*; D033161:Government Regulation; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism; D012015:Reference Standards; D018570:Risk Assessment; D000068580:Varenicline; D014867:Water / Q000737:chemistry*
chemical_list: D000730:Androstadienes; D001552:Benzazepines; D002247:Carbon Isotopes; D004364:Pharmaceutical Preparations; D011810:Quinoxalines; D014867:Water; D017963:Azithromycin; C056516:exemestane; D000068580:Varenicline