title: Predictive framework for estimating exposure of birds to pharmaceuticals.
abstract: We present and evaluate a framework for estimating concentrations of pharmaceuticals over time in wildlife feeding at wastewater treatment plants (WWTPs). The framework is composed of a series of predictive steps involving the estimation of pharmaceutical concentration in wastewater, accumulation into wildlife food items, and uptake by wildlife with subsequent distribution into, and elimination from, tissues. Because many pharmacokinetic parameters for wildlife are unavailable for the majority of drugs in use, a read-across approach was employed using either rodent or human data on absorption, distribution, metabolism, and excretion. Comparison of the different steps in the framework against experimental data for the scenario where birds are feeding on a WWTP contaminated with fluoxetine showed that estimated concentrations in wastewater treatment works were lower than measured concentrations; concentrations in food could be reasonably estimated if experimental bioaccumulation data are available; and read-across from rodent data worked better than human to bird read-across. The framework provides adequate predictions of plasma concentrations and of elimination behavior in birds but yields poor predictions of distribution in tissues. The approach holds promise, but it is important that we improve our understanding of the physiological similarities and differences between wild birds and domesticated laboratory mammals used in pharmaceutical efficacy/safety trials, so that the wealth of data available can be applied more effectively in ecological risk assessments. Environ Toxicol Chem 2017;36:2335-2344. © 2017 SETAC.
authors.affiliation: Environment Department, University of York, York, United Kingdom.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Bean
authors.affiliation: Environment Department, University of York, York, United Kingdom.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Arnold
authors.affiliation: Animal and Plant Health Agency, York, United Kingdom.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Lane
authors.affiliation: Centre of Excellence in Mass Spectrometry and Department of Chemistry, University of York, York, United Kingdom.
authors.forename: Ed
authors.initials: E
authors.lastname: Bergström
authors.affiliation: Centre of Excellence in Mass Spectrometry and Department of Chemistry, University of York, York, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Thomas-Oates
authors.affiliation: United States Geological Survey Patuxent Wildlife Research Center, Beltsville, Maryland, USA.
authors.forename: Barnett A
authors.initials: BA
authors.lastname: Rattner
authors.affiliation: Environment Department, University of York, York, United Kingdom.
authors.forename: Alistair B A
authors.initials: ABA
authors.lastname: Boxall
mesh_terms: D000818:Animals; D000835:Animals, Wild; D000928:Antidepressive Agents / Q000493:pharmacokinetics; D001717:Birds / Q000378:metabolism*; D005473:Fluoxetine / Q000493:pharmacokinetics; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012377:Rodentia; D062065:Wastewater / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D004364:Pharmaceutical Preparations; D062065:Wastewater
keywords: Ecological risk assessment; Fluoxetine; Pharmacokinetics; Read-across; Wild birds