Uptake Rate Constants Research Articles

Toxicokinetics and responses of multiple biomarkers of sediment-associated fluoroquinolones in an ecologically important freshwater snail Bellamya aeruginosa

Fluoroquinolones (FQs) have the propensity to accumulate in sediments once introduction into aquatic environments, thereby posing potential threats to benthic organisms, yet the ecotoxicity of sediment-associated FQs remains unclear. In this study, the toxicokinetics and responses of multiple biomarkers in Bellamya aeruginosa, exposed to the three commonly used FQs (norfloxacin, NOR; ciprofloxacin, CIP; levofloxacin, LEVO) at environmentally relevant concentrations were investigated under sediment exposure scenario. The results revealed that FQs were effectively ingested by B. aeruginosa from sediments, CIP showing the highest bioaccumulation (180.59 μg/kg), followed by NOR (74.49 μg/kg) and LEVO (36.02 μg/kg). CIP exhibiting a highest uptake rate constant (Ks) (4.64 g/(g.d)) and the lowest elimination rate constant (Ke) (0.05 g/(g.d)). The descending order of biological half-life is as follows: CIP (13.62 d), LEVO (8.14 d), and NOR (6.83 d). NOR induced the activity of superoxide dismutase, catalase, and glutathione-S-transferase while CIP and LEVO depressed their activities and increased malondialdehyde content, indicating a more pronounced oxidative damage to B. aeruginosa caused by CIP and LEVO than NOR. Furthermore, all three FQs were found to induce DNA damage and elevate acetylcholinesterase activity, suggesting distinct genotoxic and neurotoxic effects. Interestingly, despite its low bioaccumulation potential, LEVO exhibited high toxicity towards B. aeruginosa. These findings enhance our understanding of the ecotoxicity of FQs in sediments, providing further evidence of their potential ecological risks.

Accumulation kinetics of polystyrene nano- and microplastics in the waterflea Daphnia magna and trophic transfer to the mysid Limnomysis benedeni

Despite the pervasive presence of nano- and microplastics (NMPs) in aquatic environments, their movement through food chains remains poorly understood. In this study, we explored the uptake of polystyrene plastics (PSPs) of varying sizes (26, 500, and 4800 nm) in Daphnia magna and their subsequent transfer to the freshwater mysid Limnomysis benedeni, shedding light on the intricate dynamics of NMP transfer in freshwater ecosystems. Our results show that in D. magna the internal concentration of 4800 nm PSPs was 4–10 times higher than that of 26 and 500 nm PSPs, respectively. The uptake rate constants in daphnids decreased in the following order: 4800 nm (2.4 ± 0.5 L/g·h) > 26 nm (1.7 ± 0.4 L/g·h) > 500 nm (0.6 ± 0.1 L/g·h) PSPs. Importantly, only a small fraction (1–5 %) of the PSPs ingested by D. magna was transferred to L. benedeni. Additionally, larger particle sizes were associated with a higher extent of transfer in the food chain. Elimination rate constants in L. benedeni were found to be 0.03 ± 0.03, 0.1 ± 0.2, and 0.2 ± 0.8 per hour for 26, 500, and 4800 nm PSPs, respectively. Fluorescence observations revealed that PSPs were predominantly located in the stomach and intestine of L. benedeni. Furthermore, the calculated trophic transfer factor, based on the mass of particles accumulated in the organisms, was <1 for all PSP treatments. Our results indicate that NMPs can be transferred along the daphnia-mysids food chain, and that there is no evidence of biomagnification along this chain. These findings underscore the importance of understanding particle size effects on NMP transfer and accumulation in aquatic food webs, offering valuable insights for assessing the ecological risks associated with NMP pollution in freshwater ecosystems.

Reduced copper uptake and efflux by the mussel Mytilus coruscus after Cu exposure: Implication for biomonitoring

The hard-shell mussels Mytilus coruscus have been extensively employed in pollution biomonitoring. Earlier studies indicated that metal concentrations in Mytilus coruscus may not accurately reflect the true metal contamination levels in the sampling areas, possibly due to their modified metal uptake and efflux. Given the likelihood of mussels in the field being exposed to intermittent metal contaminants, this study investigated whether different Cu pre-exposures significantly affected its uptake and efflux upon Cu exposure. We found significant reduction in Cu uptake rate constant (ku) and efflux rate constant (ke) in the mussels with varying Cu pre-exposure regimes. Specifically, the ku decreased from 1.55 ± 0.37 L g−1 d−1 in the control group to 0.65 ± 0.19 after 5 days and 0.53 ± 0.28 after 15 days of exposure to 20 μg L−1 Cu, respectively, and then was further reduced to as low as 0.096 ± 0.046 L g−1 d−1 following a 5-day exposure at 50 μg L−1 Cu. Similarly, the ke decreased from 0.18 ± 0.020 to 0.15 ± 0.015 d−1 following 5–15 days of exposure to 20 μg L−1 Cu, and further decreased to 0.081 ± 0.023 d−1 after a 5-day exposure at 50 μg L−1 Cu. Our subcellular distribution analysis underscored the critical role of the metallothionein-like protein (MTLP) fraction in modifying both Cu ku and ke during the rapid-depuration phase (ke1), whereas the metal-rich granule (MRG) fraction influenced the ke during the second depuration phase (ke2). This study demonstrated that environmental assessments utilizing biomonitoring species should consider the exposure of these organisms to ensure accurate interpretations of metal contamination in marine ecosystems and enhance the effectiveness of these species in environmental monitoring. This crucial factor is often overlooked, potentially skewing data and leading to misinterpretations of environmental health and pollution levels.

Toxicokinetics and Mussel Watch: Addressing Interspecies Differences for Coastal Cadmium Contamination Assessment.

Bivalves are often employed for biomonitoring contaminants in marine environments; however, in these large-scale programs, unavoidably, using multiple species presents a significant challenge. Interspecies differences in contaminant bioaccumulation can complicate data interpretation, and direct comparisons among species may result in misleading conclusions. Here, we propose a robust framework based on toxicokinetic measurements that accounts for interspecies differences in bioaccumulation. Specifically, via a recently developed double stable isotope tracer technique, we determined the toxicokinetics of cadmium (Cd)─a metal known for its high concentrations in bivalves and significant interspecies bioaccumulation variability─in six widespread bivalve species including mussels (Perna viridis, Mytilus unguiculatus, Mytilus galloprovincialis) and oysters (Magallana gigas, Magallana hongkongensis, Magallana angulata). Results show that oysters generally have higher Cd uptake rate constants (ku: 1.18-3.09 L g-1 d-1) and lower elimination rate constants (ke: 0.008-0.017 d-1) than mussels (ku: 0.21-0.64 L g-1 d-1; ke: 0.018-0.037 d-1). The interspecies differences in tissue Cd concentrations are predominantly due to Cd uptake rather than elimination. Utilizing toxicokinetic parameters to back-calculate Cd concentrations in seawater, we found that the ranking of Cd contamination levels at the six sites markedly differs from those based on tissue Cd concentrations. We propose that this approach will be useful for interpreting data from past and future biomonitoring programs.

Effects of Vibrio vulnificus and Microcystis aeruginosa co-exposures on microplastic accumulation and depuration in the Eastern Oyster (Crassostrea virginica)

Microplastics are ubiquitous in the aquatic environment, and bivalves such as the Eastern oyster (Crassostrea virginica) can accumulate these particles directly from the water column. Bivalves are concurrently exposed to pathogenic and toxin-producing bacteria, including Vibrio spp. and Microcystis spp., which have been shown to adversely impact filtration rates. Exposure to these bacteria could thus affect oysters’ ability to accumulate and depurate microplastics. As climate change creates conditions that favor Vibrio spp. and Microcystis spp. growth in estuaries, it is increasingly important to understand how these co-occurring biotic stressors influence microplastic contamination in bivalves. The objective of this study was to examine how co-exposures to Vibrio vulnificus and Microcystis aeruginosa influence microplastic accumulation and depuration in Eastern oysters. Oysters were exposed to nylon microplastics (5000 particles L−1) and either V. vulnificus, M. aeruginosa, or both species (104 colony-forming units or cells mL−1, respectively) and sampled over time up to 96 h. Following exposure, remaining oysters were allowed to depurate in clean seawater and sampled over time for up to 96 h. Microplastic concentrations in oysters were quantified and compared among treatments, and rate constants for uptake (ku) and depuration (kd) were calculated using nonlinear regression and two-compartment kinetic models. Overall, microplastic concentrations in oysters exposed to V. vulnificus (X‾ = 2.885 ± 0.350 (SE) particles g−1 w.w.) and V. vulnificus with M. aeruginosa (X‾ = 3.089 ± 0.481 particles g−1 w.w.) were higher than oysters exposed to M. aeruginosa (X‾ = 1.540 ± 0.235 particles g−1 w.w.) and to microplastics alone (X‾ = 1.599 ± 0.208 particles g−1 w.w.). Characterizing microplastic accumulation and depuration in oysters co-exposed to these biotic stressors is an important first step in understanding how contaminant loads in bivalves can change. With this research, the efficacy of depuration for commonly-consumed seafood species can be estimated.

Fate of synthetic chemicals in the agronomic insect pest Spodoptera littoralis: experimental feeding-contact assay and toxicokinetic model.

Insecticides prevent or reduce insect crop damage, maintaining crop quality and quantity. Physiological traits, such as an insect's feeding behavior, influence the way insecticides are absorbed and processed in the body (toxicokinetics), which can be exploited to improve species selectivity. To fully understand the uptake of insecticides, it is essential to study their total uptake and toxicokinetics independent of their toxic effects on insects. We studied the toxicokinetics (TK) of insecticidally inactive test compounds incorporating agro-like structural motifs in larvae of the Egyptian cotton leafworm (Spodoptera littoralis,Lepidoptera),and their distribution across all biological matrices, using laboratory experiments and modeling. We measured Spodoptera larval behavior and temporal changes of whole-body concentrations of test compounds during feeding on treated soybean leaf disks and throughout a subsequent depuration period. Differences in the distribution of the total quantities of compounds were found between the biological matrices leaf, larva, and feces. Rate constants for uptake and elimination of test compounds were derived by calibrating a toxicokinetic model to the whole-body concentrations. Uptake and elimination rate constants depended on the physicochemical properties of the test compounds. Increasing hydrophobicity increased the bioaccumulation potential of test compounds. Incomplete quantities in larval matrices indicated that some compounds may undergo biotransformation. As fecal excretion was a major elimination pathway, the variable time of release and number of feces pellets led to a high variability in the body burden. We provide quantitative models to predict the toxicokinetics and bioaccumulation potential of inactive insecticide analogs (parent compounds) in Spodoptera.

Highly sensitive passive sampling of new pollutants in urban reclaimed water using hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane

Urban reclaimed water is important water resource in China, while the residual new pollutants in the water largely challenge their safety for further use. China's action program for the management of new pollutants (also known as emerging contaminants) requires effective method for monitoring diverse new pollutants in water. This work proposed a highly sensitive passive sampling method for monitoring diverse new pollutants in urban reclaimed water. Hydrophilic–lipophilic balance sorbent-embedded cellulose acetate membranes (HECAMs) were dynamically deployed in self-developed continuous flow integrative sampling device (CFISD) for sampling four types of new pollutants with wide polarity ranges (1.11 < log Kow < 9.49) in a reclaimed water network for landscape irrigation in Beijing, China. The estimated equilibrium partition ratios of most chemicals between HECAM and water were over 104, which would provide low detection limits. In the 7-d high-efficiency deployment, thirty new pollutants were detected, which indicated incompletely removal of various new pollutants in wastewater treatment process. The dynamical accumulation data were successfully fitted by first-order kinetic model and different contaminants reached different accumulation phases in the HECAMs during 7 d. Acceptable and steady uptake rate constants and sampling rates were obtained with the use of CFISD in field sampling. The estimated time-weighted average concentrations for contaminants had wide concentration range and were from 0.03 ng L−1 (pendimethalin) to 3,394 ng L−1 (dibutyl phthalate) and this may lead to environmental risk for further use the reclaimed water. Dynamical deployment results also provided sensitive information of concentration fluctuations and twelve pollutants showed concentration fluctuations during the sampling period. In summary, HECAM showed high sensitivities and credible performance of monitoring diverse new pollutants in the urban reclaimed water.

Uptake/depuration kinetics, bioaccumulation potential and metabolic transformation of a complex pharmaceutical mixture in zebrafish (Danio rerio)

Uptake and elimination kinetics, bioconcentration factors (BCFs), and metabolic transformation of 20 different pharmaceutically active compounds (PhACs), covering a wide range of therapeutic categories and physico-chemical properties, were studied using zebrafish (Danio rerio). The fish were exposed to the mixture of the selected PhACs at environmentally relevant concentrations similar to 10 µg L−1. The experiments were performed in semi-static conditions and comprised a 7-day uptake period followed by a 7-day depuration period. Most of the PhACs reached a concentration plateau within the 7-day uptake-phase which was followed by an efficient depuration, with the observed uptake (ku) and depuration rate constants (kd,) ranging between 0.002 and 3.752 L kg−1 h−1, and 0.010 to 0.217 h−1, respectively. The investigated PhACs showed low to moderate BCFs. The highest BCFs of 47.8, 28.6 and 47.6 L kg−1 were determined for sertraline, diazepam and desloratadine, respectively. A high contribution of metabolic products to the total internal concentration was observed for some PhACs such as codeine (69%), sulfamethoxazole (51%) and verapamil (87%), which has to be taken into account when assessing the bioconcentration potential. Moreover, most of the metabolites exhibited significantly longer half-lives in zebrafish than their parent compounds and affected the overall depuration kinetics.

Toxicokinetics of the Antidepressant Fluoxetine and Its Active Metabolite Norfluoxetine in Caenorhabditis elegans and Their Comparative Potency.

The nematode Caenorhabditis elegans is a valuable model for ecotoxicological research, yet limited attention has been given to understanding how it absorbs, distributes, metabolizes, and excretes chemicals. This is crucial for C. elegans because the organism is known to have strong uptake barriers that are known to be susceptible to potential confounding effects of the presence of Escherichia coli as a food source. One frequently studied compound in C. elegans is the antidepressant fluoxetine, which has an active metabolite norfluoxetine. In this study, we evaluated the toxicokinetics and relative potency of norfluoxetine and fluoxetine in chemotaxis and activity tests. Toxicokinetics experiments were conducted with varying times, concentrations of fluoxetine, and in the absence or presence of E. coli, simulated with a one-compartment model. Our findings demonstrate that C. elegans can take up fluoxetine and convert it into norfluoxetine. Norfluoxetine proved slightly more potent and had a longer elimination half-life. The bioconcentration factor, uptake, and elimination rate constants depended on exposure levels, duration, and the presence of E. coli in the exposure medium. These findings expand our understanding of toxicokinetic modeling in C. elegans for different exposure scenarios, underlining the importance of considering norfluoxetine formation in exposure and bioactivity assessments of fluoxetine.

Combined average standard uptake value and rate constant can predict expression of EGFR in hypopharyngeal squamous cell carcinoma: A pilot study with integrated PET/MRI

PurposeTo investigate whether the quantitative multiparameters of 18F-FDG PET/MRI can predict expression of epidermal growth factor receptor (EGFR) of hypopharyngeal squamous cell carcinoma (HSCC). MethodsTwenty-one patients with HSCC confirmed by biopsy underwent neck integrated 18F-FDG PET/MRI and EGFR expression detection. Quantitative parameters derived from 18F-FDG PET, difusion-weighted imaging (DWI), and dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) were measured. The efficacies of quantitative multiparameters derived from 18F-FDG PET/MRI for predicting the expression of EGFR of HSCC were evaluated. ResultsThe patients were divided into positive expression group (PEG, n = 14) and negative expression group (NEG, n = 7). Mann-Whitney U nonparametric test showed that SUVmean and Kep had statistical difference between PEG and NPG, while other parameters had no statistical difference. Using 14.50 and 2.10 min−1 as the threshold values, areas under the curve (AUCs) for SUVmean and Kep were 0.786 with specificity of 92.9 % and sensitivity of 57.1 %. The combined use of SUVmean and Kep had better efficacy to evaluate the expression of EGFR with AUC of 0.980, sensitivity of 92.9 %, and specificity of 100.0 %. ConclusionCombined use of SUVmean and Kep showed good performance in predicting the expression of EGFR in HSCC. Integrated 18F-FDG PET/MRI enables simultaneous acquisition of SUVmean and Kep, so it represents as a powerful tool to noninvasively and repeatably evaluate the expression of EGFR during the management of HSCC.

Arbuscular Mycorrhizal Fungi Alter Arsenic Translocation Characteristics of Iris tectorum Maxim.

Arsenic (As) pollution in wetlands, mainly as As(III) and As(V), has threatened wetland plant growth. It has been well documented that arbuscular mycorrhizal (AM) fungi can alleviate As stress in terrestrial plants. However, whether AM fungi can protect natural wetland plants from As stress remains largely unknown. Therefore, three hydroponic experiments were conducted in which Iris tectorum Maxim. (I. tectorum) plants were exposed to As(III) or As(V) stresses, to investigate the effects of mycorrhizal inoculation on As uptake, efflux, and accumulation. The results suggested that short-term kinetics of As influx in I. tectorum followed the Michaelis-Menten function. Mycorrhizal inoculation decreased the maximum uptake rate (Vmax) and Michaelis constant (Km) of plants for As(III) influx, while yielding no significant difference in As(V) influx. Generally, mycorrhizal plants released more As into environments after 72 h efflux, especially under As(V) exposure. Moreover, mycorrhizal plants exhibited potential higher As accumulation capacity, probably due to more active As reduction, which was one of the mechanisms through which AM fungi mitigate As phytotoxicity. Our study has revealed the role of aerobic microorganism AM fungi in regulating As translocation in wetland plants and supports the involvement of AM fungi in alleviating plant As stress in anaerobic wetlands.

Determining the effect of cardiac blood volume on accuracy of uptake rate constants by simulation

Objective. There is great interest in better understanding coronary microvascular disease using mouse models. Typical quantification requires dynamic imaging to estimate the rate constant K 1 of the tracer moving from the blood into the myocardium. In addition to K 1, it is also desirable to determine blood volume fraction V, which if known allows for more accurate fitting of K 1. Our previously published kinetic modeling software did not consider the effect of V. To ensure a better fit of experimental data to the model for myocardial SPECT imaging, in this work we updated our kinetic modeling software to include a blood volume fraction V, which adds a fraction of the arterial activity concentration into the tissue concentration. Approach. The tissue and blood time-activity curves (TACs) used for fit input were generated using ideal equations with known values in MATLAB. This allowed post-fit results to be compared to known values to determine fit errors. Parameters that were varied in generating the TACs included blood volume fraction (0, 0.05, 0.1, 0.2 and 0.3), K 1 (0.5, 1.5, 2.5 ml min−1 g−1), frame length (1, 2, 5, 10, 15, 20 s), FWHM of the input Gaussian (10, 20, 40 s), and time of the injection peak relative to frame duration. Blood volume-fraction results have low error when blood volume is lowest, but results worsen as frame length and K 1 increase. Main results. We demonstrated that blood volume can be accurately determined, and also show how fit accuracy varies across TACs with different input properties. Significance. This information allows for robust use of the fitting algorithm and aids in understanding fit performance when used in animal studies.

A toxicokinetics approach using Enchytraeus crypticus to evaluate the efficiency of hydroxyapatite to remediate soils contaminated with rare earth elements

Extensive rare earth element (REE) mining activities pose threats to agricultural soils surrounding the mining areas. Here, low and high REE-contaminated soils from farmlands around mine tailings were remediated with hydroxyapatite. A toxicokinetic approach was applied to assess whether the use of hydroxyapatite reduced the bioavailability of REEs and thus inhibited their accumulation in the terrestrial organism Enchytraeus crypticus. Our results showed that addition of hydroxyapatite increased soil pH, DOC and anion contents. CaCl2-extractable REE concentrations significantly decreased, indicating the stabilization by hydroxyapatite. The influence of hydroxyapatite on the REE accumulation in enchytraeids was quantified by fitting a toxicokinetic model to dynamic REE body concentrations. The estimated uptake (Ku) and elimination rate constants (Ke), and bioaccumulation factor (BAF) for REEs were in the range of 0.000821 – 0.122 kgsoil/kgworm day−1, 0.0224 – 0.136 day−1, and 0.00135 – 1.96, respectively. Both Ku and BAF were significantly reduced by over 80% by hydroxyapatite addition, confirming the decreased REE bioavailability. Low atomic number REEs had higher BAFs in slightly contaminated soil, suggesting a higher bioaccumulation potential of light REEs in soil organisms. Overall, chemical stabilization with amendments can attenuate the bioavailability of REEs and reduce the potential ecological risk of contaminated agricultural soils near REE mining areas.

A refined toxicokinetic model for quantifying the interaction between Cd and Cu in zebrafish larvae

The interaction between metals is ubiquitous, but there is still a lack of quantitative models considering the interaction between metals, which leads to the deviations in predicting the joint toxicity of metals. The present study estimated the uptake rate constants (kin) and elimination rate constants (kout) and elucidated how the presence of one metal (Cu or Cd) affects the absorption and excretion of another metal (Cd or Cu) in zebrafish larvae. The results showed that Cd and Cu inhibited each other in the process of absorption and excretion by comparing separately kin and kout of Cd or Cu with the other metal Cu or Cd mixed concentrations increased, thereby affecting the Cd and Cu bioaccumulation in the zebrafish larvae. Then the interactions between Cd and Cu in the uptake and elimination processes were quantified to obtain a refined toxicokinetic model. Verification with independent experiment data showed that the refined toxicokinetic model could significantly improve the prediction of the Cd or Cu bioaccumulation in the zebrafish larvae. This study contributes to understand the toxicokinetic process of the Cd-Cu mixture in the zebrafish larvae, and the developed model could be used to predict the toxicity of the metal mixtures.

Effects of nanoplastics on clam Ruditapes philippinarum at environmentally realistic concentrations: Toxicokinetics, toxicity, and gut microbiota

Nanoplastics are ubiquitous in marine environments, understanding to what extent nanoplastics accumulate in bivalves and the adverse effects derived from their retention is imperative for evaluating the detrimental effects in the benthic ecosystem. Here, using palladium-doped polystyrene nanoplastics (139.5 nm, 43.8 mV), we quantitatively determined nanoplastic accumulation in Ruditapes philippinarum and investigated its toxic effects by combining physiological damage assessments with a toxicokinetic model and 16 S rRNA sequencing. After a 14 days exposure, significant nanoplastic accumulation was observed, up to 17.2 and 137.9 mg·kg−1 for the environmentally realistic (0.02 mg·L−1) and ecologically (2 mg·L−1) relevant groups, respectively. Ecologically relevant nanoplastic concentrations evidently attenuated the total antioxidant capacity and stimulated excessive reactive oxygen species, which elicited lipid peroxidation, apoptosis, and pathological damage. The modeled uptake (k1) and elimination (k2) rate constants (from physiologically based pharmacokinetic model) were significantly negatively correlated with short-term toxicity. Although no obvious toxic effects were found, environmentally realistic exposures notably altered the intestinal microbial community structure. This work increases our understanding of how the accumulation of nanoplastics influences their toxic effects in terms of the toxicokinetics and gut microbiota, providing further evidence of their potential environmental risks.

Laboratory-Derived Bioaccumulation Kinetic Parameters for Four Per- and Polyfluoroalkyl Substances in Freshwater Mussels.

Although freshwater mussels are imperiled and identified as key conservation priorities, limited bioaccumulation information is available on these organisms for contaminants of emerging concern. In the present study we investigated the bioaccumulation of per- and polyfluoroalkyl substances (PFAS) in the model freshwater pond mussel Sagittunio subrostratus because mussels provide important ecosystem services and are important components of aquatic systems where PFAS occur. In the present study we selected four representative perfluorinated carboxylic acids and sulfonic acids, then determined the bioaccumulation kinetics of freshwater mussels in a controlled laboratory study. Because uptake (ku ) and elimination (ke ) rate constants and time to steady state are important parameters for food web bioaccumulation models, we derived bioaccumulation kinetic parameters following exposure to perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA) at 10 µg/L and perfluoroundecanoic acid (PFUnDA) at 1 µg/L during a 14-day uptake period followed by a 7-day elimination period. Kinetic and ratio-based bioaccumulation factors (BAFs) were subsequently calculated, for example ratio-based BAFs for mussel at day 7 were determined for PFHxS (0.24 ± 0.08 L/kg), PFOS (7.73 ± 1.23 L/kg), PFDA (4.80 ± 1.21 L/kg), and PFUnDA (84.0 ± 14.4 L/kg). We generally observed that, for these four model PFAS, freshwater mussels have relatively low BAF values compared with other aquatic invertebrates and fish. Environ Toxicol Chem 2023;42:1190-1198. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Interspecies calibration for biomonitoring metal contamination in coastal waters using oysters and mussels

Differences in metal bioaccumulation among species make it difficult to compare biomonitoring results obtained using different marine bivalve species. To address this challenge and improve the interpretation of biomonitoring data, we studied the toxicokinetic mechanisms underlying these differences and developed a method to estimate seawater metal concentrations based on metal concentrations in the organisms. We transplanted six common species of oysters and mussels found in Chinese coastal waters into the Jiulong River estuary and monitored metal concentrations in the organisms, water, and suspended particles every three days over a six-week period. A one-compartment first-order toxicokinetic model was used to describe the relationship between metal bioaccumulation and metal concentrations in the environment. The model parameters, including aqueous uptake (ku) and dietary assimilation (kp) rate constants, and elimination rate constant (ke), were estimated using a Markov Chain Monte Carlo fitting method with a priori information from a systematic review we conducted. The toxicokinetic model successfully fitted the temporal changes in metal bioaccumulation in all six bivalve species and explained the interspecies differences. Using the calibrated models, we were able to calculate metal concentrations in the seawater at the bivalve collection sites and enable comparisons of biomonitoring data across multiple species. In conclusion, we have established a toxicokinetic framework to explain interspecies differences in metal bioaccumulation in six commonly found bivalves and provided a useful tool for interpreting biomonitoring data in coastal environments.

Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.

Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (khe), and biliary excretion (kbh). The observed median fold-decreases in gadoxetate liver AUC were 3.8- and 1.5-fold for ciclosporin and rifampicin, respectively. Ketoconazole unexpectedly decreased systemic and liver gadoxetate AUCs; the remaining drugs investigated (asunaprevir, bosentan, and pioglitazone) caused marginal changes. Ciclosporin decreased gadoxetate khe and kbh by 3.78 and 0.09 mL/min/mL, while decreases for rifampicin were 7.20 and 0.07 mL/min/mL, respectively. The relative decrease in khe (e.g., 96% for ciclosporin) was similar to PBPK-predicted inhibition of uptake (97-98%). PBPK modelling correctly predicted changes in gadoxetate systemic AUCR, whereas underprediction of decreases in liver AUCs was evident. The current study illustrates the modelling framework and integration of liver imaging data, PBPK, and tracer-kinetic models for prospective quantification of hepatic transporter-mediated DDI in humans.

Enantiospecific Uptake and Depuration Kinetics of Chiral Metoprolol and Venlafaxine in Marine Medaka (Oryzias melastigma): Tissue Distribution and Metabolite Formation.

The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore, the tissue-specific uptake and depuration kinetics of two pairs of pharmaceutical enantiomers, S-(-)-metoprolol versus R-(+)-metoprolol and S-(+)-venlafaxine versus R-(-)-venlafaxine, were studied in marine medaka (Oryzias melastigma) during a 28-day exposure and 14-day clearance period. The toxicokinetics of the studied pharmaceuticals, including uptake and depuration rate constants, depuration half-life (t1/2), and bioconcentration factor (BCF), were reported for the first time. The whole-fish results demonstrated a higher S- than R-venlafaxine bioaccumulation potential, whereas no significant difference was observed between S- and R-metoprolol. O-desmethyl-metoprolol (ODM) and α-hydroxy-metoprolol (AHM) were the main metoprolol metabolites identified by suspect screening, and the ratios of ODM to AHM were 3.08 and 1.35 for S- and R-metoprolol, respectively. N,O-Didesmethyl-venlafaxine (NODDV) and N-desmethyl-venlafaxine (NDV) were the main venlafaxine metabolites, and the ratios of NODDV to NDV were 1.55 and 0.73 for S- and R-venlafaxine, respectively. The highest tissue-specific BCFs of the four enantiomers were all found in the eyes, meriting in-depth investigation.

Warming Affects Bioconcentration and Bioaccumulation of Per- and Polyfluoroalkyl Substances by Pelagic and Benthic Organisms in a Water-Sediment System.

Warming and exposure to emerging global pollutants, such as per- and polyfluoroalkyl substances (PFAS), are significant stressors in the aquatic ecosystem. However, little is known about the warming effect on the bioaccumulation of PFAS in aquatic organisms. In this study, the pelagic organisms Daphnia magna and zebrafish, and the benthic organism Chironomus plumosus were exposed to 13 PFAS in a sediment-water system with a known amount of each PFAS at different temperatures (16, 20, and 24 °C). The results showed that the steady-state body burden (Cb-ss) of PFAS in pelagic organisms increased with increasing temperatures, mainly attributed to increased water concentrations. The uptake rate constant (ku) and elimination rate constant (ke) in pelagic organisms increased with increasing temperature. In contrast, warming did not significantly change or even mitigate Cb-ss of PFAS in the benthic organism Chironomus plumosus, except for PFPeA and PFHpA, which was consistent with declined sediment concentrations. The mitigation could be explained by the decreased bioaccumulation factor due to a more significant percent increase in ke than ku, especially for long-chain PFAS. This study suggests that the warming effect on the PFAS concentration varies among different media, which should be considered for their ecological risk assessment under climate change.