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Toxics, Volume 3, Issue 4 (December 2015), Pages 342-514

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Open AccessArticle The Role of the Component Metals in the Toxicity of Military-Grade Tungsten Alloy
Toxics 2015, 3(4), 499-514; https://doi.org/10.3390/toxics3040499
Received: 9 November 2015 / Revised: 1 December 2015 / Accepted: 2 December 2015 / Published: 8 December 2015
Cited by 2 | PDF Full-text (1420 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tungsten-based composites have been recommended as a suitable replacement for depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W), nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg muscle of laboratory rats and mice to simulate a shrapnel
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Tungsten-based composites have been recommended as a suitable replacement for depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W), nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg muscle of laboratory rats and mice to simulate a shrapnel wound. The question arose as to whether the neoplastic effect of the mixture could be solely attributed to one or more of the metal components. To investigate this possibility, pellets with one or two of the component metals replaced with an identical amount of the biologically-inert metal tantalum (Ta) were manufactured and implanted into the quadriceps of B6C3F1 mice. The mice were followed for two years to assess potential adverse health effects. Implantation with WTa, CoTa or WNiTa resulted in decreased survival, but not to the level reported for WNiCo. Sarcomas in the implanted muscle were found in 20% of the CoTa-implanted mice and 5% of the WTa- and WCoTa-implanted rats and mice, far below the 80% reported for WNiCo-implanted mice. The data obtained from this study suggested that no single metal is solely responsible for the neoplastic effects of WNiCo and that a synergistic effect of the three metals in tumor development was likely. Full article
(This article belongs to the collection Heavy Metals Toxicology)
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Open AccessReview Oxyradical Stress, Endocannabinoids, and Atherosclerosis
Toxics 2015, 3(4), 481-498; https://doi.org/10.3390/toxics3040481
Received: 24 September 2015 / Revised: 16 November 2015 / Accepted: 23 November 2015 / Published: 3 December 2015
Cited by 12 | PDF Full-text (950 KB) | HTML Full-text | XML Full-text
Abstract
Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease
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Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG). Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology. Full article
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Open AccessReview Glyphosate in Runoff Waters and in the Root-Zone: A Review
Toxics 2015, 3(4), 462-480; https://doi.org/10.3390/toxics3040462
Received: 24 September 2015 / Revised: 8 November 2015 / Accepted: 10 November 2015 / Published: 26 November 2015
Cited by 5 | PDF Full-text (684 KB) | HTML Full-text | XML Full-text
Abstract
Glyphosate is the most commonly-used herbicide in the world. The present review summarizes the discovery, prevalence, chemical and physical properties, mode of action and effects in plants, glyphosate resistance and the environmental fate of glyphosate. Numerous studies are reviewed that demonstrate that glyphosate
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Glyphosate is the most commonly-used herbicide in the world. The present review summarizes the discovery, prevalence, chemical and physical properties, mode of action and effects in plants, glyphosate resistance and the environmental fate of glyphosate. Numerous studies are reviewed that demonstrate that glyphosate may run off of fields where it is applied, while other studies provide evidence that plant roots can take up glyphosate. Non-target vegetation may be exposed to glyphosate in the root-zone, where it has the potential to remove aqueous glyphosate from the system. Further study on the effects of root-zone glyphosate on non-target vegetation is required to develop best management practices for land managers seeking to ameliorate the effects of root-zone glyphosate exposure. Full article
(This article belongs to the collection Risk Assessment of Pesticide Exposure)
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Open AccessCommunication Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression
Toxics 2015, 3(4), 451-461; https://doi.org/10.3390/toxics3040451
Received: 4 September 2015 / Accepted: 11 November 2015 / Published: 19 November 2015
Cited by 10 | PDF Full-text (516 KB) | HTML Full-text | XML Full-text
Abstract
Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and
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Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time. Full article
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Open AccessReview Atrazine Exposure and Reproductive Dysfunction through the Hypothalamus-Pituitary-Gonadal (HPG) Axis
Toxics 2015, 3(4), 414-450; https://doi.org/10.3390/toxics3040414
Received: 6 August 2015 / Revised: 23 September 2015 / Accepted: 22 October 2015 / Published: 2 November 2015
Cited by 7 | PDF Full-text (1077 KB) | HTML Full-text | XML Full-text
Abstract
Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the
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Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG) axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L) in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies. Full article
(This article belongs to the collection Risk Assessment of Pesticide Exposure)
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Open AccessReview Nanotoxicology and Metalloestrogens: Possible Involvement in Breast Cancer
Toxics 2015, 3(4), 390-413; https://doi.org/10.3390/toxics3040390
Received: 14 July 2015 / Revised: 22 October 2015 / Accepted: 23 October 2015 / Published: 28 October 2015
Cited by 5 | PDF Full-text (663 KB) | HTML Full-text | XML Full-text
Abstract
As the use of nanotechnology has expanded, an increased number of metallic oxides have been manufactured, yet toxicology testing has lagged significantly. Metals used in nano-products include titanium, silicon, aluminum, silver, zinc, cadmium, cobalt, antimony, gold, etc. Even the noble metals, platinum and
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As the use of nanotechnology has expanded, an increased number of metallic oxides have been manufactured, yet toxicology testing has lagged significantly. Metals used in nano-products include titanium, silicon, aluminum, silver, zinc, cadmium, cobalt, antimony, gold, etc. Even the noble metals, platinum and cerium, have been used as a treatment for cancer, but the toxicity of these metals is still unknown. Significant advances have been made in our understanding and treatment of breast cancer, yet millions of women will experience invasive breast cancer in their lifetime. The pathogenesis of breast cancer can involve multiple factors; (1) genetic; (2) environmental; and (3) lifestyle-related factors. This review focuses on exposure to highly toxic metals, (“metalloestrogens” or “endocrine disruptors”) that are used as the metallic foundation for nanoparticle production and are found in a variety of consumer products such as cosmetics, household items, and processed foods, etc. The linkage between well-understood metalloestrogens such as cadmium, the use of these metals in the production of nanoparticles, and the relationship between their potential estrogenic effects and the development of breast cancer will be explored. This will underscore the need for additional testing of materials used in nano-products. Clearly, a significant amount of work needs to be done to further our understanding of these metals and their potential role in the pathogenesis of breast cancer. Full article
(This article belongs to the collection Environmental and Health Risks of Nanotechnology)
Open AccessArticle Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide
Toxics 2015, 3(4), 373-389; https://doi.org/10.3390/toxics3040373
Received: 10 August 2015 / Revised: 7 October 2015 / Accepted: 9 October 2015 / Published: 15 October 2015
Cited by 6 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male
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Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g) were randomized into four groups (I–IV). Group I (control) received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats. Full article
(This article belongs to the collection Risk Assessment of Pesticide Exposure)
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Open AccessEditorial Current State of Developmental Neurotoxicology Research
Toxics 2015, 3(4), 370-372; https://doi.org/10.3390/toxics3040370
Received: 25 September 2015 / Revised: 29 September 2015 / Accepted: 29 September 2015 / Published: 1 October 2015
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Abstract
We have been witness to significant research advances in areas such as neuroscience, neurodegeneration, cancer therapy, etc., yet, investigation in developmental neurotoxicology (DNT) has fallen behind [1]. [...] Full article
(This article belongs to the Special Issue Developmental Neurotoxicology)
Open AccessReview Additivity and Interactions in Ecotoxicity of Pollutant Mixtures: Some Patterns, Conclusions, and Open Questions
Toxics 2015, 3(4), 342-369; https://doi.org/10.3390/toxics3040342
Received: 29 June 2015 / Revised: 9 September 2015 / Accepted: 23 September 2015 / Published: 25 September 2015
Cited by 9 | PDF Full-text (525 KB) | HTML Full-text | XML Full-text
Abstract
Understanding the effects of exposure to chemical mixtures is a common goal of pharmacology and ecotoxicology. In risk assessment-oriented ecotoxicology, defining the scope of application of additivity models has received utmost attention in the last 20 years, since they potentially allow one to
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Understanding the effects of exposure to chemical mixtures is a common goal of pharmacology and ecotoxicology. In risk assessment-oriented ecotoxicology, defining the scope of application of additivity models has received utmost attention in the last 20 years, since they potentially allow one to predict the effect of any chemical mixture relying on individual chemical information only. The gold standard for additivity in ecotoxicology has demonstrated to be Loewe additivity which originated the so-called Concentration Addition (CA) additivity model. In pharmacology, the search for interactions or deviations from additivity (synergism and antagonism) has similarly captured the attention of researchers over the last 20 years and has resulted in the definition and application of the Combination Index (CI) Theorem. CI is based on Loewe additivity, but focused on the identification and quantification of synergism and antagonism. Despite additive models demonstrating a surprisingly good predictive power in chemical mixture risk assessment, concerns still exist due to the occurrence of unpredictable synergism or antagonism in certain experimental situations. In the present work, we summarize the parallel history of development of CA, IA, and CI models. We also summarize the applicability of these concepts in ecotoxicology and how their information may be integrated, as well as the possibility of prediction of synergism. Inside the box, the main question remaining is whether it is worthy to consider departures from additivity in mixture risk assessment and how to predict interactions among certain mixture components. Outside the box, the main question is whether the results observed under the experimental constraints imposed by fractional approaches are a de fide reflection of what it would be expected from chemical mixtures in real world circumstances. Full article
(This article belongs to the Special Issue Effects of Mixtures on Ecosystems)
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