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Toxics (ISSN 2305-6304; CODEN: TOXIC8) is an international peer-reviewed open access journal on all aspects of toxics, published quarterly online by MDPI.
- Open Access - free for readers, with article processing charges (APC) paid by authors or their institutions.
- High visibility: Indexed in the Emerging Sources Citation Index (ESCI - Web of Science). Covered in Scopus from Vol. 5 (2017) and in Chemical Abstracts / SciFinder. Citations available in PubMed, full-text archived in PubMed Central from Vol. 3.
- Rapid publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 17 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in the first six months of 2018).
- Recognition of reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Latest Articles
Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats
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Toxics 2018, 6(4), 71; https://doi.org/10.3390/toxics6040071 - 1 December 2018
Abstract
The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic
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The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.
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Optimization of Sample Preparation for Detection of 10 Phthalates in Non-Alcoholic Beverages in Northern Vietnam
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Toxics 2018, 6(4), 69; https://doi.org/10.3390/toxics6040069 - 19 November 2018
Abstract
A novel method was developed for the sensitive, cheap and fast quantitation of 10 phthalates in non-alcoholic beverages by liquid–liquid extraction (LLE) combined with gas chromatography tandem mass spectrometry (GC-MS/MS). The best results were obtained when n-hexane was used as extraction solvent.
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A novel method was developed for the sensitive, cheap and fast quantitation of 10 phthalates in non-alcoholic beverages by liquid–liquid extraction (LLE) combined with gas chromatography tandem mass spectrometry (GC-MS/MS). The best results were obtained when n-hexane was used as extraction solvent. A central composite design (CCD) was applied to select the most appreciated operating condition. The method performance was evaluated according to the SANTE/11945/2015 guidelines and was linear in the 0.1 to 200 µg/L range for 10 phthalate compounds, with r2 > 0.996 and individual residuals <15%. Repeatability (RSDr), within-laboratory reproducibility (RSDwr), and the trueness range were from 2.7 to 9.1%, from 3.4 to 14.3% and from 91.5 to 118.1%, respectively. The limit of detection (LOD) was between 0.5 to 1.0 ng/L and the limit of quantitation (LOQ) was between 1.5 to 3.0 ng/L for all 10 compounds. The developed method was successfully applied to the analysis of non-alcoholic beverages.
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Impact of Maternal Air Pollution Exposure on Children’s Lung Health: An Indian Perspective
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Toxics 2018, 6(4), 68; https://doi.org/10.3390/toxics6040068 - 16 November 2018
Abstract
Air pollution has become an emerging invisible killer in recent years and is a major cause of morbidity and mortality globally. More than 90% of the world’s children breathe toxic air every day. India is among the top ten most highly polluted countries
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Air pollution has become an emerging invisible killer in recent years and is a major cause of morbidity and mortality globally. More than 90% of the world’s children breathe toxic air every day. India is among the top ten most highly polluted countries with an average PM10 level of 134 μg/m3 per year. It is reported that 99% of India’s population encounters air pollution levels that exceed the World Health Organization Air Quality Guideline, advising a PM2.5 permissible level of 10 μg/m3. Maternal exposure to air pollution has serious health outcomes in offspring because it can affect embryonic phases of development during the gestation period. A fetus is more prone to effects from air pollution during embryonic developmental phases due to resulting oxidative stress as antioxidant mechanisms are lacking at that stage. Any injury during this vulnerable period (embryonic phase) will have a long-term impact on offspring health, both early and later in life. Epidemiological studies have revealed that maternal exposure to air pollution increases the risk of development of airway disease in the offspring due to impaired lung development in utero. In this review, we discuss cellular mechanisms involved in maternal exposure to air pollution and how it can impact airway disease development in offspring. A better understanding of these mechanisms in the context of maternal exposure to air pollution can offer a new avenue to prevent the development of airway disease in offspring.
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Comparative Assessment of Tungsten Toxicity in the Absence or Presence of Other Metals
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Toxics 2018, 6(4), 66; https://doi.org/10.3390/toxics6040066 - 9 November 2018
Abstract
Tungsten is a refractory metal that is used in a wide range of applications. It was initially perceived that tungsten was immobile in the environment, supporting tungsten as an alternative for lead and uranium in munition and military applications. Recent studies report movement
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Tungsten is a refractory metal that is used in a wide range of applications. It was initially perceived that tungsten was immobile in the environment, supporting tungsten as an alternative for lead and uranium in munition and military applications. Recent studies report movement and detection of tungsten in soil and potable water sources, increasing the risk of human exposure. In addition, experimental research studies observed adverse health effects associated with exposure to tungsten alloys, raising concerns on tungsten toxicity with questions surrounding the safety of exposure to tungsten alone or in mixtures with other metals. Tungsten is commonly used as an alloy with nickel and cobalt in many applications to adjust hardness and thermal and electrical conductivity. This review addresses the current state of knowledge in regard to the mechanisms of toxicity of tungsten in the absence or presence of other metals with a specific focus on mixtures containing nickel and cobalt, the most common components of tungsten alloy.
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Heavy Metal Mixture Exposure and Effects in Developing Nations: An Update
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Toxics 2018, 6(4), 65; https://doi.org/10.3390/toxics6040065 - 2 November 2018
Abstract
The drive for development and modernization has come at great cost. Various human activities in developed and developing countries, particularly in sub-Saharan Africa (SSA) have given rise to environmental safety concerns. Increased artisanal mining activities, illegal refining, use of leaded petrol, airborne dust,
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The drive for development and modernization has come at great cost. Various human activities in developed and developing countries, particularly in sub-Saharan Africa (SSA) have given rise to environmental safety concerns. Increased artisanal mining activities, illegal refining, use of leaded petrol, airborne dust, arbitrary discarding and burning of toxic waste, absorption of production industries in inhabited areas, inadequate environmental legislation, and weak implementation of policies, have given rise to the incomparable contamination and pollution associated with heavy metals in recent decades. This review evaluates the public health effects of heavy metals and their mixtures in SSA. This shows the extent and size of the problem posed by exposure to heavy metal mixtures in regard to public health.
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Pressurized Solvent Extraction with Ethyl Acetate and Liquid Chromatography—Tandem Mass Spectrometry for the Analysis of Selected Conazole Fungicides in Matcha
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Toxics 2018, 6(4), 64; https://doi.org/10.3390/toxics6040064 - 25 October 2018
Abstract
The extraction of powdered nutraceuticals is challenging due to the low water content and high concentration of matrix components that can lead to significant matrix effects in liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry (LC-ESI+-MS/MS). In this study we assess the
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The extraction of powdered nutraceuticals is challenging due to the low water content and high concentration of matrix components that can lead to significant matrix effects in liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry (LC-ESI+-MS/MS). In this study we assess the feasibility of using pressurized solvent extraction with ethyl acetate to reduce the co-extraction of polar matrix components. Pigment attributed to chlorophyll was removed with in-cell clean-up utilizing Anasorb 747, Florisil®, and C18. Visible inspection of the extracts showed that pigment was removed from matcha, a powdered green tea sample. Pressurized solvent extraction with in-cell clean-up can be utilized to remove pigments from powdered samples such as nutraceuticals. Average matrix effect of the 32 target analytes that observed mass spectrometric signal suppression or soft MS signal enhancement was −41 ± 19% with the majority of analytes having a protonated molecular ion with m/z of 250 to 412. As generally moderate signal suppression was observed for conazole fungicides and structurally related compounds analyzed by LC-ESI+-MS/MS, it is recommended that matrix matched or standard addition calibration is used for quantitation. Catachins, other polyphenols, and caffeine are expected to contribute to the matrix effects observed in LC-ESI+-MS/MS. Diniconazole, fenbuconazole, and tebufenozide were the only target analytes with severe MS signal enhancement. Low levels (0.002–0.004 mg/kg) of prothioconazole-desthio and flusilazole were detected, along with trace levels of tebuthiuron in matcha.
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Toxic Effect of Cigarette Smoke on Brainstem Nicotinic Receptor Expression: Primary Cause of Sudden Unexplained Perinatal Death
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Toxics 2018, 6(4), 63; https://doi.org/10.3390/toxics6040063 - 18 October 2018
Abstract
Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples
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Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples from 68 fetuses and early newborns, with smoking and non-smoking mothers, who died of known and unknown causes, were carried out in order to determine if nicotine had activated the α7-nicotinic acetylcholine receptors. High α7-nicotinic acetylcholine receptor expression levels were only observed in the victims with smoking mothers. Frequently, these findings were associated with the hypoplasia of the brainstem structures controlling vital functions. The results of this study indicate that the exposition to nicotine in pregnancy exerts a strong direct effect on α7-nicotinic acetylcholine receptor activity especially in perinatal life and may be one of the primary risk factors leading to the sudden unexplained death of fetuses and newborns.
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The Toxicity Assessment of Iron Oxide (Fe3O4) Nanoparticles on Physical and Biochemical Quality of Rainbow Trout Spermatozoon
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Toxics 2018, 6(4), 62; https://doi.org/10.3390/toxics6040062 - 18 October 2018
Abstract
The aim of this study was to evaluate the in vitro effect of different doses (50, 100, 200, 400, and 800 mg/L) of Fe3O4 nanoparticles (NPs) at 4 °C for 24 h on the kinematics of rainbow trout (Oncorhynchus
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The aim of this study was to evaluate the in vitro effect of different doses (50, 100, 200, 400, and 800 mg/L) of Fe3O4 nanoparticles (NPs) at 4 °C for 24 h on the kinematics of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) spermatozoon. Firstly, Fe3O4 NPs were prepared at about 30 nm from Iron (III) chloride, Iron (II) chloride, and NH3 via a co-precipitation synthesis technique. Then, the prepared Fe3O4 NPs were characterized by different instrumental techniques for their chemical structure, purity, morphology, surface properties, and thermal behavior. The size, microstructure, and morphology of the prepared Fe3O4 NPs were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) spectroscopy, and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS). The thermal properties of the Fe3O4 NPs were determined with thermogravimetric analysis (TGA), differential thermal analysis (DTA), and differential scanning calorimeter (DSC) analysis techniques. According to our results, there were statistically significant (p < 0.05) decreases in the velocities of spermatozoon after treatment with 400 mg/L Fe3O4 NPs. The superoxide dismutase (SOD) and catalase (CAT) activities were significant (p < 0.05) decrease after 100 mg/L in after exposure to Fe3O4 NPs in 24 h. As the doses of Fe3O4 NPs increases, the level of malondialdehyde (MDA) and total glutathione (tGSH) significantly (p < 0.05) increased at doses of 400 and 800 mg/L.
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Sub-Nanomolar Methylmercury Exposure Promotes Premature Differentiation of Murine Embryonic Neural Precursor at the Expense of Their Proliferation
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Toxics 2018, 6(4), 61; https://doi.org/10.3390/toxics6040061 - 10 October 2018
Abstract
Methylmercury (MeHg) is a ubiquitous environmental pollutant that is known to be neurotoxic, particularly during fetal development. However, the mechanisms responsible for MeHg-induced changes in adult neuronal function, when their exposure occurred primarily during fetal development, are not yet understood. We hypothesized that
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Methylmercury (MeHg) is a ubiquitous environmental pollutant that is known to be neurotoxic, particularly during fetal development. However, the mechanisms responsible for MeHg-induced changes in adult neuronal function, when their exposure occurred primarily during fetal development, are not yet understood. We hypothesized that fetal MeHg exposure could affect neural precursor development leading to long-term neurotoxic effects. Primary cortical precursor cultures obtained from embryonic day 12 were exposed to 0 nM, 0.25 nM, 0.5 nM, 2.5 nM, and 5 nM MeHg for 48 or 72 h. Total Hg accumulated in the harvested cells in a dose-dependent manner. Not all of the concentrations tested in the study affected cell viability. Intriguingly, we observed that cortical precursor exposed to 0.25 nM MeHg showed increased neuronal differentiation, while its proliferation was inhibited. Reduced neuronal differentiation, however, was observed in the higher dose groups. Our results suggest that sub-nanomolar MeHg exposure may deplete the pool of neural precursors by increasing premature neuronal differentiation, which can lead to long-term neurological effects in adulthood as opposed to the higher MeHg doses that cause more immediate toxicity during infant development.
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Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos
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Toxics 2018, 6(4), 60; https://doi.org/10.3390/toxics6040060 - 9 October 2018
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Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2)
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Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2) cells and their toxicity towards zebrafish embryos. XCE was isolated using a mixture of acetone and water (80:20) and verified via high performance liquid chromatography (HPLC). Both XCE and α-MG showed higher anti-proliferation effects on normoxic HepG2 cells compared to the control drug, 5-fluorouracil (IC50 = 50.23 ± 1.38, 8.39 ± 0.14, and 143.75 ± 15.31 μg/mL, respectively). In hypoxic conditions, HepG2 cells were two times less sensitive towards XCE compared to normoxic HepG2 cells (IC50 = 109.38 ± 1.80 μg/mL) and three times less sensitive when treated with >500 μg/mL 5-fluorouracil (5-FU). A similar trend was seen with the α-MG treatment on hypoxic HepG2 cells (IC50 = 10.11 ± 0.05 μg/mL) compared to normoxic HepG2 cells. However, at a concentration of 12.5 μg/mL, the α-MG treatment caused tail-bend deformities in surviving zebrafish embryos, while no malformation was observed when embryos were exposed to XCE and 5-FU treatments. Our study suggests that both XCE and α-MG are capable of inhibiting HepG2 cell proliferation during normoxic and hypoxic conditions, more effectively than 5-FU. However, XCE is the preferred option as no malformation was observed in surviving zebrafish embryos and it is more cost efficient than α-MG.
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Characterization of MS/MS Product Ions for the Differentiation of Structurally Isomeric Pesticides by High-Resolution Mass Spectrometry
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Toxics 2018, 6(4), 59; https://doi.org/10.3390/toxics6040059 - 2 October 2018
Abstract
Structural isomeric pesticides are used in agriculture and may be challenging to differentiate for accurate identification in pesticide monitoring programs. Due to structural similarity, isomeric pesticides are difficult to separate chromatographically, and thus, their accurate identification may rely solely on mass spectrometric analysis
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Structural isomeric pesticides are used in agriculture and may be challenging to differentiate for accurate identification in pesticide monitoring programs. Due to structural similarity, isomeric pesticides are difficult to separate chromatographically, and thus, their accurate identification may rely solely on mass spectrometric analysis (MS). In this study, we challenged the ability of high-resolution quadrupole-orbitrap (Q-Orbitrap) mass spectrometry to produce and evaluate the tandem mass spectrometry (MS/MS) product ions for the selected five pairs of isomeric pesticides from different classes: Pebulate and vernolate, methiocarb and ethiofencarb, uniconazole and cyproconazole, sebuthylazine and terbuthylazine, and orbencarb and thiobencarb. The use of Q-Orbitrap instrument with a mass error <3 ppm allowed proposed elucidation of the product ion structures with consideration of the ion formulae, data interpretation, and literature searches. Product ions unique to pebulate, vernolate, methiocarb, ethiofencarb, and uniconazole were observed. Elucidation of the observed MS/MS product ion structures was conducted, and the fragmentation pathways were proposed. This information is valuable to increase selectivity in MS/MS analysis and differentiate isomeric pesticides, and thereby reduce the rates of false positives in pesticide monitoring programs.
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Pattern of Paracetamol Poisoning: Influence on Outcome and Complications
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Toxics 2018, 6(4), 58; https://doi.org/10.3390/toxics6040058 - 29 September 2018
Abstract
Acute paracetamol poisoning due to a single overdose may be effectively treated by the early administration of N-acetylcysteine (NAC) as an antidote. The prognosis may be different in the case of intoxication due to multiple ingestions or when the antidote is started with
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Acute paracetamol poisoning due to a single overdose may be effectively treated by the early administration of N-acetylcysteine (NAC) as an antidote. The prognosis may be different in the case of intoxication due to multiple ingestions or when the antidote is started with delay. The aim of this work was to investigate the outcome of paracetamol poisoning according to the pattern of ingestion and determine the factors associated with the outcome. We performed a retrospective analysis over the period 2007–2017 of the patients who were referred to a tertiary hospital for paracetamol-related hepatotoxicity. Inclusion criteria were: accidental or voluntary ingestion of paracetamol, delay for NAC therapy of 12 h or more, liver enzymes (ALT) >1000 IU/L on admission. Ninety patients were considered. Poisoned patients following multiple ingestion were significantly older (45 ± 12 vs. 33 ± 14) (p = 0.001), with a higher incidence of liver steatosis (p = 0.016) or chronic ethanol abuse (p = 0.04). In comparison with the subgroup of favorable outcome, the patients with poor outcome were older, had higher values for ALT, bilirubin, lactate, and lower values for factor V and arterial pH. In multivariate analysis, the arterial lactate value was associated with a bad prognosis (p < 0.02) (adjusted odds ratio 1.74 and CI 95:1.09–2.77). The risk of poor outcome was greater in the subgroup with staggered overdose (p = 0.02), which had a higher mortality rate (p = 0.01). This retrospective analysis illustrates the different population patterns of patients who were admitted for a single ingestion of a paracetamol overdose versus multiple ingestions. This last subgroup was mainly represented by older patients with additional risk factors for hepatotoxicity; arterial lactate was a good predictor of severity.
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Real-Time Monitoring of Tetraselmis suecica in A Saline Environment as Means of Early Water Pollution Detection
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Toxics 2018, 6(4), 57; https://doi.org/10.3390/toxics6040057 - 28 September 2018
Abstract
Biological water pollution, including organic pollutants and their possible transportation, via biofouling and ballast water, has the potential to cause severe economic and health impacts on society and environment. Current water pollution monitoring methods are limited by transportation of samples to the laboratory
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Biological water pollution, including organic pollutants and their possible transportation, via biofouling and ballast water, has the potential to cause severe economic and health impacts on society and environment. Current water pollution monitoring methods are limited by transportation of samples to the laboratory for analysis, which could take weeks. There is an urgent need for a water quality monitoring technique that generates real-time data. The study aims to assess the feasibility of three sensing techniques to detect and monitor the concentrations of the model species Tetraselmis suecica in real-time using eleven samples for each method. Results showed UV-Vis spectrophotometer detected increasing concentration of Tetraselmis suecica with R2 = 0.9627 and R2 = 0.9672, at 450 nm and 650 nm wavelengths, respectively. Secondly, low-frequency capacitance measurements showed a linear relationship with increasing concentration of Tetraselmis suecica at 150 Hz (R2 = 0.8463) and 180 Hz (R2 = 0.8391). Finally, a planar electromagnetic wave sensor measuring the reflected power S11 amplitude detected increasing cell density at 4 GHz (R2 = 0.8019).
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Monthly Variations in Perfluorinated Compound Concentrations in Groundwater
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Toxics 2018, 6(3), 56; https://doi.org/10.3390/toxics6030056 - 14 September 2018
Abstract
Large-scale manufacturing of poly- and perfluorinated compounds in the second half of the 20th century has led to their ubiquity in the environment, and their unique structure has made them persistent contaminants. A recent drinking water advisory level issued by the United States
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Large-scale manufacturing of poly- and perfluorinated compounds in the second half of the 20th century has led to their ubiquity in the environment, and their unique structure has made them persistent contaminants. A recent drinking water advisory level issued by the United States Environmental Protection Agency lowered the advisory level concentration of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) from 200 nanograms per liter and 400 nanograms per liter, respectively, to 70 nanograms per liter separately or combined. Small temporal variations in PFOS and PFOA concentrations could be the difference between meeting or exceeding the recommended limit. In this study, newly sampled data from a contaminated military site in Alaska and historical data from former Pease Air Force Base were collected. Data were evaluated to determine if monthly variations within PFOS and PFOA existed. No statistically significant temporal trend was observed in the Alaska data, while the results from Pease, although statistically significant, showed the spread of observed contaminant concentrations around the fitted line is broad (as indicated by the low R2 values), indicating that collection date has little value in predicting contaminant concentrations. Though not currently the subject of a US EPA health advisory, data on perfluorobutanesulfonic acid (PFBS), perfluorohexane sulfonic acid (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) were collected for each site and their average concentrations evaluated.
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The NOAEL Metformin Dose Is Ineffective against Metabolic Disruption Induced by Chronic Cadmium Exposure in Wistar Rats
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Toxics 2018, 6(3), 55; https://doi.org/10.3390/toxics6030055 - 10 September 2018
Abstract
Previous studies have proposed that cadmium (Cd) is a metabolic disruptor, which is associated with insulin resistance, metabolic syndrome, and diabetes. This metal is not considered by international agencies for the study of metabolic diseases. In this study, we investigate the effect of
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Previous studies have proposed that cadmium (Cd) is a metabolic disruptor, which is associated with insulin resistance, metabolic syndrome, and diabetes. This metal is not considered by international agencies for the study of metabolic diseases. In this study, we investigate the effect of metformin on Cd-exposed Wistar rats at a lowest-observed-adverse-effect level (LOAEL) dose (32.5 ppm) in drinking water. Metabolic complications in the rats exposed to Cd were dysglycemia, insulin resistance, dyslipidemia, dyslipoproteinemia, and imbalance in triglyceride and glycogen storage in the liver, muscle, heart, kidney, and adipose tissue. Meanwhile, rats treated orally with a No-observable-adverse-effect level (NOAEL) dose of metformin (200 mg/kg/day) showed mild improvement on serum lipids, but not on glucose tolerance; in tissues, glycogen storage was improved, but lipid storage was ineffective. In conclusion, metformin as a first-line pharmacological therapy must take into consideration the origin and duration of metabolic disruption, because in this work the NOAEL dose of metformin (200 mg/kg/day) showed a limited efficiency in the metabolic disruption caused by chronic Cd exposure.
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Graphical abstract
Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys
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Toxics 2018, 6(3), 53; https://doi.org/10.3390/toxics6030053 - 3 September 2018
Abstract
During embryonic development, some hypoxia occurs due to incipient vascularization. Under hypoxic conditions, gene expression is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The activity of this transcription factor can be altered by the exposure to a variety of compounds; among them is
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During embryonic development, some hypoxia occurs due to incipient vascularization. Under hypoxic conditions, gene expression is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The activity of this transcription factor can be altered by the exposure to a variety of compounds; among them is cadmium (Cd), a nephrotoxic heavy metal capable of crossing the placenta and reaching fetal kidneys. The goal of the study was to determine Cd effects on HIF-1 on embryonic kidneys. Pregnant Wistar rats were exposed to a mist of isotonic saline solution or CdCl2 (DDel = 1.48 mg Cd/kg/day), from gestational day (GD) 8 to 20. Embryonic kidneys were obtained on GD 21 for RNA and protein extraction. Results show that Cd exposure had no effect on HIF-1α and prolyl hydroxylase 2 protein levels, but it reduced HIF-1 DNA-binding ability, which was confirmed by a decrease in vascular endothelial growth factor (VEGF) mRNA levels. In contrast, the protein levels of VEGF were not changed, which suggests the activation of additional regulatory mechanisms of VEGF protein expression to ensure proper kidney development. In conclusion, Cd exposure decreases HIF-1-binding activity, posing a risk on renal fetal development.
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Knockdown of Butyrylcholinesterase but Not Inhibition by Chlorpyrifos Alters Early Differentiation Mechanisms in Human Neural Stem Cells
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Toxics 2018, 6(3), 52; https://doi.org/10.3390/toxics6030052 - 1 September 2018
Abstract
Butyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through the inhibition of AChE, which results in excess cholinergic stimulation at the
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Butyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through the inhibition of AChE, which results in excess cholinergic stimulation at the synapse. We hypothesized that the inhibition of AChE and BChE by CPF may impair early neurogenesis in neural stem cells (NSCs). To model neurodevelopment in vitro, we used human NSCs derived from induced pluripotent stem cells (iPSCs) with a focus on the initial differentiation mechanisms. Over the six days of NSC differentiation, the BChE activity and mRNA expression significantly increased, while the AChE activity and expression remained unchanged. The CPF treatment (10 μM) caused 82% and 92% inhibition of AChE and BChE, respectively. The CPF exposure had no effect on the cell viability or the expression of the differentiation markers HES5, DCX, or MAP2. However, the shRNA-knockdown of the BChE expression resulted in the decreased or delayed expression of the transcription factors HES5 and HES3. BChE may have a role in the differentiation of NSCs independent of, or in addition to, its enzymatic activity.
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30 October 2018
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