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 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.

Uptake, biotransformation and elimination of selected pharmaceuticals in a freshwater invertebrate measured using liquid chromatography tandem mass spectrometry

“…Again, k 1 was observed to decrease over time. These decreases again are potentially the cause of the lack-of-fits, as suggested previously (Miller et al., 2016). The reason for the decrease in k 1 over time could be attributed to either sorption on to the cuticle of the animal during the uptake phase, toxicodynamic effects where the pharmaceuticals are reducing the ability of the organism to eliminate the compound or growth dilution of the animal.…”

“…The reason for the decrease in k 1 over time could be attributed to either sorption on to the cuticle of the animal during the uptake phase, toxicodynamic effects where the pharmaceuticals are reducing the ability of the organism to eliminate the compound or growth dilution of the animal. However, preliminary evidence in (Miller et al., 2016) and the larger decreases in k 1 at the earlier time interval (this study) suggest that sorption might be a significant cause of the decreases in k 1 over time. In the cases of warfarin, carbamazepine, diazepam and temazepam an apparent plateau had been reached indicating k 1 constancy and it was possible to use this value to estimate the BCF parent .…”

“…As a final consideration, the data presented show that at environmentally relevant exposure concentrations, pharmaceuticals remain at very low level concentrations. Furthermore, for the selected compounds herein, they do not show any significant accumulation which has also been evidenced in the literature by several authors (Boillot et al., 2015, Meredith-Williams et al., 2012, Miller et al., 2016, Paterson and Metcalfe, 2008, Sordet et al., 2016). Thus, biotransformation studies will be key in highlighting the behaviour of these contaminants inside the animal and reveal the role of metabolic clearance for regulating accumulation.…”

“…Full details of parameter estimation can be found in (Miller et al., 2016). Herein, the authors define BCF total as the summation of the BCF of both parent/precursor and biotransformation products (i.e.…”

How Biotransformation Influences Toxicokinetics of Azole Fungicides in the Aquatic Invertebrate Gammarus pulex

“…Azoles potentially adsorbed to the exoskeleton of gammarids can influence the determination of BAFs by overestimating internal concentrations and uptake rates. Miller et al (2016) 65 analyzed the exoskeletons of gammarids that molted during the exposure period. They observed that the percentage of the adsorbed fraction on the total chemical mass in the animal was between 3 and 24% for five out of eight pharmaceuticals studied.…”