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Toxics, Volume 8, Issue 3 (September 2020) – 32 articles

Cover Story (view full-size image): Even though evidence suggesting a linkage between Cd exposure and insulin resistance is growing, the debate continues over the exact role and mechanisms of Cd toxicity in insulin resistance. This review examines different model systems as they relate to the Cd’s ability to impair β cell or target tissue function leading to insulin resistance. View this paper
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Article
Spatial Distribution and Ecological Risks of the Potentially-Toxic Elements in the Surface Sediments of Lake Bosten, China
Toxics 2020, 8(3), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030077 - 22 Sep 2020
Viewed by 1783
Abstract
Aiming at the pollution and ecological hazards of the lake sediments of Bosten Lake, once China’s largest inland lake, the spatial distribution and influencing factors of the potentially-toxic elements in its surface sediments were studied with the methods of spatial autocorrelation, two-way cluster [...] Read more.
Aiming at the pollution and ecological hazards of the lake sediments of Bosten Lake, once China’s largest inland lake, the spatial distribution and influencing factors of the potentially-toxic elements in its surface sediments were studied with the methods of spatial autocorrelation, two-way cluster analysis, and redundancy analysis. Finally, based on the background value of potentially-toxic elements extracted from a sediment core, a comprehensive evaluation of the risk of these potentially-toxic elements was conducted with the potential-ecological-risk index and the pollution-load index. With data on the grain size, bulk-rock composition, and organic matter content, this comprehensive analysis suggested that with the enrichment of authigenic carbonate minerals, the content of potentially-toxic elements exhibited distinctive characteristics representative of arid regions with lower values than those in humid region. All potentially-toxic elements revealed a significant spatial autocorrelation, and high-value areas mainly occurred in the middle and southwest. The content of potentially-toxic elements is related to Al2O3, K2O, Fe2O3, TiO2, MgO, and MnO, and the storage medium of potentially-toxic elements mainly consists of small particles with a grain size <16 μm. The pollution load index (PLI) for the whole lake due to the potentially-toxic elements was 1.31, and the surface area with a PLI higher than 1 and a moderate pollution level accounted for 87.2% of the total lake area. The research conclusions have an important scientific value for future lake ecological quality assessment and lake environment governance. Full article
(This article belongs to the Section Environmental Chemistry)
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Article
In Vitro and In Vivo Evaluation of the Toxic Effects of Dodecylguanidine Hydrochloride
Toxics 2020, 8(3), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030076 - 22 Sep 2020
Viewed by 877
Abstract
The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be [...] Read more.
The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC50: 0.39 μg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m3 for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-β1, IL-1β, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC50 of DGH in rats after exposure for 4 h was estimated to be >68 mg/m3. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health. Full article
(This article belongs to the Section Toxicology)
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Article
Environmental Health and Ecological Risk Assessment of Soil Heavy Metal Pollution in the Coastal Cities of Estuarine Bay—A Case Study of Hangzhou Bay, China
Toxics 2020, 8(3), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030075 - 22 Sep 2020
Cited by 6 | Viewed by 990
Abstract
Shanghai is the major city on the north shore of Hangzhou Bay, and the administrative regions adjacent to Hangzhou Bay are the Jinshan district, Fengxian district, and Pudong new area (Nanhui district), which are the main intersection areas of manufacturing, transportation, and agriculture [...] Read more.
Shanghai is the major city on the north shore of Hangzhou Bay, and the administrative regions adjacent to Hangzhou Bay are the Jinshan district, Fengxian district, and Pudong new area (Nanhui district), which are the main intersection areas of manufacturing, transportation, and agriculture in Shanghai. In this paper, we collected a total of 75 topsoil samples from six different functional areas (agricultural areas (19), roadside areas (10), industrial areas (19), residential areas (14), education areas (6), and woodland areas (7)) in these three administrative regions, and the presence of 10 heavy metals (manganese(Mn), zinc(Zn), chromium(Cr), nickel(Ni), lead(Pb), cobalt(Co), cadmium(Cd), mercury(Hg), copper(Cu), and arsenic(As)) was investigated in each sample. The Nemerow pollution index (NPI), pollution load index (PLI), and potential ecological risk index (PERI) were calculated to assess the soil pollution levels. The hazard quotient (HQ) and carcinogenic risk (CR) assessment models were used to assess the human health risks posed by the concentrations of the heavy metals. The CR and HQ for adults and children in different functional areas descended in the following order: industrial areas > roadside areas > woodland areas > residential areas > education areas > agricultural areas. The HQ of Mn for children in industrial areas was higher than 1, and the risk was within the acceptable range. Full article
(This article belongs to the Section Risk Assessment and Management)
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Review
Environmental Health Surveillance System for a Population Using Advanced Exposure Assessment
Toxics 2020, 8(3), 74; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030074 - 18 Sep 2020
Cited by 2 | Viewed by 1231
Abstract
Human exposure to air pollution is a major public health concern. Environmental policymakers have been implementing various strategies to reduce exposure, including the 10th-day-no-driving system. To assess exposure of an entire population of a community in a highly polluted area, pollutant concentrations in [...] Read more.
Human exposure to air pollution is a major public health concern. Environmental policymakers have been implementing various strategies to reduce exposure, including the 10th-day-no-driving system. To assess exposure of an entire population of a community in a highly polluted area, pollutant concentrations in microenvironments and population time–activity patterns are required. To date, population exposure to air pollutants has been assessed using air monitoring data from fixed atmospheric monitoring stations, atmospheric dispersion modeling, or spatial interpolation techniques for pollutant concentrations. This is coupled with census data, administrative registers, and data on the patterns of the time-based activities at the individual scale. Recent technologies such as sensors, the Internet of Things (IoT), communications technology, and artificial intelligence enable the accurate evaluation of air pollution exposure for a population in an environmental health context. In this study, the latest trends in published papers on the assessment of population exposure to air pollution were reviewed. Subsequently, this study proposes a methodology that will enable policymakers to develop an environmental health surveillance system that evaluates the distribution of air pollution exposure for a population within a target area and establish countermeasures based on advanced exposure assessment. Full article
(This article belongs to the Section Toxicology)
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Article
Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis
Toxics 2020, 8(3), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030073 - 18 Sep 2020
Cited by 1 | Viewed by 1128
Abstract
Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette [...] Read more.
Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival. Full article
(This article belongs to the Special Issue Current Knowledge of E-cigarettes and Heated Tobacco Products)
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Editorial
Prevalence, Fate and Effects of Plastic in Freshwater Environments: New Findings and Next Steps
Toxics 2020, 8(3), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030072 - 17 Sep 2020
Viewed by 905
Abstract
At a time when a global pandemic rightly holds our collective attention, environmental issues have taken a backseat to the ongoing battle against Covid-19 [...] Full article
(This article belongs to the Special Issue Prevalence, Fate and Effects of Plastic in Freshwater Environments)
Article
Mechanisms of Increased Indoxacarb Toxicity in Methoxyfenozide-Resistant Cotton Bollworm Helicoverpa armigera (Lepidoptera: Noctuidae)
Toxics 2020, 8(3), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030071 - 17 Sep 2020
Cited by 1 | Viewed by 966
Abstract
Indoxacarb is an important insecticide for the selective control of Helicoverpa armigera. It can be bioactivated to the more effective N-decarbomethoxylated indoxacarb (DCJW) by esterases in pests. It was observed that both field and laboratory selected populations of H. armigera showed negative [...] Read more.
Indoxacarb is an important insecticide for the selective control of Helicoverpa armigera. It can be bioactivated to the more effective N-decarbomethoxylated indoxacarb (DCJW) by esterases in pests. It was observed that both field and laboratory selected populations of H. armigera showed negative cross-resistance between indoxacarb and methoxyfenozide. The Handan population exhibited moderate resistance to indoxacarb, but was susceptible to methoxyfenozide; the Baoding and Yishui populations exhibited moderate resistance to methoxyfenozide, but they were susceptible to indoxacarb. Moreover, the toxicity of indoxacarb was enhanced 1.83-fold in the laboratory methoxyfenozide-resistant H. armigera, and susceptibility to methoxyfenozide was increased 2.81-fold in the laboratory indoxacarb-resistant H. armigera. In vivo, DCJW concentrations in the susceptible and methoxyfenozide-selected (laboratory methoxyfenozide-resistant) populations were 4.59- and 4.31-fold greater than in the indoxacarb-resistant Handan population 1 h after dosing. After 2 h, the highest concentrations of DCJW and indoxacarb appeared in the methoxyfenozide-selected population. Meanwhile, increased carboxyl esterase (CarE) and decreased glutathione S-transferase (GST) activities were observed in the methoxyfenozide-selected population. However, the indoxacarb-selected (laboratory indoxacarb-resistant) and Handan populations showed a higher disappearance of indoxacarb and DCJW, and the activity of cytochrome P450 mono-oxygenase in these populations were significantly increased. This study showed that the improved toxicity of indoxacarb, as observed in the methoxyfenozide-selected H. armigera, was correlated with increased CarE activity, decreased GST activity, and the in vivo accumulation of indoxacarb and DCJW. The significantly increased cytochrome P450 activity and higher disappearance of indoxacarb and DCJW in indoxacarb-resistant H. armigera resulted in the decreased toxicity of indoxacarb. Full article
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Review
Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?
Toxics 2020, 8(3), 70; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030070 - 17 Sep 2020
Cited by 7 | Viewed by 1219
Abstract
Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and [...] Read more.
Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1–2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals. Full article
(This article belongs to the Special Issue Prenatal Environmental Exposure and Autism Risk)
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Article
Norepinephrine Leads to More Cardiopulmonary Toxicities than Epinephrine by Catecholamine Overdose in Rats
Toxics 2020, 8(3), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030069 - 16 Sep 2020
Cited by 2 | Viewed by 1407
Abstract
While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 [...] Read more.
While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 h intravenous injection of E and/or NE in rats. Heart rate, echocardiography, and ventricular pressure were measured throughout administration. Cardiopulmonary structure was also assessed by examining heart and lung tissue. Consecutive catecholamine injections induced severe tachycardia. Echocardiography results showed NE caused worse dysfunction than E. Simultaneously, both E and NE led to higher expression of Troponin T and connexin43 in the whole ventricles, which increased further with E+NE administration. The NE and E+NE groups showed severe pulmonary edema while all catecholamine-administering groups demonstrated reduced expression of receptor for advanced glycation end products and increased connexin43 levels in lung tissue. The right ventricle was more vulnerable to catecholamine overdose than the left. Rats injected with NE had a lower survival rate than those injected with E within 6 h. Catecholamine overdose induces acute lung injuries and ventricular cardiomyopathy, and E+NE is associated with a more severe outcome. The similarities of the results between the NE and E+NE groups may indicate a predominant role of NE in determining the overall cardiopulmonary damage. The results provide important clinical insights into the pathogenesis of catecholamine storm. Full article
(This article belongs to the Section Toxicology)
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Conference Report
Clinical, Epidemiological and Experimental Approaches to Assess Adverse Health Outcomes of Indoor Biomass Smoke Exposure: Conclusions from An Indo-Swedish Workshop in Mysuru, January 2020
Toxics 2020, 8(3), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030068 - 05 Sep 2020
Cited by 1 | Viewed by 1343
Abstract
This report summarizes the outcome of a workshop held in Mysuru, India in January 2020 addressing the adverse health effects of exposure to biomass smoke (BMS). The aim of the workshop was to identify uncertainties and gaps in knowledge and possible methods to [...] Read more.
This report summarizes the outcome of a workshop held in Mysuru, India in January 2020 addressing the adverse health effects of exposure to biomass smoke (BMS). The aim of the workshop was to identify uncertainties and gaps in knowledge and possible methods to address them in the Mysuru study on Determinants of Health in Rural Adults (MUDHRA) cohort. Specific aims were to discuss the possibility to improve and introduce new screening methods for exposure and effect, logistic limitations and other potential obstacles, and plausible strategies to overcome these in future studies. Field visits were included in the workshop prior to discussing these issues. The workshop concluded that multi-disciplinary approaches to perform: (a) indoor and personalized exposure assessment; (b) clinical and epidemiological field studies among children, adolescents, and adults; (c) controlled exposure experiments using physiologically relevant in vitro and in vivo models to understand molecular patho-mechanisms are warranted to dissect BMS-induced adverse health effects. It was perceived that assessment of dietary exposure (like phytochemical index) may serve as an important indicator for understanding potential protective mechanisms. Well trained field teams and close collaboration with the participating hospital were identified as the key requirements to successfully carry out the study objectives. Full article
(This article belongs to the Special Issue Effects of Exposure to Air Pollution on Respiratory Health)
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Article
Estimated Dietary Bisphenol-A Exposure and Adiposity in Samoan Mothers and Children
Toxics 2020, 8(3), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030067 - 02 Sep 2020
Cited by 3 | Viewed by 1086
Abstract
The Pacific Island nation of Samoa is marked by prevalent obesity and an increasing dependence on packaged foods likely to contain the endocrine disruptor bisphenol-A (BPA). We evaluated participant- and household-level characteristics associated with estimated dietary BPA exposure in Samoan mothers and their [...] Read more.
The Pacific Island nation of Samoa is marked by prevalent obesity and an increasing dependence on packaged foods likely to contain the endocrine disruptor bisphenol-A (BPA). We evaluated participant- and household-level characteristics associated with estimated dietary BPA exposure in Samoan mothers and their children and examined associations between dietary BPA exposure and body mass index (BMI) and abdominal circumference (AC). Dietary BPA exposure indices were estimated for 399 mother–child pairs by combining information from dietary questionnaires and relative concentrations of BPA measured in foods/beverages. We observed moderate to strong correlation between mother–child daily BPA indices (Spearman’s rho = 0.7, p < 0.0001). In mothers, we observed lower daily BPA indices in those who were less physically active (p = 0.0004) and living in homes with higher income (p = 0.00001). In children, we observed lower daily BPA indices in those living in homes with higher income (p = 0.0003) and following a less modern dietary pattern (p = 0.002), and higher daily BPA indices in those who were less physically active (p = 0.02). No significant associations were observed between daily BPA indices and BMI or AC. Despite this, the application of the daily BPA index identified factors associated with dietary BPA exposure and warrants further examination in Samoa and other understudied populations. Full article
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Article
Association between Heavy Metals and Rare Earth Elements with Acute Ischemic Stroke: A Case-Control Study Conducted in the Canary Islands (Spain)
Toxics 2020, 8(3), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030066 - 02 Sep 2020
Cited by 1 | Viewed by 1008
Abstract
The role of inorganic elements as risk factors for stroke has been suggested. We designed a case-control study to explore the role of 45 inorganic elements as factors associated with stroke in 92 patients and 83 controls. Nineteen elements were detected in >80% [...] Read more.
The role of inorganic elements as risk factors for stroke has been suggested. We designed a case-control study to explore the role of 45 inorganic elements as factors associated with stroke in 92 patients and 83 controls. Nineteen elements were detected in >80% of patients and 21 were detected in >80% of controls. Blood level of lead was significantly higher among patients (11.2 vs. 9.03 ng/mL) while gold and cerium were significantly higher among controls (0.013 vs. 0.007 ng/mL; and 18.0 vs. 15.0 ng/mL). Lead was associated with stroke in univariate and multivariate analysis (OR = 1.65 (95% CI, 1.09–2.50) and OR = 1.91 (95% CI, 1.20–3.04), respectively). Gold and cerium showed an inverse association with stroke in multivariate analysis (OR = 0.81 (95% CI, 0.69–0.95) and OR = 0.50 (95% CI, 0.31–0.78)). Future studies are needed to elucidate the potential sources of exposure and disclose the mechanisms of action. Full article
(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)
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Review
Insights into the Toxicity and Degradation Mechanisms of Imidacloprid Via Physicochemical and Microbial Approaches
Toxics 2020, 8(3), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030065 - 01 Sep 2020
Cited by 9 | Viewed by 1792
Abstract
Imidacloprid is a neonicotinoid insecticide that has been widely used to control insect pests in agricultural fields for decades. It shows insecticidal activity mainly by blocking the normal conduction of the central nervous system in insects. However, in recent years, imidacloprid has been [...] Read more.
Imidacloprid is a neonicotinoid insecticide that has been widely used to control insect pests in agricultural fields for decades. It shows insecticidal activity mainly by blocking the normal conduction of the central nervous system in insects. However, in recent years, imidacloprid has been reported to be an emerging contaminant in all parts of the world, and has different toxic effects on a variety of non-target organisms, including human beings, due to its large-scale use. Hence, the removal of imidacloprid from the ecosystem has received widespread attention. Different remediation approaches have been studied to eliminate imidacloprid residues from the environment, such as oxidation, hydrolysis, adsorption, ultrasound, illumination, and biodegradation. In nature, microbial degradation is one of the most important processes controlling the fate of and transformation from imidacloprid use, and from an environmental point of view, it is the most promising means, as it is the most effective, least hazardous, and most environmentally friendly. To date, several imidacloprid-degrading microbes, including Bacillus, Pseudoxanthomonas, Mycobacterium, Rhizobium, Rhodococcus, and Stenotrophomonas, have been characterized for biodegradation. In addition, previous studies have found that many insects and microorganisms have developed resistance genes to and degradation enzymes of imidacloprid. Furthermore, the metabolites and degradation pathways of imidacloprid have been reported. However, reviews of the toxicity and degradation mechanisms of imidacloprid are rare. In this review, the toxicity and degradation mechanisms of imidacloprid are summarized in order to provide a theoretical and practical basis for the remediation of imidacloprid-contaminated environments. Full article
(This article belongs to the Section Risk Assessment and Management)
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Article
Effect of Perfluorooctanoic Acid on the Epigenetic and Tight Junction Genes of the Mouse Intestine
Toxics 2020, 8(3), 64; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030064 - 28 Aug 2020
Cited by 7 | Viewed by 1486
Abstract
Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is [...] Read more.
Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudins (Cldn), Occludin (Ocln), and Tight Junction Protein (Tjp) were also heavily altered in the small intestine. TJs responded differently across the gut, in proportion to PFOA dosing. Our study reveals that PFOA triggers DNA methylation changes and alters the expression of genes essential for maintaining the physical barrier of intestine, with more profound effects in the small intestine compared to the colon. Full article
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Review
Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data
Toxics 2020, 8(3), 63; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030063 - 27 Aug 2020
Cited by 15 | Viewed by 1967
Abstract
Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved [...] Read more.
Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance. Full article
(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)
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Article
Use of Personal Care Products and Semen Quality: A Cross-Sectional Study in Young Danish Men
Toxics 2020, 8(3), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030062 - 22 Aug 2020
Viewed by 1339
Abstract
Personal care products (PCPs) may contain multiple chemicals capable of harming male reproductive function. The aim of this study was, therefore, to assess aggregated PCP exposure and potential associations with measures of semen quality in young men. Participants (n = 1058, age [...] Read more.
Personal care products (PCPs) may contain multiple chemicals capable of harming male reproductive function. The aim of this study was, therefore, to assess aggregated PCP exposure and potential associations with measures of semen quality in young men. Participants (n = 1058, age 18–21) were sampled among young men from the Danish National Birth Cohort (DNBC). Upon recruitment in 2017–2019, each man answered an online questionnaire and provided a semen sample. Exposure to 12 common types of PCPs was derived from the questionnaire, and the extent of use and co-use was analyzed. We applied a negative binomial regression model to estimate percentage differences in semen parameters between low, medium and high PCP exposure groups. All participants were exposed to at least one PCP more than once a week, resulting in a mean number (SD) of 5.3 (2.0) PCPs currently used. Most participants (92%) were also exposed to fragranced products on a weekly basis. Little association was observed between aggregated exposure to PCPs and sperm concentration, total sperm count, semen volume, sperm motility and morphology. Despite prevalent use of multiple PCPs, we found little indication of adverse effects of aggregated overall or fragranced PCP exposure on semen quality. Full article
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Article
Environmental Methamphetamine Exposures and Health Effects in 25 Case Studies
Toxics 2020, 8(3), 61; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030061 - 20 Aug 2020
Cited by 3 | Viewed by 2077
Abstract
The clandestine manufacture and use of methamphetamine can result in contamination of residential properties. It is understood that this contamination remains in homes for a significant period, however there are a lack of data available to understand the health effects of exposure to [...] Read more.
The clandestine manufacture and use of methamphetamine can result in contamination of residential properties. It is understood that this contamination remains in homes for a significant period, however there are a lack of data available to understand the health effects of exposure to environmental methamphetamine contamination (third-hand exposure). Our study collected information from 63 individuals in 25 separate case studies where the subjects had unwittingly suffered third-hand exposure to methamphetamine from former manufacture, use, or both. Data included environmental contamination data, information on subjects’ health effects, and evidence of exposure using hair analysis. This study identified a range of health effects that occur from residing in these properties, including behavioural effects or issues, sleep issues, respiratory effects, skin and eye effects, and headaches. Methamphetamine was detected in hair samples from some individuals, including children. The exposures and concomitant reported health effects covered a wide range of environmental methamphetamine levels in the properties, including low levels close to the current Australian guideline of 0.5 µg methamphetamine/100 cm2. There were no discernible differences between health effects from living in properties contaminated from former manufacture or use. This study demonstrates that residing in these properties can represent a serious public health risk. Full article
(This article belongs to the Section Toxicology)
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Review
Human Biomonitoring of Glyphosate Exposures: State-of-the-Art and Future Research Challenges
Toxics 2020, 8(3), 60; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030060 - 18 Aug 2020
Cited by 16 | Viewed by 2523
Abstract
Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic [...] Read more.
Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic (AMPA). Herein, we reviewed and compared results from 21 studies that use human biomonitoring (HBM) to measure urinary glyphosate and AMPA. Elucidation of the level and range of exposure was complicated by differences in sampling strategy, analytical methods, and data presentation. Exposure data is required to enable a more robust regulatory risk assessment, and these studies included higher occupational exposures, environmental exposures, and vulnerable groups such as children. There was also considerable uncertainty regarding the absorption and excretion pattern of glyphosate and AMPA in humans. This information is required to back-calculate exposure doses from urinary levels and thus, then compare these levels with health-based guidance values. Back-calculations based on animal-derived excretion rates suggested that there were no health concerns in relation to glyphosate exposure (when compared with EFSA acceptable daily intake (ADI)). However, recent human metabolism data has reported as low as a 1% urinary excretion rate of glyphosate. Human exposures extrapolated from urinary glyphosate concentrations found that upper-bound levels may be much closer to the ADI than previously reported. Full article
Article
Adsorption and Desorption Behaviour of Polychlorinated Biphenyls onto Microplastics’ Surfaces in Water/Sediment Systems
Toxics 2020, 8(3), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030059 - 17 Aug 2020
Cited by 10 | Viewed by 1469
Abstract
The potential of microplastics (MPLs) in marine ecosystems to adsorb and transport other micropollutants to biota, contributing to their entry in the food chain, is a primary cause of concern. However, these interactions remain poorly understood. Here, we have evaluated the adsorption/desorption behaviour [...] Read more.
The potential of microplastics (MPLs) in marine ecosystems to adsorb and transport other micropollutants to biota, contributing to their entry in the food chain, is a primary cause of concern. However, these interactions remain poorly understood. Here, we have evaluated the adsorption/desorption behaviour of marker polychlorinated biphenyls (PCBs), onto MPL surfaces of three widely used polymers—polystyrene (PS), polyethylene (PE), and polyethylene terephthalate (PET). The range of MPL sizes ranged from 1 to 600 μm. The adsorption/desorption was evaluated in sediment/water systems in marine microcosms emulating realistic environmental conditions for 21 days. The adsorption percentages ranged from 20 to 60%. PCBs with a lower degree of chlorination showed higher adsorption percentages because of conformational impediments of PCBs with high-degree chlorination, and also by their affinity to be adsorbed in sediments. Glassy plastic polymers as PET and PS showed a superior affinity for PCBs than rubbery polymers, such as PE. The polymers that can bond PCBs by π-π interactions, rather than van der Waals forces showed better adsorption percentages, as expected. Finally, the adsorption/desorption behaviour of selected PCBs onto MPLs was fitted to a Freundlich isotherm model, with correlations higher than 0.8 in most of the cases. Full article
(This article belongs to the Special Issue Underexplored Chemical Interactions in Humans and Wildlife)
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Article
Occurrence, Ecological and Health Risk Assessment of Phthalate Esters in Surface Water of U-Tapao Canal, Southern, Thailand
Toxics 2020, 8(3), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030058 - 17 Aug 2020
Cited by 5 | Viewed by 1275
Abstract
Phthalate esters (PAEs) are well known for their environmental contamination and endocrine-disrupting effects on wildlife and humans. In this study, the occurrence of PAEs and ecotoxicological risk assessments were performed in one of the significant canals in southern Thailand, named U-Tapao. Water samples [...] Read more.
Phthalate esters (PAEs) are well known for their environmental contamination and endocrine-disrupting effects on wildlife and humans. In this study, the occurrence of PAEs and ecotoxicological risk assessments were performed in one of the significant canals in southern Thailand, named U-Tapao. Water samples were collected and analyzed for the six most common PAEs by using a gas chromatograph-mass spectrometer (GC-MS). Of the 6 PAEs analyzed, only three PAEs, including di-n-butyl phthalate (DBP), di (2-Ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were detected in water samples. The total concentration of PAEs ranged from 1.44 to 12.08 µg/L, with a mean level of 4.76 µg/L. The total average concentration of PAEs found in the canal was higher than the criteria of 3 µg/L for PAEs recommended for the protection of fish and other aquatic organisms by the United States Environmental Protection Agency (USEPA). The results of the potential ecological risk assessment of the risk quotient (RQ) method revealed that DEHP and DiNP posed a high risk to algae and crustacean and crustacean and fish, respectively, whereas DBP posed a medium risk to the different aquatic species. However, current levels of noncarcinogenic and carcinogenic risks via ingestion and dermal exposure in children and adults are within acceptable limits. The baseline data of PAEs in this canal will be beneficial to the strategic and future pollutant control along the canal network. Full article
(This article belongs to the Section Risk Assessment and Management)
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Article
Phthalates, Para-Hydroxybenzoic Acids, Bisphenol-A, and Gonadal Hormones’ Effects on Susceptibility to Attention-Deficit/Hyperactivity Disorder
Toxics 2020, 8(3), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030057 - 13 Aug 2020
Cited by 3 | Viewed by 1230
Abstract
This study aimed to examine whether endocrine-disrupting chemicals (EDCs), such as phthalates, para-hydroxybenzoic acids, and bisphenol-A (BPA), affect gonadal hormones and further link to the susceptibility to attention-deficit/hyperactivity disorder (ADHD). We recruited 98 boys with ADHD, 32 girls with ADHD, 42 boys without [...] Read more.
This study aimed to examine whether endocrine-disrupting chemicals (EDCs), such as phthalates, para-hydroxybenzoic acids, and bisphenol-A (BPA), affect gonadal hormones and further link to the susceptibility to attention-deficit/hyperactivity disorder (ADHD). We recruited 98 boys with ADHD, 32 girls with ADHD, 42 boys without ADHD and any other psychiatric disorders, and 26 girls without ADHD and any other psychiatric disorders. Urine levels of EDCs, including mono-methyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoethylhexyl phthalate (MEHP), methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), and bisphenol A (BPA), were examined. Endocrine systems were evaluated by using the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, free testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), and prolactin. We found that boys with ADHD had higher levels of MnBP and EP than control boys. There were no significant differences regarding EDCs between the females with ADHD and control groups. No significant differences in testosterone, free testosterone, FSH, LH, estradiol, progesterone, or SHBG were found between the ADHD group and controls among either boys or girls. Among boys with ADHD, urine MBzP and MEHP levels were positively correlated with serum testosterone levels. Among girls, urine MEP levels were positively correlated with serum LH, testosterone, and free testosterone levels. The findings suggest that the possibility of an adverse impact of EDCs on gonadal hormones and neurodevelopment may exist. However, the results could be subject to potential selection bias, and the findings in this study should be interpreted with caution. Full article
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Article
The Immunotoxicity of Chronic Exposure to High Levels of Lead: An Ex Vivo Investigation
Toxics 2020, 8(3), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030056 - 13 Aug 2020
Cited by 1 | Viewed by 1309
Abstract
Lead (Pb) is a toxic metal known for its wide-ranging adverse health effects. However, a compound of Pb is still used in the caulking process to repair wooden fishing boats. The present study aimed to measure Pb exposure and its immunologic effects in [...] Read more.
Lead (Pb) is a toxic metal known for its wide-ranging adverse health effects. However, a compound of Pb is still used in the caulking process to repair wooden fishing boats. The present study aimed to measure Pb exposure and its immunologic effects in boatyard workers in Nakhon Si Thammarat province, Thailand, in comparison with an age-matched control group of farmers. The age, body mass index, and smoking history in workers (n = 14) and controls (n = 16) did not differ. The median blood Pb concentration was 8.7-fold higher in workers than controls (37.1 versus 4.3 µg/dL, p < 0.001). Workers had 8.4% lower phagocytic active cells than controls (89.9% versus 98.1%, p = 0.019). In response to a mitogen stimulation, the peripheral blood mononuclear cells (PBMCs) from workers produced 2-fold higher ratios of interleukin-4 (IL-4) to interferon-γ than the PBMCs from controls (p = 0.026). Furthermore, Pb-exposed workers had 33.9% lower cytotoxic T (Tc) cells than controls (24.3% versus 36.8%, p = 0.004). In stark contrast, the percentage of regulatory T (Treg) cells in workers was 2.7-fold higher than controls (6.1% versus 2.3%, p < 0.001). In all subjects, blood Pb showed positive correlations with the percentages of Treg cells (r = 0.843, p < 0.001) and IL-4 (r = 0.473, p = 0.041) while showing an inverse correlation with the percentages of Tc cells (r = −0.563, p = 0.015). These findings indicate that chronic high Pb exposure may cause a shift towards humoral immune response, together with a suppression of cellular immunity, thereby suggesting an elevation in cancer risk in Pb-exposed workers. Full article
(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)
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Article
Effects of MP Polyethylene Microparticles on Microbiome and Inflammatory Response of Larval Zebrafish
Toxics 2020, 8(3), 55; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030055 - 11 Aug 2020
Cited by 7 | Viewed by 2041
Abstract
Plastic polymers have quickly become one of the most abundant materials on Earth due to their low production cost and high versatility. Unfortunately, some of the discarded plastic can make its way into the environment and become fragmented into smaller microscopic particles, termed [...] Read more.
Plastic polymers have quickly become one of the most abundant materials on Earth due to their low production cost and high versatility. Unfortunately, some of the discarded plastic can make its way into the environment and become fragmented into smaller microscopic particles, termed secondary microplastics (MP). In addition, primary MP, purposely manufactured microscopic plastic particles, can also make their way into our environment via various routes. Owing to their size and resilience, these MP can then be easily ingested by living organisms. The effect of MP particles on living organisms is suspected to have negative implications, especially during early development. In this study, we examined the effects of polyethylene MP ingestion for four and ten days of exposure starting at 5 days post-fertilization (dpf). In particular, we examined the effects of polyethylene MP exposure on resting metabolic rate, on gene expression of several inflammatory and oxidative stress linked genes, and on microbiome composition between treatments. Overall, we found no evidence of broad metabolic disturbances or inflammatory markers in MP-exposed fish for either period of time. However, there was a significant increase in the oxidative stress mediator L-FABP that occurred at 15 dpf. Furthermore, the microbiome was disrupted by MP exposure, with evidence of an increased abundance of Bacteroidetes in MP fish, a combination frequently found in intestinal pathologies. Thus, it appears that acute polyethylene MP exposure can increase oxidative stress and dysbiosis, which may render the animal more susceptible to diseases. Full article
(This article belongs to the Special Issue Prevalence, Fate and Effects of Plastic in Freshwater Environments)
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Article
Orally Administered 6:2 Chlorinated Polyfluorinated Ether Sulfonate (F-53B) Causes Thyroid Dysfunction in Rats
Toxics 2020, 8(3), 54; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030054 - 08 Aug 2020
Cited by 1 | Viewed by 1542
Abstract
The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, [...] Read more.
The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, in this study, we performed a subchronic oral toxicity study of F-53B in Sprague Dawley (SD) rats. F-53B was administered orally once daily to male and female rats for 28 days at doses of 5, 20, and 100 mg/kg/day. There were no toxicologically significant changes in F-53B-treated rats, except in the thyroid gland. However, F-53B slightly reduced the serum concentrations of thyroid hormones, including triiodothyronine and thyroxine, compared with their concentrations in the vehicle group. F-53B also induced follicular hyperplasia and was associated with increased thyroid hormone biosynthesis-associated protein expression. These results demonstrate that F-53B is a strong regulator of thyroid hormones in SD rats as it disrupts thyroid function. Thus, caution should be exercised in the industrial application of F-53B as an alternative for PFOS. Full article
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Article
Sustained Effects on Lung Function in Community Members Following Exposure to Hazardous PM2.5 Levels from Wildfire Smoke
Toxics 2020, 8(3), 53; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030053 - 05 Aug 2020
Cited by 12 | Viewed by 4904
Abstract
Extreme wildfire events are becoming more common and while the immediate risks of particulate exposures to susceptible populations (i.e., elderly, asthmatics) are appreciated, the long-term health effects are not known. In 2017, the Seeley Lake (SL), MT area experienced unprecedented levels of wildfire [...] Read more.
Extreme wildfire events are becoming more common and while the immediate risks of particulate exposures to susceptible populations (i.e., elderly, asthmatics) are appreciated, the long-term health effects are not known. In 2017, the Seeley Lake (SL), MT area experienced unprecedented levels of wildfire smoke from July 31 to September 18, with a daily average of 220.9 μg/m3. The aim of this study was to conduct health assessments in the community and evaluate potential adverse health effects. The study resulted in the recruitment of a cohort (n = 95, average age: 63 years), for a rapid response screening activity following the wildland fire event, and two follow-up visits in 2018 and 2019. Analysis of spirometry data found a significant decrease in lung function (FEV1/FVC ratio: forced expiratory volume in first second/forced vital capacity) and a more than doubling of participants that fell below the lower limit of normal (10.2% in 2017 to 45.9% in 2018) one year following the wildfire event, and remained decreased two years (33.9%) post exposure. In addition, observed FEV1 was significantly lower than predicted values. These findings suggest that wildfire smoke can have long-lasting effects on human health. As wildfires continue to increase both here and globally, understanding the health implications is vital to understanding the respiratory impacts of these events as well as developing public health strategies to mitigate the effects. Full article
(This article belongs to the Special Issue Molecular Basis of Air-Pollution-Induced Disease Risk)
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Article
Ambient Exposure to Agricultural Pesticides during Pregnancy and Risk of Cerebral Palsy: A Population-Based Study in California
Toxics 2020, 8(3), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030052 - 31 Jul 2020
Cited by 2 | Viewed by 2668
Abstract
Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control [...] Read more.
Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control study of 3905 CP cases and 39,377 controls born between 1998 and 2010 in California to mothers who lived in proximity (within 2 km) to any agricultural pesticide application recorded in the California Pesticide Use Reporting (PUR) system. We focused on 23 pesticides considered endocrine disruptors that are frequently used, and we found that exposure to any of the 23 pesticides in the first trimester was associated with elevated CP risks in female offspring (OR = 1.19; 95% CI: 1.05–1.35) but not males (OR = 0.99; 95% CI: 0.89–1.09) compared to the unexposed offspring. Positive associations were estimated for 15 pesticides suspected to affect the estrogen and 7 pesticides suspected to affect the thyroid hormone system. Our study suggests that first trimester exposure to pesticides that are suspected endocrine disruptors are associated with CP risk in female offspring. Pesticide exposures in early pregnancy may have sex-specific influences on the neuro-motor development of the fetus by interfering with endocrine systems. Full article
Article
Astrocytes Are More Vulnerable than Neurons to Silicon Dioxide Nanoparticle Toxicity in Vitro
Toxics 2020, 8(3), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030051 - 29 Jul 2020
Cited by 1 | Viewed by 1185
Abstract
Some studies have shown that silicon dioxide nanoparticles (SiO2-NPs) can reach different regions of the brain and cause toxicity; however, the consequences of SiO2-NPs exposure on the diverse brain cell lineages is limited. We aimed to investigate the neurotoxic [...] Read more.
Some studies have shown that silicon dioxide nanoparticles (SiO2-NPs) can reach different regions of the brain and cause toxicity; however, the consequences of SiO2-NPs exposure on the diverse brain cell lineages is limited. We aimed to investigate the neurotoxic effects of SiO2-NP (0–100 µg/mL) on rat astrocyte-rich cultures or neuron-rich cultures using scanning electron microscopy, Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR), FTIR microspectroscopy mapping (IQ mapping), and cell viability tests. SiO2-NPs were amorphous particles and aggregated in saline and culture media. Both astrocytes and neurons treated with SiO2-NPs showed alterations in cell morphology and changes in the IR spectral regions corresponding to nucleic acids, proteins, and lipids. The analysis by the second derivative revealed a significant decrease in the signal of the amide I (α-helix, parallel β-strand, and random coil) at the concentration of 10 µg/mL in astrocytes but not in neurons. IQ mapping confirmed changes in nucleic acids, proteins, and lipids in astrocytes; cell death was higher in astrocytes than in neurons (10–100 µg/mL). We conclude that astrocytes were more vulnerable than neurons to SiO2-NPs toxicity. Therefore, the evaluation of human exposure to SiO2-NPs and possible neurotoxic effects must be followed up. Full article
(This article belongs to the Collection Environmental and Health Risks of Nanotechnology)
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Article
Increased Mitochondrial Fragmentation Mediated by Dynamin-Related Protein 1 Contributes to Hexavalent Chromium-Induced Mitochondrial Respiratory Chain Complex I-Dependent Cytotoxicity
Toxics 2020, 8(3), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030050 - 29 Jul 2020
Viewed by 843
Abstract
Hexavalent chromium (Cr(VI)) pollution is a severe public health problem in the world. Although it is believed that mitochondrial fragmentation is a common phenomenon in apoptosis, whether excessive fission is crucial for apoptosis remains controversial. We previously confirmed that Cr(VI) mainly targeted mitochondrial [...] Read more.
Hexavalent chromium (Cr(VI)) pollution is a severe public health problem in the world. Although it is believed that mitochondrial fragmentation is a common phenomenon in apoptosis, whether excessive fission is crucial for apoptosis remains controversial. We previously confirmed that Cr(VI) mainly targeted mitochondrial respiratory chain complex I (MRCC I) to induce reactive oxygen species (ROS)-mediated apoptosis, but the related mechanism was unclear. In this study, we found Cr(VI) targeted MRCC I to induce ROS accumulation and triggered mitochondria-related cytotoxicity. Cr(VI)-induced cytotoxicity was alleviated by pretreatment of Glutamate/malate (Glu/Mal; MRCC I substrates), and was aggravated by cotreatment of rotenone (ROT; MRCC I inhibitor). Cr(VI) induced excessive mitochondrial fragmentation and mitochondrial dynamin-related protein 1 (Drp1) translocation, the application of Drp1-siRNA alleviated Cr(VI)-induced apoptosis. The cytotoxicity in the Drp1-si plus Cr(VI) treatment group was alleviated by the application of Glu/Mal, and was aggravated by the application of ROT. Drp1 siRNA promoted the inhibition of Glu/Mal on Cr(VI)-induced cytotoxicity, and alleviated the aggravation of ROT on Cr(VI)-induced cytotoxicity. Taken together, Cr(VI)-induced Drp1 modulation was dependent on MRCC I inhibition-mediated ROS production, and Drp1-mediated mitochondrial fragmentation contributed to Cr(VI)-induced MRCC I-dependent cytotoxicity, which provided the experimental basis for further elucidating Cr(VI)-induced cytotoxicity. Full article
(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)
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Article
Mechanism of Vascular Toxicity in Rats Subjected to Treatment with a Tyrosine Kinase Inhibitor
Toxics 2020, 8(3), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030049 - 20 Jul 2020
Cited by 1 | Viewed by 978
Abstract
Sunitinib (Su) is a tyrosine kinase inhibitor with antiangiogenic and antineoplastic effects that is recommended therapy for renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. Arterial hypertension is one of the adverse effects observed in the treatment with Su. The aim [...] Read more.
Sunitinib (Su) is a tyrosine kinase inhibitor with antiangiogenic and antineoplastic effects that is recommended therapy for renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. Arterial hypertension is one of the adverse effects observed in the treatment with Su. The aim of this work was to deepen our understanding of the underlying mechanisms involved in the development of this side effect. Studies on endothelial function, vascular remodeling and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) system were carried out in thoracic aortas from rats treated with Su for three weeks. Animals subjected to Su treatment presented with increased blood pressure and reduced endothelium-dependent vasodilation, the latter being reverted by NADPH oxidase blockade. Furthermore, vascular remodeling and stronger Masson trichrome staining, together with enhanced immunofluorescence signal for collagen 1 alpha 1 (Col1α1), were observed in aortas from treated animals. These results were accompanied by a significant elevation in superoxide anion production and the activity/protein/gene expression of NADPH oxidase isoforms (NOX1, NOX2, and NOX4), which was also prevented by NOX inhibition. Furthermore, a decrease in nitric oxide (NO) levels and endothelial nitric oxide synthase (eNOS) activation was observed in aortas from Su-treated animals. All these results indicate that endothelial dysfunction secondary to changes in vascular remodeling and oxidative stress might be responsible for the typical arterial hypertension that develops following treatment with Su. Full article
(This article belongs to the Section Toxicology)
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Case Report
Recycling Waste Electrical and Electronic Equipment (WEEE) and the Management of Its Toxic Substances in Taiwan—A Case Study
Toxics 2020, 8(3), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/toxics8030048 - 07 Jul 2020
Cited by 1 | Viewed by 1239
Abstract
In the past two decades, the waste electrical and electronic equipment (WEEE) management has become an important environmental issue internationally because it contained hazardous substances like heavy metals and brominated flame retardants. Moreover, some valuable substances were used in the electrical and electronic [...] Read more.
In the past two decades, the waste electrical and electronic equipment (WEEE) management has become an important environmental issue internationally because it contained hazardous substances like heavy metals and brominated flame retardants. Moreover, some valuable substances were used in the electrical and electronic products, thus representing a circular industry for recycling of WEEE. Therefore, the Taiwan government formulated a legal WEEE recycling system since 1998 in response to the international trends of sustainable waste management and extended producer responsibility (EPR). This article adopted the national statistics in Taiwan regarding the online reporting amounts of collected WEEE since it has been officially designated as one of the mandatory recyclable wastes. Furthermore, the regulatory measures were addressed to update the status and subsidiary fee rates of WEEE recycling in Taiwan. In addition, this article also put emphasis on the regulations governing the toxic chemical substances contained in the WEEE. It showed that the average annual recycling amounts of home electronic appliances, information technology products and lighting in Taiwan during the 2017–2018 were around 117,000, 18,000 and 4500 metric tons, respectively. It was also indicated that the current WEEE recycling market in Taiwan has become saturated, reflecting the regulatory promulgation and promotional measures successfully. In response to the Stockholm Convention on persistent organic pollutants (POPs) and the Minamata Convention on Mercury, the Taiwan government declared some brominated flame retardants and heavy metals (i.e., mercury and cadmium) as a “toxic chemical substance” under the Toxic and Concerned Chemical Substance Control Act (TCCSCA), which shall be prohibited to use in the preparation of electrical and electronic equipment (EEE) since 1 January 2016. Through the central governing authority, local governments, and private recyclers in Taiwan, the successful WEEE recycling system not only reduce the pressure on sanitary disposal systems, but also prevent the chemical hazards from solid waste incineration systems. More significantly, the WEEE recycling in Taiwan echoed the United Nations (UN) Agenda 2030 for sustainable development goals. Full article
(This article belongs to the Special Issue Electronic-Waste: Management and Challenges)
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