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J. Xenobiot., Volume 15, Issue 4 (August 2025) – 29 articles

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32 pages, 995 KiB  
Case Report
Phytotoxic Effects and Agricultural Potential of Nanofertilizers: A Case Study Using Zeolite, Zinc Oxide, and Titanium Dioxide Under Controlled Conditions
by Ezequiel Zamora-Ledezma, Glenda Leonela Loor Aragundi, Willian Stalyn Guamán Marquines, Michael Anibal Macías Pro, José Vicente García Díaz, Henry Antonio Pacheco Gil, Julián Mauricio Botero Londoño, Mónica Andrea Botero Londoño and Camilo Zamora-Ledezma
J. Xenobiot. 2025, 15(4), 123; https://doi.org/10.3390/jox15040123 (registering DOI) - 1 Aug 2025
Abstract
Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO2), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K [...] Read more.
Nanofertilizers (NFs) and engineered nanoparticles (NPs) are increasingly used in agriculture, yet their environmental safety remains poorly understood. This study evaluated the comparative phytotoxicity of zinc oxide (ZnO), titanium dioxide (TiO2), and clinoptilolite nanoparticles, three commercial nanofertilizers, and potassium dichromate (K2Cr2O7) using Lactuca sativa seeds under adapted OECD-208 protocol conditions. Seeds were exposed to varying concentrations of each xenobiotic material (0.5–3% for NFs; 10–50% for NPs), with systematic assessment of seedling survival, root and hypocotyl length, dry biomass, germination index (GI), and median effective concentration (EC50) values. Nanofertilizers demonstrated significantly greater phytotoxicity than engineered nanoparticles despite lower application concentrations. The toxicity ranking was established as NF1 > NF3 > NF2 > NM2 > NM1 > NM3, with NF1 being most toxic (EC50 = 1.2%). Nanofertilizers caused 45–78% reductions in root length and 30–65% decreases in dry biomass compared with controls. GI values dropped to ≤70% in NF1 and NF3 treatments, indicating concentration-dependent growth inhibition. While nanofertilizers offer agricultural benefits, their elevated phytotoxicity compared with conventional nanoparticles necessitates rigorous pre-application safety assessment. These findings emphasize the critical need for standardized evaluation protocols incorporating both physiological and ecotoxicological endpoints to ensure safe xenobiotic nanomaterial deployment in agricultural systems. Full article
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22 pages, 2376 KiB  
Review
Hypertension in People Exposed to Environmental Cadmium: Roles for 20-Hydroxyeicosatetraenoic Acid in the Kidney
by Soisungwan Satarug
J. Xenobiot. 2025, 15(4), 122; https://doi.org/10.3390/jox15040122 (registering DOI) - 1 Aug 2025
Abstract
Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to [...] Read more.
Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m2 (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β2-microglobulin (β2M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article
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20 pages, 1266 KiB  
Systematic Review
A Systematic Review on Contamination of Marine Species by Chromium and Zinc: Effects on Animal Health and Risk to Consumer Health
by Alexandre Mendes Ramos-Filho, Paloma de Almeida Rodrigues, Adriano Teixeira de Oliveira and Carlos Adam Conte-Junior
J. Xenobiot. 2025, 15(4), 121; https://doi.org/10.3390/jox15040121 - 1 Aug 2025
Abstract
Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of [...] Read more.
Potentially toxic elements, such as chromium (Cr) and zinc (Zn), play essential roles in humans and animals. However, the harmful effects of excessive exposure to these elements through food remain unknown. In this sense, this study aimed to evaluate the anthropogenic contamination of chromium and zinc in aquatic biota and seafood consumers. Based on the PRISMA protocol, 67 articles were selected for this systematic review. The main results point to a wide distribution of these elements, which have familiar emission sources in the aquatic environment, especially in highly industrialized regions. Significant concentrations of both have been reported in different fish species, which sometimes represent a non-carcinogenic risk to consumer health and a carcinogenic risk related to Cr exposure. New studies should be encouraged to fill gaps, such as the characterization of the toxicity of these essential elements through fish consumption, determination of limit concentrations updated by international regulatory institutions, especially for zinc, studies on the influence of abiotic factors on the toxicity and bioavailability of elements in the environment, and those that evaluate the bioaccessibility of these elements in a simulated digestion system when in high concentrations. Full article
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23 pages, 2437 KiB  
Article
From Farmworkers to Urban Residents: Mapping Multi-Class Pesticide Exposure Gradients in Morocco via Urinary Biomonitoring
by Zineb Ben Khadda, Andrei-Flavius Radu, Souleiman El Balkhi, Fagroud Mustapha, Yahya El Karmoudi, Gabriela Bungau, Pierre Marquet, Tarik Sqalli Houssaini and Sanae Achour
J. Xenobiot. 2025, 15(4), 120; https://doi.org/10.3390/jox15040120 - 23 Jul 2025
Viewed by 280
Abstract
Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using [...] Read more.
Pesticide exposure gradients between occupational, para-occupational, and general populations remain poorly characterized in North African agricultural contexts. This study evaluates urinary pesticide levels among farmers, indirectly exposed individuals, and a control group in Morocco’s Fez-Meknes region. A cross-sectional survey measured pesticide concentrations using LC-MS/MS in urine samples collected from 154 adults residing in both rural and urban areas. A questionnaire was used to gather information from participants regarding factors that may elevate the risk of pesticide exposure. The results revealed that farmers exhibited the highest concentrations of pesticides in their urine, including compounds classified as Ia/Ib by the World Health Organization. Indirectly exposed individuals showed moderate levels of contamination, with notable detections such as dichlofluanid (22.13 µg/L), while the control group had residual traces of neonicotinoids, notably imidacloprid (2.05 µg/L). Multivariate analyses revealed several sociodemographic factors significantly associated with increased pesticide exposure. The main risk factors identified included low education, residence in an agricultural area, and the consumption of untreated water (wells/rivers). Conversely, wearing personal protective equipment was associated with reduced urinary concentrations. This study highlights intense occupational exposure among farmers, secondary environmental contamination among residents living near treated areas, and the widespread dispersion of pesticide residues into urban areas. Full article
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22 pages, 1643 KiB  
Article
Skin Wound Healing: The Impact of Treatment with Antimicrobial Nanoparticles and Mesenchymal Stem Cells
by Pavel Rossner, Eliska Javorkova, Michal Sima, Zuzana Simova, Barbora Hermankova, Katerina Palacka, Zuzana Novakova, Irena Chvojkova, Tereza Cervena, Kristyna Vrbova, Anezka Vimrova, Jiri Klema, Andrea Rossnerova and Vladimir Holan
J. Xenobiot. 2025, 15(4), 119; https://doi.org/10.3390/jox15040119 - 18 Jul 2025
Viewed by 354
Abstract
An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing [...] Read more.
An investigation into the biological mechanisms initiated in wounded skin following the application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), either alone or combined, was performed in mice, with the aim of determining the optimal approach to accelerate the healing process. This combined treatment was hypothesized to be beneficial, as it is associated with the production of molecules supporting the healing process and antimicrobial activity. The samples were collected seven days after injury. When compared with untreated wounded animals (controls), the combined (MSCs+NPs) treatment induced the expression of Sprr2b, encoding small proline-rich protein 2B, which is involved in keratinocyte differentiation, the response to tissue injury, and inflammation. Pathways associated with keratinocyte differentiation were also affected. Ag NP treatment (alone or combined) modulated DNA methylation changes in genes involved in desmosome organization. The percentage of activated regulatory macrophages at the wound site was increased by MSC-alone and Ag-alone treatments, while the production of nitric oxide, an inflammatory marker, by stimulated macrophages was decreased by both MSC/Ag-alone and MSCs+Ag treatments. Ag induced the expression of Col1, encoding collagen-1, at the injury site. The results of the MSC and NP treatment of skin wounds (alone or combined) suggest an induction of processes accelerating the proliferative phase of healing. Thus, MSC-NP interactions are a key factor affecting global mRNA expression changes in the wound. Full article
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42 pages, 8737 KiB  
Review
Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease
by Ana Filipa Sobral, Andrea Cunha, Inês Costa, Mariana Silva-Carvalho, Renata Silva and Daniel José Barbosa
J. Xenobiot. 2025, 15(4), 118; https://doi.org/10.3390/jox15040118 - 13 Jul 2025
Viewed by 1008
Abstract
Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis [...] Read more.
Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article
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33 pages, 2301 KiB  
Review
An Integrative Approach to Assessing the Impact of Mercury (Hg) on Avian Behaviour: From Molecule to Movement
by Dora Bjedov, Mirta Sudarić Bogojević, Jorge Bernal-Alviz, Goran Klobučar, Jean-Paul Bourdineaud, K. M. Aarif and Alma Mikuška
J. Xenobiot. 2025, 15(4), 117; https://doi.org/10.3390/jox15040117 - 9 Jul 2025
Viewed by 509
Abstract
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and [...] Read more.
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and evolution, as an integrative framework. Mechanistically, Hg disrupts neuroendocrine pathways, gene expression, immune function, and hormone regulation, leading to behavioural changes such as reduced foraging, altered parental care, and impaired predator avoidance. Early-life exposure affects neural development, learning, and social behaviour into adulthood. Functionally, these changes reduce fitness by compromising reproduction and survival. Phylogenetic comparisons show interspecific variability, with piscivorous and insectivorous birds exhibiting high Hg burdens and sensitivity, linked to ecological roles and exposure. Behavioural responses often precede physiological or demographic effects, highlighting their value as early indicators. Both field and laboratory studies show that even low Hg concentrations can alter behaviour, though outcomes vary by species, life stage, and exposure route. Integrating behavioural endpoints into ecotoxicological risk assessments is essential to improve conservation strategies and understanding of sublethal pollutant effects on wildlife. Full article
(This article belongs to the Section Ecotoxicology)
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17 pages, 4340 KiB  
Article
Butylated Hydroxyanisole (BHA) Disrupts Brain Signalling in Embryo–Larval Stage of Zebrafish Leading to Attention Deficit Hyperactivity Disorder (ADHD)
by Kandhasamy Veshaal, Ramasamy Vasantharekha, Usha Rani Balu, Mahesh Vallabi Aayush, Saheshnu Sai Balaji Pillai, Winkins Santosh and Barathi Seetharaman
J. Xenobiot. 2025, 15(4), 116; https://doi.org/10.3390/jox15040116 - 9 Jul 2025
Viewed by 343
Abstract
Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses [...] Read more.
Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article
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17 pages, 635 KiB  
Article
Environmental Arsenic Exposure, Biomarkers and Lung Function in Children from Yaqui Communities in Sonora, Mexico
by Ana G. Dévora-Figueroa, Anaid Estrada-Vargas, Jefferey L. Burgess, Paloma I. Beamer, José M. Guillen-Rodríguez, Leticia García-Rico, Diana Evelyn Villa-Guillen, Iram Mondaca-Fernández and Maria M. Meza-Montenegro
J. Xenobiot. 2025, 15(4), 115; https://doi.org/10.3390/jox15040115 - 8 Jul 2025
Viewed by 483
Abstract
Arsenic exposure in children and adults has been associated with respiratory symptoms, respiratory infections, and decreased lung function. The goal of this study was to evaluate the relationship between environmental arsenic exposure and serum pneumoproteins and lung function. A cross-sectional study was conducted [...] Read more.
Arsenic exposure in children and adults has been associated with respiratory symptoms, respiratory infections, and decreased lung function. The goal of this study was to evaluate the relationship between environmental arsenic exposure and serum pneumoproteins and lung function. A cross-sectional study was conducted including 175 children exposed to arsenic by drinking water (range: 7.4 to 91 µg/L) and soil (range: 4.76 to 35.93 mg/kg), from some Yaqui villages. Arsenic was analyzed in dust and urine using field-portable X-ray fluorescence spectrometry and ICP/OES, respectively. Serum was analyzed for Clara Cell protein (CC16) and Matrix Metalloproteinase-9 (MMP-9) using immunoassays, and lung function was evaluated by spirometry. The results showed that increased arsenic in drinking water was associated with reduced forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (β = −0.027, p = 0.0000) whereas, contrary to expectations, arsenic in dust was associated with increased FEV1/FVC (β = 0.004, p = 0.0076). Increased urinary arsenic was associated with reduced % predicted FEV1 (β = −0.723, p = 0.0152) and reduced FEV1/FVC ratio (β = −0.022, p = 0.0222). Increased serum MMP-9 was associated with reduced FEV1/FVC ratio (β = −0.017, p = 0.0167). Children with % predicted FEV1 values less than 80 had the lowest levels of CC16 (Median 29.0 ng/mL, IQR 21.3, 37.4, p = 0.0148). As a conclusion, our study evidenced an impairment in lung function in children exposed to low arsenic levels. Full article
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14 pages, 893 KiB  
Review
Aspartame and Human Health: A Mini-Review of Carcinogenic and Systemic Effects
by Nour El Doueihy, Joya Ghaleb, Karl Kfoury, Katy Kaleen Khouzami, Nicolas Nassif, Philippe Attieh, Hilda E. Ghadieh, Sami Azar, Amjad Kanaan and Frederic Harb
J. Xenobiot. 2025, 15(4), 114; https://doi.org/10.3390/jox15040114 - 7 Jul 2025
Viewed by 1234
Abstract
Aspartame, a widely used artificial sweetener, has been at the center of ongoing debates concerning its safety, particularly its potential role in cancer development. This review provides an overview and analysis of the current research exploring the carcinogenic effects of aspartame. It examines [...] Read more.
Aspartame, a widely used artificial sweetener, has been at the center of ongoing debates concerning its safety, particularly its potential role in cancer development. This review provides an overview and analysis of the current research exploring the carcinogenic effects of aspartame. It examines findings from in vitro studies, in vivo experiments, and epidemiological investigations to offer a comprehensive perspective on the controversy. The results from these studies remain inconsistent—some suggest a possible association between high aspartame intake and increased cancer risk, while others fail to establish a conclusive link. Additionally, this review explores potential mechanisms by which aspartame could exert carcinogenic effects, focusing on its metabolic byproducts and their influence on cellular and molecular processes. Despite these investigations, the question of aspartame’s safety remains unresolved. Continued research is essential to clarify its role in cancer risk and to inform evidence-based dietary guidelines. Full article
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19 pages, 1321 KiB  
Article
Combined Effects of Nano-Polystyrene and Heavy Metal Mixture on the Bioaccumulation of Heavy Metals and Physiological Changes in Macrobrachium rosenbergii
by Mahdi Banaee, Amir Zeidi, Amal Beitsayah, Cristiana Roberta Multisanti and Caterina Faggio
J. Xenobiot. 2025, 15(4), 113; https://doi.org/10.3390/jox15040113 - 7 Jul 2025
Viewed by 468
Abstract
Contaminants such as nano-polystyrenes (NPs) and heavy metal cocktail (HMC) have been found to disrupt physiological functions in aquatic organisms. Although HMC and NPs alone induce oxidative stress, their combined effects are not well understood. This study aimed to assess the combined effects [...] Read more.
Contaminants such as nano-polystyrenes (NPs) and heavy metal cocktail (HMC) have been found to disrupt physiological functions in aquatic organisms. Although HMC and NPs alone induce oxidative stress, their combined effects are not well understood. This study aimed to assess the combined effects of HMC and NPs on the freshwater shrimp (Macrobrachium rosenbergii). Shrimp were divided into seven groups, including the control group, and the experimental groups co-exposed to 0, 50, 100, 150, 200, and 250 µg/L NPs combined with 0.5 mg/L HMC. After 14 days, shrimp were sampled, and their hepatopancreas and muscle tissues were analyzed for oxidative biomarkers, biochemical parameters, and metabolic profiles. Moreover, the bioaccumulation rate of heavy metals was measured. Results showed that co-exposure to NPs and HMC increased superoxide dismutase, glutathione peroxidase, glutathione reductase activities, and malondialdehyde levels, while reducing glutathione and total antioxidant capacity. The integrated biomarker response indicated that co-exposure to HMC and NPs induces oxidative stress. A significant decrease was observed in aspartate aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase activities, glycogen, triglyceride, and total protein levels. However, lactate dehydrogenase activity was significantly increased. Co-exposure to HMC and NPs increased heavy metal bioaccumulation, induced oxidative stress, biochemical changes, and enhanced HMC toxicity in shrimp. Full article
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17 pages, 959 KiB  
Article
Ecotoxicological Effects of Environmentally Relevant Concentrations of Nickel Nanoparticles on Aquatic Organisms from Three Trophic Levels: Insights from Oxidative Stress Biomarkers
by Alberto Teodorico Correia, Eduardo Motta, David Daniel, Bruno Nunes and José Neves
J. Xenobiot. 2025, 15(4), 112; https://doi.org/10.3390/jox15040112 - 4 Jul 2025
Viewed by 369
Abstract
This study investigated the ecotoxicological impacts of environmentally relevant concentrations (0.05, 0.50, and 5.00 mg/L) of nickel nanoparticles (Ni-NPs) by assessing oxidative stress biomarkers. The worm Hediste diversicolor, the bivalve Mytilus spp., and the fish Sparus aurata were chronically exposed to Ni-NPs [...] Read more.
This study investigated the ecotoxicological impacts of environmentally relevant concentrations (0.05, 0.50, and 5.00 mg/L) of nickel nanoparticles (Ni-NPs) by assessing oxidative stress biomarkers. The worm Hediste diversicolor, the bivalve Mytilus spp., and the fish Sparus aurata were chronically exposed to Ni-NPs for 28 days, and glutathione S-transferases (GST), catalase (CAT), and thiobarbituric acid reactive substances (TBARS) levels were measured to evaluate biochemical responses. GST activity increased in H. diversicolor and the liver of S. aurata, suggesting a key role for this enzyme in Ni-NPs detoxification. CAT activity was inhibited in the digestive gland of Mytilus spp. at the highest Ni-NPs concentration, indicating possible disruption of antioxidant defense. TBARS levels rose significantly in the gills of Mytilus spp. exposed to high Ni-NP concentrations, suggesting oxidative damage beyond detoxification capacity. In contrast, TBARS decreased in the digestive gland of Mytilus and in H. diversicolor, possibly due to compensatory upstream antioxidant responses. These findings indicate that each species exhibits distinct adaptive responses to Ni-NP exposure. Overall, this study highlights the need to consider species- and tissue-specific responses when performing ecotoxicological risk assessments of nanomaterials. Full article
(This article belongs to the Special Issue Environmental Toxicology and Animal Health: 2nd Edition)
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24 pages, 1294 KiB  
Review
Effects of Docosahexaenoic Acid on Prostate Cancer
by Guilherme Henrique Tamarindo, Gustavo Matheus Amaro, Alana Della Torre da Silva and Rejane Maira Góes
J. Xenobiot. 2025, 15(4), 111; https://doi.org/10.3390/jox15040111 - 4 Jul 2025
Viewed by 692
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Impact of Nutrition and the Environment on Human Metabolism)
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32 pages, 1739 KiB  
Review
Effects of Pharmaceuticals and Endocrine-Disrupting Chemicals on Reproductive Biology of Aquatic Fauna: Penguins as Sentinel Species
by Grace Emily Okuthe, Edith Dube and Patrick Siyambulela Mafunda
J. Xenobiot. 2025, 15(4), 110; https://doi.org/10.3390/jox15040110 - 4 Jul 2025
Viewed by 724
Abstract
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 [...] Read more.
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
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21 pages, 1325 KiB  
Article
Antioxidant Potential and Antibacterial Activities of Caucasian Endemic Plants Sempervivum transcaucasicum and Paeonia daurica subsp. mlokosewitschii Extracts and Molecular In Silico Mechanism Insights
by Valentina Mittova, Marina Pirtskhalava, Zurab R. Tsetskhladze, Khatuna Makalatia, Alexander Loladze, Irakli Bebiashvili, Tinatin Barblishvili, Ana Gogoladze and Giovanni N. Roviello
J. Xenobiot. 2025, 15(4), 109; https://doi.org/10.3390/jox15040109 - 4 Jul 2025
Viewed by 1026
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Impact of Nutrition and the Environment on Human Metabolism)
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14 pages, 1682 KiB  
Article
Immobilization of Pleurotus eryngii Laccase via a Protein–Inorganic Hybrid for Efficient Degradation of Bisphenol A as a Potent Xenobiotic
by Sanjay K. S. Patel, Rahul K. Gupta and Jung-Kul Lee
J. Xenobiot. 2025, 15(4), 108; https://doi.org/10.3390/jox15040108 - 3 Jul 2025
Viewed by 344
Abstract
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 [...] Read more.
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
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16 pages, 1266 KiB  
Article
A Novel HPLC-MS/MS Method for the Intracellular Quantification of the Active Triphosphate Metabolite of Remdesivir: GS-443902
by Alice Palermiti, Amedeo De Nicolò, Miriam Antonucci, Sara Soloperto, Martina Billi, Alessandra Manca, Jessica Cusato, Giorgia Menegatti, Mohammed Lamorde, Andrea Calcagno, Catriona Waitt and Antonio D’Avolio
J. Xenobiot. 2025, 15(4), 107; https://doi.org/10.3390/jox15040107 - 3 Jul 2025
Viewed by 350
Abstract
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, [...] Read more.
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
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19 pages, 3549 KiB  
Article
Oxidative Stress, Phytochemical Screening, and Antioxidant Activity on Microalgae (Arthrospira platensis) After Exposure to Glyphosate and Microplastics
by Dércia Santos, Edna Cabecinha, Jesús Gago, Sandra Mariza Monteiro and Ana Luzio
J. Xenobiot. 2025, 15(4), 106; https://doi.org/10.3390/jox15040106 - 3 Jul 2025
Viewed by 395
Abstract
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 [...] Read more.
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
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21 pages, 1246 KiB  
Review
Impacts of Metals on Infectious Diseases in Wildlife and Zoonotic Spillover
by Joel Henrique Ellwanger, Marina Ziliotto and José Artur Bogo Chies
J. Xenobiot. 2025, 15(4), 105; https://doi.org/10.3390/jox15040105 - 3 Jul 2025
Viewed by 470
Abstract
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 [...] Read more.
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
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31 pages, 3799 KiB  
Article
Pesticide Surveillance in Fruits and Vegetables from Romanian Supply: A Data-Driven Approach
by Diana Ionela Popescu (Stegarus), Ana-Maria Nasture, Violeta-Carolina Niculescu, Corina Mihaela Oprita (Cioara) and Nicoleta Anca Șuțan (Ionescu)
J. Xenobiot. 2025, 15(4), 104; https://doi.org/10.3390/jox15040104 - 2 Jul 2025
Viewed by 609
Abstract
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 [...] Read more.
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
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20 pages, 3290 KiB  
Article
The Impact of High Urban Temperatures on Pesticide Residues Accumulation in Vegetables Grown in the Greater Accra Metropolitan Area of Ghana
by Joyce Kumah, Eric Kofi Doe, Benedicta Yayra Fosu-Mensah, Benjamin Denkyira Ofori, Millicent A. S. Kwawu, Ebenezer Boahen, Doreen Larkailey Lartey, Sampson D. D. P. Dordaa and Christopher Gordon
J. Xenobiot. 2025, 15(4), 103; https://doi.org/10.3390/jox15040103 - 2 Jul 2025
Viewed by 692
Abstract
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 [...] Read more.
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
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14 pages, 1369 KiB  
Article
Rapid and Simplified Determination of Amphetamine-Type Stimulants Using One-Pot Synthesized Magnetic Adsorbents with Built-In pH Regulation Coupled with Liquid Chromatography–Tandem Mass Spectrometry
by Yabing Shan, Ying Chen, Jiayi Li, Xianbin Zeng, Rui Jia, Yuwei Liu, Dongmei Li and Di Chen
J. Xenobiot. 2025, 15(4), 102; https://doi.org/10.3390/jox15040102 - 2 Jul 2025
Viewed by 321
Abstract
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 [...] Read more.
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
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23 pages, 1403 KiB  
Review
Cataloging Actionable Pharmacogenomic Variants for Indian Clinical Practice: A Scoping Review
by Sacheta Sudhendra Kulkarni, Venkatesh R, Anuradha Das and Gayatri Rangarajan Iyer
J. Xenobiot. 2025, 15(4), 101; https://doi.org/10.3390/jox15040101 - 1 Jul 2025
Viewed by 666
Abstract
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 [...] Read more.
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
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15 pages, 987 KiB  
Article
Valorization of Agro-Industrial Wastes as Organic Amendments to Reduce Herbicide Leaching into Soil
by Gabriel Pérez-Lucas, Andrea Martínez-Zapata and Simón Navarro
J. Xenobiot. 2025, 15(4), 100; https://doi.org/10.3390/jox15040100 - 30 Jun 2025
Viewed by 326
Abstract
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 [...] Read more.
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 (KOC) 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
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15 pages, 2327 KiB  
Article
Metabolic Costs of Emerging Contaminants: Cellular Energy Allocation in Zebrafish Embryos
by Bárbara S. Diogo, Daniela Rebelo, Sara C. Antunes and Sara Rodrigues
J. Xenobiot. 2025, 15(4), 99; https://doi.org/10.3390/jox15040099 - 29 Jun 2025
Cited by 1 | Viewed by 319
Abstract
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 [...] Read more.
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
(This article belongs to the Section Ecotoxicology)
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19 pages, 1135 KiB  
Article
A Comparison of the QUECHERSER Mega-Method for Pesticide Determination in Loamy-Clayed Soil and the Effect of Organic Amendments on Pendimethalin, Oxyfluorfen, and Trifloxystrobin Soil Persistence
by Rafael Boluda, Alejandro Alejos-Campo, Eva Fernández-Gómez, Miguel Gamón, Luis Roca-Pérez and Oscar Andreu-Sánchez
J. Xenobiot. 2025, 15(4), 98; https://doi.org/10.3390/jox15040098 - 26 Jun 2025
Viewed by 491
Abstract
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 [...] Read more.
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
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22 pages, 2668 KiB  
Article
2D Hexagonal Boron Nitride (h-BN) and 1D Boron Nitride Nanotubes (BNNTs): Distinct Effects at the Cellular Level in Fish Cell Lines
by Mona Connolly, Emmanuel Flahaut and José María Navas
J. Xenobiot. 2025, 15(4), 97; https://doi.org/10.3390/jox15040097 - 24 Jun 2025
Viewed by 514
Abstract
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. [...] Read more.
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
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11 pages, 775 KiB  
Review
Cooperation Between Aflatoxin-Induced p53 Aberrations and Hepatitis B Virus in Hepatocellular Carcinoma
by Carolina Moreno-León and Francisco Aguayo
J. Xenobiot. 2025, 15(4), 96; https://doi.org/10.3390/jox15040096 - 20 Jun 2025
Viewed by 570
Abstract
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 [...] Read more.
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
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21 pages, 793 KiB  
Article
Development and Validation of LC–MS/MS and IC–HRMS Methods for Highly Polar Pesticide Detection in Honeybees: A Multicenter Study for the Determination of Pesticides in Honeybees to Support Pollinators and Environmental Protection
by Tommaso Pacini, Emanuela Verdini, Serenella Orsini, Katia Russo, Tabita Mauti, Mara Gasparini, Marialuisa Borgia, Barbara Angelone, Teresa D’Amore and Ivan Pecorelli
J. Xenobiot. 2025, 15(4), 95; https://doi.org/10.3390/jox15040095 - 20 Jun 2025
Cited by 1 | Viewed by 498
Abstract
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 [...] Read more.
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 RSDr from 1.6% to 19.7% and recoveries between 70% and 119%. Interlaboratory precision at 0.020 mg/kg across two labs showed RSDR 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 RSDr from 2% to 14%. Intralaboratory precision showed mean recoveries from 87% to 119%, with RSDwR values between 10% and 18%. These methods enable accurate monitoring of HPP contamination, supporting risk assessment and sustainable agriculture. Full article
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