Journal of Xenobiotics

The polyunsaturated fatty acids of the omega-3 class have been widely investigated due to their antitumor properties, including in prostate cancer (PCa). Among them is docosahexaenoic acid (DHA, C22:6 ω-3), whose biological activity is higher than other omega-3s, exhibiting a stronger impact on PCa. The specific mechanisms triggered by DHA are blurred by studies that used a blend of omega-3s, delaying the understanding of its biological role, and hence alternative therapeutic approaches. DHA is differentially processed between normal and malignant epithelial PCa cells, which suggests its function as a tumor suppressor. At cell-specific level, it downregulates key pathways in PCa, such as androgen signaling and lipid metabolism, but also changes membrane composition by disrupting phospholipid balance and increasing unsaturation status, arrests the cell cycle, and induces apoptosis and reactive oxygen species (ROS) overproduction. At the tissue level, DHA seems to influence stromal components, such as the inhibition of cancer-associated fibroblast differentiation and resolution of inflammation, which generates a microenvironment favorable to PCa initiation and progression. Considering that such effects are misunderstood and assigned to omega-3s in general, this review aims to discuss the specific effects of DHA on PCa based on in vitro and in vivo evidence. Full article

The escalating global contamination of aquatic ecosystems by pharmaceuticals and endocrine-disrupting chemicals (EDCs) stemming from diverse anthropogenic sources represents a critical and pervasive threat to planetary Earth. These contaminants exhibit bioaccumulative properties in long-lived organisms and undergo trophic biomagnification, leading to elevated concentrations in apex predators. This review synthesizes current knowledge regarding the far-reaching impacts of pharmaceutical and EDC pollution on the reproductive biology of aquatic fauna, focusing on the heightened vulnerability of the endangered African penguin. A rigorous literature review across key scientific databases—PubMed, Scopus, Web of Science, and Google Scholar—using targeted search terms (e.g., penguins, contaminants of emerging concern, penguin species, seabird species, Antarctica, pharmaceuticals, personal care products, EDCs) underpins this analysis. This review explores the anthropogenic sources of pharmaceuticals and EDCs in aquatic ecosystems. It discusses the mechanisms by which these chemicals disrupt the reproductive physiology of aquatic fauna. Recent studies on the ecological and population-level consequences of these contaminants are also reviewed. Furthermore, the review elaborates on the urgent need for comprehensive mitigating strategies to address their effects on vulnerable penguin populations. These approaches hold the potential to unlock innovative pathways for conservation initiatives and the formulation of robust environmental management policies aimed at safeguarding aquatic ecosystems and the diverse life they support. Full article

Antioxidants derived from plant extracts have attracted considerable attention due to their potential in mitigating oxidative damage through free radical scavenging mechanisms. Although 700 species have been used for centuries in Georgian traditional medicine, the chemical composition and antioxidant and antibacterial properties of Caucasian endemic medicinal plants remain largely unknown. In this study, the antioxidant and antibacterial activities of leaf and root extracts of Caucasian endemic medicinal plants Sempervivum transcaucasicum Muirhead and Paeonia daurica subsp. mlokosewitschii (Lomakin) D. Y. Hong were investigated. The highest antioxidant activity and phenolic and flavonoid content were revealed in Paeonia daurica leaf extract. The analysis of the content of water-soluble antioxidants revealed the highest content of reduced glutathione and ascorbate in Paeonia daurica leaves. Moreover, the antibacterial activity of leaf and root extracts against Escherichia coli ATCC 25922 strain was investigated, and minimal inhibitory concentration (MIC) values were determined. While the antibacterial activity against E. coli ATCC 25922 was not revealed for the Sempervivum transcaucasicum leaf extract, antibacterial properties were detected for the root extract (MIC 5 mg/mL). Collectively, the highest antibacterial activity was revealed for Paeonia daurica leaf and root extracts (MIC 2 mg/mL and 3 mg/mL, respectively). From a molecular perspective, molecular docking simulations were performed using HDOCK software, with reduced glutathione and ascorbic acid as ligands, in order to analyse their potential binding affinity to the OmpX protein. Inhibiting this protein would likely disrupt bacterial function and produce an antibacterial effect. Our results provide a possible mechanism for the antibacterial activity of Paeonia daurica subsp. mlokosewitschii. Overall, the results of the study demonstrate the potential of Caucasian endemic medicinal plants as natural antioxidants and antimicrobial agents. Full article

In the present investigation, an eco-friendly biocatalyst was developed using Pleurotus eryngii laccase (PeLac) through a copper (Cu)-based protein–inorganic hybrid system for the degradation of bisphenol A, a representative xenobiotic. After partial purification, the specific activity of crude PeLac was 92.6 U/mg of total protein. Immobilization of PeLac as Cu₃(PO₄)₂–Lac (Cu–PeLac) nanoflowers (NFs) at 4 °C resulted in a relative activity 333% higher than that of the free enzyme. The Cu–PeLac NFs exhibited greater pH and temperature stability and enhanced catalytic activity compared to free laccase. This enhanced activity was validated through improved electrochemical properties. After immobilization, Cu–PeLac NFs retained up to 8.7-fold higher residual activity after storage at 4 °C for 30 days. Free and immobilized laccase degraded bisphenol A by 41.6% and 99.8%, respectively, after 2 h of incubation at 30 °C. After ten cycles, Cu–PeLac NFs retained 91.2% degradation efficiency. In the presence of potent laccase inhibitors, Cu–PeLac NFs exhibited a 47.3-fold improvement in bisphenol A degradation compared to free PeLac. Additionally, the synthesized Cu–PeLac NFs demonstrated lower acute toxicity against Vibrio fischeri than Cu nanoparticles. This study presents the first report of PeLac immobilization through an eco-friendly protein–inorganic hybrid system, with promising potential for degrading bisphenol A in the presence of inhibitors to support sustainable development. Full article

Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, and it was the first antiviral drug to receive EMA and FDA approval for treating COVID-19. Nevertheless, its intracellular pharmacokinetics in real life are poorly explored, particularly due to technical challenges. Methods: The aim of this study was to validate an HPLC-MS/MS method for the direct quantification of GS-443902 in peripheral blood mononuclear cells (PBMCs) with a chromatographic separation of 15 min. Results: The method was validated following EMA and FDA guidelines in terms of sensitivity, specificity, accuracy, precision, matrix effect, recovery, carryover, and stability, and then applied to PBMC isolates from a small cohort of patients with severe COVID-19 who received RDV. Conclusions: This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug–drug interaction studies. Full article

The knowledge about the potential toxic effects of microplastics (MPs) combined with herbicides at lower trophic levels is still largely unknown. The present study aimed to evaluate the potential toxic effects of polyethylene terephthalate (PET) and polyamide (PA), isolated or combined with the pesticide glyphosate (GLY), on the microalgae Arthrospira platensis. For this, microalgae were exposed to control, GLY (3 μg/L), PET (0.5 and 1 mg/L), PA (0.5 and 1 mg/L), and the respective mixtures of each MP with GLY, for 12 days. The photosynthetic pigment content, phytochemicals, antioxidants, and enzymatic activity were determined. Cell growth was significantly enhanced on day 4 in the GLY+PA1 group (~80%), compared to the control. At day 12, biomass was significantly higher in the GLY (~25%) and GLY+PET0.5 (~26%) groups relative to the control. Significant effects on the enzymatic and detoxification mechanisms were observed, including increased SOD (PET0.5, p = 0.011) and CarE (GLY, PA and GLY+PA, p < 0.01), and decreased GST in combined exposures, which support stress-induced enzymatic activation and adaptive biochemical responses. Significant effects on phytochemicals and antioxidant activity were also observed, with PET0.5 significantly reducing total carotenoids (~65%), and flavonoids (p < 0.001) and ortho-diphenols (p < 0.05) being decreased in all exposure groups, in comparison to the control group. The decrease in flavonoids and ortho-diphenols, important antioxidant molecules, suggests the depletion of these key compounds under stress. DPPH scavenging activity, a measure of antioxidant potential, was inhibited in the GLY+PA groups, indicating compromised antioxidant defense. Results confirmed that combined stressors elicit distinct and sometimes deleterious responses not predicted by single exposures. Our findings highlight that the combined exposure to glyphosate and MPs significantly disrupts antioxidant defenses and enzymatic activity in A. platensis, indicating potential risks to primary producers in aquatic ecosystems and underscoring the ecological implications of co-contaminant stressors. In fact, the results indicate that MPs can modify herbicide toxicity, posing enhanced risks to microalgal physiology and potentially affecting primary productivity and nutrient cycling in aquatic ecosystems. In turn, negative effects of MPs on microalgae can have serious consequences for food webs, food security, and ecological health. Full article

Climate change, mining activities, pollution and other human impacts on the natural environment cause significant changes in the concentrations and mixtures of metallic elements found in different ecosystems. Metals such as cadmium, copper, lead and mercury affect multiple aspects of host–pathogen interactions, influencing the risk of infectious diseases caused by various classes of pathogens. Notably, exposure to metals in doses and combinations toxic to the immune system can favor the dissemination of pathogens in natural environments, threatening the reproduction, well-being and survival of varied animal species. However, these problems remain neglected, since the influences of metals on infectious diseases are studied with a primary focus on human medicine. Therefore, this article aims to review the influence of metals/metalloids (e.g., arsenic, cadmium, chromium, copper, iron, lead, mercury, nickel, zinc) on infectious and parasitic diseases in animals living in natural environments. The potential impact of metals on the risk of zoonotic spillover events is also discussed. Metal pollution tends to increase as the demand for elements used in the manufacture of industrial products, batteries, and electronic devices increases globally. This problem can aggravate the biodiversity crisis and facilitate the emergence of infectious diseases. Considering the interconnections between pollution and immunity, measures to limit metal pollution are necessary to protect human health and biodiversity from the risks posed by pathogens. This review helps fill the gap in the literature regarding the connections between metal pollution and various aspects of infectious diseases. Full article

The evolution of global agriculture encourages the extensive use of pesticides although significant concerns regarding their impact on human health and the environment must be considered. The present paper highlights the presence and concentrations of various pesticide residues in fruits and vegetables available on Romanian markets. A total of 74 pesticide compounds authorized for agricultural use were identified and quantified in 620 randomly selected samples spanning a wide range of horticultural products by employing the QuEChERS extraction method and liquid chromatography–mass spectrometry (LC-MS/MS). The most often detected pesticides comprised boscalid and azoxystrobin, present in 42% and 37% of apple and strawberry samples, respectively, with mean concentrations of 0.12 mg/kg and 0.09 mg/kg. In cucumbers and tomatoes, difenoconazole and acetamiprid were predominant, detected in 35% and 40% of samples, with average residue amounts of 0.08 mg/kg and 0.07 mg/kg, respectively. Statistical analysis, achieved with Python 3.13.2, the pandas library (alongside descriptive statistics), and ANOVA, revealed significant variations in residue levels based on the product type and geographic origin. Boscalid and azoxystrobin were commonly encountered in apples and strawberries while difenoconazole and acetamiprid predominated in cucumbers and tomatoes. Even though the majority of pesticide residues conformed to EU maximum residue limits (MRLs), about 6% of samples, generally from imported products, displayed some residue concentrations approaching critical thresholds, with the highest exceedance observed for chlorpyrifos and lambda-cyhalothrin at concentrations of up to 0.25 mg/kg. This research provides a comprehensive overview of pesticide residues prevalence in Romania’s fresh product supply while, at the same time, supporting consumer awareness initiatives and evidencing the critical demand for continuous monitoring and strengthened regulatory frameworks for food safety. Full article

This study investigates the effect of high urban land temperatures on pesticide residue (PR) accumulation in cabbage and lettuce and on public health in the Greater Accra Metropolitan Area (GAMA) in Ghana. A comparative toxicological analysis regarding the food system was conducted with 66 farmers across three land surface temperatures: low (Atomic, n = 22), moderate (Ashaiman, n = 22), and high (Korle-Bu, n = 22). Pesticide residue concentrations were assessed using an ANOVA to examine spatial variations across sites. The results indicate a strong correlation between high land surface temperatures and pesticide residue accumulation, with lettuce recording significantly (p < 0.05) higher PR levels than cabbage. Several pesticides, including carbendazim (CBZ), Imidacloprid (IMI), Thiamethoxam (TMX), and Chlorpyrifos (CHL), exceeded the maximum residue limits (MRLs) set by the World Health Organization (WHO) and the European Union (EU) at moderate and high-temperature sites. carbendazim was the dominant pesticide detected, with a concentration of 19.0 mg/kg in lettuce, which far exceeded its maximum residue limit (MRL) of 0.10 mg/kg across all study sites. Statistical analyses (PERMANOVA) confirmed that land surface temperatures and pesticide types significantly influenced the PR concentrations. Public health risk assessments indicate that children are more vulnerable to pesticide exposure than adults. The toxicity hazard quotient (THQ) for organophosphate pesticides, particularly CHL and Dimethoate (DMT), exceeded safe thresholds at moderate and high-temperature sites. Full article

Background: Amphetamine-type stimulants (ATS) in water pose significant public health and ecological risks, necessitating reliable and efficient detection methods. Current approaches often involve time-consuming pH adjustments and post-processing steps, limiting their practicality for high-throughput analysis. This study aimed to develop a streamlined method integrating pH regulation and adsorption into a single material to simplify sample preparation and enhance analytical efficiency. Methods: A novel Fe₃O₄/MWCNTs-OH/CaO composite adsorbent was synthesized via a one-pot grinding method, embedding pH adjustment and adsorption functionalities within a single material. This innovation enabled magnetic solid-phase extraction (MSPE) without pre-adjusting sample pH or post-desorption steps. The method was coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS) for ATS detection. Optimization included evaluating adsorption/desorption conditions and validating performance in real water matrices. Results: The method demonstrated exceptional linearity (R² > 0.98), low detection limits (0.020–0.060 ng/mL), and high accuracy with relative recoveries of 92.8–104.8%. Precision was robust, with intra-/inter-day relative standard deviations (RSDs) below 11.6%. Single-blind experiments confirmed practical applicability, yielding consistent recoveries (relative errors: 1–8%) for ATS-spiked samples at 0.8 and 8 ng/mL. Compared to existing techniques, the approach reduced processing time to ~5 min by eliminating external pH adjustments and post-concentration steps. Conclusions: This work presents a rapid, reliable, and user-friendly method for ATS detection in complex environmental matrices. The integration of pH regulation and adsorption into a single adsorbent significantly simplifies workflows while maintaining high sensitivity and precision. The technique holds promise for large-scale environmental monitoring and forensic toxicology, offering a practical solution for high-throughput analysis of emerging contaminants. Full article

Background: Pharmacogenomics (PGx), a pivotal branch of personalized medicine, studies how genetic variations influence drug responses. Despite its transformative potential, the adoption of PGx in Indian clinical practice faces challenges, such as the lack of population-specific data, evidence-based guidelines, and complexities in interpreting genomic reports. Comprehensive datasets tailored to Indian patients are essential to facilitate the integration of PGx into clinical settings. Methodology: The study collates pharmacogenomic data from multiple sources, including essential drugs listed by the World Health Organization (WHO), drugs used in neonatal intensive care units (NICUs), minimum sets of alleles recommended by the Association for Molecular Pathology (AMP), and catalogs the allele frequencies from the IndiGenomes database to address gaps in actionable PGx for the Indian population. Curated datasets were used to identify pharmacogenomic variants relevant to clinical practice. Results: Overall, 24 prime genes are essential for the outcomes of 57 drugs. In adults, 18 genes influence the metabolism of 44 drugs whereas, in pediatric populations, genotypes of 18 genes significantly impact the metabolism of 18 drugs. Two over-the-counter drugs with actionable PGx variants were identified: ibuprofen and omeprazole. These findings emphasize the clinical relevance of PGx for commonly used drugs, underscoring the need for population-specific data. Conclusions: As the data of several Indian human genome projects become available, an overarching need exists to establish and regulate the dynamic actionable PGx in Indian clinical practice. This will facilitate the integration of pharmacogenomic data into healthcare, enabling effective and personalized drug therapies. Full article

High levels of pesticide use are associated with intensive crop production. Pesticides are increasingly prevalent in surface and groundwater, which is a major environmental concern. Various methods have been proposed to improve the retention and/or degradation of pesticides in soils. These methods are mainly based on soil adaptation with organic wastes to mitigate soil and water pollution. In addition, there has recently been increased interest in assessing the influence of organic waste additions on pesticide movement in soils with low contents of organic matter. Agriculture and related industries generate large amounts of waste each year. Because of their components, they have the great ability to produce high-value products for environmental restoration. This study reports on the influence of four different agro-industrial wastes (orange peel, beer bagasse, grape pomace, and gazpacho waste) used as organic amendments on the leaching of metobromuron and chlorbromuron (phenylurea herbicides) on a silty clay loam soil (gypsic–calcaric regosol) with low organic matter contents from a semiarid area (southeastern Spain). The adsorption, leaching, and dissipation processes of these herbicides were evaluated on a laboratory scale in amended and unamended soils. In addition, the main leaching indices (GUS, LIX, LEACH, M LEACH, LIN, GLI, HI, and ELI) commonly used to assess groundwater protection against pesticide pollution were evaluated. The sorption coefficients (K_OC) increased in the amended soils. Metobromuron was found in leachates in all cases, although a marked reduction was observed in amended soils, while chlorbromuron was mainly retained in soils, especially in the top layer. The disappearance time (DT₅₀) for metobromuron and chlorbromuron in soil ranged from 11 to 56 d and 18 to 95 d, respectively. All indices except GLI categorize metobromuron as mobile or very mobile in unamended soil. For chlorbromuron, GUS, LIX, LEACH, MLEACH, and Hornsby classify this compound as a medium-to-high leache, while GLI and ELI classify it as having low mobility. In amended soils, most indices classify metobromuron as transitioning to mobile, while most indices catalog chlorbromuron as immobile/transition. Full article

The use of cellular energy allocation (CEA) as a physiological energetic biomarker is useful for detecting the sublethal effects of environmental contaminants. The CEA assesses the health and energy status of organisms, serving as a reliable indicator for monitoring the health of aquatic ecosystems. This study aimed to evaluate the impact of emerging contaminants already listed as a priority for monitoring in freshwater ecosystems, namely sulfamethoxazole (0.156–2.50 mg/L), trimethoprim (25.0–400 mg/L), 4-chloroaniline (5.21–20.0 mg/L), and 3,4-dichloroaniline (0.38–4.00 mg/L), on the CEA of D. rerio embryos. A standard fish embryo toxicity test was conducted, and an adaptation of the allometric scaling approach was developed through the relationship between the size and the fresh weight of the embryos. All the compounds affected the fractions of the energy reserves (total carbohydrate, lipid, and protein contents) differently, with carbohydrates being the predominant energy fraction and the most responsive indicator. Although the energy consumed showed no significant changes, the CEA was notably altered after exposure to all the contaminants, indicating a direct connection to shifts in the available energy. The CEA alterations may indicate a reallocation of energy toward detoxification, combating the stress of contaminant exposure. Energy allocation biomarkers provide a comprehensive assessment of an organism’s physiological state, which is essential for evaluating emerging contaminants’ impacts, safeguarding aquatic ecosystems, and shaping effective environmental policies. Full article

The intensive use of pesticides has raised environmental concerns due to their persistence and slow degradation, posing ecotoxicological risks. Despite regulatory measures, pesticide application remains high, leading to soil and water contamination. To effectively monitor and mitigate these impacts, selecting an appropriate and efficient extraction method for detecting pesticides in soil is critical. This study evaluated the effectiveness of two extraction methods in soil—QuEChERS and QuEChERSER—and assessed the persistence of three commonly used pesticides. A test was conducted using 13 pesticide standards, representing a wide variety of functional groups, to compare the two extraction methods. For the persistence study, a microcosm experiment was performed with three selected pesticides: pendimethalin, oxyfluorfen, and trifloxystrobin. These were chosen due to their agricultural relevance, potential human toxicity, and persistence in various environmental compartments. The impact of two organic amendments on their dissipation was also evaluated. The microcosms were incubated in dark chambers at room temperature for 21 days, and pesticide concentrations were analyzed using ultra-high-performance liquid chromatography–tandem mass spectrometry. Both methods were effective, though performance varied depending on the compound. QuEChERSER proved to be more efficient, requiring less time and fewer resources than the traditional QuEChERS method. Among the three pesticides tested, the herbicide oxyfluorfen was the most persistent, while the fungicide trifloxystrobin showed the least persistence. The application of organic amendments enhanced the dissipation of all three pesticides. These findings highlight the importance of selecting appropriate extraction techniques and adopting sustainable agricultural practices to mitigate pesticide residues in the environment. Full article

Hexagonal boron nitride (h-BN) and boron nitride nanotubes (BNNTs) are emerging advanced nanomaterials with analogous structures to graphene and carbon nanotubes, respectively. However, little is known about what effect replacing carbon atoms with boron and nitrogen will have on the materials’ safety profile. This study’s aim was to first identify if multi-walled nanotubes of BN could produce a hazard profile similar to that evidenced already for multi-walled carbon nanotubes (MWCNTs) and secondly if the material when present in a sheet-like structure increases or decreases the hazard profile. Fish are aquatic organisms sensitive to boron compounds; however, the potential hazard following exposure to BN and especially when present in such nanostructures has not yet been investigated. An in vitro testing platform consisting of multiple cell lines of the rainbow trout, Oncorhynchus mykiss (RTH-149, RTG-2, RTL-W1 and RTgill-W1), was used in a first-hazard screening approach for cytotoxicity and to gain information on material–cellular interaction. Clear differences were evidenced in material uptake, leading to plasma membrane disruption accompanied with a loss in metabolic activity for BNNTs at lower exposure concentrations compared to h-BN. As in the case of carbon nanotubes, close attention must be given to potential interferences with assays based on optical readouts. Full article

Hepatocellular carcinoma (HCC) imposes a significant burden on global public health. Exposure to aflatoxins, potent mycotoxins produced by Aspergillus fungi contaminating staple foods, and chronic hepatitis B virus (HBV) infection are major etiological factors, especially where they co-exist. This review examines the critical role of the p53 tumor suppressor pathway as a primary target and convergence point for the carcinogenic actions of aflatoxins and HBV. Aflatoxin B₁ (AFB₁), a Group 1 carcinogen, exerts significant genotoxicity, characteristically inducing a specific hotspot mutation (R249S) in the TP53 gene via DNA adduct formation, thereby compromising p53’s critical tumor suppressor functions. This R249S mutation is considered a molecular fingerprint of aflatoxin exposure. Concurrently, the HBV X protein (HBx) functionally inactivates wild-type p53 through direct binding and by promoting its degradation. The synergistic disruption of the p53 pathway, driven by AFB₁-induced mutation and amplified by HBV-mediated functional inhibition, significantly enhances the risk of HCC development. This review addresses how aflatoxin exposure alters key aspects of p53 and how this damage interacts with HBV-mediated p53 suppression, providing crucial insights into hepatocarcinogenesis. The knowledge synthesized here underscores the importance of mitigating aflatoxin exposure alongside HBV control for effective HCC prevention and treatment strategies. Full article

The widespread use of agrochemicals raises concerns about environmental impacts, particularly on pollinators, such as bees, which serve as bioindicators of contamination. Developing methods to assess contamination risks in bioindicators supports regulatory frameworks, including EU regulations on the maximum residue limits (MRLs) for pesticides in food and the environment. This study presents the development and validation of two complementary analytical methods (LC–MS/MS and IC–HRMS) for highly polar pesticide (HPP) detection and quantification in bee matrices. Both methods were validated according to document SANTE/11312/2021 v2. LC–MS/MS was validated with a limit of quantification (LOQ) of 0.005 mg/kg for all the analytes. Repeatability at 0.005, 0.010, 0.020, and 0.100 mg/kg showed RSD_r from 1.6% to 19.7% and recoveries between 70% and 119%. Interlaboratory precision at 0.020 mg/kg across two labs showed RSD_R from 5.5% to 13.6%, with recoveries between 91% and 103%. The IC–HRMS method achieved LOQs of 0.01 mg/kg (glufosinate, N-acetyl glufosinate, MPPA, glyphosate, N-acetyl glyphosate, N-acetyl AMPA) and 0.1 mg/kg (fosetyl, phosphonic acid, AMPA), with mean recoveries in repeatability conditions from 84% to 114% and RSD_r from 2% to 14%. Intralaboratory precision showed mean recoveries from 87% to 119%, with RSD_wR values between 10% and 18%. These methods enable accurate monitoring of HPP contamination, supporting risk assessment and sustainable agriculture. Full article

Environmental exposures to heavy metals, polychlorinated biphenyls (PCBs), dioxins, and furans have been associated with adverse cardiovascular outcomes, yet their combined effects remain underexplored. This study examined the joint influence of these contaminants on cardiovascular risk indicators in a representative sample of U.S. adults from the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Biomarkers of exposure included lead, cadmium, mercury, twelve PCB congeners, seven dioxins, and ten furans. Cardiovascular outcomes were assessed using blood pressure, Framingham Risk Score (FRS), and lipid profiles. Associations were analyzed using multivariable linear regression and Bayesian Kernel Machine Regression (BKMR), adjusting for age, sex, ethnicity, body mass index, smoking, alcohol consumption, and income. The results demonstrated that metals, particularly mercury, were strongly associated with increased blood pressure and altered HDL cholesterol. PCBs were predominantly linked to elevated systolic blood pressure and FRS, with PCB156 and PCB126 identified as principal contributors. Furans exhibited the strongest associations with dyslipidemia, including elevated LDL cholesterol, total cholesterol, and triglycerides. Combined exposure analysis revealed a complex pattern, with increasing pollutant burdens associated with rising blood pressure and risk scores but declining lipid levels. These findings underscore the outcome-specific effects of pollutant mixtures and suggest that chronic low-level exposure to multiple environmental contaminants may contribute to cardiovascular dysfunction in the general population. Further longitudinal research is needed to confirm these associations and guide risk reduction strategies. Full article

The development of alternative methods that link cellular and predictive toxicity to high-level toxicity is a key focus of current research within the framework of the 3Rs in animal experimentation. In this context, this study aimed to evaluate the previously developed in vitro approach using the zebrafish liver cell line (ZFL) for assessing bioaccumulation and biotransformation of the compound BDE-47, which is more hydrophobic than phenanthrene, and is the compound used in the previous study. For this purpose, experimentally, the internal concentrations in the cells (C_cell) and the exposure medium of both BDE-47 and its main metabolites were quantified at different exposure times by GC-MS. Additionally, the free bioavailable concentration (C_free) was determined with a solid-phase microextraction (SPME) experiment. With the aim of refine models, C_cell and C_free were also estimated using a predictive chemical distribution model (MBM). Bioconcentration factors (BCFs) were determined by relating all these values, as well as by toxicokinetic fitting and by in vitro–in vivo extrapolation modelling (IVIVE). The results showed a high concordance with the values obtained in vivo. Moreover, the study highlighted the importance of experimentally determining C_free and C_cell, as the predicted values can vary depending on the chemical, thereby influencing the BCF outcome. This variation occurs because models do not account for the absorption and biotransformation kinetics of the compounds. The data presented may contribute to refining predictive models. Full article