Lower Elimination Rate Research Articles

Occurrence, analysis and removal processes of emerging pharmaceuticals from waters for the protection and preservation of a sustainable environment: A review

Pharmaceuticals are a group of man-made commercial and synthetic products and an important mainstay of modern society. However, their presence in aquatic environments is identified as a potential risk, causing harm to living things even at low concentrations ranging from ng L−1 to μg L−1. Due to their pseudo-persistence, bio-accumulation, and low elimination rate by conventional treatments, the majority of these xenobiotic contaminants and their metabolites are routinely released into the environment by sewage treatment plants and last longer in an aquatic environment. This review aims to provide an extensive report and a current state of knowledge concerning various classes of pharmaceutical compounds (PCs). It also discusses the occurrence, the analytical methods for the determination of PC micro-pollutants, and the remediation methods noted in recent literature focusing on the most recent advances. In this context, this review highlights the statistical data regarding the status of PCs in detection, analysis, and removal methods in aqueous media. In addition, this review provides an overview of the conventional and advanced technologies for the removal of PCs from water sources, offering critical comments, and discussing the challenges related to improving existing technologies for sustainable and eco-friendly management of water resources. It likewise emphasizes the importance of the combination of different treatment methods to reach up to 100% PC removal.Finally, gaps in the literature were found, and recommendations for further research were also cited in accordance with this paper. To the best of our knowledge, this review paper is among the rare works that deal with both: i) the analysis of large varieties of PCs in different water matrices, ii) the removal and identification of target analytes and their by-products generated during the elimination processes, and iii) the possible degradation pathways proposed by different studies.

Cadmium neurotoxicity and therapeutic strategies.

Cadmium (Cd) is a multitarget, carcinogenic, nonessential environmental pollutant. Due to its toxic effects at very low concentrations, lengthy biological half-life, and low excretion rate, exposure to Cd carries a concern. Prolonged exposure to Cd causes severe injury to the nervous system of both humans and animals. Nevertheless, the precise mechanisms responsible for the neurotoxic effects of Cd have yet to be fully elucidated. The accurate chemical mechanism potentially entails the destruction of metal-ion homeostasis, inducing oxidative stress, apoptosis, and autophagy. Here we review the evidence of the neurotoxic effects of Cd and corresponding strategies to protect against Cd-induced central nervous system injury.

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium from five exposome-relevant databases using a data-centric approach, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs). By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.

Low soil Moisture Slows Uptake and Elimination Rates of Phenanthrene in Springtails

This study investigated the influence of soil water status on the toxicokinetics of phenanthrene in the springtail Folsomia candida allowing estimation of uptake and elimination rates at two contrasting soil water potentials. Fitting a three-phase model to the observations showed that uptake rate (ku) was almost two times higher in moist soil (-2 kPa) than in dry soil (-360 kPa). During the first days of the exposure, elimination rate (ke) was not significantly different in moist and dry soil, but after eight days ke had increased significantly more in moist soil than in dry soil. Our results confirm the general notion that the exposure route via soil pore water is important. Understanding the significance of soil moisture in exposure and effects of contaminants on soil invertebrates is crucial for assessing the ecological risks associated with soil pollution in a changing climate.

Ibuprofen-enhanced biodegradation in solution and sewage sludge by a mineralizing microbial consortium. Shift in associated bacterial communities

Ibuprofen (IBP) is a widely used drug of environmental concern as emerging contaminant due to its low elimination rates by wastewater treatment plants (WWTPs), leading to the contamination of the environment, where IBP is introduced mainly from wastewater discharge and sewage sludge used as fertilizer. This study describes the application of a consortium from sewage sludge and acclimated with ibuprofen (consortium C7) to accelerate its biodegradation both in solution and sewage sludge. 500 mg L-1 IBP was degraded in solution in 28 h, and 66% mineralized in 3 days. IBP adsorbed in sewage sludge (10 mg kg-1) was removed after bioaugmentation with C7 up to 90% in 16 days, with a 5-fold increase in degradation rate. This is the first time that bioaugmentation with bacterial consortia or isolated bacterial strains have been used for IBP degradation in sewage sludge. The bacterial community of consortium C7 was significantly enriched in Sphingomonas wittichii, Bordetella petrii, Pseudomonas stutzeri and Bosea genosp. after IBP degradation, with a special increase in abundance of S. wittichii, probably the main potential bacterial specie responsible for IBP mineralization. Thirteen bacterial strains were isolated from C7 consortium. All of them degraded IBP in presence of glucose, especially Labrys neptuniae. Eight of these bacterial strains (B. tritici, L. neptuniae, S. zoogloeoides, B. petrii, A. denitrificans, S. acidaminiphila, P. nitroreducens, C. flaccumfaciens) had not been previously described as IBP-degraders. The bacterial community that makes up the indigenous consortium C7 appears to have a highly efficient biotic degradation potential to facilitate bioremediation of ibuprofen in contaminated effluents as well as in sewage sludge generated in WWTPs.

Cadmium as an ovarian toxicant: A review.

Cadmium (Cd) is a ubiquitous heavy metal toxicant with no biological function in the human body. Considerably, because of its long biological half-life and very low excretion rate, Cd is inclined to accumulate and cause deleterious effects on various body organs (e.g., liver, kidney, and ovary) in humans and animals. Ovaries are the most vulnerable targets of Cd toxicity. Cd has been shown to induce oxidative stress, follicular atresia, hormonal imbalance, and impairment of oocyte growth and development. Moreover, Cd toxicity has been associated with increasing incidences of menstrual disorders, pregnancy loss, preterm births, delayed puberty, and female infertility. Therefore, it is crucial to understand how Cd poisoning impacts specific ovarian processes for the development of preventive interventions to enhance female fertility. The current review attempts to collate the recent findings on Cd-induced oxidative stress, follicular apoptosis, steroid synthesis inhibition, and teratogenic toxicity, along with their possible mechanisms in the ovarian tissue of different animal species. Additionally, the review also summarizes the studies related to the use of many antioxidants, medicinal herbs, and other compounds as remedial approaches for managing Cd-induced ovarian toxicity.

Enantioselective uptake, translocation, and biotransformation of pydiflumetofen in wheat (Triticum aestivum L.): Insights from chiral profiling and molecular simulation

Pydiflumetofen (PYD), a highly effective and broad-spectrum fungicide, is commonly employed for the control of fungal diseases. In this study, the uptake, translocation, and biotransformation of PYD by wheat (Triticum aestivum L.) were firstly investigated at a chiral level. The findings revealed that the residue concentration of R-PYD in wheat was higher than that of S-PYD, because of its higher uptake rate (k1 = 0.0421 h−1) and lower elimination rate (k2 = 0.0459 h−1). Additionally, R-PYD exhibited higher root bioconcentration factors and translocation factors compared with S-enantiomer, indicating R-PYD was more easily accumulating in roots and translocating to shoots. Furthermore, a total of 9 metabolites, including hydroxylated, demethylated, demethoxylated, dechlorinated, hydrolyzed, and glycosylated-conjugated products, were detected qualitatively in wheat roots or shoots. Symplastic pathway-mediated uptake, which predominantly relied on aquaporins and anion channels, was confirmed by root adsorption and inhibition experiments, without displaying any enantioselective effect. Molecular simulations demonstrated that R-PYD exhibited stronger binding affinity with TaLTP 1.1 with a lower grid score (−6.79 kcal/mol), whereas weaker interaction with the metabolic enzyme (CYP71C6v1) compared to the S-enantiomer. These findings highlight the significance of plant biomacromolecules in the enantioselective bioaccumulation and biotransformation processes. Importantly, a combination of experimental and theoretical evidence provide a comprehensive understanding of the fate of chiral pesticides in plants from an enantioselective perspective.

Pre-Ride Biomarkers and Endurance Horse Welfare: Analyzing the Impact of the Elimination of Superoxide Dismutase, δ-Aminolevulinic-Dehydratase, Thiobarbituric Acid Reactive Substances, Iron, and Serum Amyloid A Levels in Elite 160 km Endurance Rides.

High elimination rates and concerns for horse welfare are important issues in endurance riding. Improved understanding of the causes of elimination could increase completion rates in this sport. We have identified pre-ride laboratory risk factors that enable an assessment of potential elimination before the ride. A longitudinal cohort study was performed among 49 healthy horses competing in the 160 km endurance ride at the 2016 World Championship of Endurance Riding in Samorin/Slovakia. Blood samples were taken before the event. For statistical evaluation, horses were categorized into three groups: finishers, lame horses, and metabolically eliminated horses. Risk factors were calculated for each group using multinominal logistic regression. δ-Aminolevulinic-dehydratase (ALAD), thiobarbituric acid reactive substances (TBARSs), iron, and serum amyloid A (SAA) were measured and did not show an impact on the race outcome, but elevated pre-ride superoxide dismutase (SOD) was shown to have an effect on lameness elimination (p = 0.011). It might serve as an indicator for withdrawing horses at risk of later elimination before endurance rides, ultimately resulting in lower elimination rates and an increase in overall horse welfare.

A review of freshwater benthic clams (Corbicula fluminea): Accumulation capacity, underlying physiological mechanisms and environmental applications.

Asian clams (Corbicula fluminea) have been extensively applied in biomonitoring and other environmental fields based on their high enrichment capacity and rapid response to pollutants. This review first summarizes the kinetic process of metals and organic pollutants enriched by C. fluminea and discusses the environmental behavior and application. The accumulation ability of Cu, Zn, and Mn were significantly higher than that of other metals, which were attributed to their high uptake rate constant and low elimination rate constant. The visceral mass was found to be the major burden tissue. However, large knowledge gaps existed regarding the accumulation capacity of C. fluminea for organic pollutants and nanoparticles. Moreover, physiological mechanisms underlying the accumulation of environmental pollutants were proposed. C. fluminea can improve the niche of benthic algae by ingesting pelagic algae, mitigating water eutrophication. It can also remove pathogens and parasites based on the biological assimilation of nonspecific immunity, interrupting disease transmission. The novel insight into the application of C. fluminea in wastewater treatment further broadens the range of pest management strategies and offers the feasibility of blocking the spread of invasive bivalves.

Lowly-buffered biorelevant dissolution testing is not necessarily biopredictive of human bioequivalence study outcome: Relationship between dissolution and pharmacokinetics

It has been revealed that buffer capacity of aspirated human intraluminal fluid is much lower than that of in vitro compendial dissolution media. Since buffer capacity significantly alters the dissolution profile of certain drug products, dissolution testing in highly buffered media dictates poor predictability of in vivo drug performance. To mitigate this inconsistency, low buffer capacity medium was suggested as an in vivo representation (biorelevant dissolution testing). The purpose of this study was to characterize the dissolution profiles of enteric-coated drug products in different buffer capacity media in a flow through cell dissolution apparatus, and to evaluate the in vivo predictability of human bioequivalence study outcomes conducted in the fasted state. It was confirmed that the lower the buffer capacity of dissolution media, the higher the discriminatory power of esomeprazole magnesium hydrate enteric-coated pellets, reflecting human bioequivalence failure. In the meantime, two duloxetine hydrochloride enteric-coated pellets also exhibited distinct dissolution profiles in such a lowly buffered medium despite the fact that these two are bioequivalent in human. Biopharmaceutical and pharmacokinetic characteristics comparison suggested that low intestinal permeability and small systemic elimination rate of duloxetine hinders the clear impact of different dissolution profile on its in vivo performance. These data suggest that dissolution comparison in physiologically-relevant low buffer capacity media is not always indicative of human bioequivalence. Instead, biopharmaceutical and pharmacokinetic aspects must be taken into consideration to make biorelevant dissolution testing biopredictive.

Mechanisms of Cadmium-Induced Testicular Injury: A Risk to Male Fertility.

Cadmium is a heavy toxic metal with unknown biological functions in the human body. Over time, cadmium accretion in the different visceral organs (liver, lungs, kidney, and testis) is said to impair the function of these organs, which is associated with a relatively long biological half-life and a very low rate of excretion. Recently studies have revealed that the testes are highly sensitive to cadmium. In this review, we discussed the adverse effect of cadmium on the development and biological functions of the testis. The Sertoli cells (SCs), seminiferous tubules, and Blood Testis Barrier are severely structurally damaged by cadmium, which results in sperm loss. The development and function of Leydig cells are hindered by cadmium, which also induces Leydig cell tumors. The testis's vascular system is severely disturbed by cadmium. Cadmium also perturbs the function of somatic cells and germ cells through epigenetic regulation, giving rise to infertile or sub-fertile males. In addition, we also summarized the other findings related to cadmium-induced oxidative toxicity, apoptotic toxicity, and autophagic toxicity, along with their possible mechanisms in the testicular tissue of different animal species. Consequently, cadmium represents a high-risk factor for male fertility.

Contrasting seasonality of 137Cs concentrations in two stream animals that share a trophic niche

Understanding the seasonality of 137Cs concentrations in aquatic animals is crucial for reviving local inland fisheries. The seasonality of 137Cs concentrations in animals is expected to vary, even if focal species consume similarly contaminated foods because the 137Cs excretion rate is species-specific, and 137Cs uptake by foraging autochthonous food resources also vary among seasons. Here, we conducted a seasonal monitoring survey of dissolved 137Cs concentrations as an indicator of the contamination level of food resources and measured 137Cs concentrations in two carnivorous aquatic animals (Palaemon paucidens and Rhinogobius sp.) that share a trophic niche in a stream connected to a dam reservoir. The dissolved 137Cs concentration had clear seasonality—high in summer and low in winter. The 137Cs concentrations in the animals revealed a different seasonal pattern—it peaked in October in P. paucidens and peaked in February in Rhinogobius. Overall, the 137Cs concentration was relatively higher in P. paucidens than in Rhinogobius, suggesting that P. paucidens has a lower excretion rate than Rhinogobius. Consequently, the seasonality of the 137Cs concentration in P. paucidens showed temporal changes similar to those of the dissolved 137Cs concentration, which were likely affected by 137Cs uptake through foraging, whereas that in Rhinogobius was controlled by 137Cs excretion. This study shows that the seasonality of 137Cs concentration can differ between sympatric animals that share a trophic niche. Accumulating knowledge and comparing the seasonality of 137Cs concentrations in fisheries species based on the balance between uptake and excretion will be valuable to determine the appropriate seasons to obtain less-contaminated products.

Simulation modelling the structure related bioaccumulation and biomagnification of per- and polyfluoroalkyl substances in aquatic food web

Until now, there is no bioaccumulation model to predict bioaccumulation of polyfluoroalkyl substances (PFASs) in aquatic organisms due to their unique amphiphilic properties. For the first time, protein contents instead of lipid contents of organisms were used in bioaccumulation models to predict the concentrations and reveal the accumulation mechanisms of PFASs in various aquatic organisms, based on the available data. Comparison between the modeled and measured results indicated the models were promising to predict the PFAS concentrations in the fishes at different trophic levels very well, as well as their bioaccumulation factors (BAF) and trophic magnification factors (TMF) of PFASs in fish. Both water and sediment are important exposure sources of PFASs in aquatic organisms. As the two main uptake pathways, the contribution of gill respiratory decreases while that of dietary intake increases with the chain length of PFASs increasing. Fecal excretion and gill respiration are the main pathways for fish to eliminate PFASs, and their relative contributions increase and decrease respectively with chain length. The short-chain (C6–C8) perfluoroalkyl acids (PFAAs) are greatly eliminated via gill respiratory quickly, leading to their very low BAFs. As the carbon chain length increases, dietary intake becomes dominant in the uptake, while elimination is mainly through fecal excretion with relatively low rates, especially in the fishes with high protein contents. For the very long chain (C12–C16) PFASs, they are very difficult to excrete with a low total elimination rate constant (ke = 0.463–0.743 d−1), thus leading to their high BAFs and TMFs. The high intake rate but low elimination rate, as well as the high water and sediment concentrations together contribute to the highest accumulated concentration perfluorooctane sulfonic acid in the fish of Taihu Lake.

Effect of Stocking Density on Behavior and Pen Cleanliness of Grouped Growing Pigs

In recent years, animal cleanliness during production has gradually attracted increasing attention. Although pigs by nature tend to excrete in dark and humid corners, in the prevalent highly intensive pig production, excessive stocking density often restricts the ability of pigs to excrete at designated points, thereby leading to pollution of the pens. To study the effect of stocking density on pen cleanliness and the relevant pig behavior, a total of 216 Landrace × Yorkshire × Duroc hybrid pigs were randomly grouped at 0.5, 0.7, or 0.9 m2 per pig at 59 ± 3 days of age. The temporal and spatial distributions of lying and excreting behavior of pigs were monitored on days 1, 7, and 35 after transfer, and the cleanliness of pig pens under three stocking densities was scored. The results showed that there were no significant differences in excreting or lying time rhythms among the three treatments. In the initial and stable periods of group transfer, the excretion rate of pigs on slatted floors was significantly higher than that on solid floors at 0.9 m2/pig (p < 0.01). During the group stabilization stage and at the end of the experiment, the lying rate of pigs on solid floors under 0.9 m2/pig was 10.81%, that is, 7.43% higher than that of 0.7 m2/pig, and the differences were significant. Judging from the pollution score of the solid floors, the three stocking densities all showed more serious pollution at the corners, and the pollution score of the pens with a density of 0.9 m2/pig was lower than that of the pens with a density of 0.5 and 0.7 m2/pig. The analysis of whether pigs had corresponding behaviors in specific functional areas showed that pigs at a density of 0.9 m2/pig had a 10.14% lower lying rate on slatted floors (the expected excretion area) than on solid floors, whereas the densities of 0.5 and 0.7 m2/pig showed the opposite pattern. Pigs at a density of 0.9 m2/pig had lower excretion rates in both corners of the solid floors (the desired lying area) than that of the 0.5 m2/pig group (p < 0.05) and 0.7 m2/pig group (p > 0.05). These results indicate that when the effective occupied space of pigs was larger, specific behaviors were more likely to occur in the set functional areas, and the cleanliness of the pen was higher. Under the conditions of this experiment, the recommended stocking density for growing pigs was 0.9 m2/pig. Of course, a larger space may be more beneficial to animal health and welfare, but the economic costs must also be considered.

Pharmacokinetic, Metabolomic, and Stability Assessment of Ganoderic Acid H Based Triterpenoid Enriched Fraction of Ganoderma lucidum P. Karst.

Ganoderma lucidum P. karst is an edible fungus that is used in traditional medicine and contains triterpenoids as the major phytoconstituents. Ganoderic acids are the most abundant triterpenoids that showed pharmacological activity. As Indian varieties contain ganoderic acid H (GA-H), we aimed to prepare GA-H-based triterpenoid enriched fraction (TEF) and evaluated its pharmacokinetics, metabolomics, and stability analysis. A high-performance liquid chromatography (HPLC) method was developed to quantify GA-H in TEF and rat plasma. Based on GA-H content, a stability assessment and pharmacokinetic study of TEF were also performed. After its oral administration to rats, TEF’s the metabolic pattern recognition was performed through ultra-performance liquid chromatography mass spectroscopy (UPLC–MS). The developed HPLC method was found to be simple, sensitive, precise (<15%), and accurate (>90% recovery) for the quantification of GA-H. Pharmacokinetic analysis showed that GA-H reached its maximum plasma concentration (Cmax 2509.9 ng/mL) within two hours and sustained quantifiable amount up to 12 h with a low elimination rate (Kel) 0.05 L/h. TEF contained ten bioavailable constituents. The prepared TEF was found to be stable for up to one year at room temperature. The prepared TEF, enriched with ganoderic acid, is stable, contains bioavailable constituents, and can be explored as phytopharmaceuticals for different pharmacological properties. Highlights: (1). Preparation of triterpenoid enriched fraction (TEF) from Ganoderma lucidum. (2). Major triterpenoid in TEF is ganoderic acid H (GA-H). (3). TEF contains several bioavailable phytoconstituents. (4). TEF (considering only GA-H) is stable for up to one year at room temperature. (5). GA-H is rapidly absorbed and has high systemic exposure.

Assessment of Human Exposure to Deoxynivalenol, Ochratoxin A, Zearalenone and Their Metabolites Biomarker in Urine Samples Using LC-ESI-qTOF.

Human are exposed to a wide range of mycotoxins through dietary food intake, including processed food. Even most of the mycotoxin exposure assessment studies are based on analysis of foodstuffs, and evaluation of dietary intake through food consumption patterns and human biomonitoring methods are rising as a reliable alternative to approach the individual exposures, overcoming the limitations of the indirect dietary assessment. In this study, human urine samples were analyzed, seeking the presence of deoxynivalenol (DON), ochratoxin A (OTA), zearalenone (ZEA), and their metabolites. For this purpose, 40 urine samples from female and male adult residents in the city of Valencia (Spain) were evaluated by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-ESI-qTOF) after salting-out liquid–liquid extraction. Analytical data showed that 72.5% of analyzed samples were contaminated by at least one mycotoxin at variable levels. The most prevalent mycotoxins were de-epoxy DON (DOM-1) (53%), ZEA (40%), and α-zearalenol (αZOL) (43%), while OTA was only detected in one sample. The mean concentrations in positive samples were DON (9.07 ng/mL), DOM-1 (20.28 ng/mL), ZEA (6.70 ng/mL), ZEA-14 glucoside (ZEA-14-Glc) (12.43 ng/mL), αZOL (27.44 ng/mL), αZOL-14 glucoside (αZOL-14-Glc) (12.84 ng/mL), and OTA (11.73 ng/mL). Finally, probable daily intakes (PDIs) were calculated and compared with the established tolerable daily intakes (TDIs) to estimate the potential risk of exposure to the studied mycotoxins. The calculated PDI was below the TDI value established for DON in both female and male adults, reaching a percentage up to 30%; however, this percentage increased up to 92% considering total DON (DON + DOM-1). On the other hand, the PDI obtained for ZEA and its metabolites were higher than the TDI value fixed, but the low urine excretion rate (10%) considered should be highlighted. Finally, the PDI calculated in the detected positive sample for OTA exceeded the TDI value. The findings of the present study confirm the presence of the studied mycotoxins and their metabolites as some of the most prevalent in urine.

Human metabolism and kinetics of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) after oral administration

2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328; CAS: 25973-55-1) is an ultraviolet light (UV) absorber which belongs to the class of hydroxy phenol benzotriazoles. Therefore, UV 328 is added to plastics and other polymers due to its photostability to prevent discoloration and prolong product stability which may result in an exposure of consumers. However, information about the toxic effects on humans and the human metabolism are still lacking. In the present study, human metabolism pathways of UV 328 and its elimination kinetics were explored. For that purpose, three healthy volunteers were orally exposed to a single dose of 0.3 mg UV 328/kg bodyweight. UV 328 and its metabolites were investigated in blood and urine samples collected until 48 and 72 h after exposure, respectively. Thereby, previously published analytical procedures were applied for the sample analysis using dispersive liquid–liquid microextraction and subsequent measurement via gas chromatography coupled to tandem mass spectrometry with advanced electron ionization. UV 328 was found to be oxidized at its alkyl side chains leading to the formation of hydroxy and/or oxo function with maximum blood concentrations at 8–10 h after exposure for UV 328-6/3-OH, UV 328-4/3-OH and UV 328-4/3-CO. In contrast, a plateau for UV 328-4/3-CO-6/3-OH levels was reached around 10 h post-dosage. The highest blood levels were found for native UV 328 at 8 h after ingestion. Furthermore, biphasic elimination kinetics in blood were revealed for almost all detected metabolites. UV 328 and its metabolites did not occur in blood as conjugates. The renal elimination kinetics were very similar with the kinetics in blood. However, the prominence of the metabolites in urine was somewhat different compared to blood. In contrast, mostly conjugated metabolites occurred for renal elimination. In urine, UV 328-4/3-CO-6/3-OH was found to be the most dominant urinary biomarker followed by UV 328-6/3-OH and UV 328-4/3-OH. In total, approximately 0.1% of the orally administered dose was recovered in urine within 72 h. Although high levels of UV 328 in blood proved good resorption and high systemic availability of the substance in the human body, the urine results revealed a rather low quantitative metabolism and urinary excretion rate. Consequently, biliary excretion as part of the enterohepatic cycle and elimination via feces are assumed to be the preferred pathways instead of renal elimination.

Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)

Depression is a serious health issue and, being such, treatment for it has become a topic of increasing concern. Consequently, the prescription rates of antidepressants have increased by about 50% over the past decade. Among antidepressants, citalopram and venlafaxine are the most frequently prescribed in Germany. Due to the high consumption and low elimination rates of both antidepressants during wastewater purification, they are frequently found in surface waters, where they may pose a risk to the aquatic environment. For the present study, we conducted experiments with the big ramshorn snail, which we exposed to environmentally relevant and explicitly higher concentrations (1–1000 µg/L) of the antidepressants citalopram and venlafaxine. We investigated apical endpoints, such as weight, mortality, behavioural changes, B-esterase activity, Hsp70 stress protein level and superoxide dismutase activity, as well as the tissue integrity of the hepatopancreas in the exposed snails. Citalopram and venlafaxine had no effects on the B-esterase activity, Hsp70 level and superoxide dismutase activity. Citalopram exposure resulted in weight reduction and tissue reactions in the hepatopancreas of snails exposed to 1000 µg/L. In contrast, venlafaxine did not induce comparable effects, but impacted the behaviour (sole detachment) of snails exposed to 100 µg/L and 1000 µg/L of the antidepressant. These results revealed that venlafaxine can affect snails at concentrations 10 times lower than citalopram. For this, in 2020 venlafaxine was introduced in the “Surface Water Watch List”, a list of potential pollutants that should be carefully monitored in surface water by the EU Member States.

Occurrence of areca alkaloids in wastewater of major Chinese cities

Areca nut is a widely used psychoactive product that can cause multiple health problems, such as oral and pharyngeal cancers. Therefore, it is important to estimate areca nut use and the exposure levels of areca alkaloids that are responsible for its health effects. China is a major producer of areca nut and has a large number of areca nut chewers. In this study, occurrence of areca alkaloids and metabolites in wastewater of major cities across China was examined via wastewater-based epidemiology (WBE). Arecoline, arecaidine, and their metabolite, N-methylnipecotic acid (NMNA) were detected in the overwhelming majority of wastewater samples, with concentrations up to several μg/L. In contrast, guvacoline was only occasionally detected and guvacine was below detection limit in all samples, possibly due to their low contents in areca nut products, low excretion rates, and/or low stability in sewer systems. Strong positive correlations existed between arecoline, arecaidine, and NMNA concentrations. In addition, their loads were much higher in Central and Southern China. This geographic pattern is consistent with previous survey results on prevalence of areca nut chewing. These results indicate that WBE is a potentially useful method to monitor areca nut consumption and to estimate the exposure levels of areca alkaloids.

Transplacental Behaviors of Organophosphate Tri- and Diesters Based on Paired Human Maternal and Cord Whole Blood: Efficiencies and Impact Factors.

Organophosphate tri- and diesters (tri-OPEs and di-OPEs) were quantified in 63 paired maternal and cord whole blood samples collected in Hubei, China, in which tri-o-cresyl phosphate (ToCP) was predominant. The transplacental transfer efficiencies (expressed as cord blood to maternal blood (C:M) concentration ratios) of aryl-tri-OPEs, such as ToCP (1.61) and triphenyl phosphate (TPHP) (1.06), were higher than those of alkyl-tri-OPEs (0.66-0.76). For the target tri-OPEs and some traditional organic compounds, the C:M ratios first increased with log Kow in the range of 1.63-5.23 and then decreased, showing a parabolic relationship. However, ToCP, with a log Kow of 6.34, deviated from this relationship and displayed the highest C:M ratio (1.61). Molecular docking indicated a very strong binding affinity between ToCP and transthyretin, suggesting that ToCP might be actively transported by transthyretin in the placenta. The di-OPE levels in the blood samples were significantly lower than the corresponding tri-OPE levels, and those in the cord blood were influenced not only by their transplacental behaviors but also by their low excretion rates and the metabolic characteristics of their parent compounds in the fetus. This study provides useful information for accurately assessing the health risks posed by tri-OPEs to pregnant women and fetuses.