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J. Xenobiot., Volume 14, Issue 2 (June 2024) – 20 articles

Cover Story (view full-size image): Marine pollution has attracted great interest amongst the research community, as pollutants disturb the natural balance of ecosystems and might threaten environmental and human health. In this work, pesticides, pharmaceuticals, and macro and trace elements were investigated in two major fish species, Dicentrarchus labrax and Solea solea, collected from Thermaikos Gulf, in Greece. A low prevalence of pesticides and selected pharmaceuticals was reported. At the same time, health risk assessment did not unveil an unacceptable risk for adults, apart from one sample with Hg above the regulatory levels. However, for children, the calculated hazard quotient values for Hg in all cases and for two cases of As detection were higher than the threshold value of 1, indicating a potential risk. View this paper
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15 pages, 2939 KiB  
Article
Microplastic Contamination of Non-Mulched Agricultural Soils in Bangladesh: Detection, Characterization, Source Apportionment and Probabilistic Health Risk Assessment
by Sumaya Sharmin, Qingyue Wang, Md. Rezwanul Islam, Weiqian Wang and Christian Ebere Enyoh
J. Xenobiot. 2024, 14(2), 812-826; https://doi.org/10.3390/jox14020046 - 19 Jun 2024
Viewed by 970
Abstract
Microplastic contamination in agricultural soil is an emerging problem worldwide as it contaminates the food chain. Therefore, this research investigated the distribution of microplastics (MPs) in agricultural soils without mulch at various depths (0–5, 5–10, and 10–15 cm) across different zones: rural, local [...] Read more.
Microplastic contamination in agricultural soil is an emerging problem worldwide as it contaminates the food chain. Therefore, this research investigated the distribution of microplastics (MPs) in agricultural soils without mulch at various depths (0–5, 5–10, and 10–15 cm) across different zones: rural, local market, industrial, coastal, and research areas. The detection of MP types and morphology was conducted using FTIR and fluorescence microscopy, respectively. Eight types of MPs were identified, including high-density polyethylene (HDPE), low-density polyethylene (LDPE), polypropylene (PP), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyvinyl fluoride (PVF), polyvinyl alcohol (PVA), and polytetrafluoroethylene (PTFE), with concentrations ranging from 0.6 ± 0.21 to 3.71 ± 2.36 MPs/g of soil. The study found no significant trends in MP concentration, with ranges of 0–2.1 ± 0.38, 0–2.87 ± 0.55, and 0–2.0 ± 0.34 MPs/g of soil at depths of 0–5 cm, 5–10 cm, and 10–15 cm, respectively. The highest MP quantity was recorded at 8.67 in coastal area, while the lowest was 6.44 in the local market area. Various MP shapes, e.g., fiber, film, pellet, fragment, and irregular, were observed across all layers. PCA suggested irrigation and organic manure as potential sources of MPs. The estimated concentrations of MPs possessed low non-carcinogenic and carcinogenic risks to the farming community of Bangladesh. Full article
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14 pages, 2117 KiB  
Article
Carcinogenic Risk from Lead and Cadmium Contaminating Cow Milk and Soya Beverage Brands Available in the Portuguese Market
by Vanda Lopes de Andrade, Iolanda Ribeiro, Ana Paula Marreilha dos Santos, Michael Aschner and Maria Luisa Mateus
J. Xenobiot. 2024, 14(2), 798-811; https://doi.org/10.3390/jox14020045 - 13 Jun 2024
Viewed by 860
Abstract
Our previous work demonstrated the presence of lead (Pb) and cadmium (Cd) contamination in cow milk (CM) and soy beverages (SBs) in Portugal. These metals share carcinogenic mechanisms, suggesting at least additive effects. Our goals were to assess carcinogenic risks from Pb and [...] Read more.
Our previous work demonstrated the presence of lead (Pb) and cadmium (Cd) contamination in cow milk (CM) and soy beverages (SBs) in Portugal. These metals share carcinogenic mechanisms, suggesting at least additive effects. Our goals were to assess carcinogenic risks from Pb and Cd intake detected in various CM and SB brands on the Portuguese market and to determine the relative contributions of Pb and Cd. Furthermore, we modeled different consumption scenarios for various age/body weight groups to estimate cumulative Excess Lifetime Carcinogenic Risk (ELCR). ELCR was computed by multiplying chronic daily intake by a cancer slope factor for each metal, with an ELCR > 1 × 10−4 indicating carcinogenic risk. Five CM and three SB brands posed cancer risks in children, with the highest values at 1.75 × 10−4 and 9.12 × 10−5, respectively; Pb had mean relative contributions of 87.8 ± 3.1% in CM and 54.9 ± 12.1% in SB. Carcinogenic risks were observed for children, adolescents, and adults in several CM or SB consumption scenarios, albeit at levels above typical Portuguese intakes. Strict monitoring of metal levels, such as Pb and Cd, is advised because CM is a component of many foods, including baby food. Full article
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26 pages, 4474 KiB  
Article
Mechanistic Insights into the Neurotoxicity of 2,5-Dimethoxyphenethylamines (2C) and Corresponding N-(2-methoxybenzyl)phenethylamine (NBOMe) Drugs
by Eva Gil-Martins, Fernando Cagide-Fagín, Daniel Martins, Ana Borer, Daniel José Barbosa, Carlos Fernandes, Daniel Chavarria, Fernando Remião, Fernanda Borges and Renata Silva
J. Xenobiot. 2024, 14(2), 772-797; https://doi.org/10.3390/jox14020044 - 5 Jun 2024
Viewed by 1439
Abstract
Substituted phenethylamines including 2C (2,5-dimethoxyphenethylamines) and NBOMe (N-(2-methoxybenzyl)phenethylamines) drugs are potent psychoactive substances with little to no knowledge available on their toxicity. In the present in vitro study, we explored the mechanisms underlying the neurotoxicity of six substituted phenethylamines: 2C-T-2, 2C-T-4, [...] Read more.
Substituted phenethylamines including 2C (2,5-dimethoxyphenethylamines) and NBOMe (N-(2-methoxybenzyl)phenethylamines) drugs are potent psychoactive substances with little to no knowledge available on their toxicity. In the present in vitro study, we explored the mechanisms underlying the neurotoxicity of six substituted phenethylamines: 2C-T-2, 2C-T-4, 2C-T-7 and their corresponding NBOMes. These drugs were synthesized and chemically characterized, and their cytotoxicity (0–1000 μM) was evaluated in differentiated SH-SY5Y cells and primary rat cortical cultures, by the NR uptake and MTT reduction assays. In differentiated SH-SY5Y cells, mitochondrial membrane potential, intracellular ATP and calcium levels, reactive oxygen species production, and intracellular total glutathione levels were also evaluated. All the tested drugs exhibited concentration-dependent cytotoxic effects towards differentiated SH-SY5Y cells and primary rat cortical cultures. The NBOMe drugs presented higher cytotoxicity than their counterparts, which correlates with the drug’s lipophilicity. These cytotoxic effects were associated with mitochondrial dysfunction, evident through mitochondrial membrane depolarization and lowered intracellular ATP levels. Intracellular calcium imbalance was observed for 2C-T-7 and 25T7-NBOMe, implying a disrupted calcium regulation. Although reactive species levels remained unchanged, a reduction in intracellular total GSH content was observed. Overall, these findings contribute to a deeper understanding of these drugs, shedding light on the mechanisms underpinning their neurotoxicity. Full article
(This article belongs to the Section Drug Therapeutics)
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19 pages, 353 KiB  
Review
Microbial Symbiont-Based Detoxification of Different Phytotoxins and Synthetic Toxic Chemicals in Insect Pests and Pollinators
by Olivia Kline and Neelendra K. Joshi
J. Xenobiot. 2024, 14(2), 753-771; https://doi.org/10.3390/jox14020043 - 4 Jun 2024
Cited by 1 | Viewed by 1378
Abstract
Insects are the most diverse form of life, and as such, they interact closely with humans, impacting our health, economy, and agriculture. Beneficial insect species contribute to pollination, biological control of pests, decomposition, and nutrient cycling. Pest species can cause damage to agricultural [...] Read more.
Insects are the most diverse form of life, and as such, they interact closely with humans, impacting our health, economy, and agriculture. Beneficial insect species contribute to pollination, biological control of pests, decomposition, and nutrient cycling. Pest species can cause damage to agricultural crops and vector diseases to humans and livestock. Insects are often exposed to toxic xenobiotics in the environment, both naturally occurring toxins like plant secondary metabolites and synthetic chemicals like herbicides, fungicides, and insecticides. Because of this, insects have evolved several mechanisms of resistance to toxic xenobiotics, including sequestration, behavioral avoidance, and enzymatic degradation, and in many cases had developed symbiotic relationships with microbes that can aid in this detoxification. As research progresses, the important roles of these microbes in insect health and function have become more apparent. Bacterial symbionts that degrade plant phytotoxins allow host insects to feed on otherwise chemically defended plants. They can also confer pesticide resistance to their hosts, especially in frequently treated agricultural fields. It is important to study these interactions between insects and the toxic chemicals they are exposed to in order to further the understanding of pest insect resistance and to mitigate the negative effect of pesticides on nontarget insect species like Hymenopteran pollinators. Full article
(This article belongs to the Special Issue Environmental Toxicology and Animal Health)
36 pages, 1996 KiB  
Review
A Review on Fluoroquinolones’ Toxicity to Freshwater Organisms and a Risk Assessment
by Marianna Pauletto and Marco De Liguoro
J. Xenobiot. 2024, 14(2), 717-752; https://doi.org/10.3390/jox14020042 - 4 Jun 2024
Cited by 1 | Viewed by 1113
Abstract
Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses [...] Read more.
Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L−1) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L−1), sarafloxacin and clinafloxacin (12.23 µg L−1), and ofloxacin (17.12 µg L−1). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use. Full article
(This article belongs to the Special Issue Environmental Toxicology and Animal Health)
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16 pages, 2890 KiB  
Article
Bioaccumulation of Organic and Inorganic Pollutants in Fish from Thermaikos Gulf: Preliminary Human Health Risk Assessment Assisted by a Computational Approach
by Konstantinos M. Kasiotis, Effrosyni Zafeiraki, Electra Manea-Karga, Demetrios Kouretas, Fotis Tekos, Zoi Skaperda, Nikolaos Doumpas and Kyriaki Machera
J. Xenobiot. 2024, 14(2), 701-716; https://doi.org/10.3390/jox14020041 - 1 Jun 2024
Cited by 2 | Viewed by 1534
Abstract
The monitoring of contaminants in fish species is pivotal for fishes’ health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, [...] Read more.
The monitoring of contaminants in fish species is pivotal for fishes’ health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, Dicentrarchus labrax and Solea solea, collected from Thermaikos Gulf, in Greece. To achieve this goal, three analytical methods using LC-MS/MS, GC-MS/MS, and ICP-MS were developed, validated, and applied to the collected fish samples. The results indicated a very low prevalence of caffeine and acetaminophen, both not exceeding 3.8 μg/kg fish. Similarly, thiabendazole, cypermethrin, and tricyclazole (pesticides) were found in a concentration range of 0.9 to 13.7 μg/kg fish, while in one D. labrax sample, traces of the metabolite of organochlorine pesticide DDT, o,p’-DDE were detected. Al, Mn, Fe, Zn, and Sr were the predominant trace elements in a concentration range of 500–20,000 μg/kg fish. Macro elements levels varied from 280 to 5405 mg/kg fish. Health risk assessment did not unveil an unacceptable risk for the human health of adults, apart from one sample presenting Hg above the regulatory levels. On the contrary, for children, the calculated hazard quotient values for Hg in all cases and for two As detections were higher than the threshold value of 1, indicating a potential risk. Full article
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11 pages, 1533 KiB  
Article
Plastic Analysis with a Plasmonic Nano-Gold Sensor Coated with Plastic-Binding Peptides
by Francois Gagné, Maxime Gauthier and Chantale André
J. Xenobiot. 2024, 14(2), 690-700; https://doi.org/10.3390/jox14020040 - 1 Jun 2024
Cited by 1 | Viewed by 736
Abstract
Contamination with plastics of small dimensions (<1 µm) represents a health concern for many terrestrial and aquatic organisms. This study examined the use of plastic-binding peptides as a coating probe to detect various types of plastic using a plasmon nano-gold sensor. Plastic-binding peptides [...] Read more.
Contamination with plastics of small dimensions (<1 µm) represents a health concern for many terrestrial and aquatic organisms. This study examined the use of plastic-binding peptides as a coating probe to detect various types of plastic using a plasmon nano-gold sensor. Plastic-binding peptides were selected for polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), and polystyrene (PS) based on the reported literature. Using nAu with each of these peptides to test the target plastics revealed high signal, at 525/630 nm, suggesting that the target plastic limited HCl-induced nAu aggregation. Testing with other plastics revealed some lack of specificity but the signal was always lower than that of the target plastic. This suggests that these peptides, although reacting mainly with their target plastic, show partial reactivity with the other target plastics. By using a multiple regression model, the relative levels of a given plastic could be corrected by the presence of other plastics. This approach was tested in freshwater mussels caged for 3 months at sites suspected to release plastic materials: in rainfall overflow discharges, downstream a largely populated city, and in a municipal effluent dispersion plume. The data revealed that the digestive glands of the mussels contained higher levels of PP, PE, and PET plastic particles at the rainfall overflow and downstream city sites compared to the treated municipal effluent site. This corroborated earlier findings that wastewater treatment could remove nanoparticles, at least in part. A quick and inexpensive screening test for plastic nanoparticles in biological samples with plasmonic nAu-peptides is proposed. Full article
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11 pages, 1400 KiB  
Article
The Underlying Mechanism of Poisoning after the Accidental Inhalation of Aerosolised Waterproofing Spray
by Alexander C. Ø. Jensen, Niels E. Ebbehøj, Anja J. Huusom, Keld A. Jensen, Ulla B. Vogel and Jorid B. Sørli
J. Xenobiot. 2024, 14(2), 679-689; https://doi.org/10.3390/jox14020039 - 28 May 2024
Viewed by 890
Abstract
Waterproofing sprays can cause acute respiratory symptoms after inhalation, including coughing and dyspnoea shortly after use. Here, we describe two cases where persons used the same brand of waterproofing spray product. In both cases the persons followed the instructions on the product and [...] Read more.
Waterproofing sprays can cause acute respiratory symptoms after inhalation, including coughing and dyspnoea shortly after use. Here, we describe two cases where persons used the same brand of waterproofing spray product. In both cases the persons followed the instructions on the product and maximized the ventilation by opening windows and doors; however, they still became affected during the application of the product. Products with the same batch number as that used in one case were tested for their effect on respiration patterns of mice in whole-body plethysmographs and lung surfactant function inhibition in vitro. The product was used in spraying experiments to determine the particle size distribution of the aerosol, both using a can from one case and a can with an identical batch number. In addition, the aerosols in the mouse exposure chamber were measured. Aerosol data from a small-scale exposure chamber and data on the physical and temporal dimensions of the spraying during one case were used to estimate the deposited dose during the spraying events. All collected data point to the spraying of the waterproofing product being the reason that two people became ill, and that the inhibition of lung surfactant function was a key component of this illness. Full article
(This article belongs to the Section Emerging Chemicals)
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28 pages, 3684 KiB  
Review
How Per- and Poly-Fluoroalkyl Substances Affect Gamete Viability and Fertilization Capability: Insights from the Literature
by Cielle Lockington and Laura A. Favetta
J. Xenobiot. 2024, 14(2), 651-678; https://doi.org/10.3390/jox14020038 - 17 May 2024
Viewed by 1330
Abstract
There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3–8.5 years). In females, PFAS inhibit the [...] Read more.
There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3–8.5 years). In females, PFAS inhibit the hypothalamic–pituitary–gonadal (HPG) axis, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to the inhibition of androgen and estradiol production. PFAS have been found to cause detrimental effects on egg quality through impairing folliculogenesis. In males, PFAS can impair sperm motility and morphology: two fundamental qualities of successful fertilization. PFAS exposure has been proven to inhibit testosterone production, sperm capacitation, and acrosomal reaction. After fertilization, the results of PFAS exposure to embryos have also been investigated, showing reduced development to the blastocyst stage. The aim of this review is to report the main findings in the literature on the impact of PFAS exposure to gamete competency and fertilization capability by highlighting key studies on both male and female fertility. We report that there is significant evidence demonstrating the negative impacts on fertility after PFAS exposure. At high doses, these environmentally abundant and widespread compounds can significantly affect human fertility. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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17 pages, 1741 KiB  
Article
Heavy Metal(oid)s Contamination and Potential Ecological Risk Assessment in Agricultural Soils
by Muhammad Saleem, David Pierce, Yuqiang Wang, Donald A. Sens, Seema Somji and Scott H. Garrett
J. Xenobiot. 2024, 14(2), 634-650; https://doi.org/10.3390/jox14020037 - 14 May 2024
Cited by 4 | Viewed by 1230
Abstract
Soil pollution caused by heavy metal(oid)s has generated great concern worldwide due to their toxicity, persistence, and bio-accumulation properties. To assess the baseline data, the heavy metal(oid)s, including manganese (Mn), iron (Fe), Cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead [...] Read more.
Soil pollution caused by heavy metal(oid)s has generated great concern worldwide due to their toxicity, persistence, and bio-accumulation properties. To assess the baseline data, the heavy metal(oid)s, including manganese (Mn), iron (Fe), Cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), and cadmium (Cd), were evaluated in surface soil samples collected from the farmlands of Grand Forks County, North Dakota. Samples were digested via acid mixture and analyzed via inductively coupled plasma mass spectrometry (ICP MS) analysis to assess the levels, ecological risks, and possible sources. The heavy metal(oid) median levels exhibited the following decreasing trend: Fe > Mn > Zn > Ni > Cr > Cu > Pb > Co > As > Cd > Hg. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested the main lithogenic source for the studied metal(oid)s. Metal(oid) levels in the current investigation, except Mn, are lower than most of the guideline values set by international agencies. The contamination factor (Cf), geo accumulation index (Igeo) and enrichment factor (EF) showed considerable contamination, moderate contamination, and significant enrichment, respectively, for As and Cd on median value basis. Ecological risk factor (Er) results exhibited low ecological risk for all studied metal(oid)s except Cd, which showed considerable ecological risk. The potential ecological risk index (PERI) levels indicated low ecological risk to considerable risk. Overall, the results indicate the accumulation of As and Cd in the study area. The high nutrients of the soils potentially affect their accumulation in crops and impact on consumers’ health. This drives the impetus for continued environmental monitoring programs. Full article
(This article belongs to the Section Ecotoxicology)
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21 pages, 14620 KiB  
Article
Traditional Plant-Derived Compounds Inhibit Cell Migration and Induce Novel Cytoskeletal Effects in Glioblastoma Cells
by Evan Thompson, Sally Prior and Anke Brüning-Richardson
J. Xenobiot. 2024, 14(2), 613-633; https://doi.org/10.3390/jox14020036 - 9 May 2024
Viewed by 1753
Abstract
Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumour recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumour dissemination and [...] Read more.
Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumour recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumour dissemination and regrowth. One current aim of GBM research focuses on assessing the anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine the specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all the timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and the focal adhesion dynamics. As our in vitro results determined that Turmeric, Indigo and Magnolia are promising migrastatic drugs, we suggest additional experimentation at the whole organism level to further validate these novel findings. Full article
(This article belongs to the Section Natural Products/Herbal Medicines)
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9 pages, 1854 KiB  
Article
Aminomethylphosphonic Acid (AMPA), a Glyphosate Metabolite, Decreases Plasma Cholinesterase Activity in Rats
by Jesús Chávez-Reyes, Fernando Saráchaga-Terrazas, Oliver Alejandro Colis-Arenas, Carlos H. López-Lariz, Carlos M. Villalón and Bruno A. Marichal-Cancino
J. Xenobiot. 2024, 14(2), 604-612; https://doi.org/10.3390/jox14020035 - 7 May 2024
Viewed by 1399
Abstract
Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little [...] Read more.
Glyphosate, a widely used herbicide, is linked to a plethora of deleterious effects in both clinical and preclinical studies. Nevertheless, the effects of its main metabolite, aminomethylphosphonic acid (AMPA), whose half-life in soil is even longer than that of glyphosate, have been little explored. On this basis, as a first approach, in this work, we report that intraperitoneal (i.p.) administration of AMPA or glyphosate (at 10, 56, and 100 mg/kg) decreased, to a similar extent, plasma cholinesterase (ChE) activity in acutely exposed rats. Moreover, we designed an experimental protocol to analyze and compare the effects of AMPA and glyphosate on human plasma ChE activity; this protocol consisted of adding these compounds to human plasma to subsequently test the effects of this plasma on the contraction to acetylcholine (ACh) in the frog rectus abdominis muscle (an indirect estimate of ChE activity). Accordingly, this muscular contraction to ACh was evaluated before and after pre-incubation of ACh with (i) plasma alone, (ii) plasma with AMPA, and (iii) plasma with glyphosate. Our results indicate that AMPA, like glyphosate, decreased ChE activity in the plasma of rats (when given i.p.) and humans (when added in vitro), suggesting that both xenobiotics may exert similar toxicological effects. Full article
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29 pages, 2072 KiB  
Review
Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity
by Isabel S. Barata, José Rueff, Michel Kranendonk and Francisco Esteves
J. Xenobiot. 2024, 14(2), 575-603; https://doi.org/10.3390/jox14020034 - 1 May 2024
Viewed by 1278
Abstract
Progesterone receptor membrane component 1 (PGRMC1) is one of few proteins that have been recently described as direct modulators of the activity of human cytochrome P450 enzymes (CYP)s. These enzymes form a superfamily of membrane-bound hemoproteins that metabolize a wide variety of physiological, [...] Read more.
Progesterone receptor membrane component 1 (PGRMC1) is one of few proteins that have been recently described as direct modulators of the activity of human cytochrome P450 enzymes (CYP)s. These enzymes form a superfamily of membrane-bound hemoproteins that metabolize a wide variety of physiological, dietary, environmental, and pharmacological compounds. Modulation of CYP activity impacts the detoxification of xenobiotics as well as endogenous pathways such as steroid and fatty acid metabolism, thus playing a central role in homeostasis. This review is focused on nine main topics that include the most relevant aspects of past and current PGRMC1 research, focusing on its role in CYP-mediated drug metabolism. Firstly, a general overview of the main aspects of xenobiotic metabolism is presented (I), followed by an overview of the role of the CYP enzymatic complex (IIa), a section on human disorders associated with defects in CYP enzyme complex activity (IIb), and a brief account of cytochrome b5 (cyt b5)’s effect on CYP activity (IIc). Subsequently, we present a background overview of the history of the molecular characterization of PGRMC1 (III), regarding its structure, expression, and intracellular location (IIIa), and its heme-binding capability and dimerization (IIIb). The next section reflects the different effects PGRMC1 may have on CYP activity (IV), presenting a description of studies on the direct effects on CYP activity (IVa), and a summary of pathways in which PGRMC1’s involvement may indirectly affect CYP activity (IVb). The last section of the review is focused on the current challenges of research on the effect of PGRMC1 on CYP activity (V), presenting some future perspectives of research in the field (VI). Full article
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21 pages, 4396 KiB  
Article
Screening Disinfection Byproducts in Arid-Coastal Wastewater: A Workflow Using GC×GC-TOFMS, Passive Sampling, and NMF Deconvolution Algorithm
by Muhammad Usman Siddiqui, Muhammad Sibtain, Farrukh Ahmad, Yasuyuki Zushi and Deedar Nabi
J. Xenobiot. 2024, 14(2), 554-574; https://doi.org/10.3390/jox14020033 - 1 May 2024
Viewed by 1684
Abstract
Disinfection during tertiary municipal wastewater treatment is a necessary step to control the spread of pathogens; unfortunately, it also gives rise to numerous disinfection byproducts (DBPs), only a few of which are regulated because of the analytical challenges associated with the vast number [...] Read more.
Disinfection during tertiary municipal wastewater treatment is a necessary step to control the spread of pathogens; unfortunately, it also gives rise to numerous disinfection byproducts (DBPs), only a few of which are regulated because of the analytical challenges associated with the vast number of potential DBPs. This study utilized polydimethylsiloxane (PDMS) passive samplers, comprehensive two-dimensional gas chromatography (GC×GC) coupled with time-of-flight mass spectrometry (TOFMS), and non-negative matrix factorization (NMF) spectral deconvolution for suspect screening of DBPs in treated wastewater. PDMS samplers were deployed upstream and downstream of the chlorination unit in a municipal wastewater treatment plant located in Abu Dhabi, and their extracts were analyzed using GC×GC-TOFMS. A workflow incorporating a multi-tiered, eight-filter screening process was developed, which successfully enabled the reliable isolation of 22 candidate DBPs from thousands of peaks. The NMF spectral deconvolution improved the match factor score of unknown mass spectra to the reference mass spectra available in the NIST library by 17% and facilitated the identification of seven additional DBPs. The close match of the first-dimension retention index data and the GC×GC elution patterns of DBPs, both predicted using the Abraham solvation model, with their respective experimental counterparts—with the measured data available in the NIST WebBook and the GC×GC elution patterns being those observed for the candidate peaks—significantly enhanced the accuracy of peak assignment. Isotopic pattern analysis revealed a close correspondence for 11 DBPs with clearly visible isotopologues in reference spectra, thereby further strengthening the confidence in the peak assignment of these DBPs. Brominated analogues were prevalent among the detected DBPs, possibly due to seawater intrusion. The fate, behavior, persistence, and toxicity of tentatively identified DBPs were assessed using EPI Suite™ and the CompTox Chemicals Dashboard. This revealed their significant toxicity to aquatic organisms, including developmental, mutagenic, and endocrine-disrupting effects in certain DBPs. Some DBPs also showed activity in various CompTox bioassays, implicating them in adverse molecular pathways. Additionally, 11 DBPs demonstrated high environmental persistence and resistance to biodegradation. This combined approach offers a powerful tool for future research and environmental monitoring, enabling accurate identification and assessment of DBPs and their potential risks. Full article
(This article belongs to the Section Emerging Chemicals)
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17 pages, 3619 KiB  
Article
Toxicity of UV Filter Benzophenone-3 in Brine Shrimp Nauplii (Artemia salina) and Zebrafish (Danio rerio) Embryos
by Melissa I. Ortiz-Román, Ileska M. Casiano-Muñiz and Felix R. Román-Velázquez
J. Xenobiot. 2024, 14(2), 537-553; https://doi.org/10.3390/jox14020032 - 29 Apr 2024
Viewed by 1294
Abstract
The benzophenone (BP) family, including oxybenzone (BP-3), a prevalent sunscreen ingredient and environmental contaminant, has raised concerns since the year 2005. This study investigated oxybenzone toxicity in zebrafish (Danio rerio) eleutheroembryos and brine shrimp (Artemia salina) nauplii, focusing on [...] Read more.
The benzophenone (BP) family, including oxybenzone (BP-3), a prevalent sunscreen ingredient and environmental contaminant, has raised concerns since the year 2005. This study investigated oxybenzone toxicity in zebrafish (Danio rerio) eleutheroembryos and brine shrimp (Artemia salina) nauplii, focusing on the LC50 and developmental impacts. Zebrafish embryos (0.100–1.50 mg/L BP-3, 96 h) and A. salina (0.100–5.00 mg/L BP-3, 48 h) were tested with ultrasound-assisted emulsified liquid-phase microextraction (UA-ELPME) used for zebrafish tissue analysis. HPLC-DAD determined BP-3 concentrations (highest: 0.74 ± 0.13 mg/L). Although no significant zebrafish embryo mortality or hatching changes occurred, developmental effects were evident. Lethal concentrations were determined (A. salina LC50 at 24 h = 3.19 ± 2.02 mg/L; D. rerio embryos LC50 at 24 h = 4.19 ± 3.60 mg/L), with malformations indicating potential teratogenic effects. A. salina displayed intestinal tract alterations and D. rerio embryos exhibited pericardial edema and spinal deformities. These findings highlight oxybenzone’s environmental risks, posing threats to species and ecosystem health. Full article
(This article belongs to the Special Issue Environmental Toxicology and Animal Health)
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21 pages, 2501 KiB  
Article
Association of Combined PFOA, PFOS, Metals and Allostatic Load on Hepatic Disease Risk
by Mary Balogun and Emmanuel Obeng-Gyasi
J. Xenobiot. 2024, 14(2), 516-536; https://doi.org/10.3390/jox14020031 - 28 Apr 2024
Cited by 2 | Viewed by 1403
Abstract
This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2017–2018 data to explore the relationship between exposure to perfluoroalkyl substances (specifically perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), metals lead (Pb), mercury (Hg), and cadmium (Cd), allostatic load, and hepatic disease [...] Read more.
This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2017–2018 data to explore the relationship between exposure to perfluoroalkyl substances (specifically perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), metals lead (Pb), mercury (Hg), and cadmium (Cd), allostatic load, and hepatic disease markers, including the fatty liver index a measure of the likelihood of non-alcoholic fatty liver disease, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin. The paper identified significant associations and interaction effects by employing descriptive statistics, Spearman’s correlation analysis, linear regression, and Bayesian kernel machine regression (BKMR). Descriptive statistics highlight sex-specific differences in contaminant levels. Spearman’s analysis underscores strong correlations among metals and per- and polyfluoroalkyl substances (PFAS). Linear regression reveals significant impacts of specific contaminants on AST, ALT, ALP, and bilirubin levels, adjusting for age and alcohol consumption. BKMR results further elucidate the complex, potentially synergistic relationships between these environmental exposures and the likelihood of non-alcoholic fatty liver disease, offering nuanced insights into their combined effects on liver health. The findings emphasize the intricate dynamics of environmental exposures on hepatic function, advocating for targeted public health interventions. Full article
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19 pages, 3399 KiB  
Article
Exposure to DEP Modifies the Human Umbilical Artery Vascular Resistance Contributing to Hypertension in Pregnancy
by Melissa Mariana, Amadeu M. V. M. Soares, Miguel Castelo-Branco and Elisa Cairrao
J. Xenobiot. 2024, 14(2), 497-515; https://doi.org/10.3390/jox14020030 - 18 Apr 2024
Viewed by 1274
Abstract
Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness [...] Read more.
Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness and endocrine disrupting properties, have been implicated in HDP in some epidemiological studies. Nevertheless, phthalates’ vascular impacts still need to be clarified. Thus, we aimed to understand the connection between phthalates exposure and the occurrence of gestational hypertension, as well as the pathway involved in the pathological vascular effects. We investigated diethyl phthalate’s (DEP) effect on the vascular reactivity of the human umbilical arteries (HUAs) from normotensive and hypertensive pregnant women. Both DEP’s nongenomic (within minutes effect) and genomic (24 h exposure to DEP) actions were evaluated, as well as the contribution of cyclic guanosine monophosphate and Ca2+ channel pathways. The results show that short-term exposure to DEP interferes with serotonin and histamine receptors, while after prolonged exposure, DEP seems to share the same vasorelaxant mechanism as estrogens, through the NO/sGC/cGMP/PKG signaling pathway, and to interfere with the L-type Ca2+ channels. Thus, the vascular effect induced by DEP is similar to that observed in HUA from hypertensive pregnancies, demonstrating that the development of HDP may be a consequence of DEP exposure. Full article
(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)
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13 pages, 4308 KiB  
Article
Exploring the Effects of Graphene-Based Nanoparticles on Early Salmonids Cardiorespiratory Responses, Swimming and Nesting Behavior
by Tomas Makaras, Magdalena Jakubowska-Lehrmann, Živilė Jurgelėnė and Sergej Šemčuk
J. Xenobiot. 2024, 14(2), 484-496; https://doi.org/10.3390/jox14020029 - 14 Apr 2024
Viewed by 1070
Abstract
Graphene-based nanomaterials are exceptionally attractive for a wide range of applications, raising the likelihood of the release of graphene-containing nanoparticles into aquatic environments. The growing use of these carbon nanomaterials in different industries highlights the crucial need to investigate their environmental impact and [...] Read more.
Graphene-based nanomaterials are exceptionally attractive for a wide range of applications, raising the likelihood of the release of graphene-containing nanoparticles into aquatic environments. The growing use of these carbon nanomaterials in different industries highlights the crucial need to investigate their environmental impact and evaluate potential risks to living organisms. The current investigation evaluated the nanotoxicity of graphene (nanoflakes) and graphene oxide (GO) nanoparticles on the cardiorespiratory responses (heart rate, gill ventilation frequency), as well as the swimming and nesting behavioral parameters of early stage larvae and juvenile salmonids. Both short-term (96 h) and long-term (23 days) exposure experiments were conducted using two common species: brown trout (Salmo trutta) and rainbow trout (Oncorhynchus mykiss). The findings demonstrated notable alterations in fish nesting behavior, swimming performance, and cardiorespiratory functions, indicating the potential toxicity of nanoparticles. This impact was observed at both physiological and whole-organismal levels in salmonids at early stages. Future investigations should explore different types of nanocarbons and their potential enduring effects on fish population structure, considering not only individual survival but also broader aspects of development, including feeding, reproductive, and other social dynamics. Full article
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17 pages, 4889 KiB  
Article
Aquatic Fate and Ecotoxicology Effect of ZnS:Mn Quantum Dots on Chlorella vulgaris in Fresh Water
by Bingbing Deng, Rania Maaloul, Sophie Nowak, Yann Sivry, Claude Yéprémian, Souad Ammar, Fayna Mammeri and Roberta Brayner
J. Xenobiot. 2024, 14(2), 467-483; https://doi.org/10.3390/jox14020028 - 26 Mar 2024
Viewed by 1152
Abstract
With the increasing integration of nanomaterials into daily life, the potential ecotoxicological impacts of nanoparticles (NPs) have attracted increased attention from the scientific community. This study assessed the ecotoxicity of ZnS quantum dots (QDs) doped with varying molar concentrations of Mn2+ on [...] Read more.
With the increasing integration of nanomaterials into daily life, the potential ecotoxicological impacts of nanoparticles (NPs) have attracted increased attention from the scientific community. This study assessed the ecotoxicity of ZnS quantum dots (QDs) doped with varying molar concentrations of Mn2+ on Chlorella vulgaris. The ZnS:Mn QDs were synthesized using the polyol method. The size of the ZnS:Mn QDs ranged from approximately 1.1 nm to 2 nm, while the aggregation size in Seine River water was 341 nm at pH 6 and 8. The presence of ZnS:Mn (10%) NPs exhibited profound toxicity to Chlorella vulgaris, with immediate reductions in viability (survival cells) from 71%, 60% to 51%, 52% in BG11 and Seine River water, respectively, at a concentration of 100 mg L−1 of ZnS:Mn (10%) NPs. Additionally, the ATP content in Chlorella vulgaris significantly decreased in Seine River water (by 20%) after 3 h of exposure to ZnS:Mn (10%) NPs. Concurrently, SOD activity significantly increased in Seine River water, indicating that the ZnS:Mn (10%) NPs induced ROS production and triggered an oxidative stress response in microalgae cells. Full article
(This article belongs to the Special Issue Feature Papers in Ecotoxicology)
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15 pages, 3184 KiB  
Article
Effects of Acute and Developmental Exposure to Bisphenol S on Chinese Medaka (Oryzias sinensis)
by Bingying Li, Yongsi Huang, Duan Pi, Xiang Li, Yafen Guo, Zhiying Liang, Xiaohong Song, Junjie Wang and Xuegeng Wang
J. Xenobiot. 2024, 14(2), 452-466; https://doi.org/10.3390/jox14020027 - 22 Mar 2024
Cited by 1 | Viewed by 1201
Abstract
Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about [...] Read more.
Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about its health and ecological effects on aquatic organisms. For this study, we conducted a 96 h acute toxicity test and a 15-day developmental exposure test to assess the adverse effects of BPS exposure in Chinese medaka (Oryzias sinensis), a new local aquatic animal model. The results indicate that the acute exposure of Chinese medaka embryos to BPS led to relatively low toxicity. However, developmental exposure to BPS was found to cause developmental abnormalities, such as decreased hatching rate and body length, at 15 dpf. A transcriptome analysis showed that exposure to different concentrations of bisphenol S often induced different reactions. In summary, environmental concentrations of BPS can have adverse effects on the hatching and physical development of Chinese medaka, and further attention needs to be paid to the potential toxicity of environmental BPS. Full article
(This article belongs to the Section Ecotoxicology)
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