Editor’s Choice Articles

Tebuconazole (TEB) is a triazole fungicide used to increase crop production by controlling fungi, insects, and weeds. Despite their extensive use, people are concerned about the health risks associated with pesticides and fungicides. Numerous studies have defined the cellular toxicity of triazole groups in pesticides, but the mechanisms of TEB toxicity in bovine mammary gland epithelial cells (MAC-T cells) have not yet been studied. Damage to the mammary glands of dairy cows directly affects milk production. This study investigated the toxicological effects of TEB on MAC-T cells. We found that TEB decreases both cell viability and proliferation and activates apoptotic cell death via the upregulation of pro-apoptotic proteins, such as cleaved caspases 3 and 8 and BAX. TEB also induced endoplasmic reticulum (ER) stress via the upregulation of Bip/GRP78; PDI; ATF4; CHOP; and ERO1-Lα. We found that TEB induced mitochondria-mediated apoptotic MAC-T cell death by activating ER stress. This cell damage eventually led to a dramatic reduction in the expression levels of the milk-protein-synthesis-related genes LGB; LALA; CSN1S1; CSN1S2; and CSNK in MAC-T cells. Our data suggest that the exposure of dairy cows to TEB may negatively affect milk production by damaging the mammary glands. Full article

The mixture of 5-chloro-2-methylisothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one, CMIT/MIT, is an isothiazolinone biocide that is consistently detected in aquatic environments because of its broad-spectrum usage in industrial fields. Despite concerns about ecotoxicological risks and possible multigenerational exposure, toxicological information on CMIT/MIT is very limited to human health and within-generational toxicity. Furthermore, epigenetic markers altered by chemical exposure can be transmitted over generations, but the role of these changes in phenotypic responses and toxicity with respect to trans- and multigenerational effects is poorly understood. In this study, the toxicity of CMIT/MIT on Daphnia magna was evaluated by measuring various endpoints (mortality, reproduction, body size, swimming behavior, and proteomic expression), and its trans- and multigenerational effects were investigated over four consecutive generations. The genotoxicity and epigenotoxicity of CMIT/MIT were examined using a comet assay and global DNA methylation measurements. The results show deleterious effects on various endpoints and differences in response patterns according to different exposure histories. Parental effects were transgenerational or recovered after exposure termination, while multigenerational exposure led to acclimatory/defensive responses. Changes in DNA damage were closely associated with altered reproduction in daphnids, but their possible relationship with global DNA methylation was not found. Overall, this study provides ecotoxicological information on CMIT/MIT relative to multifaceted endpoints and aids in understanding multigenerational phenomena under CMIT/MIT exposure. It also emphasizes the consideration of exposure duration and multigenerational observations in evaluating ecotoxicity and the risk management of isothiazolinone biocides. Full article

Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this study, we compared the effects on the kidneys and aging for two different types of multiwall carbon nanotubes (MWCNTs): pristine MWCNTs (PMWCNTs) and acid-treated MWCNTs (TMWCNTs), with TMWCNTs being the preferred form for use as a composite material due to its superior dispersion properties. We used tracheal instillation and maximum tolerated dose (MTD) for both types of CNTs. MTD was determined as a 10% weight loss dose in a 3-month subchronic study, and the appropriate dosage for 1-year exposure was 0.1 mg/mouse. Serum and kidney samples were analyzed using ELISA, Western blot, and immunohistochemistry after 6 months and 1 year of treatment. PMWCNT-administered mice showed the activation of pathways for inflammation, apoptosis, and insufficient autophagy, as well as decreased serum Klotho levels and increased serum levels of DKK-1, FGF-23, and sclerostin, while TMWCNTs did not. Our study suggests that lung exposure to PMWCNTs can induce premature kidney aging and highlights a possible toxic effect of using MWCNTs on the kidneys in the industrial field, further highlighting that dispersibility can affect the toxicity of the nanotubes. Full article

Chromium (Cr) is a major pollutant affecting the environment and human health and microbial remediation is considered to be the most promising technology for the restoration of the heavily metal-polluted soil. However, the difference between rhizosphere and endophytic bacteria on the potential of crop safety production in Cr-contaminated farmland is not clearly elucidated. Therefore, eight Cr-tolerant endophytic strains of three species: Serratia (SR-1~2), Lysinebacillus (LB-1~5) and Pseudomonas (PA-1) were isolated from rice and maize. Additionally, one Cr-tolerant strain of Alcaligenes faecalis (AF-1) was isolated from the rhizosphere of maize. A randomized group pot experiment with heavily Cr-contaminated (a total Cr concentration of 1020.18 mg kg⁻¹) paddy clay soil was conducted and the effects of different bacteria on plant growth, absorption and accumulation of Cr in lettuce (Lactuca sativa var. Hort) were compared. The results show that: (i) the addition of SR-2, PA-1 and LB-5 could promote the accumulation of plant fresh weight by 10.3%, 13.5% and 14.2%, respectively; (ii) most of the bacteria could significantly increase the activities of rhizosphere soil catalase and sucrase, among which LB-1 promotes catalase activity by 224.60% and PA-1 increases sucrase activity by 247%; (iii) AF-1, SR-1, LB-1, SR-2, LB-2, LB-3, LB-4 and LB-5 strains could significantly decrease shoot the Cr concentration by 19.2–83.6%. The results reveal that Cr-tolerant bacteria have good potential to reduce shoot Cr concentration at the heavily contaminated soil and endophytic bacteria have the same or even better effects than rhizosphere bacteria; this suggests that bacteria in plants are more ecological friendly than bacteria in soil, thus aiming to safely produce crops in Cr-polluted farmland and alleviate Cr contamination from the food chain. Full article

Thermal oxidation is efficient for enhancing the photocatalysis performance of graphitic carbon nitride (g-C₃N₄), while its effect on adsorption performance has not been fully studied, which is crucial to the application of g-C₃N₄ as adsorbents and photocatalysts. In this study, thermal oxidation was used to prepare sheet-like g-C₃N₄ (TCN), and its application for adsorption of humic acids (HA) and fulvic acids (FA) was evaluated. The results showed that thermal oxidation clearly affected the properties of TCN. After thermal oxidation, the adsorption performance of TCN was enhanced significantly, and the adsorption amount of HA increased from 63.23 (the bulk g-C₃N₄) to 145.35 mg/g [TCN prepared at 600 °C (TCN-600)]. Based on fitting results using the Sips model, the maximum adsorption amounts of TCN-600 for HA and FA were 327.88 and 213.58 mg/g, respectively. The adsorption for HA and FA was markedly affected by pH, alkaline, and alkaline earth metals due to electrostatic interactions. The major adsorption mechanisms included electrostatic interactions, π-π interactions, hydrogen bonding, along with a special pH-dependent conformation (for HA). These findings implied that TCN prepared from environmental-friendly thermal oxidation showed promising prospects for humic substances (HSs) adsorption in natural water and wastewater. Full article

Organic solvents are often used in aquatic toxicity tests to facilitate the testing of hydrophobic or poorly water-soluble substances such as ultraviolet (UV) filters, pesticides, or polycyclic aromatic hydrocarbons (PAHs). Knowledge of intrinsic effects (i.e., measured as standardized and non-standardized endpoints) of such carrier solvents in non-standardized organisms (i.e., corals), is critical to regulatory processes. Therefore, we exposed the reef-building coral Montipora digitata to the most commonly used carrier solvents ethanol, methanol, dimethyl sulfoxide, and dimethylformamide in the range of 10–100 µL L⁻¹ for 16 days. The effects on mortality, photobiological, morphological, and oxidative stress markers were evaluated. In our study, all solvents resulted in significant morphological and/or oxidative stress responses, but not in mortality. Moreover, ethanol led to a rapid increase in turbidity, thus questioning its suitability as a carrier solvent in aquatic studies in general. Based on our observations, we could rank the solvent effects as follows: dimethylformamide < dimethyl sulfoxide ≈ methanol ≤ ethanol, with dimethylformamide showing the least and ethanol the most pronounced effects. We conclude that the use of solvents in toxicity studies with corals, particularly by examining non-standardized (e.g., morphological, physiological) endpoints, should be taken with caution and requires further elaboration. Full article

Arsenic (As) and Cadmium (Cd) are toxic to rice plants. However, selenium (Se) has the potential to regulate As and Cd toxicity. The present study aimed to evaluate the co-exposure to As⁵⁺ and Se⁶⁺ species in two rice cultivars, BRS Pampa and EPAGRI 108. The plants were divided into six groups and cultivated until complete maturation of the grains, under greenhouse conditions. Regarding total As and inorganic As (i-As) accumulation in grains, the highest concentrations were found for BRS Pampa. For Se, EPAGRI 108 presented the highest concentration of inorganic and organic Se (i-Se and o-Se). The exposure assessments showed that Se biofortification can mitigate the As accumulation in rice and, consequently, the risk of As and Cd toxicity in grains for human consumption. The combined effect of As and Se in rice plants could represent an alternative to biofortify this food in a safe way and with a higher percentage of bioavailable Se. Although Se is able to mitigate As toxicity in rice plants, in the present study we showed that co-exposure in different cultivars under the same growing conditions may present different responses to As and Se exposure. Full article

Micro and nanoplastics (MNPs) as emerging contaminants have become a global environmental issue due to their small size and high bioavailability. However, very little information is available regarding their impact on zooplankton, especially when food availability is a limiting factor. Therefore, the present study aims at evaluating the long-term effects of two different sizes (50 nm and 1 μm) of amnio-modified polystyrene (PS-NH₂) particles on brine shrimp, Artemia parthenogenetica, by providing different levels of food (microalgae) supply. Larvae were exposed to three environmentally relevant concentrations (5.5, 55, and 550 μg/L) of MNPs over a 14-days of exposure with two food levels, high (3 × 10⁵~1 × 10⁷ cells/mL), and low (1 × 10⁵ cells/mL) food conditions. When exposed to high food levels, the survival, growth, and development of A. parthenogenetica were not negatively affected at the studied exposure concentrations. By comparison, when exposed to a low food level, a U shape trend was observed for the three measured effects (survival rate, body length, and instar). Significant interactions between food level and exposure concentration were found for all three measured effects (three-way ANOVA, p < 0.05). The activities of additives extracted from 50 nm PS-NH₂ suspensions were below toxic levels, while those from 1-μm PS-NH₂ showed an impact on artemia growth and development. Our results demonstrate the long-term risks posed by MNPs when zooplankton have low levels of food intake. Full article

Microbial toxicity tests are considered efficient screening tools for the assessment of water contamination. The objective of this study was to develop a sulfur-oxidizing bacteria (SOB)-based ecotoxicity test with high sensitivity and reproducibility for simple and rapid on-site application. To attain this goal, we developed a 25 mL vial-based toxicity kit and improved our earlier SOB toxicity test technique. The current study applied a suspended form of SOB and shortened the processing time to 30 min. Moreover, we optimized the test conditions of the SOB toxicity kit in terms of initial cell density, incubating temperature, and mixing intensity during incubation. We determined that 2 × 10⁵ cells/mL initial cell density, 32 °C incubating temperature, and 120 rpm mixing intensity are the optimal test conditions. Using these test conditions, we performed SOB toxicity tests for heavy metals and petrochemicals, and obtained better detection sensitivity and test reproducibility, compared to earlier SOB tests. Our SOB toxicity kit tests have numerous advantages, including a straightforward test protocol, no requirement of sophisticated laboratory equipment, and no distortion of test results from false readings of end-points and properties of test samples, making it suitable for simple and rapid on-site application. Full article

Imidacloprid is a neonicotinoid pesticide used in large-scale agricultural systems, home gardens, and veterinary pharmaceuticals. Imidacloprid is a small molecule that is more water-soluble than other insecticides, increasing the likelihood of large-scale environmental accumulation and chronic exposure of non-targeted species. Imidacloprid can be converted to the bioactive metabolite desnitro-imidacloprid in the environment and body. Little is known about the mechanisms by which imidacloprid and desnitro-imidacloprid induce ovarian toxicity. Thus, we tested the hypothesis that imidacloprid and desnitro-imidacloprid differentially affect antral follicle growth and steroidogenesis in vitro. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing vehicle control or 0.2 µg/mL–200 µg/mL of imidacloprid or desnitro-imidacloprid for 96 h. Follicle morphology was monitored, and follicle size was measured every 24 h. At the end of the culture periods, media were used to quantify follicular hormone levels, and follicles were used for gene expression analysis of steroidogenic regulators, hormone receptors, and apoptotic factors. Imidacloprid did not affect follicle growth or morphology compared to the control. Desnitro-imidacloprid inhibited follicle growth and caused follicles to rupture in culture compared to the control. Imidacloprid increased progesterone, whereas desnitro-imidacloprid decreased testosterone and progesterone compared to the control. Desnitro-imidacloprid also changed estradiol compared to the control. At 48 h, IMI decreased the expression of Star, Cyp17a1, Hsd17b1, Cyp19a1, and Esr2 and increased the expression of Cyp11a1, Cyp19a1, Bax, and Bcl2 compared to the control. IMI also changed the expression of Esr1 compared to the control. At 48 h, DNI decreased the expression of Cyp11a1, Cyp17a1, Hsd3b1, Cyp19a1, and Esr1 and increased the expression of Cyp11a1, Hsd3b1, and Bax compared to the control. At 72 h of culture, IMI significantly decreased the expression of Cyp19a1 and increased the expression of Star and Hsd17b1 compared to the control. At 72 h, DNI significantly decreased the expression of Cyp11a1, Cyp17a1, Hsd3b1, and Bax and increased the expression of Esr1 and Esr2. At 96 h, IMI decreased the expression of Hsd3b1, Cyp19a1, Esr1, Bax, and Bcl2 compared to the control. At 96 h, DNI decreased the expression of Cyp17a1, Bax, and Bcl2 and increased the expression of Cyp11a1, Hsd3b1, and Bax compared to the control. Together, these data suggest mouse antral follicles are targets of neonicotinoid toxicity, and the mechanisms of toxicity differ between parent compounds and metabolites. Full article

Submerged munitions are present in marine waters across the globe. They contain energetic compounds (ECs), such as TNT and metabolites thereof, which are considered carcinogenic, exhibit toxic effects in marine organisms, and may affect human health. The aim of this study was to investigate the occurrence of ECs and their trends in blue mussels from the annual collections of the German Environmental Specimen Bank sampled over the last 30 years at three different locations along the coastline of the Baltic and North Sea. Samples were analyzed by GC-MS/MS for 1,3-dinitrobenzene (1,3-DNB), 2,4-dinitrotoluene (2,4-DNT), 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2-ADNT), and 4-amino-2,6-dinitrotoluene (4-ADNT). The first signals indicating trace levels of 1,3-DNB were observed in samples from 1999 and 2000. ECs were also found below the limit of detection (LoD) in subsequent years. From 2012 onwards, signals just above the LoD were detected. The highest signal intensities of 2-ADNT and 4-ADNT, just below the LoQ (0.14 ng/g d.w. and 0.17 ng/g d.w., respectively), were measured in 2019 and 2020. This study clearly shows that corroding submerged munitions are gradually releasing ECs into the waters that can be detected in randomly sampled blue mussels, even though the concentrations measured are still in the non-quantifiable trace range. Full article

Hexamethylenetetramine, an aldehyde-releasing agent, is used as a preservative in various food, cosmetics, and medical treatments, such as a treatment for urinary tract infections. It has been reported to be allergenic on contact with the skin, with the additional possibility of causing toxicity once absorbed systemically. Despite its potential toxicity, there are no reports on the in vivo bioavailability of hexamethylenetetramine following oral or dermal administration. In this study, we developed a new simple and sensitive LC–MS/MS method for the determination of hexamethylenetetramine in plasma and applied this method to characterize the toxicokinetics. The developed assay had a sufficient specificity and sensitivity for toxicokinetic characterization, and its accuracy and precision were verified. Following iv injection, the plasma concentration of hexamethylenetetramine showed mono exponential decay, with an elimination half-life of about 1.3 h. Following oral administration, the T_max reached an average of 0.47 h and bioavailability was estimated as 89.93%. After percutaneous administration, it reached C_max on average at 2.9–3.6 h. Although the absorption rate was relatively slow, its average bioavailability was calculated as 77.19–78.91%. Overall, most of the orally and percutaneously administered hexamethylenetetramine was absorbed into systemic circulation. The derived results in this study are expected to be utilized as the scientific evidence for further toxicokinetic study and risk assessment. Full article

Emerging contaminants are produced globally at high rates and often ultimately find their way into the aquatic environment. These include substances contained in anti-seizure medication (ASM), which are currently appearing in surface waters at increasing concentrations in Germany. Unintentional and sublethal, chronic exposure to pharmaceuticals such as ASMs has unknown consequences for aquatic wildlife. Adverse effects of ASMs on the brain development are documented in mammals. Top predators such as Eurasian otters (Lutra lutra) are susceptible to the bioaccumulation of environmental pollutants. Still little is known about the health status of the otter population in Germany, while the detection of various pollutants in otter tissue samples has highlighted their role as an indicator species. To investigate potential contamination with pharmaceuticals, Eurasian otter brain samples were screened for selected ASMs via high-performance liquid chromatography and mass spectrometry. Via histology, brain sections were analyzed for the presence of potential associated neuropathological changes. In addition to 20 wild otters that were found dead, a control group of 5 deceased otters in human care was studied. Even though none of the targeted ASMs were detected in the otters, unidentified substances in many otter brains were measured. No obvious pathology was observed histologically, although the sample quality limited the investigations. Full article

As two commonly used fungicides, carbendazim and tebuconazole are widely found in the environment and in foods. Studies have reported that these fungicides can induce hepatic oxidative stress and other health risks. Nevertheless, the influences of exposure to carbendazim and tebuconazole at their acceptable daily intake (ADI) doses on hepatic oxidative stress, and the residual distributions in mice remain unclear. To fill these gaps, ICR (CD-1) mice were exposed to carbendazim and tebuconazole at their ADI doses by oral administration for 4 weeks in this study. The results showed that tebuconazole accumulated primarily in the epididymal fat of mice (16.84 μg/kg), whereas no significant residues of carbendazim in the tissues were observed. In addition, exposure to ADI doses of tebuconazole significantly reduced liver coefficients and induced hepatic oxidative stress in mice, including elevating the levels of glutathione and malonaldehyde. However, no significant impacts were observed on the hepatic redox homeostasis in mice after exposure to carbendazim at its ADI dose. The results could be helpful for understanding the exposure risks of carbendazim and tebuconazole in terms of low doses and long term. Full article

Pharmaceuticals pose a great threat to organisms inhabiting the aquatic environment. Non-steroidal anti-inflammatory drugs (NSAIDs) are major pharmaceutical pollutants with a significant presence in freshwater ecosystems. In this study, the impact of indomethacin and ibuprofen, two of the most commonly prescribed NSAIDs, was assessed on Daphnia magna. Toxicity was assessed as the immobilization of animals and used to determine non-lethal exposure concentrations. Feeding was assessed as a phenotypic endpoint and key enzymes were used as molecular endpoints of physiology. Feeding was decreased in mixture exposures for five-day-old daphnids and neonates. Furthermore, animals were exposed to NSAIDs and their mixture in chronic and transgenerational scenarios revealing changes in key enzyme activities. Alkaline and acid phosphatases, lipase, peptidase, β-galactosidase, and glutathione-S-transferase were shown to have significant changes in the first generation at the first and third week of exposure, and these were enhanced in the second generation. On the other hand, the third recovery generation did not exhibit these changes, and animals were able to recover from the induced changes and revert back to the control levels. Overall, our study points towards transgenerational exposures as more impactful laboratory studies to understand pharmaceutical stressors with a combination of molecular and phenotypic markers of physiology. Full article

Polycyclic aromatic hydrocarbons (PAHs) are an important class of pollutants in China. The land use regression (LUR) model has been used to predict the selected PAH concentrations and screen the key influencing factors. However, most previous studies have focused on particle-associated PAHs, and research on gaseous PAHs was limited. This study measured representative PAHs in both gaseous phases and particle-associated during the windy, non-heating and heating seasons from 25 sampling sites in different areas of Taiyuan City. We established separate prediction models of 15 PAHs. Acenaphthene (Ace), Fluorene (Flo), and benzo [g,h,i] perylene (BghiP) were selected to analyze the relationship between PAH concentration and influencing factors. The stability and accuracy of the LUR models were quantitatively evaluated using leave-one-out cross-validation. We found that Ace and Flo models show good performance in the gaseous phase (Ace: adj. R² = 0.14–0.82; Flo: adj. R² = 0.21–0.85), and the model performance of BghiP is better in the particle phase (adj. R² = 0.20–0.42). Additionally, better model performance was observed in the heating season (adj R² = 0.68–0.83) than in the non-heating (adj R² = 0.23–0.76) and windy seasons (adj R² = 0.37–0.59). Those gaseous PAHs were highly affected by traffic emissions, elevation, and latitude, whereas BghiP was affected by point sources. This study reveals the strong seasonal and phase dependence of PAH concentrations. Building separate LUR models in different phases and seasons improves the prediction accuracy of PAHs. Full article

The effect of the chronic consumption of water contaminated with residual concentrations of DDT’s metabolites (DDD—dichlorodiphenyldichloroethane and DDE—dichlorodiphenyldichloroethylene) found in the environment were evaluated on the biometric, hematological and antioxidant system parameters of the hepatic, muscular, renal and nervous tissues of Wistar rats. The results showed that the studied concentrations (0.002 mg.L⁻¹ of DDD plus 0.005 mg.L⁻¹ of DDE) could not cause significant changes in the hematological parameters. However, the tissues showed significant alteration in the activity of the antioxidant system represented by the increase in the activity of the enzymes gluthathione S-transferases in the liver, superoxide dismutase in the kidney, gluthathione peroxidase in the brain, and several changes in enzymatic activity in muscle (SOD, GPx and LPO). The enzymes alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were also evaluated for the amino acids’ metabolism in the liver, with ALT showing a significant increase in the exposed animals. In the integrative analysis of biomarkers (Permanova and PCOA), the studied concentrations showed possible metabolic changes and damage to cellular structures evidenced by increased oxidative stress and body weight gain among the treated animals. This study highlights the need for further studies on the impact of banned pesticides still present in soils that may induce adverse effects in organisms that may prevail in future generations and the environment. Full article

The present work evaluated the influence of eight different soil remediation techniques, based on the use of residual materials (gypsum, marble, vermicompost) on the reduction in metal(loid)s toxicity (Cu, Zn, As, Pb and Cd) in a polluted natural area. Selected remediation treatments were applied in a field exposed to real conditions and they were evaluated one year after the application. More specifically, five ecotoxicological tests were carried out using different organisms on either the solid or the aqueous (leachate) fraction of the amended soils. Likewise, the main soil properties and the total, water-soluble and bioavailable metal fractions were determined to evaluate their influence on soil toxicity. According to the toxicity bioassays performed, the response of organisms to the treatments differed depending on whether the solid or the aqueous fraction was used. Our results highlighted that the use of a single bioassay may not be sufficient as an indicator of toxicity pathways to select soil remediation methods, so that the joint determination of metal availability and ecotoxicological response will be determinant for the correct establishment of any remediation technique carried out under natural conditions. Our results indicated that, of the different treatments used, the best technique for the remediation of metal(loid)s toxicity was the addition of marble sludge with vermicompost. Full article

Drug-induced nephrotoxicity is a major cause of kidney dysfunction with potentially fatal consequences. The poor prediction of clinical responses based on preclinical research hampers the development of new pharmaceuticals. This emphasises the need for new methods for earlier and more accurate diagnosis to avoid drug-induced kidney injuries. Computational predictions of drug-induced nephrotoxicity are an attractive approach to facilitate such an assessment and such models could serve as robust and reliable replacements for animal testing. To provide the chemical information for computational prediction, we used the convenient and common SMILES format. We examined several versions of so-called optimal SMILES-based descriptors. We obtained the highest statistical values, considering the specificity, sensitivity and accuracy of the prediction, by applying recently suggested atoms pairs proportions vectors and the index of ideality of correlation, which is a special statistical measure of the predictive potential. Implementation of this tool in the drug development process might lead to safer drugs in the future. Full article

The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd²⁺ in the bloodstream, we employed an anion-exchange HPLC coupled to a flame atomic absorption spectrometer (FAAS) using a mobile phase of 100 mM NaCl with 5 mM Tris-buffer (pH 7.4) to resemble protein-free blood plasma. The injection of Cd²⁺ onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl₃]⁻/[CdCl₄]²⁻ complexes. The addition of 0.1–10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd²⁺, which was rationalized by the on-column formation of mixed CdCys_xCl_y complexes. From a toxicological point of view, the results obtained with 0.1 and 0.2 mM Cys were the most relevant because they resembled plasma concentrations. The corresponding Cd-containing (~30 μM) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd²⁺ when the Cys concentration was increased from 0.1 to 0.2 mM. The putative formation of these toxicologically relevant Cd species in blood plasma was implicated in the Cd uptake into target organs and underscores the notion that a better understanding of the metabolism of Cd in the bloodstream is critical to causally link human exposure with organ-based toxicological effects. Full article

cC₆O₄ is a new-generation perfluoroalkyl surfactant used in the chemical industry for the synthesis of perfluoroalkyl polymers. It was introduced as a less biopersistent substitute of traditional perfluoroalkyl surfactants such as PFOA, but its kinetics in humans was never investigated. This work is aimed to investigate the kinetics of elimination of cC₆O₄ in exposed workers. Eighteen male individuals occupationally exposed to cC₆O₄ in the production of fluoropolymers volunteered for the study. Blood and urine samples were collected from the end of a work-shift for the following 5 days off work. Serum and urinary cC₆O₄ were measured by LC-MS/MS. Seventy-two samples with serum cC₆O₄ ranging from 0.38 to 11.29 µg/L were obtained; mean levels were 3.07, 2.82, 2.67 and 2.01 µg/L at times 0, 18, 42 and 114 h. Two hundred and fifty-four urine samples with cC₆O₄ ranging from 0.19 to 5.92 µg/L were obtained. A random-intercept multiple regression model was applied to serum data and a half-life of 184 (95% CI 162–213) h for a first-order kinetics elimination was calculated; a mean distribution volume of 80 mL/kg was also estimated. Pearson’s correlation between ln-transformed serum and daily urine concentrations was good, with r ranging from 0.802 to 0.838. The amount of cC₆O₄ excreted daily in urine was about 20% of the amount present in serum. The study allowed calculating a half-life for cC₆O₄ in blood of about 8 days in humans, supporting its much shorter biopersistence in comparison with legacy PFAS. The good correlation between urine and serum cC₆O₄ suggests urine as a possible non-invasive matrix for biomonitoring. The amount of cC₆O₄ excreted daily in urine suggests urine as the sole elimination route. Full article

Alterations of the normal gut microbiota can cause various human health concerns. Environmental chemicals are one of the drivers of such disturbances. The aim of our study was to examine the effects of exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS)—specifically, perfluorooctane sulfonate (PFOS) and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoic acid (GenX)—on the microbiome of the small intestine and colon, as well as on liver metabolism. Male CD-1 mice were exposed to PFOS and GenX in different concentrations and compared to controls. GenX and PFOS were found to have different effects on the bacterial community in both the small intestine and colon based on 16S rRNA profiles. High GenX doses predominantly led to increases in the abundance of Clostridium sensu stricto, Alistipes, and Ruminococcus, while PFOS generally altered Lactobacillus, Limosilactobacillus, Parabacteroides, Staphylococcus, and Ligilactobacillus. These treatments were associated with alterations in several important microbial metabolic pathways in both the small intestine and colon. Untargeted LC-MS/MS metabolomic analysis of the liver, small intestine, and colon yielded a set of compounds significantly altered by PFOS and GenX. In the liver, these metabolites were associated with the important host metabolic pathways implicated in the synthesis of lipids, steroidogenesis, and in the metabolism of amino acids, nitrogen, and bile acids. Collectively, our results suggest that PFOS and GenX exposure can cause major perturbations in the gastrointestinal tract, aggravating microbiome toxicity, hepatotoxicity, and metabolic disorders. Full article

[Background] Metal exposure is suspected to be correlated to kidney function. However, the combined effects of co-exposing to multiple metals, especially both toxic and protective metals, have not been completely evaluated. [Method] A prospective cohort study was conducted with the “135” cohort for the evaluation of how plasma metal levels are correlated to kidney function in a midlife and elderly community in southern China. An amount of 1368 subjects without kidney disease at baseline were enrolled in the final analysis. By using linear regression and logistic regression models, the correlation of individual metal values with renal function parameters was assessed. Measuring of the multiple metal exposure level was performed by principal component analysis (PCA). [Results] Diminished renal function, as evaluated based on fast kidney function decline, or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², was positively associated with the plasma concentrations of chromium and potassium, but it was negatively associated with selenium and iron (p < 0.05). In multiple-metal analyses, linear and logistic regression models showed that the iron and chromium exposure pattern had a protective effect on renal function, whereas the sodium and potassium exposure pattern and the cadmium and lead exposure pattern increased the risk for fast kidney function decline, and eGFR < 60 mL/min/1.73 m². [Conclusions] Certain metals, including chromium, potassium, selenium, and iron, were correlated with kidney function in a midlife and elderly community in China. In addition, the potential combined influences of co-exposing to multiple metals were observed. Full article

Indoor household pollution is not yet sufficiently studied in the general population. Over 4 million people die prematurely every year due to air pollution in households. This study aimed to propose quantitative data research through the administration of a KAP (Knowledge, Attitudes, and Practices) Survey Questionnaire. This cross-sectional study administered questionnaires to adults from the metropolitan city of Naples (Italy). Three Multiple Linear Regression Analyses (MLRA) were developed, including Knowledge, Attitudes, and Behavior regarding household chemical air pollution and the related risks. One thousand six hundred seventy subjects received a questionnaire to be filled out and collected anonymously. The mean age of the sample was 44.68 years, ranging from 21–78 years. Most of the people interviewed (76.13%) had good attitudes toward house cleaning, and 56.69% stated paying attention to cleaning products. Results of the regression analysis indicated that positive attitudes were significantly higher among subjects who graduated, with older age, male and non-smokers, but they were correlated with lower knowledge. In conclusion, a behavioral and attitudinal program targeted those with knowledge, such as younger subjects with high educational levels, but do not engage in correct practices towards household indoor chemical pollution. Full article

To improve household air quality, the Chinese government has launched a number of pilot stove renovation projects, but few studies have explored the impact of the project on people’s perception of and willingness to participate in these renovations; moreover, factors affecting willingness to pay for the project in rural China are not yet clear. We conducted a field measurement and a corresponding door-to-door questionnaire survey using the renovated group and the unrenovated group. The results showed that (1) the stove renovation project could not only reduce PM_2.5 exposure and the excess mortality risk of rural residents, but also (2) improve residents’ risk perception and self-protective willingness. (3) Specifically, the project had a deeper impact on female and low-income residents. (4) Meanwhile, the higher the income and the larger family size, the higher the risk perception and self-protective willingness. (5) Furthermore, willingness to pay for the project was related with residents’ support for the project, benefit from renovation, income, and family size. Our results recommended that stove renovation policies should pay more attention to families with lower income and smaller size. Full article

Recent studies have confirmed that changes in the physical properties of microplastics (MPs) trigger toxicological effects and ecological risks. To explore the toxicity of different types of MPs on plants, and the influence of MP photoaging, this study investigated the toxicity mechanisms of pristine, 7 and 14 d photoaged polystyrene (PS), polyamide (PA), polyethylene (PE), and polyethylene terephthalate (PET) MPs on seed germination, root growth, nutrient fraction, oxidative stress, and antioxidant systems of Pisum sativum L. (pea) seedlings. The results showed that pristine PS and 14 d photoaged PET inhibited seed germination. Compared to the pristine MPs, photoaged MPs had negative effects on root elongation. Moreover, photoaged PA and PE impeded the nutrient transport of soluble sugars from roots to stems. Notably, the production of superoxide anion radicals (•O₂⁻) and hydroxyl radicals (•OH) through the photoaging of MPs exacerbated oxidative stress and reactive oxygen species formation in roots. Antioxidant enzyme data revealed that the activities of superoxide dismutase and catalase were significantly activated in photoaged PS and PE, respectively, in order to scavenge •O₂⁻ and hydrogen peroxide (H₂O₂) accumulation and alleviate lipid peroxidation levels in cells. These findings provide a new research perspective on the phytotoxicity and ecological risk of photoaged MPs. Full article

After World War II, large amounts of ammunition were dumped in surface waters worldwide, potentially releasing harmful and toxic compounds to the environment. To study their degradation, ammunition items dumped in the Eastern Scheldt in The Netherlands were surfaced. Severe damage due to corrosion and leak paths through the casings were observed, making the explosives in the ammunition accessible to sea water. Using novel techniques, the concentrations of ammunition-related compounds in the surrounding seabed and in the seawater were analyzed at 15 different locations. In the direct vicinity of ammunition, elevated concentrations of ammunition-related compounds (both metals and organic substances) were found. Concentrations of energetic compounds ranged from below the limit of detection (LoD) up to the low two-digit ng/L range in water samples, and from below the LoD up to the one-digit ng/g dry weight range in sediment samples. Concentrations of metals were found up to the low microgram/L range in water and up the low ng/g dry weight in sediment. However, even though the water and sediment samples were collected as close to the ammunition items as possible, the concentrations of these compounds were low and, as far as available, no quality standards or limits were exceeded. The presence of fouling, the low solubility of the energetic compounds, and dilution by the high local water current were concluded to be the main causes for the absence of high concentrations of ammunition-related compounds. As a conclusion, these new analytical methods should be applied to continuously monitor the Eastern Scheldt munitions dump site. Full article

Oil spill is a major marine environmental pollution issue. Research regarding the long-term effects of oil spills on the early life stage of marine fish is still limited. In this study, the potential adverse impact of crude oil from one oil spill accident which occurred in the Bohai Sea on the early life stages of marine medaka (Oryzias melastigma, McClelland, 1839) was evaluated. A 96-h acute test (larvae) and a 21-d chronic test (embryo–larvae) of water-accommodated fractions (WAFs) from crude oil were conducted, respectively. The results of the acute test showed that only the highest concentration of WAFs (100.00%) significantly affected the mortality of larvae (p < 0.01) and that the 96 h-LC₅₀ was 68.92% (4.11 mg·L^-1 expressed as total petroleum hydrocarbons (TPHs)). Larval heart demonstrated histopathological alterations in all WAF-exposed groups. The chronic test results showed that, except for larval mortality, the total hatching success (%)/hatching time of embryos in WAF treatments was not significantly different from those of the control group (p > 0.05), and no malformation was found in surviving larvae after 21 d of exposure. Nevertheless, the exposed embryos and larvae in the highest concentration of WAFs (60.00%) demonstrated significantly reduced heart rate (p < 0.05) and increased mortality (p < 0.01), respectively. Overall, our results indicated that both acute and chronic WAF exposures had adverse impacts on the survival of marine medaka. In the early life stages, the heart of the marine medaka was the most sensitive organ which showed both structural alteration and cardiac dysfunction. Full article

This paper present seasonal variation in the equivalent concentration (BaP_eq) of PAHs in order to assess the potential cancer risk for two different groups of residents via ingestion, dermal contact and inhalation pathways. The possible ecological risk caused by PAH atmospheric deposition based on risk quotient was also estimated. A bulk (total, wet and dry) deposition and PM₁₀ particle fraction (particles with an equivalent aerodynamic diameter < 10 µm) were collected from June 2020 to May 2021 at an urban residential location in the northern part of Zagreb, Croatia. The monthly average of total equivalent BaP_eq mass concentrations of PM₁₀ varied from 0.057 ng m⁻³ in July to 3.656 ng m⁻³ in December; the annul ∑BaP_eq average was 1.348 ng m⁻³. In bulk deposition, ∑BaP_eq mass concentrations varied from 1.94 to 57.60 ng L⁻¹. In both investigated media, BaP had the highest contribution in carcinogenic activity. For PM₁₀ media, dermal absorption implied the greatest potential cancer risk, followed by ingestion and inhalation. For bulk media, a moderate ecological risk for BaA, BbF and BaP was observed according to the risk quotient approach. Full article

Agriculture is fundamental for human development, but it may also have a range of unwanted effects on ecosystems when pesticides inadvertently enter the environment. We determined the toxicity of difenoconazole and atrazine, as well as their photodegradation products, on the bioindicators Lemna minor and Daphnia magna. For L. minor, we assessed the number of leaves, biomass, and chlorophyll content exposed to different concentrations of difenoconazole (0–8 mg/L) and atrazine (0–3.84 mg/L). For D. magna, we assessed the mortality to difenoconazole (0–1.6 mg/L) and atrazine (0–80 mg/L). We found that the higher the concentrations of the pesticides, the higher the toxicity for both bioindicators. In L. minor, the highest toxicity for atrazine was 0.96 mg/L, whereas for difenoconazole, it was 8 mg/L. For D. magna, the 48 h LC₅₀ for difenoconazole was 0.97 mg/L, while for atrazine, it was 86.19 mg/L. For L. minor, the toxicity of difenoconazole and atrazine was not different compared to that of their photodegradation products. In contrast, for D. magna, difenoconazole, but not atrazine, was more toxic compared to its respective photodegradation products. Pesticides are a serious threat to aquatic biota, and their photodegradation products remain toxic in the environment. Additionally, the use of bioindicators can help monitor these pollutants in aquatic ecosystems in countries where the application of pesticides is imperative for agricultural production. Full article

Xenobiotics released in the environment can be taken up by aquatic and terrestrial organisms and can accumulate at higher concentrations through the trophic chain. Bioaccumulation is therefore one of the PBT properties that authorities require to assess for the evaluation of the risks that chemicals may pose to humans and the environment. The use of an integrated testing strategy (ITS) and the use of multiple sources of information are strongly encouraged by authorities in order to maximize the information available and reduce testing costs. Moreover, considering the increasing demand for development and the application of new approaches and alternatives to animal testing, the development of in silico cost-effective tools such as QSAR models becomes increasingly important. In this study, a large and curated literature database of fish laboratory-based values of dietary biomagnification factor (BMF) was used to create externally validated QSARs. The quality categories (high, medium, low) available in the database were used to extract reliable data to train and validate the models, and to further address the uncertainty in low-quality data. This procedure was useful for highlighting problematic compounds for which additional experimental effort would be required, such as siloxanes, highly brominated and chlorinated compounds. Two models were suggested as final outputs in this study, one based on good-quality data and the other developed on a larger dataset of consistent Log BMF_L values, which included lower-quality data. The models had similar predictive ability; however, the second model had a larger applicability domain. These QSARs were based on simple MLR equations that could easily be applied for the predictions of dietary BMF_L in fish, and support bioaccumulation assessment procedures at the regulatory level. To ease the application and dissemination of these QSARs, they were included with technical documentation (as QMRF Reports) in the QSAR-ME Profiler software for QSAR predictions available online. Full article

Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that are in our body at one point in time. Network analysis applied to such data may provide insight into real-life mixtures by visualizing chemical exposure patterns. The identification of groups of more densely correlated biomarkers, so-called “communities”, within these networks highlights which combination of substances should be considered in terms of real-life mixtures to which a population is exposed. We applied network analyses to HBM datasets from Belgium, Czech Republic, Germany, and Spain, with the aim to explore its added value for exposure and risk assessment. The datasets varied in study population, study design, and chemicals analysed. Sensitivity analysis was performed to address the influence of different approaches to standardise for creatinine content of urine. Our approach demonstrates that network analysis applied to HBM data of highly varying origin provides useful information with regards to the existence of groups of biomarkers that are densely correlated. This information is relevant for regulatory risk assessment, as well as for the design of relevant mixture exposure experiments. Full article

Silver nanoparticles (Ag NPs) are among the most widely used metal-based nanomaterials (NMs) and their applications in different products, also as antibacterial additives, are increasing. In the present manuscript, according to an adverse outcome pathway (AOP) approach, we tested two safe-by-design (SbD) newly developed Ag NPs coated with hydroxyethyl cellulose (HEC), namely AgHEC powder and AgHEC solution. These novel Ag NPs were compared to two reference Ag NPs (naked and coated with polyvinylpyrrolidone—PVP). Cell viability, inflammatory response, reactive oxygen species, oxidative DNA damage, cell cycle, and cell–particle interactions were analyzed in the alveolar in vitro model, A549 cells. The results show a different toxicity pattern of the novel Ag NPs compared to reference NPs and that between the two novel NPs, the AgHEC solution is the one with the lower toxicity and to be further developed within the SbD framework. Full article

The environmental transformation and health effects of endocrine disruptors (EDCs) need urgent attention, particularly the formation of transformation products with higher toxicity than parent EDCs. In this paper, an important transformation product dimer (short for ethyl 4-hydroxy-3-(2-((4-hydroxybenzoyl) oxy) ethyl) benzoate) with estrogenic activity was investigated and detected in the photolysis of preservative ethyl-paraben (EPB) dissolved in actual water. The environmental factors, such as the higher initial concentration of EPB, the stronger optical power and the lower pH could stimulate the formation of the dimer. Simultaneously, the interaction of multiple environmental factors was significant, especially the initial concentration and pH using the response surface methodology. Furthermore, the relationship between the environmental factors and the formation of the product dimer was further explained and the empirical model equation was built for predicting the amount of dimer in actual water. Quantum chemical and toxicological calculations showed the estrogenic effect mechanism of the product dimer and it was revealed further that the hydrogen bonds of the dimer and ERα proteins (ARG-394, Glu-353, His-524, GYY-521) were formed, with a lowest binding energy of −8.38 Kcal/mol during molecular docking. In addition, the health effect risk of the product dimer was higher than the parent compound in the blood, cardiovascular system, gastrointestinal system, kidney and liver. In short, the present study was of great significance for the transformation product in pollution control and health effects in the photolysis of EDCs. Full article

Mercury (Hg) is a dangerous and persistent trace element. Its organic and highly toxic form, methylmercury (MeHg), easily crosses biological membranes and accumulates in biota. Nevertheless, understanding the mechanisms of dietary MeHg toxicity in fish remains a challenge. A time-course experiment was conducted with juvenile white seabreams, Diplodus sargus (Linnaeus, 1758), exposed to realistic levels of MeHg in feed (8.7 μg g⁻¹, dry weight), comprising exposure (E; 7 and 14 days) and post-exposure (PE; 28 days) periods. Total Hg levels increased with time in gills and liver during E and decreased significantly in PE (though levels of control fish were reached only for gills), with liver exhibiting higher levels (2.7 times) than gills. Nuclear magnetic resonance (NMR)-based metabolomics revealed multiple and often differential metabolic changes between fish organs. Gills exhibited protein catabolism, disturbances in cholinergic neurotransmission, and changes in osmoregulation and lipid and energy metabolism. However, dietary MeHg exposure provoked altered protein metabolism in the liver with decreased amino acids, likely for activation of defensive strategies. PE allowed for the partial recovery of both organs, even if with occurrence of oxidative stress and changes of energy metabolism. Overall, these findings support organ-specific responses according to their sensitivity to Hg exposure, pointing out that indications obtained in biomonitoring studies may depend also on the selected organ. Full article

The South River located in the city of Waynesboro, Virginia, contains mercury (Hg) contamination due to historical releases from an industrial facility operating between 1929 and 1950. In 2015, two sampling events were conducted in two of the contaminated bank regions (Constitution Park and North Park) to evaluate non-particulate total mercury (THg) and methylmercury (MeHg) concentrations in bank interstitial waters during river base flows and during bank drainage after flooding events. Porewater THg and MeHg at the bank–water interface were measured using diffusive gradient in thin-film devices (DGTs). The results showed THg mercury concentrations during bank drainage were approximately a factor of 3 higher than during base flow conditions. To have a better understanding of the parameters that control Hg leaching, a series of laboratory experiments were designed using South River sediments. The field and laboratory assessment showed that drainage/inundation cycles can lead to high THg concentration leachate from contaminated sediment due to increased partitioning from solids under oxic bank conditions and mobilization by the drainage waters. The results also demonstrated that methyl mercury concentrations at the bank–water interface are highest under base flow when conditions are more reduced due to the absence of oxic water exchange with the surface water. A remedial approach was implemented involving partial removal of surficial sediments and placement of biochar (to reduce non-particulate THg) and an armoring layer (to reduce erosion). DGT Measurements after bank stabilization showed THg decreased by a factor of ~200 and MeHg concentration by a factor of more than 20. Full article

Bisphenol A (BPA) is one of the most widely produced chemicals in the world used in the production of epoxy resins and polycarbonate plastics. BPA is easily migrated from the outer packaging to the contents. Due to the lipophilic property, BPA is easily accumulated in organisms. Perinatal low-dose BPA exposure alters brain neural development in later generations. In this study, after BPA treatment, the spontaneous movement of zebrafish larvae from the cleavage period to the segmentation period (1–24 hpf) was significantly decreased, with speed decreasing by 18.97% and distance decreasing between 18.4 and 29.7% compared to controls. Transcriptomics analysis showed that 131 genes were significantly differentially expressed in the exposed group during the 1–24 hpf period, among which 39 genes were significantly upregulated and 92 genes were significantly downregulated. The GO enrichment analysis, gene function analysis and real-time quantitative PCR of differentially expressed genes showed that the mRNA level of guanine deaminase (cypin) decreased significantly in the 1–24 hpf period. Moreover, during the 1–24 hpf period, BPA exposure reduced guanine deaminase activity. Therefore, we confirmed that cypin is a key sensitive gene for BPA during this period. Finally, the cypin mRNA microinjection verified that the cypin level of zebrafish larvae was restored, leading to the restoration of the locomotor activity. Taken together, the current results show that the sensitive period of BPA to zebrafish embryos is from the cleavage period to the segmentation period (1–24 hpf), and cypin is a potential target for BPA-induced neurodevelopmental toxicity. This study provides a potential sensitive period and a potential target for the deep understanding of neurodevelopmental toxicity mechanisms caused by BPA. Full article

According to European regulations, migration from food packaging must be safe. However, currently, there is no consensus on how to evaluate its safety, especially for non-intentionally added substances (NIAS). The intensive and laborious approach, involving identification and then quantification of all migrating substances followed by a toxicological evaluation, is not practical or feasible. In alignment with the International Life Sciences Institute (ILSI) and the European Union (EU) guidelines on packaging materials, efforts are focused on combining data from analytics, bioassays and in silico toxicology approaches for the risk assessment of packaging materials. Advancement of non-targeted screening approaches using both analytical methods and in vitro bioassays is key. A protocol was developed for the chemical and biological screening of migrants from coated metal packaging materials. This protocol includes guidance on sample preparation, migrant simulation, chemical analysis using liquid chromatography (LC-MS) and validated bioassays covering endocrine activity, genotoxicity and metabolism-related targets. An inter-laboratory study was set-up to evaluate the consistency in biological activity and analytical results generated between three independent laboratories applying the developed protocol and guidance. Coated packaging metal panels were used in this case study. In general, the inter-laboratory chemical analysis and bioassay results displayed acceptable consistency between laboratories, but technical differences led to different data interpretations (e.g., cytotoxicity, cell passages, chemical analysis). The study observations with the greatest impact on the quality of the data and ultimately resulting in discrepancies in the results are given and suggestions for improvement of the protocol are made (e.g., sample preparation, chemical analysis approaches). Finally, there was agreement on the need for an aligned protocol to be utilized by qualified laboratories for chemical and biological analyses, following best practices and guidance for packaging safety assessment of intentionally added substances (IAS) and NIAS to avoid inconsistency in data and the final interpretation. Full article

Selective serotonin reuptake inhibitors (SSRIs) are currently the most prescribed class of psychotropic medications. Their increased global manufacture and use have become growing concerns for aquatic toxicologists and environmental biologists, who assess both the direct and indirect effects of substances on the environment and on human health. In order to assess the potential impact of environmentally relevant levels of SSRIs on fish development, behaviour and reproduction, we exposed juvenile and adult zebrafish to a select group of SSRIs using two separate exposure paradigms. In the first paradigm, juvenile zebrafish were exposed to Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) or a mixture of the three beginning at environmentally relevant levels (10 µg/L) for 135 days (long-term exposure) beginning at 5 days post fertilization (dpf). In the second paradigm, adult zebrafish were exposed to matching concentrations of the same SSRIs for 35 days (short-term exposure). The long-term exposure paradigm proved to have little to no overt effect on growth or development at sub-lethal concentrations (10 and 100 µg/L). However, both the stress/anxiety response (novel tank tests) and reproduction (fecundity and fertility) were dramatically reduced. Importantly, the short-term exposure of reproductively mature fish led to similar adverse effects on both the stress response and reproduction. Following both the short and long duration exposure paradigms, a 2-week washout period led to a small reduction in the adverse effects. These findings highlight the potential for SSRIs to negatively impact population dynamics in zebrafish and may be of particular value should they be found in other fish species in the environment. Full article

Using the parametric g-formula, we estimated the 27-year risk of all-cause and specific causes of mortality under different potential interventions for blood lead (BLLs) and urinary cadmium (UCd) levels. We used data on 14,311 adults aged ≥20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through 31 Dec 31 2015. Time and cause of death were determined from the National Death Index records. We used the parametric g-formula with pooled logistic regression models to estimate the relative and absolute risk of all-cause, cardiovascular, and cancer mortality under different potential threshold interventions for BLLs and UCd concentrations. Median follow-up was 22.5 years. A total of 5167 (36%) participants died by the end of the study, including 1550 from cardiovascular diseases and 1135 from cancer. Increases in BLLs and creatinine-corrected UCd levels from the 5th to the 95th percentiles were associated with risk differences of 4.17% (1.54 to 8.77) and 6.22% (4.51 to 12.00) for all-cause mortality, 1.52% (0.09 to 3.74) and 1.06% (−0.57 to 3.50) for cardiovascular disease mortality, and 1.32% (−0.09 to 3.67) and 0.64% (−0.98 to 2.80) for cancer mortality, respectively. Interventions to reduce historical exposures to lead and cadmium may have prevented premature deaths, especially from cardiovascular disease. Full article

Heavy metal (HM) pollution of soil is an increasingly serious problem worldwide. The current study assessed the metal levels and ecological and human health risk associated with HMs in Grand Forks urban soils. A total 40 composite surface soil samples were investigated for Mn, Fe, Co, Ni, Cu, Zn, As, Pb, Hg, Cr, Cd and Tl using microwave-assisted HNO₃-HCl acid digestion and inductively coupled plasma mass spectrometry (ICP-MS) analysis. The enrichment factor (EF), contamination factor (CF), geoaccumulation index (Igeo), ecological risk and potential ecological risk index were used for ecological risk assessment. The park soils revealed the following decreasing trend for metal levels: Fe > Mn > Zn > Cr > Ni > Cu > Pb > As > Co > Cd > Tl > Hg. Based on mean levels, all the studied HMs except As and Cr were lower than guideline limits set by international agencies. Principal component analysis (PCA) indicated that Mn, Fe, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Tl may originate from natural sources, while Hg, Pb, As and Cd may come from anthropogenic/mixed sources. The Igeo results showed that the soil was moderately polluted by As and Cd and, based on EF results, As and Cd exhibited significant enrichment. The contamination factor analysis revealed that Zn and Pb showed moderate contamination, Hg exhibited low to moderate contamination and As and Cd showed high contamination in the soil. Comparatively higher risk was noted for children over adults and, overall, As was the major contributor (>50%), followed by Cr (>13%), in the non-carcinogenic risk assessment. Carcinogenic risk assessment revealed that As and Cr pose significant risks to the populations associated with this urban soil. Lastly, this study showed that the soil was moderately contaminated by As, Cd, Pb and Hg and should be regularly monitored for metal contamination. Full article

Advances in nanotechnology have led to an increased use of engineered nanoparticles (ENPs) and the likelihood for occupational exposures. However, how to assess such exposure remains a challenge. In this study, a methodology for human biomonitoring, based on Single Particle Inductively Coupled Plasma Mass Spectrometry (SP-ICP-MS), was developed as a tool to assess the ENPs exposure of workers involved in nanomaterial activities in two Italian Companies. The method was validated for size and number concentration determination of Ag, Au, In₂O₃, Ir, Pd, Pt, and TiO₂ NPs in urine and blood samples. The results showed the presence of In₂O₃ NPs in blood of exposed workers (mean, 38 nm and 10,371 particles/mL), but not in blood of controls. Silver, Au, and TiO₂ NPs were found in urine (mean, Ag 29 nm and 16,568 particles/mL) or blood (mean, Au 15 nm and 126,635 particles/mL; TiO₂ 84 nm and 27,705 particles/mL) of workers, though these NPs were found also in controls. The presence of ENPs in both workers and controls suggested that the extra-professional exposure is a source of ENPs that cannot be disregarded. Iridium, Pd, and Pt NPs were not detected neither in blood nor in urine. Overall, the findings provided a rational basis to evaluate the exposure assessment to ENPs in cohorts of workers as part of risk assessment and risk management processes in workplaces. Full article

While numerous studies have demonstrated the adverse effects of fine particulate matter (PM) on human health, little attention has been paid to its impact on offspring health. The multigenerational toxic effects on Caenorhabditis elegans (C. elegans) were investigated by acute exposure. PM_2.5 and PM₁ samples were collected and analysed for their chemical composition (inorganic ions, metals, OM, PAHs) in different seasons from April 2019 to January 2020 in Lin’an, China. A higher proportion of organic carbon components (34.3%, 35.9%) and PAHs (0.0144%, 0.0200%) occupied the PM_2.5 and PM₁ samples in winter, respectively. PM₁ in summer was enriched with some metal elements (2.7%). Exposure to fine PM caused developmental slowing and increased germ cell apoptosis, as well as inducing intestinal autofluorescence and reactive oxygen species (ROS) production. PM₁ caused stronger toxic effects than PM_2.5. The correlation between PM component and F0 generation toxicity index was analysed. Body length, germ cell apoptosis and intestinal autofluorescence were all highly correlated with Cu, As, Pb, OC and PAHs, most strongly with PAHs. The highest correlation coefficients between ROS and each component are SO₄²⁻ (R = 0.743), Cd (R = 0.816) and OC (R = 0.716). The results imply that OC, PAHs and some transition metals play an important role in the toxicity of fine PM to C. elegans, where the organic fraction may be the key toxicogenic component. The multigenerational studies show that PM toxicity can be passed from parent to offspring, and gradually returns to control levels in the F3–F4 generation with germ cell apoptosis being restored in the F4 generation. Therefore, the adverse effects of PM on reproductive damage are more profound. Full article

A novel method was developed and optimized for the fast-screening analysis of additives in electronics and plastic consumer products using atmospheric pressure matrix-assisted laser desorption ionization (AP-MALDI) coupled with a high-resolution quadrupole time-of-flight (qTOF) mass spectrometer (MS). To simplify sample preparation and increase sample throughput, an innovative 48 well graphene nanoplatelets (GNP) doped AP-MALDI target plate was developed. The GNP incorporated in the target plate fulfilled the role of the MALDI matrix and, therefore, sample extracts could be directly transferred to the AP-MALDI 48 well target plate and analyzed without a subsequent matrix addition. The homogeneously dispersed and immobilized GNP target plates also provided increased signal intensity and reproducibility. Furthermore, analytical standards of various plastic additives and plastic products with known concentrations of additives were studied to assess the AP-MALDI ionization mechanisms and method capability. The analysis time was 15 s per measurement using an automated sequence. The GNP-doped target plates exhibited high desorption/ionization of low molecular weight molecules (<1000 Da) and can be used in both positive and negative ionization modes. The AP-MALDI-qTOF-MS method was applied to screen for additives in various electronics and plastic consumer products. Suspect screening was performed using a database containing 1366 compounds. A total of 56 additives including antioxidants, flame retardants, plasticizers, UV-stabilizers, and UV-filters were identified (confidence level 4). Identification of certain plastic additives in plastic children’s toys may indicate that they are recycled from waste electronic and electronic equipment (WEEE). Full article

Evaluating vaping parameters that influence electronic nicotine delivery system (ENDS) emission profiles and potentially hazardous exposure levels is essential to protecting human health. We developed an automated multi-channel ENDS aerosol generation system (EAGS) for characterizing size-resolved particle emissions across pod- and mod-type devices using real-time monitoring instruments, an exposure chamber, and vaping parameters including different ventilation rates, device type and age, e-liquid formulation, and atomizer setup. Results show the ENDS device type, e-liquid flavoring, and nicotine content can affect particle emissions. In general, pod-type devices have unimodal particle size distributions and higher number emissions, while mod-type devices have bimodal size distributions and higher mass emissions. For pod-type devices, later puff fractions emit lower aerosols, which is potentially associated with the change of coil resistance and power during ageing. For a mod-type device, an atomizer with a lower resistance coil and higher power generates larger particle emissions than an atomizer with a greater resistance coil and lower power. The unventilated scenario produces higher particle emission factors, except for particle mass emission from pod-type devices. The data provided herein indicate the EAGS can produce realistic and reproducible puff profiles of pod- and mod-type ENDS devices and therefore is a suitable platform for characterizing ENDS-associated exposure risks. Full article

Chemotherapy-induced peripheral neurotoxicity is one of the most common dose-limiting toxicities of several widely used anticancer drugs such as platinum derivatives (cisplatin) and taxanes (paclitaxel). Several molecular mechanisms related to the onset of neurotoxicity have already been proposed, most of them having the sensory neurons of the dorsal root ganglia (DRG) and the peripheral nerve fibers as principal targets. In this study we explore chemotherapy-induced peripheral neurotoxicity beyond the neuronocentric view, investigating the changes induced by paclitaxel (PTX) and cisplatin (CDDP) on satellite glial cells (SGC) in the DRG and their crosstalk. Rats were chronically treated with PTX (10 mg/Kg, 1qwx4) or CDDP (2 mg/Kg 2qwx4) or respective vehicles. Morpho-functional analyses were performed to verify the features of drug-induced peripheral neurotoxicity. Qualitative and quantitative immunohistochemistry, 3D immunofluorescence, immunoblotting, and transmission electron microscopy analyses were also performed to detect alterations in SGCs and their interconnections. We demonstrated that PTX, but not CDDP, produces a strong activation of SGCs in the DRG, by altering their interconnections and their physical contact with sensory neurons. SGCs may act as principal actors in PTX-induced peripheral neurotoxicity, paving the way for the identification of new druggable targets for the treatment and prevention of chemotherapy-induced peripheral neurotoxicity. Full article

Arsenic (As) is extremely toxic to living organisms at high concentrations. Arsenobetaine (AsB), confirmed to be a non-toxic form, is the main contributor to As in the muscle tissue of marine fish. However, few studies have investigated the biotransformation and biodegradation of AsB in mammals. In the current study, C57BL/6J mice were fed four different diets, namely, Yangjiang and Zhanjiang fish diets spiked with marine fish muscle containing AsB, and arsenite (As(III)) and arsenate (As(V)) diets spiked with As(III) and As(V), respectively, to investigate the biotransformation and bioaccumulation of AsB in mouse tissues for 42 d. Different diets exhibited different As species distributions, which contributed to varying levels of As bioaccumulation in different tissues. The intestines accumulated the highest level of As, regardless of form, which played a major part in As absorption and distribution in mice. We observed a significant biotransformation of AsB to As(V) following its diet exposure, and the liver, lungs, and spleen of AsB-treated mice showed higher As accumulation levels than those of As(III)- or As(V)-treated mice. Inorganic As showed relatively high accumulation levels in the lungs and spleen after long-term exposure to AsB. Overall, these findings provided strong evidence that AsB undergoes biotransformation to As(V) in mammals, indicating the potential health risk associated with long-term AsB intake in mammals. Full article

Inflammation is a major regulator of drug-metabolizing enzymes (DMEs), therefore contributing to the interindividual variability of drug effects. However, whether prenatal inflammation affects DMEs expression in offspring remains obscure. This study investigated the effects of prenatal lipopolysaccharide (LPS) exposure on hepatic expression of inflammatory-related genes, nuclear receptors, and DMEs in offspring mice. Prenatal LPS exposure on gestational day (GD) 10 led to higher expression of NF-κB, Pxr, and Cyp2b10, while lower expression of Car, Ahr, Cyp3a11, and Ugt1a1 in postnatal day (PD) 30 offspring. However, multiple doses of LPS exposure on GD10-14 resulted in higher levels of inflammatory-related genes, Cyp1a2, and Cyp2b10, and lower levels of Pxr and Cyp3a11 in PD30 offspring liver. For PD60 offspring, decreased hepatic expression of NF-κB and IL-6, and increased expression of Pxr and Cyp3a11 were seen in single-dose LPS groups, whereas opposite results were observed in the multiple-dose LPS groups. Notably, enhanced H3K4me3 levels in the PXR response elements of the Cyp3a11 promoter were observed in the liver of PD60 offspring mice from dams treated with multiple doses of LPS during pregnancy. Overall, this study suggests that parental LPS exposure could persistently alter the hepatic expression of DMEs, and histone modifications may contribute to the long-term effects. Full article

Limited availability of fish metabolic pathways for PFAS may lead to risk assessments with inherent uncertainties based only upon the parent chemical or the assumption that the biodegradation or mammalian metabolism map data will serve as an adequate surrogate. A rapid and transparent process, utilizing a recently created database of systematically collected information for fish, mammals, poultry, plant, earthworm, sediment, sludge, bacteria, and fungus using data evaluation tools in the previously described metabolism pathway software system MetaPath, is presented. The fish metabolism maps for 10 PFAS, heptadecafluorooctyl(tridecafluorohexyl)phosphinic acid (C6/C8 PFPiA), bis(perfluorooctyl)phosphinic acid (C8/C8 PFPiA), 2-[(6-chloro-1,1,2,2,3,3,4,4,5,5,6,6-dodecafluorohexyl)oxy]-1,1,2,2-tetrafluoroethanesulfonic acid (6:2 Cl-PFESA), N-Ethylperfluorooctane-1-sulfonamide (Sulfuramid; N-EtFOSA), N-Ethyl Perfluorooctane Sulfonamido Ethanol phosphate diester (SAmPAP), Perfluorooctanesulfonamide (FOSA), 8:2 Fluorotelomer phosphate diester (8:2 diPAP), 8:2 fluorotelomer alcohol (8:2 FTOH), 10:2 fluorotelomer alcohol (10:2 FTOH), and 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB), were compared across multiple species and systems. The approach demonstrates how comparisons of metabolic maps across species are aided by considering the sample matrix in which metabolites were quantified for each species, differences in analytical methods used to identify metabolites in each study, and the relative amounts of metabolites quantified. Overall, the pathways appear to be well conserved across species and systems. For PFAS lacking a fish metabolism study, a composite map consisting of all available maps would serve as the best basis for metabolite prediction. This emphasizes the importance and utility of collating metabolism into a searchable database such as that created in this effort. Full article

The extensive use of organic dyes in industry has caused serious environmental problems, and photocatalysis is a potential solution to water pollution by organic dyes. The practical application of powdery photocatalysts is usually limited by the rapid recombination of charge carriers and difficulty in recycling. In this study, recyclable carbon cloth-supported ZnO@Ag₃PO₄ composite with a core–shell structure was successfully prepared by solvothermal treatment and subsequent impregnation–deposition. The as-prepared carbon cloth-supported ZnO@Ag₃PO₄ composite showed an improved photocatalytic activity and stability for the degradation of rhodamine B (RhB), a model organic dye, under visible light irradiation. The decomposition ratio of RhB reached 87.1% after exposure to visible light for 100 min, corresponding to a reaction rate constant that was 4.8 and 15.9 times that of carbon cloth-supported Ag₃PO₄ or ZnO alone. The enhanced performance of the composite can be attributed to the effectively inhibited recombination of photoinduced electron–hole pairs by the S-scheme heterojunction. The carbon fibers further promoted the transfer of charges. Moreover, the carbon cloth-supported ZnO@Ag₃PO₄ can be easily separated from the solution and repeatedly used, demonstrating a fair recyclability and potential in practical applications. Full article