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 96h 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 rantidine, 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.

Highlights

  • The pseudo-persistent nature of pharmaceuticals and personal care products (PPCPs) has been highlighted in recent years as an environmental concern and has led to the introduction of a watch list under the EU Water Framework Directive which includes an anti-inflammatory, diclofenac, and two hormones, the synthetic ethinyl-estradiol (EE2) and natural estradiol (2013/39/EU, 2013)

  • Aquatic invertebrates such as molluscs and smaller crustacean species have been previously utilised for monitoring PPCPs in the natural aquatic environment

  • The rate of PPCP uptake measured in the exposed G. pulex corresponds to the decreases in PPCP concentration measured in the spiked artificial freshwater (AFW)

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Summary

Introduction

The pseudo-persistent nature of pharmaceuticals and personal care products (PPCPs) has been highlighted in recent years as an environmental concern and has led to the introduction of a watch list under the EU Water Framework Directive which includes an anti-inflammatory, diclofenac, and two hormones, the synthetic ethinyl-estradiol (EE2) and natural estradiol (2013/39/EU, 2013). Several thousand PPCPs are currently available worldwide and whilst measured environmental concentrations typically range from low ng L−1 to high μg L−1, their potential to effect an ecotoxicological response and/or bioaccumulate in a range of biota still remains understudied (De Lange et al, 2006; Contardo-Jara et al, 2011). Chronic exposure has been linked to behavioural activity changes, increased oxidative stress and alterations to the function of several vital organs in fish and invertebrates (Heckmann et al, 2007; Fernández et al, 2013). Aquatic invertebrates such as molluscs and smaller crustacean species have been previously utilised for monitoring PPCPs in the natural aquatic environment. A lack of published research generally exists on the uptake and depuration kinetics of PPCPs both in target and non-target aquatic species to help elucidate potential acute versus chronic effects

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