Journal of Xenobiotics

46 pages, 5926 KiB

Open AccessEditor’s ChoiceReview

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics

by Mirza Salman Baig, Anas Ahmad, Rijawan Rajjak Pathan and Rakesh Kumar Mishra

J. Xenobiot. 2024, 14(3), 827-872; https://doi.org/10.3390/jox14030047 - 24 Jun 2024

Cited by 3 | Viewed by 2445

Abstract

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and [...] Read more.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances—which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes. Full article

(This article belongs to the Section Drug Therapeutics)

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19 pages, 353 KiB

Open AccessEditor’s ChoiceReview

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 1757

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

Open AccessEditor’s ChoiceReview

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 1383

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 EC_50s 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

Open AccessEditor’s ChoiceArticle

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 1707

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

(This article belongs to the Special Issue Legacy and Emerging Pollutants and Their Effects through the Lens of Environmental Management)

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36 pages, 3709 KiB

Open AccessEditor’s ChoiceReview

Bamboo-Based Biochar: A Still Too Little-Studied Black Gold and Its Current Applications

by Silvana Alfei and Omar Ginoble Pandoli

J. Xenobiot. 2024, 14(1), 416-451; https://doi.org/10.3390/jox14010026 - 20 Mar 2024

Cited by 5 | Viewed by 3955

Abstract

Biochar (BC), also referred to as “black gold”, is a carbon heterogeneous material rich in aromatic systems and minerals, preparable by the thermal decomposition of vegetable and animal biomasses in controlled conditions and with clean technology. Due to its adsorption ability and presence [...] Read more.

Biochar (BC), also referred to as “black gold”, is a carbon heterogeneous material rich in aromatic systems and minerals, preparable by the thermal decomposition of vegetable and animal biomasses in controlled conditions and with clean technology. Due to its adsorption ability and presence of persistent free radicals (PFRs), BC has demonstrated, among other uses, great potential in the removal of environmental organic and inorganic xenobiotics. Bamboo is an evergreen perennial flowering plant characterized by a short five-year growth period, fast harvesting, and large production in many tropical and subtropical countries worldwide, thus representing an attractive, low-cost, eco-friendly, and renewable bioresource for producing BC. Due to their large surface area and increased porosity, the pyrolyzed derivatives of bamboo, including bamboo biochar (BBC) or activated BBC (ABBC), are considered great bio-adsorbent materials for removing heavy metals, as well as organic and inorganic contaminants from wastewater and soil, thus improving plant growth and production yield. Nowadays, the increasing technological applications of BBC and ABBC also include their employment as energy sources, to catalyze chemical reactions, to develop thermoelectrical devices, as 3D solar vapor-generation devices for water desalination, and as efficient photothermal-conversion devices. Anyway, although it has great potential as an alternative biomass to wood to produce BC, thus paving the way for new bio- and circular economy solutions, the study of bamboo-derived biomasses is still in its infancy. In this context, the main scope of this review was to support an increasing production of BBC and ABBC and to stimulate further studies about their possible applications, thus enlarging the current knowledge about these materials and allowing their more rational, safer, and optimized application. To this end, after having provided background concerning BC, its production methods, and its main applications, we have reviewed and discussed the main studies on BBC and ABBC and their applications reported in recent years. Full article

(This article belongs to the Special Issue Feature Papers in Ecotoxicology)

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18 pages, 2303 KiB

Open AccessEditor’s ChoiceArticle

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children

by Raymond F. Palmer, David Kattari, Rodolfo Rincon and Claudia S. Miller

J. Xenobiot. 2024, 14(1), 350-367; https://doi.org/10.3390/jox14010022 - 5 Mar 2024

Viewed by 5864

Abstract

Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for [...] Read more.

Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link. Methods: In a population-based survey of U.S. adults, we used the internationally validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess symptom severity and chemical intolerance. Parents were asked how many of their biological children had been diagnosed with autism and/or ADHD. Results: Parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for ADHD. Conclusions: High chemical intolerance scores among parents of children with autism, coupled with our 2021 discovery of mast cell activation as a plausible biomechanism for chemical intolerance, suggest that (1) the QEESI can identify individuals at increased risk, (2) environmental counseling may reduce personal exposures and risk, and (3) the global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically “turning on” or “turning off” critical mast cell genes that can be transmitted transgenerationally. It is important to note that this study was observational in nature; as such, further research is needed using controlled trials to confirm causality and explore the proposed mechanism. Full article

(This article belongs to the Special Issue Environmental Conditions and Autism Spectrum Disorders)

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13 pages, 1983 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Pyriproxyfen Contamination in Daphnia magna: Identifying Early Warning Biomarkers

by Beatriz Salesa, Javier Torres-Gavilá, María Dolores Ferrando-Rodrigo and Encarnación Sancho

J. Xenobiot. 2024, 14(1), 214-226; https://doi.org/10.3390/jox14010013 - 2 Feb 2024

Cited by 1 | Viewed by 1437

Abstract

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. [...] Read more.

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, Daphnia magna organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in D. magna exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. Fabd expression was decreased by approximately 20% in exposed daphnids, while vtg expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the hgb1 and hgb2 genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in Daphnia magna during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations. Full article

(This article belongs to the Special Issue Legacy and Emerging Pollutants and Their Effects through the Lens of Environmental Management)

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10 pages, 1056 KiB

Open AccessEditor’s ChoiceArticle

Early Female Transgender Identity after Prenatal Exposure to Diethylstilbestrol: Report from a French National Diethylstilbestrol (DES) Cohort

by Laura Gaspari, Marie-Odile Soyer-Gobillard, Scott Kerlin, Françoise Paris and Charles Sultan

J. Xenobiot. 2024, 14(1), 166-175; https://doi.org/10.3390/jox14010010 - 12 Jan 2024

Cited by 1 | Viewed by 9140

Abstract

Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies [...] Read more.

Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies and lives as a woman. In recent decades, a significant increase in the number of transgender people has been reported. Although, its etiology is unknown, biological, anatomical, genetic, environmental and cultural factors have been suggested to contribute to gender variation. In XY animals, it has been shown that environmental endocrine disruptors, through their anti-androgenic activity, induce a female identity. In this work, we described four XY individuals who were exposed in utero to the xenoestrogen diethylstilbesterol (DES) and were part of the French HHORAGES cohort. They all reported a female transgender identity starting from childhood and adolescence. This high prevalence of male to female transgenderism (1.58%) in our cohort of 253 DES sons suggests that exposure to chemicals with xenoestrogen activity during fetal life may affect the male sex identity and behavior. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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36 pages, 2294 KiB

Open AccessEditor’s ChoiceReview

Bisphenol A (BPA) and Cardiovascular or Cardiometabolic Diseases

by Jeong-Hun Kang, Daisuke Asai and Riki Toita

J. Xenobiot. 2023, 13(4), 775-810; https://doi.org/10.3390/jox13040049 - 5 Dec 2023

Cited by 12 | Viewed by 4361

Abstract

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes [...] Read more.

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases. Full article

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14 pages, 2145 KiB

Open AccessEditor’s ChoiceArticle

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

by François Gagné, Eva Roubeau-Dumont, Chantale André and Joëlle Auclair

J. Xenobiot. 2023, 13(4), 761-774; https://doi.org/10.3390/jox13040048 - 5 Dec 2023

Cited by 5 | Viewed by 1750

Abstract

Plastic-based contamination has become a major cause of concern as it pervades many environments such as air, water, sediments, and soils. This study sought to examine the presence of microplastics (MPs) and nanoplastics (NPs) in freshwater mussels placed at rainfall/street runoff overflows, downstream [...] Read more.

Plastic-based contamination has become a major cause of concern as it pervades many environments such as air, water, sediments, and soils. This study sought to examine the presence of microplastics (MPs) and nanoplastics (NPs) in freshwater mussels placed at rainfall/street runoff overflows, downstream (15 km) of the city centre of Montréal, and 8 km downstream of a municipal effluent dispersion plume. MPs and NPs were determined using flow cytometry and size exclusion chromatography using fluorescence detection. Following 3 months of exposure during the summer season, mussels contained elevated amounts of both MPs and NPs. The rainfall overflow and downstream of the city centre were the most contaminated sites. Lipid peroxidation, metallothioneins, and protein aggregates (amyloids) were significantly increased at the most contaminated sites and were significantly correlated with NPs in tissues. Based on the levels of MPs and NPs in mussels exposed to municipal effluent, wastewater treatment plants appear to mitigate plastic contamination albeit not completely. In conclusion, the data support the hypothesis that mussels placed in urbanized areas are more contaminated by plastics, which are associated with oxidative damage. The highest responses observed at the overflow site suggest that tire wear and/or asphalt (road) erosion MPs/NPs represent important sources of contamination for the aquatic biota. Full article

(This article belongs to the Topic Plastics, Water-Soluble Polymers and Rubberized Materials: Ecotoxicological Aspects in the Aquatic Environments)

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32 pages, 2761 KiB

Open AccessEditor’s ChoiceReview

Microbial Exudates as Biostimulants: Role in Plant Growth Promotion and Stress Mitigation

by Mariya Ansari, B. Megala Devi, Ankita Sarkar, Anirudha Chattopadhyay, Lovkush Satnami, Pooraniammal Balu, Manoj Choudhary, Muhammad Adnan Shahid and A. Abdul Kader Jailani

J. Xenobiot. 2023, 13(4), 572-603; https://doi.org/10.3390/jox13040037 - 1 Oct 2023

Cited by 11 | Viewed by 4018

Abstract

Microbes hold immense potential, based on the fact that they are widely acknowledged for their role in mitigating the detrimental impacts of chemical fertilizers and pesticides, which were extensively employed during the Green Revolution era. The consequence of this extensive use has been [...] Read more.

Microbes hold immense potential, based on the fact that they are widely acknowledged for their role in mitigating the detrimental impacts of chemical fertilizers and pesticides, which were extensively employed during the Green Revolution era. The consequence of this extensive use has been the degradation of agricultural land, soil health and fertility deterioration, and a decline in crop quality. Despite the existence of environmentally friendly and sustainable alternatives, microbial bioinoculants encounter numerous challenges in real-world agricultural settings. These challenges include harsh environmental conditions like unfavorable soil pH, temperature extremes, and nutrient imbalances, as well as stiff competition with native microbial species and host plant specificity. Moreover, obstacles spanning from large-scale production to commercialization persist. Therefore, substantial efforts are underway to identify superior solutions that can foster a sustainable and eco-conscious agricultural system. In this context, attention has shifted towards the utilization of cell-free microbial exudates as opposed to traditional microbial inoculants. Microbial exudates refer to the diverse array of cellular metabolites secreted by microbial cells. These metabolites enclose a wide range of chemical compounds, including sugars, organic acids, amino acids, peptides, siderophores, volatiles, and more. The composition and function of these compounds in exudates can vary considerably, depending on the specific microbial strains and prevailing environmental conditions. Remarkably, they possess the capability to modulate and influence various plant physiological processes, thereby inducing tolerance to both biotic and abiotic stresses. Furthermore, these exudates facilitate plant growth and aid in the remediation of environmental pollutants such as chemicals and heavy metals in agroecosystems. Much like live microbes, when applied, these exudates actively participate in the phyllosphere and rhizosphere, engaging in continuous interactions with plants and plant-associated microbes. Consequently, they play a pivotal role in reshaping the microbiome. The biostimulant properties exhibited by these exudates position them as promising biological components for fostering cleaner and more sustainable agricultural systems. Full article

(This article belongs to the Special Issue Plant Biostimulants - a Promising Tool in Organic Farming)

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20 pages, 846 KiB

Open AccessEditor’s ChoiceReview

Indigo Carmine: Between Necessity and Concern

by Madalina-Elena Ristea and Otilia Zarnescu

J. Xenobiot. 2023, 13(3), 509-528; https://doi.org/10.3390/jox13030033 - 20 Sep 2023

Cited by 20 | Viewed by 6774

Abstract

Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum [...] Read more.

Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum permitted level is 500 mg/kg. Indigo carmine is one of the most used dyes in the textile industry, especially for dyeing denim, and it is also used in medicine due to its impressive applicability in diagnostic methods and surgical procedures, such as in gynecological and urological surgeries and microsurgery. It is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine; its use in various industries and medicine; the adverse effects of its ingestion, injection, or skin contact; the effects on environmental pollution; and its toxicity testing. For this review, 147 studies were considered relevant. Most of the cited articles were those about environmental pollution with indigo carmine (51), uses of indigo carmine in medicine (45), and indigo carmine as a food additive (17). Full article

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22 pages, 1070 KiB

Open AccessEditor’s ChoiceReview

Cytochrome P450 Gene Families: Role in Plant Secondary Metabolites Production and Plant Defense

by Panchali Chakraborty, Ashok Biswas, Susmita Dey, Tuli Bhattacharjee and Swapan Chakrabarty

J. Xenobiot. 2023, 13(3), 402-423; https://doi.org/10.3390/jox13030026 - 25 Jul 2023

Cited by 23 | Viewed by 7744

Abstract

Cytochrome P450s (CYPs) are the most prominent family of enzymes involved in NADPH- and O₂-dependent hydroxylation processes throughout all spheres of life. CYPs are crucial for the detoxification of xenobiotics in plants, insects, and other organisms. In addition to performing this [...] Read more.

Cytochrome P450s (CYPs) are the most prominent family of enzymes involved in NADPH- and O₂-dependent hydroxylation processes throughout all spheres of life. CYPs are crucial for the detoxification of xenobiotics in plants, insects, and other organisms. In addition to performing this function, CYPs serve as flexible catalysts and are essential for producing secondary metabolites, antioxidants, and phytohormones in higher plants. Numerous biotic and abiotic stresses frequently affect the growth and development of plants. They cause a dramatic decrease in crop yield and a deterioration in crop quality. Plants protect themselves against these stresses through different mechanisms, which are accomplished by the active participation of CYPs in several biosynthetic and detoxifying pathways. There are immense potentialities for using CYPs as a candidate for developing agricultural crop species resistant to biotic and abiotic stressors. This review provides an overview of the plant CYP families and their functions to plant secondary metabolite production and defense against different biotic and abiotic stresses. Full article

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19 pages, 769 KiB

Open AccessEditor’s ChoiceSystematic Review

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users

by Jonathan D. Vignali, Kevin C. Pak, Holly R. Beverley, Jesse P. DeLuca, John W. Downs, Adrian T. Kress, Brett W. Sadowski and Daniel J. Selig

J. Xenobiot. 2023, 13(2), 218-236; https://doi.org/10.3390/jox13020017 - 10 May 2023

Cited by 18 | Viewed by 10303

Abstract

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety [...] Read more.

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI. Full article

(This article belongs to the Section Drug Therapeutics)

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21 pages, 1838 KiB

Open AccessEditor’s ChoiceReview

Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier

by Carlos Martins-Gomes and Amélia M. Silva

J. Xenobiot. 2023, 13(2), 172-192; https://doi.org/10.3390/jox13020014 - 25 Mar 2023

Cited by 9 | Viewed by 3903

Abstract

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, [...] Read more.

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell’s defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters’ activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance. Full article

(This article belongs to the Special Issue Journal of Xenobiotics: Feature Papers)

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15 pages, 462 KiB

Open AccessEditor’s ChoiceArticle

Phytotherapy and Drugs: Can Their Interactions Increase Side Effects in Cancer Patients?

by Sarah Allegra, Silvia De Francia, Francesca Turco, Ilenia Bertaggia, Francesco Chiara, Tiziana Armando, Silvana Storto and Maria Valentina Mussa

J. Xenobiot. 2023, 13(1), 75-89; https://doi.org/10.3390/jox13010007 - 1 Feb 2023

Cited by 13 | Viewed by 4304

Abstract

Background: The use of herbs to treat illnesses was common in all historical eras. Our aim was to describe the phytotherapeutic substances that cancer patients use most commonly, and to determine whether their use can increase side effects. Methods: This was a retrospective [...] Read more.

Background: The use of herbs to treat illnesses was common in all historical eras. Our aim was to describe the phytotherapeutic substances that cancer patients use most commonly, and to determine whether their use can increase side effects. Methods: This was a retrospective and descriptive study conducted among older adults actively undergoing chemotherapy, admitted at the Oncology DH Unit (COES) of the Molinette Hospital AOU Città della Salute e della Scienza in Turin (Italy). Data collection was conducted through the distribution of self-compiled and closed-ended questionnaires during chemotherapy treatment. Results: A total of 281 patients were enrolled. Evaluating retching and sage consumption was statistically significant in multivariate analysis. The only risk factor for dysgeusia was chamomile consumption. Ginger, pomegranate, and vinegar use were retained as mucositis predictors. Conclusions: Phytotherapeutic use needs more attention in order to decrease the risks of side effects, toxicity, and ineffective treatment. The conscious administration of these substances should be promoted for safe use and to provide the reported benefits. Full article

(This article belongs to the Section Natural Products/Herbal Medicines)

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33 pages, 6178 KiB

Open AccessEditor’s ChoiceArticle

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

by Albert Stuart Reece and Gary Kenneth Hulse

J. Xenobiot. 2023, 13(1), 42-74; https://doi.org/10.3390/jox13010006 - 1 Feb 2023

Cited by 5 | Viewed by 2633

Abstract

Introduction. Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. Methods. CA data were [...] Read more.

Introduction. Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. Methods. CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank’s online sources. Results. On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies—orofacial clefts, anotia, congenital cataract, and holoprosencephaly—had positive and significant cannabis coefficients of p = 2.65 × 10⁻⁵, 1.04 × 10⁻⁸, 5.88 × 10⁻¹⁶, and 3.21 × 10⁻¹³, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10⁻⁹, 0.0011, 3.36 × 10⁻⁸, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range). Conclusion. Rising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration. Full article

(This article belongs to the Section Natural Products/Herbal Medicines)

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13 pages, 1293 KiB

Open AccessEditor’s ChoiceReview

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials

by Muhammad Ashar Ali, Muhammad Yasir Anwar, Wajeeha Aiman, Gurneel Dhanesar, Zainab Omar, Mohammad Hamza, Maha Zafar, Harish Kumar Rengarajan and Michael Maroules

J. Xenobiot. 2023, 13(1), 29-41; https://doi.org/10.3390/jox13010005 - 28 Jan 2023

Cited by 7 | Viewed by 3877

Abstract

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain [...] Read more.

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, “tyrosine kinase” and “idiopathic thrombocytopenic purpura”. PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP. Full article

(This article belongs to the Section Drug Therapeutics)

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23 pages, 1593 KiB

Open AccessEditor’s ChoiceReview

Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms

by Hong Lu

J. Xenobiot. 2022, 12(4), 266-288; https://doi.org/10.3390/jox12040019 - 21 Sep 2022

Cited by 6 | Viewed by 3787

Abstract

Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects [...] Read more.

Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients. Full article

(This article belongs to the Section Drug Therapeutics)

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33 pages, 1033 KiB

Open AccessEditor’s ChoiceReview

Endocrine-Disrupting Effects of Bisphenol A on the Cardiovascular System: A Review

by Maria Inês Fonseca, Margarida Lorigo and Elisa Cairrao

J. Xenobiot. 2022, 12(3), 181-213; https://doi.org/10.3390/jox12030015 - 13 Jul 2022

Cited by 40 | Viewed by 7935

Abstract

Currently, the plastic monomer and plasticizer bisphenol A (BPA) is one of the most widely used chemicals. BPA is present in polycarbonate plastics and epoxy resins, commonly used in food storage and industrial or medical products. However, the use of this synthetic compound [...] Read more.

Currently, the plastic monomer and plasticizer bisphenol A (BPA) is one of the most widely used chemicals. BPA is present in polycarbonate plastics and epoxy resins, commonly used in food storage and industrial or medical products. However, the use of this synthetic compound is a growing concern, as BPA is an endocrine-disrupting compound and can bind mainly to estrogen receptors, interfering with different functions at the cardiovascular level. Several studies have investigated the disruptive effects of BPA; however, its cardiotoxicity remains unclear. Therefore, this review’s purpose is to address the most recent studies on the implications of BPA on the cardiovascular system. Our findings suggest that BPA impairs cardiac excitability through intracellular mechanisms, involving the inhibition of the main ion channels, changes in Ca²⁺ handling, the induction of oxidative stress, and epigenetic modifications. Our data support that BPA exposure increases the risk of developing cardiovascular diseases (CVDs) including atherosclerosis and its risk factors such as hypertension and diabetes. Furthermore, BPA exposure is also particularly harmful in pregnancy, promoting the development of hypertensive disorders during pregnancy. In summary, BPA exposure compromises human health, promoting the development and progression of CVDs and risk factors. Further studies are needed to clarify the human health effects of BPA-induced cardiotoxicity. Full article

(This article belongs to the Section Emerging Chemicals)

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13 pages, 1722 KiB

Open AccessEditor’s ChoiceArticle

Isolation and Quantification of Polystyrene Nanoplastics in Tissues by Low Pressure Size Exclusion Chromatography

by François Gagné

J. Xenobiot. 2022, 12(2), 109-121; https://doi.org/10.3390/jox12020010 - 9 May 2022

Cited by 12 | Viewed by 3649

Abstract

Ecotoxicity investigations of plastic nanoparticles (NPs) should pay more attention to their ability to pass barriers, accumulate, and initiate toxicity in cells. The purpose of this study was to develop a simple size exclusion chromatography (SEC) methodology to measure plastic NPs in biological [...] Read more.

Ecotoxicity investigations of plastic nanoparticles (NPs) should pay more attention to their ability to pass barriers, accumulate, and initiate toxicity in cells. The purpose of this study was to develop a simple size exclusion chromatography (SEC) methodology to measure plastic NPs in biological tissues. A SEC column was prepared using a high-resolution gel for large macromolecules to separate plastic NPs from the protein/lipid pools in tissues. It was necessary to prepare the samples in high salt and non-ionic detergent (0.5 M NaCl and 0.2% Tween-20) and apply 0.2% Tween-20 containing 14 mM NaCl for the elution buffer to limit proteins adsorption to NPs. This methodology was able to resolve 50 and 100 nm polystyrene NPs from the protein/lipid pools in tissue homogenates. The fluorescent dye neutral red (NR) was also used for transparent NPs. Moreover, a sample fractionation step was also proposed for plastic NPs concentration using a salting-out methodology with saturated NaCl (5 M) and acetonitrile. Polystyrene NPs partition in acetonitrile, which were further analyzed by SEC. This methodology was tested in two case studies with clams collected in a high boat traffic (harbor) area and with caged freshwater mussels downstream of a large urban area. Although the present methodology was developed with polystyrene NPs it should be amenable to other plastic polymers that react with the NR fluorescent probe. Full article

(This article belongs to the Topic Aquatic Emerging Contaminants and Their Ecotoxicological Consequences)

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12 pages, 834 KiB

Open AccessEditor’s ChoiceReview

Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?

by Maurizio Coppola, Francesco Bevione and Raffaella Mondola

J. Xenobiot. 2022, 12(1), 41-52; https://doi.org/10.3390/jox12010004 - 7 Feb 2022

Cited by 14 | Viewed by 10037

Abstract

Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. In 1957, Dr. Hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although there were limitations related to the [...] Read more.

Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. In 1957, Dr. Hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although there were limitations related to the scientific design of many studies, clinical observations performed during the 1950s and 1960s showed a potential therapeutic effect of psilocybin for patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination with psychedelics has remained almost unchanged over time, promoting a new scientific interest starting in the 1990s. Recent studies have provided further evidence supporting the suggestive hypothesis of the therapeutic use of psilocybin for treating various psychiatric disorders, including pathological anxiety, mood depressive disorder, and addiction. Full article

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20 pages, 521 KiB

Open AccessEditor’s ChoiceReview

Glyphosate vs. Glyphosate-Based Herbicides Exposure: A Review on Their Toxicity

by Carlos Martins-Gomes, Tânia L. Silva, Tatiana Andreani and Amélia M. Silva

J. Xenobiot. 2022, 12(1), 21-40; https://doi.org/10.3390/jox12010003 - 17 Jan 2022

Cited by 65 | Viewed by 10989

Abstract

Glyphosate-based herbicide has been the first choice for weed management worldwide since the 1970s, mainly due to its efficacy and reported low toxicity, which contributed to its high acceptance. Many of the recent studies focus solely on the persistence of pesticides in soils, [...] Read more.

Glyphosate-based herbicide has been the first choice for weed management worldwide since the 1970s, mainly due to its efficacy and reported low toxicity, which contributed to its high acceptance. Many of the recent studies focus solely on the persistence of pesticides in soils, air, water or food products, or even on the degree of exposure of animals, since their potential hazards to human health have raised concerns. Given the unaware exposure of the general population to pesticides, and the absence of a significant number of studies on occupational hazards, new glyphosate-induced toxicity data obtained for both residual and acute doses should be analyzed and systematized. Additionally, recent studies also highlight the persistence and toxicity of both glyphosate metabolites and surfactants present in herbicide formulations. To renew or ban the use of glyphosate, recently published studies must be taken into account, aiming to define new levels of safety for exposure to herbicide, its metabolites, and the toxic excipients of its formulations. This review aims to provide an overview of recent publications (2010–present) on in vitro and in vivo studies aimed at verifying the animal toxicity induced by glyphosate, its metabolite aminomethylphosphonic acid (AMPA) and glyphosate-based formulations, evaluated in various experimental models. Apart from glyphosate-induced toxicity, recent data concerning the role of surfactants in the toxicity of glyphosate-based formulations are discussed. Full article

(This article belongs to the Special Issue Xenobiotics as Emerging Environmental Contaminants)

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12 pages, 302 KiB

Open AccessEditor’s ChoiceReview

Non-Negligible Effects of UV Irradiation on Transformation and Environmental Risks of Microplastics in the Water Environment

by Fangyuan Cheng, Tingting Zhang, Yue Liu, Yanan Zhang and Jiao Qu

J. Xenobiot. 2022, 12(1), 1-12; https://doi.org/10.3390/jox12010001 - 21 Dec 2021

Cited by 26 | Viewed by 6268

Abstract

Microplastics (MPs) are ubiquitous in environmental media, and their harmful effects on MPs on the ecosystem have attracted more and more attention. Once released into the environment, MPs can trigger oxidative degradation through ultraviolet (UV) to cause photoaging. Photoaging significantly affects the properties [...] Read more.

Microplastics (MPs) are ubiquitous in environmental media, and their harmful effects on MPs on the ecosystem have attracted more and more attention. Once released into the environment, MPs can trigger oxidative degradation through ultraviolet (UV) to cause photoaging. Photoaging significantly affects the properties of MPs, which leads to changing their environmental behaviors and increasing environmental risks. In this review, the generation of MPs under UV irradiation and the influence of environmental factors on the photoaging of MPs were discussed. Photoaging of MPs is an important process affecting the migration, transformation and interaction of pollutants in water and soil. In order to fully predict the fate and environmental interaction of MPs, more researches are needed in the future to explore the photoaging behavior of different types of MPs under natural environmental conditions. Full article

(This article belongs to the Special Issue Xenobiotics as Emerging Environmental Contaminants)

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