title: Assessing the reliability of uptake and elimination kinetics modelling approaches for estimating bioconcentration factors in the freshwater invertebrate, Gammarus pulex.
abstract: This study considers whether the current standard toxicokinetic methods are an accurate and applicable assessment of xenobiotic exposure in an aquatic freshwater invertebrate. An in vivo exposure examined the uptake and elimination kinetics for eight pharmaceutical compounds in the amphipod crustacean, Gammarus pulex by measuring their concentrations in both biological material and in the exposure medium over a 96 h period. Selected pharmaceuticals included two anti-inflammatories (diclofenac and ibuprofen), two beta-blockers (propranolol and metoprolol), an anti-depressant (imipramine), an anti-histamine (ranitidine) and two beta-agonists (formoterol and terbutaline). Kinetic bioconcentration factors (BCFs) for the selected pharmaceuticals were derived from a first-order one-compartment model using either the simultaneous or sequential modelling methods. Using the simultaneous method for parameter estimation, BCF values ranged from 12 to 212. In contrast, the sequential method for parameter estimation resulted in bioconcentration factors ranging from 19 to 4533. Observed toxicokinetic plots showed statistically significant lack-of-fits and further interrogation of the models revealed a decreasing trend in the uptake rate constant over time for ranitidine, diclofenac, imipramine, metoprolol, formoterol and terbutaline. Previous published toxicokinetic data for 14 organic micro-pollutants were also assessed and similar trends were identified to those observed in this study. The decreasing trend of the uptake rate constant over time highlights the need to interpret modelled data more comprehensively to ensure uncertainties associated with uptake and elimination parameters for determining bioconcentration factors are minimised.
authors.affiliation: Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom; AstraZeneca, Global Environment, Alderley Park, Macclesfield, Cheshire SK10 4TF, United Kingdom.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Miller
authors.affiliation: Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: McEneff
authors.affiliation: Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Stott
authors.affiliation: AstraZeneca, Global Environment, Alderley Park, Macclesfield, Cheshire SK10 4TF, United Kingdom.
authors.forename: Stewart F
authors.initials: SF
authors.lastname: Owen
authors.affiliation: Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
authors.forename: Nicolas R
authors.initials: NR
authors.lastname: Bury
authors.affiliation: Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom. Electronic address: leon.barron@kcl.ac.uk.
authors.forename: Leon P
authors.initials: LP
authors.lastname: Barron
mesh_terms: D033304:Amphipoda / Q000378:metabolism*; D000818:Animals; D004784:Environmental Monitoring / Q000379:methods*; D005618:Fresh Water; D007700:Kinetics; D008956:Models, Chemical; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000378:metabolism*; D015262:Xenobiotics / Q000032:analysis / Q000378:metabolism*
chemical_list: D014874:Water Pollutants, Chemical; D015262:Xenobiotics
keywords: Bioconcentration; Invertebrates; Pesticides; Pharmaceuticals; Toxicokinetics