Journal Description
Journal of Xenobiotics
Journal of Xenobiotics
is an international, peer-reviewed, open access journal on xenobiotics published bimonthly online by MDPI (from Volume 10, Issue 1 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, Embase, and other databases
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q2 (Pollution)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 28 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review and reviewer names are published annually in the journal.
Impact Factor:
6.8 (2023);
5-Year Impact Factor:
6.2 (2023)
Latest Articles
Effects of a Proteinase Inhibitor from Inga laurina Seeds (ILTI) on Aedes aegypti Larval Development
J. Xenobiot. 2025, 15(3), 77; https://doi.org/10.3390/jox15030077 (registering DOI) - 22 May 2025
Abstract
Aedes aegypti (Linnaeus, 1762) is Brazil’s primary vector of epidemiologically significant arboviruses such as yellow fever, dengue, Zika, and chikungunya. Despite using conventional chemical control measures, this species has developed resistance to standard chemical insecticides, prompting the search for natural larvicidal compounds. Plant
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Aedes aegypti (Linnaeus, 1762) is Brazil’s primary vector of epidemiologically significant arboviruses such as yellow fever, dengue, Zika, and chikungunya. Despite using conventional chemical control measures, this species has developed resistance to standard chemical insecticides, prompting the search for natural larvicidal compounds. Plant protease inhibitors offer an insecticidal alternative as the primary digestive enzymes in the midgut of Ae. aegypti are proteases (trypsin and chymotrypsin). Ae. aegypti larvae fed with ILTI, a Kunitz-type trypsin inhibitor derived from Inga laurina seeds, at concentrations between 0.03 mg of protein per mL (mgP/mL) and 0.12 mgP/mL, exhibited delayed larval development, with a lethal concentration (LC50) of 0.095 mgP mL−1 of ILTI for 50% of fourth-instar larvae (L4). The ex vivo assay indicated that ILTI effectively inhibited the activity of larval trypsin, which remained susceptible to the inhibitor. Additionally, molecular modelling and docking studies were conducted to predict the three-dimensional ILTI/enzyme molecular complexes at the atomic level. Therefore, the results demonstrate that ILTI functions as a protease inhibitor in this species, presenting itself as a promising larvicidal tool in the control of Ae. aegypti.
Full article
(This article belongs to the Section Natural Products/Herbal Medicines)
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Open AccessReview
Carbon-Nanotube-Based Nanocomposites in Environmental Remediation: An Overview of Typologies and Applications and an Analysis of Their Paradoxical Double-Sided Effects
by
Silvana Alfei and Guendalina Zuccari
J. Xenobiot. 2025, 15(3), 76; https://doi.org/10.3390/jox15030076 - 21 May 2025
Abstract
Incessant urbanization and industrialization have resulted in several pollutants being increasingly produced and continuously discharged into the environment, altering its equilibrium, with a high risk for living organisms’ health. To restore it, new advanced materials for remediating gas streams, polluted soil, water, wastewater,
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Incessant urbanization and industrialization have resulted in several pollutants being increasingly produced and continuously discharged into the environment, altering its equilibrium, with a high risk for living organisms’ health. To restore it, new advanced materials for remediating gas streams, polluted soil, water, wastewater, groundwater and industrial waste are continually explored. Carbon-based nanomaterials (CNMs), including quantum dots, nanotubes, fullerenes and graphene, have displayed outstanding effectiveness in the decontamination of the environment by several processes. Carbon nanotubes (CNTs), due to their nonpareil characteristics and architecture, when included in absorbents, filter membranes, gas sensors, etc., have significantly improved the efficiency of these technologies in detecting and/or removing inorganic, organic and gaseous xenobiotics and pathogens from air, soil and aqueous matrices. Moreover, CNT-based membranes have displayed significant potential for efficient, fast and low-energy water desalination. However, despite CNTs serving as very potent instruments for environmental detoxification, their extensive utilization could, paradoxically, be highly noxious to the environment and, therefore, humans, due to their toxicity. The functionalization of CNTs (F-CNTs), in addition to further enhancing their absorption capacity and selectivity, has increased their hydrophilicity, thus minimizing their toxicity and carcinogenic effects. In this scenario, this review aims to provide evidence of both the enormous potential of CNTs in sustainable environmental remediation and the concerning hazards to the environment and living organisms that could derive from their extensive and uncontrolled utilization. To this end, an introduction to CNTs, including their eco-friendly production from biomass, is first reported. Several literature reports on CNTs’ possible utilization for environmental remediation, their potential toxicity due to environmental accumulation and the challenges of their regeneration are provided using several reader-friendly tools, to better capture readers’ attention and make reading easier.
Full article
(This article belongs to the Special Issue Integrative Studies on Environmental Toxicity, Bioaccumulation and Remediation Strategies for Hazardous Substances)
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Open AccessSystematic Review
Assessing the Impact of Nanoplastics in Biological Systems: Systematic Review of In Vitro Animal Studies
by
Maria Viana, Fernanda S. Tonin and Carina Ladeira
J. Xenobiot. 2025, 15(3), 75; https://doi.org/10.3390/jox15030075 - 17 May 2025
Abstract
Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map
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Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map the current evidence on the biological effects of NPs. In vitro animal studies assessing cellular damage caused by exposure to any type of NP were searched on PubMed, Web of Science, and Scopus. Data on primary outcomes related to genotoxicity and cytotoxicity (cell viability, oxidative stress, inflammation, DNA and cytoplasmic damage, apoptosis) were extracted from the included studies, and overall reporting quality was assessed. A total of 108 articles published between 2018 and 2024, mostly by China (54%), Spain (14%), and Italy (9%), were included. Polystyrene (PS) was the most frequently studied polymer (85%). NP sizes in solution ranged from 15 to 531 nm, with a higher prevalence in the 40–100 nm range (38%). The overall quality of studies was rated as moderate (60%), with many lacking essential details about cell culture conditions (e.g., pH of the medium, passage number, substances used). A higher frequency of negative effects from NP exposure was observed in respiratory cell lines, while immune, digestive, and hepatic cell lines showed greater resistance. Nervous, urinary, and connective tissue systems were impacted by NPs. Positively charged and smaller PS particles were consistently associated with higher toxicity across all systems. In summary, this review highlights the multifactorial nature of NP toxicity, influenced by size, surface charge, and polymer type. It also reveals a significant knowledge gap, stemming from the predominant use of immortalized monocultures exposed to commercially available PS NPs, the limited use of environmentally relevant particles, and the underutilization of advanced experimental models (e.g., organ-on-chip systems) that better mimic physiological conditions.
Full article
(This article belongs to the Section Nanotoxicology and Nanopharmacology)
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Open AccessArticle
Assessment of Selected Heavy Metals and Arsenic Concentrations in Wild Boar (Sus scrofa L.) from Papuk Nature Park (Croatia)
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Domagoj Vidosavljević, Miroslav Venus, Dinko Puntarić, Lidija Kalinić, Marina Vidosavljević, Mario Begović, Marta Despot and Vlatka Gvozdić
J. Xenobiot. 2025, 15(3), 74; https://doi.org/10.3390/jox15030074 - 15 May 2025
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The aim of this study was to measure the concentrations of As, Cd, Hg, Pb, Cr, Cu, Fe and Zn in the muscle, liver and kidney of wild boar (Sus scrofa) in Papuk Nature Park, Eastern Croatia. Muscles, liver and kidney
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The aim of this study was to measure the concentrations of As, Cd, Hg, Pb, Cr, Cu, Fe and Zn in the muscle, liver and kidney of wild boar (Sus scrofa) in Papuk Nature Park, Eastern Croatia. Muscles, liver and kidney of 38 wild boars, up to 3 years of age, were collected and the concentrations of elements were determined by ICP-MS. Cadmium exceeded the permitted levels acceptable for human consumption in 50% of kidney samples (max. = 6.64 mg kg−1), 20% of liver samples (max. = 4.60 mg kg−1) and 43% of muscle samples (max. = 0.672 mg kg−1). Lead exceeded acceptable levels in 63% of liver samples (max. = 0.463 mg kg−1), 51% of kidney samples (max. = 11.8 mg kg−1) and 65% of muscle samples (max. = 9.10 mg kg−1). Mercury concentrations in the liver were higher than allowed in 13% (max. = 0.552 mg kg−1) in kidneys in 27% (max. = 0.484 mg kg−1), and in the muscles in 15% (max. = 0.103 mg kg−1) of cases. Arsenic concentrations in muscles exceeded the permissible value in 30% of cases (max. = 0.286 mg kg−1). The concentrations of Cr, Cu, Fe and Zn did not significantly differ from the values reported in other studies. Median concentrations of Cr, Cu, Fe and Zn ranged as follows: muscle (0.193, 2.94, 44.5 and 20.6 mg kg−1), kidney (0.140, 5.32, 110 and 23.3 mg kg−1) and liver (0.130, 3.71, 278 and 36.0 mg kg−1).
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Open AccessReview
The Exposome and the Kidney: A Silent Dialogue Shaping Chronic Kidney Disease
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Livia Alvarenga, Marcia Ribeiro, Ludmila F. M. F. Cardozo, Natália A. Borges, Peter Stenvinkel and Denise Mafra
J. Xenobiot. 2025, 15(3), 73; https://doi.org/10.3390/jox15030073 - 14 May 2025
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Genetic predisposition accounts for less than 20% of the global disease burden, highlighting the substantial role of environmental factors in health outcomes. In chronic kidney disease (CKD), a growing global prevalence, understanding the interplay between genes and the environment is crucial. Emerging research
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Genetic predisposition accounts for less than 20% of the global disease burden, highlighting the substantial role of environmental factors in health outcomes. In chronic kidney disease (CKD), a growing global prevalence, understanding the interplay between genes and the environment is crucial. Emerging research in the exposome and genome underscores how environmental exposures interact with genetic variants to influence the development and progression of CKD. The term “exposome” encompasses a variety of factors, including personal behaviors like smoking, a sedentary lifestyle, and making specific dietary choices (such as consuming ultra-processed foods, sugar, or fat). It also includes broader determinants such as pesticides, air, water, and soil pollution, nanoplastics, global warming, stressful life events, and socioeconomic status. Research on the exposome significantly increases our understanding of toxicological processes and individual variations in susceptibility to environmental stressors. This narrative review aims to explore the exposome associated with CKD, highlight key environmental exposures in its development, and discuss potential preventive and therapeutic strategies informed by these exposure-related factors.
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Open AccessReview
Dysregulation of microRNA (miRNA) Due to Phthalate/Phthalate Metabolite Exposure and Associated Health Effects: A Narrative Review
by
Aamer Mohammed, Stephen L. Atkin and Edwina Brennan
J. Xenobiot. 2025, 15(3), 72; https://doi.org/10.3390/jox15030072 - 12 May 2025
Abstract
Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs
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Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications.
Full article
Open AccessReview
Air Pollution and Pituitary Adenoma Pathogenesis: Unraveling Environmental Impacts on Neuroendocrine Function and Tumorigenesis
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Andre E. Boyke, Simon A. Menaker, Alberto Nunez, Keith L. Black and Vladimir A. Ljubimov
J. Xenobiot. 2025, 15(3), 71; https://doi.org/10.3390/jox15030071 - 12 May 2025
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Pituitary adenomas, although predominantly benign, can lead to significant clinical complications due to endocrine imbalances and mass effects on adjacent structures. Traditional research has focused on intrinsic factors like genetic mutations and hormonal dysregulation; however, emerging evidence implicates environmental pollutants—particularly urban air contaminants—in
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Pituitary adenomas, although predominantly benign, can lead to significant clinical complications due to endocrine imbalances and mass effects on adjacent structures. Traditional research has focused on intrinsic factors like genetic mutations and hormonal dysregulation; however, emerging evidence implicates environmental pollutants—particularly urban air contaminants—in pituitary tumorigenesis. This review consolidates current findings on how chronic exposure to pollutants such as benzene, di(2-ethylhexyl) phthalate (DEHP), and polychlorinated biphenyls (PCBs) may trigger neuroinflammation, disrupt the hypothalamic–pituitary–adrenal (HPA) axis, and alter pituitary cell proliferation and hormone secretion. We explore mechanistic pathways involving inflammatory cytokines, oxidative stress, and microenvironmental modifications that contribute to neoplastic transformation and tumor progression. Epidemiological studies, supported by in vitro experiments, suggest that air pollutants not only initiate the development of pituitary adenomas but may also enhance the secretory activity of functioning tumors, potentially increasing their aggressiveness. Given the escalating global burden of air pollution and its far-reaching public health implications, further investigation is essential to elucidate these complex interactions. Advancing our understanding in this area could inform preventive strategies and therapeutic interventions aimed at mitigating the environmental impact on pituitary tumor behavior.
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Open AccessArticle
Role of Native Arbuscular Mycorrhizal Fungi in Modulating Nutrient Subcellular Distribution in Wheat Grown in Mn-Toxic Soil
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Jorge Miguel Silva Faria, Ana Paula Pinto, Pedro Barrulas, Isabel Brito and Dora M. Teixeira
J. Xenobiot. 2025, 15(3), 70; https://doi.org/10.3390/jox15030070 - 11 May 2025
Abstract
Heavy metal toxicity leads to impaired crop growth and reduced crop yields and product quality by disrupting plant nutrient uptake, inhibiting development, inducing oxidative stress, and causing cellular toxicity. Arbuscular mycorrhizal fungi (AMF) can play a crucial role in crops’ adaptation to manganese
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Heavy metal toxicity leads to impaired crop growth and reduced crop yields and product quality by disrupting plant nutrient uptake, inhibiting development, inducing oxidative stress, and causing cellular toxicity. Arbuscular mycorrhizal fungi (AMF) can play a crucial role in crops’ adaptation to manganese (Mn) toxicity by regulating nutrient uptake and altering subcellular compartmentalization. The present study examines the influence of intact extraradical mycelia (ERMs) from native AMF on wheat (Triticum aestivum) grown in Mn-toxic soil, with a focus on the tissue-specific and subcellular Ca, Mg, P, and Mn distribution. Wheat cultivated in soil pre-colonized using an intact ERM associated with Lolium rigidum or Ornithopus compressus exhibited enhanced growth and improved P contents. During the first week of growth, the Mn concentrations increased in the wheat’s roots and shoots, but Mn was subsequently reduced and sequestered within the cell wall. In contrast, in the absence of an intact ERM, the Mn accumulation in wheat followed an apparent continuous time-course pattern. AMF-mediated cell wall sequestration seems to contribute to Mn detoxification by limiting excessive cytoplasmic accumulation. Furthermore, AMF-driven changes in the element distribution suggest a dynamic response, wherein an early-stage nutrient uptake transitions into a long-term protective mechanism. These findings highlight the potential of AMF in mitigating Mn stress in crops, providing insights for sustainable agriculture and soil remediation strategies.
Full article
(This article belongs to the Special Issue Plant Biostimulants - a Promising Tool in Organic Farming)
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Open AccessArticle
Effect of Retinoic Acid on the Cerebral Vasculature: Analysis of the Vasoactive Response of Smooth Muscle Cells in Normal and Ischemic Contexts
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Manuel R. Pouso, Emanuel Farinha, Henrique E. Costa, Margarida Lorigo, Graça Baltazar and Elisa Cairrao
J. Xenobiot. 2025, 15(3), 69; https://doi.org/10.3390/jox15030069 - 10 May 2025
Abstract
Retinoic acid (RA), a vitamin A derivative, has been shown to prevent the development of neurological disorders by ensuring the integrity of the physiological structure of the neurovascular unit and regulating the physiological cell’s function. After an ischemia event, RA reduces the effects
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Retinoic acid (RA), a vitamin A derivative, has been shown to prevent the development of neurological disorders by ensuring the integrity of the physiological structure of the neurovascular unit and regulating the physiological cell’s function. After an ischemia event, RA reduces the effects of blood–brain barrier disruption by blocking the apoptotic signaling pathway. However, the effect of RA on smooth muscle cells (SMCs), which are crucial to maintaining blood perfusion, has never been investigated. This study aimed to evaluate the effect of RA on the vasoactive response of middle cerebral artery SMCs in normal and ischemic contexts (O2 and glucose deprivation, OGD). For this purpose, SMCs cultures were incubated with RA, and the vasoactive response was evaluated in both conditions (OGD and non-OGD). To simulate OGD, co-cultures of neurons and astrocytes were made and incubated with RA to analyze the effect of the secretome released by these cells on SMCs contractility. In non-OGD conditions, RA induced rapid relaxation of SMCs and, in the long term (24 h), promoted cell contraction. In OGD conditions, SMCs contractility patterns were different when pre-incubated with RA. In these conditions, NA loses its contractility effect, and SNP seems to revert its relaxant effect. However, SMCs pre-incubated with 5 uM RA show the vasorelaxant pattern typical of SNP, despite the OGD condition. These effects demonstrate an effect of RA on the vasoactive profile of SMCs, with therapeutic potential in OGD conditions.
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(This article belongs to the Topic Environmental Toxicology and Human Health—2nd Edition)
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Open AccessArticle
Investigating the Interplay of Toxic Metals and Essential Elements in Cardiovascular Disease
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Aderonke Gbemi Adetunji and Emmanuel Obeng-Gyasi
J. Xenobiot. 2025, 15(3), 68; https://doi.org/10.3390/jox15030068 - 9 May 2025
Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality globally, accounting for approximately one-third of all deaths. Exposure to toxic metals poses significant risks to cardiovascular health, contributing to the development of CVDs. Essential elements are crucial for maintaining cardiovascular function; however, imbalances
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Cardiovascular diseases (CVDs) are the leading cause of mortality globally, accounting for approximately one-third of all deaths. Exposure to toxic metals poses significant risks to cardiovascular health, contributing to the development of CVDs. Essential elements are crucial for maintaining cardiovascular function; however, imbalances or deficiencies in these elements can exacerbate the risk and progression of CVDs. Understanding the interactions between toxic metals and essential elements is crucial for elucidating their impact on cardiovascular health. This study aims to examine the individual and combined effects of toxic metals—lead (Pb), cadmium (Cd), and mercury (Hg)—along with essential elements—manganese (Mn), iron (Fe), and selenium (Se)—on CVDs. We explored the effects of toxic metals and essential elements using data from the National Health and Nutrition Examination Survey (NHANES, 2017–2018). We conducted descriptive analyses and applied advanced statistical methods, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and quantile g-computation, to assess the associations between these toxic metals and essential elements on key cardiovascular-related biomarkers. The results revealed distinct patterns of influence across the toxic metals and essential elements. Spearman correlation showed a stronger association among toxic metals than essential elements. Bayesian kernel machine regression (BKMR) and posterior inclusion probability (PIP) analysis identified lead, mercury, iron, and selenium as key contributors to CVD risk, with lead strongly linked to high-density lipoprotein (HDL), diastolic blood pressure (DBP), and systolic blood pressure (SBP). Selenium was linked to low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol. Univariate and bivariate analyses confirmed lead and mercury’s strong associations with triglycerides and blood pressure, while lead, selenium, and iron were linked to different cholesterol outcomes. Single-variable analysis revealed an interaction between individual exposures and combined exposures. The overall exposure effect assessing the impact of all exposures combined on CVD markers revealed a steady positive association with triglycerides, total cholesterol, LDL, non-HDL cholesterol, and DBP, with HDL and SBP increasing from the 65th percentile. Quantile g-computation and WQSR confirmed lead’s consistent positive association across all outcomes, with variations among other toxic metals and essential elements. In conclusion, our study suggests that toxic metals and essential elements are important factors in CVD outcomes, with different metals and elements associated with variations in specific biomarkers.
Full article
(This article belongs to the Special Issue New Insights into the Effects of Multi-Pollutant Mixtures on the Environment and Populations)
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Open AccessArticle
Ames Assay Transferred from the Microtiter Plate to the Planar Assay Format
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Katharina Schmidtmann, Johanna Lemme and Gertrud E. Morlock
J. Xenobiot. 2025, 15(3), 67; https://doi.org/10.3390/jox15030067 - 7 May 2025
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The International Agency for Research on Cancer has studied and classified 1045 potential substances. It is therefore important to develop rapid screening methods to identify the mutagenicity of compounds and, further on, the intensity and number of individual mutagenic substances in complex sample
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The International Agency for Research on Cancer has studied and classified 1045 potential substances. It is therefore important to develop rapid screening methods to identify the mutagenicity of compounds and, further on, the intensity and number of individual mutagenic substances in complex sample mixtures. The current in vitro Ames assay in the microtiter plate format (MPF) uses a pH-sensitive detection as endpoint, however, acidic substances in complex mixtures may interfere the mutagenicity result. Hence, it was transferred to the planar assay format to be more selective for complex mixture testing. The co-culture of Salmonella Typhimurium strains TA98 and TA100 with an optical density of 0.4 at 600 nm was applied on a high-performance thin-layer chromatography silica gel 60 chromatogram and on-surface incubated for 5 h, which period was limited due to zone diffusion. Various positive controls were tested, and 4-nitrochinolin-N-oxide with a limit of detection of 100 ng was established as a positive control. However, due to the shorter incubation time, no mutagenic compounds were detectable or differentiable in the tested perfumes, herbal teas, margarines, and hand creams. This does not mean that the samples are mutagen-free, but it suggests that further improvements to the bioassay are urgently needed to increase the sensitivity and selectivity of the response. Compared to conventional sum value assays, a planar Ames assay performed on the separated and adsorbed sample components advances toxicology research because mutagenic compounds are separated from interfering molecules due to the integrated separation. It thus would provide a more selective detection of mutagens in complex mixtures and allow testing of large sample volumes or concentrated samples without matrix interference.
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Open AccessArticle
COMT Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study
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Alessandra Manca, Cristina Valz, Francesco Chiara, Alice Palermiti, Jacopo Mula, Sara Soloperto, Miriam Antonucci, Amedeo De Nicolò, Nicola Luxardo, Daniele Imperiale, Flavio Vischia, David De Cori, Jessica Cusato and Antonio D’Avolio
J. Xenobiot. 2025, 15(3), 66; https://doi.org/10.3390/jox15030066 - 7 May 2025
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Cannabis sativa L. shows potent anti-inflammatory activity, resulting in an interesting pharmacological option for pain management. The aim of the study was to evaluate the association between pharmacogenetics, neurological and inflammatory biomarkers, and cannabinoid plasma exposure in patients treated with cannabis. A total
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Cannabis sativa L. shows potent anti-inflammatory activity, resulting in an interesting pharmacological option for pain management. The aim of the study was to evaluate the association between pharmacogenetics, neurological and inflammatory biomarkers, and cannabinoid plasma exposure in patients treated with cannabis. A total of 58 patients with a diagnosis of neuropathic and chronic pain treated with medical cannabis were analyzed. Cannabis was administered as a decoction (n = 47) and as inhaled cannabis (n = 11): 30 patients were treated with cannabis with high THC, while 28 patients were treated with cannabis with reduced THC (plus CBD). Cannabinoid plasma concentrations were obtained with UHPLC-MS/MS. Allelic discrimination was assessed by real-time PCR. Inflammation biomarkers (e.g., interleukin-10) were analyzed by ELISA, neurofilaments light chain (NFL), and brain-derived neurotrophic factor (BDNF) by Single Molecule Array. A statistically significant difference in IL-10 (p = 0.009) and BDNF (p = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the COMT 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (p = 0.017). Conclusions: This study shows a possible impact of some genetic variants on cannabinoid plasma exposure, other than a possible role of medical cannabis on inflammation-related and neuronal impairment factor levels. Further studies in larger cohorts are required.
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Open AccessArticle
Do Isopropylammonium Glyphosate and LiCl Impact the Spore Diversity and Functions of Aquatic Fungi Involved in Plant Litter Decomposition in Streams?
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Jorge Rodrigues, Hernâni Gerós, Manuela Côrte-Real and Fernanda Cássio
J. Xenobiot. 2025, 15(3), 65; https://doi.org/10.3390/jox15030065 - 1 May 2025
Abstract
Glyphosate based-herbicides are stressors of great concern because they can impact aquatic ecosystems. Similarly, lithium, a metal, is currently of concern because of its increasing use worldwide. Because glyphosate-based herbicides and lithium might co-occur in aquatic environments, there is a need to assess
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Glyphosate based-herbicides are stressors of great concern because they can impact aquatic ecosystems. Similarly, lithium, a metal, is currently of concern because of its increasing use worldwide. Because glyphosate-based herbicides and lithium might co-occur in aquatic environments, there is a need to assess their impacts on aquatic organisms, such as aquatic fungi, as they play a key role in plant litter decomposition in streams. Microcosm assays were used to examine the effects of lithium and the herbicide isopropylammonium glyphosate (IPAG), alone or in mixtures, on microbial leaf mass loss, total fungal sporulation and biomass production. IPAG (alone and combined with LiCl) neither affected plant litter decomposition nor fungal biomass production, but boosted total fungal sporulation. Dimorphospora foliicola, the most tolerant species among the twelfth leaf inhabitant fungal species, is the major contributor to total fungal sporulation. IPAG interacts with LiCl in the total fungal sporulation and sporulation of D. foliicola, A. tetracladia, and F. curvula, indicating a species dependent-effect. IPAG alone or combined with LiCl greatly decreased the diversity of spores, as did as LiCl alone, but to a lesser extent. Finally, aquatic fungal communities reveal redundancy and resiliency to IPAG and LiCL, maintaining the health of aquatic ecosystems.
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(This article belongs to the Special Issue New Challenges in the Monitoring, Risk Assessment and Management of Pesticides and Biocides in the “One Health Era”)
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Open AccessArticle
Evaluation of the Effects of Monosodium Glutamate Overconsumption on the Functions of the Liver, Kidney, and Heart of Male Rats: The Involvement of Dyslipidemia, Oxidative Stress, and Inflammatory Responses
by
Heba M. Abdou, Amel H. El-Gendy, Rania Gaber Aly, Mekky M. Abouzied, Heba M. Eltahir, Sultan S. Al thagfan and Saber M. Eweda
J. Xenobiot. 2025, 15(3), 64; https://doi.org/10.3390/jox15030064 - 29 Apr 2025
Abstract
The excessive intake of monosodium glutamate (MSG) increases its cellular levels in different organs and induces organ toxicity. The current study aims to investigate the metabolic changes and possible causes of hepatic, renal, and cardiac toxicity induced by MSG overconsumption. Thirty adult male
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The excessive intake of monosodium glutamate (MSG) increases its cellular levels in different organs and induces organ toxicity. The current study aims to investigate the metabolic changes and possible causes of hepatic, renal, and cardiac toxicity induced by MSG overconsumption. Thirty adult male rats were randomly allocated into five groups: control, MSG0.8, MSG1, MSG2, and MSG3, which were orally treated with a daily oral dose of saline, 0.8, 1, 2, and 3 g MSG/kg BW, respectively, for eight weeks. The hepatic, renal, and cardiac biochemical markers; lipid profile; glucose; electrolytes; iNOS; α-KGD; oxidative stress; and inflammatory markers were investigated. The histopathological examination of hepatic and renal tissues was also performed. The results revealed MSG-induced hepato-renal and cardiac toxicity, as indicated by the changes in the biochemical markers and tissue architecture of these organs. The toxicity is observed in the form of dyslipidemia, oxidative stress (increased MDA and NO and decreased GSH, SOD, CAT, and GST), and inflammatory responses (increased TNF-α and IL-6). The histopathological changes in liver and kidney architecture confirmed the obtained results. In conclusion, the MSG-induced hepatic, renal, and cardiac toxicity was dose-dependent, and awareness should be raised about the side effects of the overconsumption of MSG.
Full article
(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)
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Open AccessReview
Innovative Approaches and Evolving Strategies in Heavy Metal Bioremediation: Current Limitations and Future Opportunities
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Cristina Firincă, Lucian-Gabriel Zamfir, Mariana Constantin, Iuliana Răut, Maria-Luiza Jecu, Mihaela Doni, Ana-Maria Gurban and Tatiana Eugenia Șesan
J. Xenobiot. 2025, 15(3), 63; https://doi.org/10.3390/jox15030063 - 26 Apr 2025
Abstract
Decades of technological advancements have led to major environmental concerns, particularly the bioaccumulation of heavy metals, which pose persistent risks to ecosystems and human health. Consequently, research has increasingly shifted from conventional remediation techniques toward more sustainable, environmentally friendly solutions. This review explores
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Decades of technological advancements have led to major environmental concerns, particularly the bioaccumulation of heavy metals, which pose persistent risks to ecosystems and human health. Consequently, research has increasingly shifted from conventional remediation techniques toward more sustainable, environmentally friendly solutions. This review explores recent advancements, ongoing challenges, and future perspectives in the field of bioremediation, emphasizing its potential as a green technology for heavy metal decontamination. Despite significant progress, key challenges remain, including scalability limitations and the management of bioremediation by-products, along with the influence of regulatory policies and public perception on its large-scale implementation. Emerging approaches such as genetic engineering and nanotechnology show promise in overcoming these limitations. Gene editing allows the tailoring of specific metabolic traits for bioprocesses targeted towards increased tolerance to pollutants and higher biodegradation efficiency, higher enzymatic specificity and affinity, and improved yield and fitness in plants. Nanotechnologies, particularly biogenic nanostructures, open up the possibility of repurposing waste materials as well as harnessing the advantages of the biosynthesis of NPs with higher stability, biocompatibility, and biostimulant capacities. Furthermore, biopolymers and bio-based nanocomposites can improve the efficiency and costs of bioremediation protocols. Even so, further research is essential to evaluate their long-term risks and feasibility.
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(This article belongs to the Special Issue Integrative Studies on Environmental Toxicity, Bioaccumulation and Remediation Strategies for Hazardous Substances)
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Open AccessEditorial
Feature Papers in Ecotoxicology
by
Valerio Matozzo and Maria Gabriella Marin
J. Xenobiot. 2025, 15(3), 62; https://doi.org/10.3390/jox15030062 - 26 Apr 2025
Abstract
Ecotoxicology has progressively evolved as a key scientific discipline for evaluating the impact of both traditional and emerging contaminants on ecosystems [...]
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(This article belongs to the Special Issue Feature Papers in Ecotoxicology)
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Naphthenic Acid Fraction Components-Induced Metabolic and Mitochondrial Alterations in Rat Hepatoma Cells: Monitoring Metabolic Reprogramming with Tryptophan–Kynurenine Ratio
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Laiba Jamshed, Amica Marie-Lucas, Genevieve A. Perono, Gregg T. Tomy, Jim J. Petrik, Richard A. Frank, L. Mark Hewitt, Philippe J. Thomas and Alison C. Holloway
J. Xenobiot. 2025, 15(3), 61; https://doi.org/10.3390/jox15030061 - 24 Apr 2025
Abstract
Altered body condition and diminished growth in wildlife in the Alberta Oil Sands Region (AOSR) are prompting investigations into the impact of oil sands industrial activity on wildlife in the region. Chemical constituents from bitumen-influenced waters, including oil sands process-affected water (OSPW), can
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Altered body condition and diminished growth in wildlife in the Alberta Oil Sands Region (AOSR) are prompting investigations into the impact of oil sands industrial activity on wildlife in the region. Chemical constituents from bitumen-influenced waters, including oil sands process-affected water (OSPW), can disrupt endocrine signaling, leading to aberrant lipid accumulation and altered glycemic control in mammals. This study aimed to investigate the effects of naphthenic acid fraction components (NAFCs), derived from OSPW, on energy homeostasis using the McA-RH7777 rat hepatocyte model. Cells were exposed to NAFCs at nominal concentrations of 0, 0.73, 14.7, and 73.4 mg/L for 24 and 48 h. We assessed gene expression related to lipid and glucose metabolism and measured triglyceride accumulation, glucose, and fatty acid uptake. NAFC exposure (14.7 and 73.4 mg/L) reduced triglyceride levels and glucose uptake and increased fatty acid uptake and the expression of beta-oxidation genes, suggesting a metabolic switch from glucose to fatty acid oxidation. This switch in substrate availability signifies a shift in cellular energy dynamics, potentially linked to altered mitochondrial function. To investigate this, we conducted adenosine triphosphate (ATP), mitochondrial membrane potential, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays to measure cellular ATP levels, mitochondrial membrane potential, and apoptosis, respectively. At both time points, 73.4 mg/L NAFC exposure resulted in increased ATP levels, induced mitochondrial membrane hyperpolarization, and increased apoptosis. These results suggest that mitochondrial efficiency is compromised, necessitating metabolic adaptations to maintain energy homeostasis. Given that cells exhibit metabolic flexibility that allows them to dynamically respond to changes in substrate availability, we further demonstrated that the kynurenine–tryptophan ratio (KTR) serves as a marker for a shift in energy metabolism under these stress conditions. This work provides a mechanistic framework for understanding how bitumen-derived organic contaminants may disrupt metabolic function in wildlife living in the AOSR. These findings further support the use of molecular markers like KTR to evaluate sub-lethal metabolic stress in environmental health monitoring.
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(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)
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Open AccessArticle
Genetic Interactions of Phase II Xenobiotic-Metabolizing Enzymes GSTO1 and GCLC in Relation to Alcohol Abuse and Psoriasis Risk
by
Roman Saranyuk, Olga Bushueva, Ekaterina Efanova, Maria Solodilova, Mikhail Churnosov and Alexey Polonikov
J. Xenobiot. 2025, 15(2), 60; https://doi.org/10.3390/jox15020060 - 20 Apr 2025
Abstract
The present pilot study aimed to investigate whether common single nucleotide polymorphisms (SNPs) in the gene encoding glutathione S-transferase omega 1 (GSTO1), both individually and in combination with variants of the catalytic subunit of the glutamate cysteine ligase (GCLC)
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The present pilot study aimed to investigate whether common single nucleotide polymorphisms (SNPs) in the gene encoding glutathione S-transferase omega 1 (GSTO1), both individually and in combination with variants of the catalytic subunit of the glutamate cysteine ligase (GCLC) gene and environmental risk factors, are associated with the risk of psoriasis. The research included a total of 944 participants, comprising 474 individuals diagnosed with psoriasis and 470 healthy control subjects. Five common SNPs in the GSTO1 gene—specifically, rs11191736, rs34040810, rs2289964, rs11191979, and rs187304410—were genotyped in the study groups using the MassARRAY-4 system. The allele rs187304410-A (OR = 0.19, 95% CI 0.04–0.86, Pperm = 0.02) and the genotype rs187304410-G/A (OR = 0.19, 95% CI 0.04–0.85, Pperm = 0.01) were found to be associated with psoriasis in females. The model-based multifactor dimensionality reduction approach facilitated the identification of higher-order epistatic interactions between the variants of the GSTO1 and GCLC genes (Pperm < 0.0001). These interactions, along with the risk factor of alcohol abuse, collectively contribute to the pathogenesis of psoriasis. This study is the first to demonstrate that polymorphisms in the GSTO1 gene, both individually and in combination with variants of the GCLC gene and alcohol abuse, are associated with an increased risk of psoriasis.
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(This article belongs to the Topic Phase I and Phase II Xenobiotic-Metabolizing Enzymes: Structure, Function, and Regulation)
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Open AccessReview
Bioaccumulation and Trophic Transfer of Heavy Metals in Marine Fish: Ecological and Ecosystem-Level Impacts
by
Andra Oros
J. Xenobiot. 2025, 15(2), 59; https://doi.org/10.3390/jox15020059 - 18 Apr 2025
Abstract
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Heavy metal contamination in marine ecosystems poses a critical environmental challenge, with significant implications for biodiversity, trophic dynamics, and human health. Marine fish are key bioindicators of heavy metal pollution because of their role in food webs and their capacity for bioaccumulation and
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Heavy metal contamination in marine ecosystems poses a critical environmental challenge, with significant implications for biodiversity, trophic dynamics, and human health. Marine fish are key bioindicators of heavy metal pollution because of their role in food webs and their capacity for bioaccumulation and trophic transfer. This review synthesizes current knowledge on the pathways and mechanisms of heavy metal accumulation in marine fish, focusing on factors that influence the uptake, retention, and tissue distribution. We explore the processes governing trophic transfer and biomagnification, highlighting species-specific accumulation patterns and the risks posed to apex predators, including humans. Additionally, we assess the ecological consequences of heavy metal contamination at population, community, and ecosystem levels, emphasizing its effects on fish reproduction, community structure, and trophic interactions. By integrating recent findings, this review highlights key knowledge gaps and suggests future research directions to improve environmental monitoring and risk assessment. Given the persistence and bioavailability of heavy metals in marine environments, effective pollution control strategies and sustainable fisheries management are imperative to mitigate long-term ecological and public health risks.
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Open AccessArticle
Bacterial Cytochrome P450 Involvement in the Biodegradation of Fluorinated Pyrethroids
by
Mohd Faheem Khan, Jun Liao, Zhenyang Liu and Gaurav Chugh
J. Xenobiot. 2025, 15(2), 58; https://doi.org/10.3390/jox15020058 - 18 Apr 2025
Abstract
Fluorinated pyrethroids, such as cyfluthrin and cyhalothrin, are more effective insecticides due to their enhanced stability and lipophilicity. However, they pose greater risks to non-target organisms. Their persistence in the environment and accumulation in tissues can lead to increased toxicity and ecological concerns.
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Fluorinated pyrethroids, such as cyfluthrin and cyhalothrin, are more effective insecticides due to their enhanced stability and lipophilicity. However, they pose greater risks to non-target organisms. Their persistence in the environment and accumulation in tissues can lead to increased toxicity and ecological concerns. This study investigates the biodegradation of the fluorinated pyrethroids β-cyfluthrin (BCF) and λ-cyhalothrin (LCH) using a newly isolated Bacillus sp. MFK14 from a garden soil microbial consortium. Initial screening using 19F NMR analysis showed that the microbial consortium degraded both pyrethroids, leading to the isolation of Bacillus sp. MFK14. Subsequent GC-MS analysis revealed various degradation intermediates in both pyrethroids after incubation with Bacillus sp. MFK14. Notably, Bacillus sp. MFK14 completely degraded β-cyfluthrin and λ-cyhalothrin within 48 h at 30 °C. Fluoride ions from β-cyfluthrin and trifluoroacetic acid (TFA) from λ-cyhalothrin were detected as the end-products by 19F NMR analysis of the aqueous fraction. The pathway of the degradation was proposed for both the pyrethroids indicating shared biodegradation pathways despite different fluorinations. Inhibition studies with 1-ABT suggested the involvement of bacterial cytochrome P450 (CYP) enzymes in their biodegradation. The CYPome of Bacillus sp. MFK14 includes 23 CYP variants that showed significant sequence similarity to known bacterial CYPs, suggesting potential roles in pyrethroid biodegradation and environmental persistence. These findings highlight the potential for bioremediation of fluorinated pesticides, offering an environmentally sustainable approach to mitigate their ecological impact.
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(This article belongs to the Special Issue New Challenges in the Monitoring, Risk Assessment and Management of Pesticides and Biocides in the “One Health Era”)
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