Comparative Toxicokinetics of Organic Micropollutants in Freshwater Crustaceans

Abstract

Exposure and depuration experiments for Gammarus pulex and Daphnia magna were conducted to quantitatively analyze biotransformation products (BTPs) of organic micropollutants (tramadol, irgarol, and terbutryn). Quantification for BTPs without available standards was performed using an estimation method based on physicochemical properties. Time-series of internal concentrations of micropollutants and BTPs were used to estimate the toxicokinetic rates describing uptake, elimination, and biotransformation processes. Bioaccumulation factors (BAF) for the parents and retention potential factors (RPF), representing the ratio of the internal amount of BTPs to the parent at steady state, were calculated. Nonlinear correlation of excretion rates with hydrophobicity indicates that BTPs with lower hydrophobicity are not always excreted faster than the parent compound. For irgarol, G.pulex showed comparable elimination, but greater uptake and BAF/RPF values than D.magna. Further, G. pulex had a whole set of secondary transformations that D. magna lacked. Tramadol was transformed more and faster than irgarol and there were large differences in toxicokinetic rates for the structurally similar compounds irgarol and terbutryn. Thus, predictability of toxicokinetics across species and compounds needs to consider biotransformation and may be more challenging than previously thought because we found large differences in closely related species and similar chemical structures.

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

“…As the targeted LC-MS/MS method only determines the amount of parent compound, the BCF parent values presented above (Table 2) do not take into account the accumulation of any biotransformation products. The biotransformation product half-lives in the body can be longer or shorter than the parent compound as they are modified by biotransformation processes and potentially may lead to increased or decreased accumulation (Jeon et al., 2013a) and thus will not be accounted for by estimations of BCF parent .…”

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

“…If the assumption of steady state was inaccurate, then rather lower BAFs based on internal concentrations would be expected compared to BAF k s. Our kinetic and steady state BAFs (approximately 9−50 L kg ww ) for micropollutants with similar log K ow values. 6,30,31,63 As defined in REACH, Annex XIII compounds are considered as bioaccumulative with BAFs > 2000 L kg −1 . 64 Thus, azoles showed low bioaccumulation compared to the REACH criteria.…”

“…These findings are in agreement with the results of other studies, that did not observe a simple relationship between elimination kinetics and hydrophobicity either. 30,31,63,66 The slower elimination of hydrophilic molecules can be explained by the impaired transport across hydrophobic cell membranes, although their intracellular mobility is increased. 67 Biotransformation kinetics of organic compounds in gammarids differ widely among compounds.…”

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology

“…Total body burden is frequently used as a surrogate measure of internal concentrations in studies aimed at elucidation of uptake, biotransformation and elimination processes (Rubach et al, 2010;Kretschmann et al, 2012;MeredithWilliams et al, 2012;Jeon et al, 2013). However, recently the importance of organism-internal distribution for species sensitivity has also been demonstrated .…”