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Toxicology of Xenobiotic Mixtures and Health
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Toxicology of Xenobiotic Mixtures and Health

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 33423

Special Issue Editors

Prof. Dr. David R. Wallace

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Guest Editor
Department of Pharmacology & Physiology, School of Biomedical Science, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107-1898, USA
Interests: pancreatic cancer; environmental toxicants; mitochondrial toxicity; apoptosis; cellular regulation; tryptophan-kynurenine pathway; indoleamine 2,3-dioxygenase
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ashok Vaseashta

E-Mail Website
Guest Editor
Applied Research, International Clean Water Institute, Manassas, VA, USA
Interests: water; risk assessment; nanotechnology; sensors; cyber-physical systems; IoTs; AI; foresight
Special Issues, Collections and Topics in MDPI journals
Dr. Aleksandra Buha Djordjevic

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Guest Editor
Department of Toxicology, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, Serbia
Interests: toxicology of mixtures; endocrine disrupting chemicals; human health risk assessment; chemical carcinogenicity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Today, society is exposed to hundreds of various agents in the form of particulate matter (nanoparticles), gases and vapors (air pollution), water pollution, multiple drugs and chemicals that have been either reported to be toxic or just suspected of being toxic (water pollution, food contamination, etc.). These confirmed or alleged toxicants can enter the body via inhalation of dust, ingestion of contaminated water, or consumption of foods or crops which are contaminated. The importance of the toxicological study of mixtures cannot be understated. Multiple scientific committees of the European Commission have concluded that understanding the toxicology of chemical mixtures is vital to human health. The Environmental Protection Agency and the Food and Drug Administration in the United States have echoed these sentiments, calling for increased funding and research on the toxicology of mixtures. Exposures to multiple chemicals, even at concentrations well below the toxic threshold for individual compounds, could have robust effects on health after long-term exposure. Major concerns linked to the exposure to multiple chemicals regard: a) Chemical interaction between agents that may alter the reported functioning of the individual chemicals, b) Combinations of agents that may cause effects classified as potentiating, additive, synergistic, or even antagonistic, leading to unforeseen health outcomes, and c) Mechanisms of action of different chemical classes, many of which are unknown, making the prediction of their health effects difficult if not impossible.

Over the last five years, there has been an increased interest in the toxicology of mixtures, as indicated by special editions on multiple environmental exposures and, more specifically, on their effects on children’s health. For this Special Issue on “Toxicology of Xenobiotic Mixtures and Health” in the International Journal of Environmental Research and Public Health, we are interested in broad-scope original research, case studies, and review articles examining the effect of xenobiotic mixtures (chemicals, drugs, environmental toxicants, etc.) on health. Submissions can focus on naturally occurring or man-made agents as long as the focus of the research report is the toxicology of combined mixture(s). The goal of this Special Issue is to compile a repository of current, diverse works investigating the various health effects associated with the exposure to combinations and mixtures of multiple agents.

Prof. David R. Wallace
Prof. Ashok Vaseashta
Assoc. Prof. Aleksandra Buha
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Environmental Research and Public Health is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (4 papers)

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Research

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19 pages, 2660 KiB  
Article
Developmental Neurotoxicity of Environmentally Relevant Pharmaceuticals and Mixtures Thereof in a Zebrafish Embryo Behavioural Test
by Alessandro Atzei, Ingrid Jense, Edwin P. Zwart, Jessica Legradi, Bastiaan J. Venhuis, Leo T.M. van der Ven, Harm J. Heusinkveld and Ellen V.S. Hessel
Int. J. Environ. Res. Public Health 2021, 18(13), 6717; https://doi.org/10.3390/ijerph18136717 - 22 Jun 2021
Cited by 23 | Viewed by 3944
Abstract
Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in [...] Read more.
Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance. There is a need for a combination of in vitro and in silico tests for the assessment of chemically induced DNT in humans. The zebrafish (Danio rerio) embryo (ZFE) provides a powerful model to study DNT because it shows fast neurodevelopment with a large resemblance to the higher vertebrate, including the human system. One of the suitable readouts for DNT testing in the zebrafish is neurobehaviour (stimulus-provoked locomotion) since this provides integrated information on the functionality and status of the entire nervous system of the embryo. In the current study, environmentally relevant pharmaceuticals and their mixtures were investigated using the zebrafish light-dark transition test. Zebrafish embryos were exposed to three neuroactive compounds of concern, carbamazepine (CBZ), fluoxetine (FLX), and venlafaxine (VNX), as well as their main metabolites, carbamazepine 10,11-epoxide (CBZ 10,11E), norfluoxetine (norFLX), and desvenlafaxine (desVNX). All the studied compounds, except CBZ 10,11E, dose-dependently inhibited zebrafish locomotor activity, providing a distinct behavioural phenotype. Mixture experiments with these pharmaceuticals identified that dose addition was confirmed for all the studied binary mixtures (CBZ-FLX, CBZ-VNX, and VNX-FLX), thereby supporting the zebrafish embryo as a model for studying the cumulative effect of chemical mixtures in DNT. This study shows that pharmaceuticals and a mixture thereof affect locomotor activity in zebrafish. The test is directly applicable in environmental risk assessment; however, further studies are required to assess the relevance of these findings for developmental neurotoxicity in humans. Full article
(This article belongs to the Special Issue Toxicology of Xenobiotic Mixtures and Health)
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24 pages, 1724 KiB  
Article
Toxic Effects of the Mixture of Phthalates and Bisphenol A—Subacute Oral Toxicity Study in Wistar Rats
by Katarina Baralić, Aleksandra Buha Djordjevic, Katarina Živančević, Evica Antonijević, Milena Anđelković, Dragana Javorac, Marijana Ćurčić, Zorica Bulat, Biljana Antonijević and Danijela Đukić-Ćosić
Int. J. Environ. Res. Public Health 2020, 17(3), 746; https://doi.org/10.3390/ijerph17030746 - 23 Jan 2020
Cited by 49 | Viewed by 6586
Abstract
Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate [...] Read more.
Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA)) with the effects of their mixture through different biochemical, hormonal, and hematological parameters. Rats were divided into five experimental groups: Control (corn oil), DEHP (50 mg/kg b.w./day), DBP (50 mg/kg b.w./day), BPA (25 mg/kg b.w./day), and MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral treatment and blood was collected for further analysis. The results demonstrated that the mixture produced significant changes in lipid profile, liver-related biochemical parameters, and glucose level. Furthermore, the opposite effects of single substances on the thyroxine level have been shown in comparison with the mixture, as well as a more pronounced effect of the mixture on testosterone level. This study contributes to the body of knowledge on the toxicology of mixtures and gives one more evidence of the paramount importance of mixture toxicity studies, especially in assessing the endocrine disruptive effects of chemicals. Full article
(This article belongs to the Special Issue Toxicology of Xenobiotic Mixtures and Health)
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Review

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27 pages, 1776 KiB  
Review
Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors
by Denisa Margină, Anca Ungurianu, Carmen Purdel, Dimitris Tsoukalas, Evangelia Sarandi, Maria Thanasoula, Fotios Tekos, Robin Mesnage, Demetrios Kouretas and Aristidis Tsatsakis
Int. J. Environ. Res. Public Health 2020, 17(11), 4135; https://doi.org/10.3390/ijerph17114135 - 10 Jun 2020
Cited by 80 | Viewed by 16893
Abstract
The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such [...] Read more.
The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kβ (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases. Full article
(This article belongs to the Special Issue Toxicology of Xenobiotic Mixtures and Health)
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11 pages, 741 KiB  
Review
Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies
by Jan Aaseth, Aleksandra Buha, David R. Wallace and Geir Bjørklund
Int. J. Environ. Res. Public Health 2020, 17(4), 1269; https://doi.org/10.3390/ijerph17041269 - 17 Feb 2020
Cited by 7 | Viewed by 4699
Abstract
Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records [...] Read more.
Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies. Full article
(This article belongs to the Special Issue Toxicology of Xenobiotic Mixtures and Health)
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