Elimination Resistance: Characterizing Multi-compartment Toxicokinetics of the Neonicotinoid Thiacloprid in the Amphipod Gammarus pulex Using Bioconcentration and Receptor-Binding Assays

Delayed toxicity is a phenomenon observed for aquatic
invertebrates
exposed to nicotinic acetylcholine receptor (nAChR) agonists, such
as neonicotinoids. Furthermore, recent studies have described an incomplete
elimination of neonicotinoids by exposed amphipods. However, a mechanistic
link between receptor binding and toxicokinetic modeling has not been
demonstrated yet. The elimination of the neonicotinoid thiacloprid
in the freshwater amphipod Gammarus pulex was studied in several toxicokinetic exposure experiments, complemented
with in vitro and in vivo receptor-binding assays. Based on the results,
a two-compartment model was developed to predict the uptake and elimination
kinetics of thiacloprid in G. pulex. An incomplete elimination of thiacloprid, independent of elimination
phase duration, exposure concentrations, and pulses, was observed.
Additionally, the receptor-binding assays indicated irreversible binding
of thiacloprid to the nAChRs. Accordingly, a toxicokinetic-receptor
model consisting of a structural and a membrane protein (including
nAChRs) compartment was developed. The model successfully predicted
internal thiacloprid concentrations across various experiments. Our
results help in understanding the delayed toxic and receptor-mediated
effects toward arthropods caused by neonicotinoids. Furthermore, the
results suggest that more awareness toward long-term toxic effects
of irreversible receptor binding is needed in a regulatory context.
The developed model supports the future toxicokinetic assessment of
receptor-binding contaminants.