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Toxics
Volume 9
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Toxics, Volume 9, Issue 9 (September 2021) – 32 articles

Cover Story (view full-size image): Schuller et al. here report differential DNA methylation in the sperm of wildfire-smoke exposed mice compared to fresh-air controls, as measured using reduced-representation bisulfite sequencing. Wildfire smoke exposure has been associated with cardiac and respiratory morbidities, and is thought to contribute to aberrant reproductive outcomes and cognitive function. Epigenetic patterns are useful in measuring tissue exposure to toxicants and may help to elucidate mechanisms which underlie the adverse health outcomes associated with exposure. Continued study of wildfire smoke health effects is necessary as wildfire events are burning more land and producing record amounts of harmful chemicals concurrent with climate change. View this paper.
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11 pages, 3613 KiB  
Systematic Review
Insecticide Exposure and Risk of Asthmatic Symptoms: A Systematic Review and Meta-Analysis
by Jiraporn Chittrakul, Ratana Sapbamrer and Wachiranun Sirikul
Toxics 2021, 9(9), 228; https://doi.org/10.3390/toxics9090228 - 21 Sep 2021
Cited by 10 | Viewed by 2822
Abstract
The incidence of respiratory disease is increasing. In relation to this, in addition to infection, factors associated with working with chemical insecticides are a cause for concern. Some of the chemicals involved have been shown to affect the respiratory system, and consequentially workers [...] Read more.
The incidence of respiratory disease is increasing. In relation to this, in addition to infection, factors associated with working with chemical insecticides are a cause for concern. Some of the chemicals involved have been shown to affect the respiratory system, and consequentially workers are at increased risk of conditions such as asthma. However, medical opinion around this area is still controversial; therefore, the objective of this study is to investigate the association between exposure to insecticides and asthma by means of a systematic review of the relevant literature. Relevant literature was identified, and a systematic review was conducted to investigate the association between exposure to insecticides and asthma. A total of five studies (three cross sectional and two cohort) including 45,435 subjects were identified as relevant. The summary odds ratios related to the impact of exposure to specific insecticides on asthma were organophosphates 1.31 (95%CI = 1.17–1.48, I2 = 27%, p = 0.172), carbamates 1.44 (95%CI 1.08–1.92, I2 = 56.7%, p = 0.031) and organochlorines 1.31 (95%CI 1.19–1.64, I2 = 37.3%, p = 0.131). Farmers exposed to certain insecticides may have an increased risk of asthma and asthmatic symptoms, but further research on that issue is urgently needed. Full article
(This article belongs to the Special Issue Frontiers in Occupational and Environmental Exposures: Their Impact on Public Health)
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15 pages, 1842 KiB  
Article
Short-Term Exposure to Wood Smoke Increases the Expression of Pro-Inflammatory Cytokines, Gelatinases, and TIMPs in Guinea Pigs
by Carlos Ramos, Rebeca Cañedo-Mondragón, Carina Becerril, Georgina González-Ávila, Ana Laura Esquivel, Ana Lilia Torres-Machorro and Martha Montaño
Toxics 2021, 9(9), 227; https://doi.org/10.3390/toxics9090227 - 20 Sep 2021
Cited by 9 | Viewed by 2676
Abstract
Exposure to air pollutants in wildfire smoke and indoor pollution causes lung diseases. Short-term exposure to wood smoke (WS) is partially known to alter the expression of human matrix metalloproteinases (MMPs), inflammatory cytokines, and tissue inhibitors of metalloproteinases (TIMPs). Accordingly, we investigated the [...] Read more.
Exposure to air pollutants in wildfire smoke and indoor pollution causes lung diseases. Short-term exposure to wood smoke (WS) is partially known to alter the expression of human matrix metalloproteinases (MMPs), inflammatory cytokines, and tissue inhibitors of metalloproteinases (TIMPs). Accordingly, we investigated the effect of exposing guinea pigs to WS for two and four three-hour periods on different days. The daily content of particles reported by indoor pollution was produced by 60 g of pinewood. We analyzed the cell profile and collagen content in bronchoalveolar lavages (BAL). The mRNA expression of pro-inflammatory cytokines, MMPs, and TIMPs was studied in lung tissue. Cytokines and gelatinolytic activity were analyzed in BAL and serum. The results showed that total cells, macrophages, neutrophils, and collagen increased in BAL, whereas neutrophils and lymphocytes decreased. TGF-β1, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MMP-2, MMP-9, TIMP-1, and TIMP-2 were upregulated in lungs, downregulating IL-12. TNF-α, IFN-γ, TGF-β1, IL-1β, IL-6, and IL-8 were increased in BAL and serum, decreasing IL-12. Gelatinase activity was increased in serum. Thus, guinea pigs exposed to short-term domestic doses of WS overexpressed pro-inflammatory cytokines, MMPs, and TIMPs. These results are similar to ECM remodeling and pulmonary and systemic inflammation reported in humans. Full article
(This article belongs to the Special Issue Exposure to Indoor Hazardous Chemicals and Harmful Impacts on Human Body)
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11 pages, 3513 KiB  
Article
Rutin Exerts Cytotoxic and Senescence-Inducing Properties in Human Melanoma Cells
by Iulia Pinzaru, Raul Chioibas, Iasmina Marcovici, Dorina Coricovac, Razvan Susan, Denisa Predut, Doina Georgescu and Cristina Dehelean
Toxics 2021, 9(9), 226; https://doi.org/10.3390/toxics9090226 - 19 Sep 2021
Cited by 16 | Viewed by 2860
Abstract
Malignant melanoma represents the deadliest type of skin cancer with narrow treatment options in advanced stages. Herbal constituents possessing anticancer properties occupy a particular spot in melanoma research as potential chemotherapeutics. Rutin (RUT) is a natural compound exerting antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and [...] Read more.
Malignant melanoma represents the deadliest type of skin cancer with narrow treatment options in advanced stages. Herbal constituents possessing anticancer properties occupy a particular spot in melanoma research as potential chemotherapeutics. Rutin (RUT) is a natural compound exerting antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and SPF-enhancing activities that are beneficial to the skin; however, its effect as an anti-melanoma agent is less investigated. The current study is focused on assessing the cytotoxic potential of RUT against two different human melanoma cell lines: RPMI-7951 and SK-MEL-28 by evaluating its impact in terms of cell viability, cells’ morphology, and nuclear aspect assessment, and senescence-inducing properties. The results indicate a dose-dependent decrease in the viability of both cell lines, with calculated IC50 values of 64.49 ± 13.27 µM for RPMI-7951 cells and 47.44 ± 2.41 µM for SK-MEL-28, respectively, accompanied by a visible reduction in the cell confluency and apoptotic features within the cell nuclei. RUT exerted a senescence-inducing property highlighted by the elevated expression of senescent-associated beta-galactosidase (SA-β-gal) in SK-MEL-28 cells. Despite the in vitro anti-melanoma effect revealed by our results, further studies are required to elucidate the mechanisms of RUT-induced cytotoxicity and senescence in melanoma cells. Full article
(This article belongs to the Special Issue Toxicity of Cosmetic and Cosmeceutics Formulations)
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13 pages, 2116 KiB  
Article
The Relationship between Metabolic Syndrome and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms
by Tzu-Hua Chen, Wei-Shyang Kung, Hung-Yu Sun, Joh-Jong Huang, Jia-Yi Lu, Kuei-Hau Luo and Hung-Yi Chuang
Toxics 2021, 9(9), 225; https://doi.org/10.3390/toxics9090225 - 16 Sep 2021
Cited by 2 | Viewed by 1958
Abstract
With the escalating global prevalence of metabolic syndrome (MetS), it is crucial to detect the high-risk population early and to prevent chronic diseases. Exposure to various metals has been indicated to promote MetS, but the findings were controversial, and the effect of genetic [...] Read more.
With the escalating global prevalence of metabolic syndrome (MetS), it is crucial to detect the high-risk population early and to prevent chronic diseases. Exposure to various metals has been indicated to promote MetS, but the findings were controversial, and the effect of genetic modification was not considered. Epidermal growth factor receptor (EGFR) was proposed to be involved in the pathway of metabolic disorders, and tumor necrotic factor-α (TNF-α) was regarded as an early inflammatory biomarker for MetS. This research aimed to analyze the impact of EGFR and TNF-α gene polymorphisms on the prevalence of MetS under environmental or occupational exposure to metals. We gathered data from 376 metal industrial workers and 639 non-metal workers, including physical parameters, biochemical data, and plasma concentrations of six metals. According to the genomic database of Taiwan Biobank, 23 single nucleotide polymorphisms (SNPs) on EGFR gene and 6 SNPs on TNF-α gene were incorporated in our research. We applied multivariable logistic regression to analyze the probability of MetS with various SNPs and metals. Our study revealed some susceptible and protective EGFR and TNF-α genotypes under excessive exposure to cobalt, zinc, selenium, and lead. Thus, we remind the high-risk population of taking measures to prevent MetS. Full article
(This article belongs to the Section Toxicology)
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30 pages, 7683 KiB  
Review
Microplastics in the Environment: Intake through the Food Web, Human Exposure and Toxicological Effects
by Concetta Pironti, Maria Ricciardi, Oriana Motta, Ylenia Miele, Antonio Proto and Luigi Montano
Toxics 2021, 9(9), 224; https://doi.org/10.3390/toxics9090224 - 16 Sep 2021
Cited by 102 | Viewed by 19358
Abstract
Recently, studies on microplastics (MPs) have increased rapidly due to the growing awareness of the potential health risks related to their occurrence. The first part of this review is devoted to MP occurrence, distribution, and quantification. MPs can be transferred from the environment [...] Read more.
Recently, studies on microplastics (MPs) have increased rapidly due to the growing awareness of the potential health risks related to their occurrence. The first part of this review is devoted to MP occurrence, distribution, and quantification. MPs can be transferred from the environment to humans mainly through inhalation, secondly from ingestion, and, to a lesser extent, through dermal contact. As regards food web contamination, we discuss the microplastic presence not only in the most investigated sources, such as seafood, drinking water, and salts, but also in other foods such as honey, sugar, milk, fruit, and meat (chickens, cows, and pigs). All literature data suggest not-negligible human exposure to MPs through the above-mentioned routes. Consequently, several research efforts have been devoted to assessing potential human health risks. Initially, toxicological studies were conducted with aquatic organisms and then with experimental mammal animal models and human cell cultures. In the latter case, toxicological effects were observed at high concentrations of MPs (polystyrene is the most common MP benchmark) for a short time. Further studies must be performed to assess the real consequences of MP contamination at low concentrations and prolonged exposure. Full article
(This article belongs to the Special Issue Fate and Effects of Micro- and Nanoplastics in Soil and Aquatic Ecosystems)
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12 pages, 2260 KiB  
Article
Removal of Carbon Nanotubes from Aqueous Solutions by Sodium Hypochlorite: Effects of Treatment Conditions
by Mei Yang, Toshiya Okazaki and Minfang Zhang
Toxics 2021, 9(9), 223; https://doi.org/10.3390/toxics9090223 - 16 Sep 2021
Cited by 4 | Viewed by 1908
Abstract
The treatment of carbon nanotubes (CNTs) containing wastewater has become an important issue with increasing industrial application due to the risk CNTs may pose to the environment and human health. However, an effective method for treating wastewater containing CNTs has not been established. [...] Read more.
The treatment of carbon nanotubes (CNTs) containing wastewater has become an important issue with increasing industrial application due to the risk CNTs may pose to the environment and human health. However, an effective method for treating wastewater containing CNTs has not been established. Recently, we proposed a method to remove CNTs from aqueous dispersions using sodium hypochlorite (NaClO). To explore the practical applications of this method, we herein investigate the influence of different conditions, such as NaClO concentration, reaction temperature, pH value, and CNT concentration, on the CNT degradation rate. The results showed that the degradation of CNTs depends strongly on temperature and NaClO concentration: the higher the temperature and NaClO concentration, the faster the degradation rate. The optimal temperature and NaClO concentration are 50–70 °C and 2–3 wt%, respectively. Lower pH accelerated the degradation rate but induced the decomposition of NaClO. Furthermore, dispersants and other substances in the solution may also consume NaClO, thus affecting the degradation of CNTs. These findings are of significance for establishing a standard technique for CNT-containing industrial wastewater treatment, and for advancing the environmental sustainability of the CNT industry. Full article
(This article belongs to the Special Issue Advanced Technologies to Remove Toxic Compounds in Wastewater)
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20 pages, 9340 KiB  
Article
Synthesis and Decontamination Effect on Chemical and Biological Agents of Benzoxonium-Like Salts
by Aneta Markova, Michaela Hympanova, Marek Matula, Lukas Prchal, Radek Sleha, Marketa Benkova, Lenka Pulkrabkova, Ondrej Soukup, Zuzana Krocova, Daniel Jun and Jan Marek
Toxics 2021, 9(9), 222; https://doi.org/10.3390/toxics9090222 - 15 Sep 2021
Cited by 2 | Viewed by 2384
Abstract
Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C10-C18 set of benzoxonium-like [...] Read more.
Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C10-C18 set of benzoxonium-like salts to evaluate the effect of their chemical and biological decontamination capabilities. In particular, biocidal activity against a panel of bacterial strains including Staphylococcus aureus in biofilm form was screened. In addition, the most promising compounds were successfully tested against Francisella tularensis as a representative of potential biological warfare agents. From a point of view of chemical warfare protection, the efficiency of BOC-like compounds to degrade the organophosphate simulant fenitrothion was examined. Notwithstanding that no single compound with universal effectiveness was identified, a mixture of only two compounds from this group would be able to satisfactorily cover the proposed decontamination spectrum. In addition, the compounds were evaluated for their cytotoxicity as a basic safety parameter for potential use in practice. In summary, the dual effect on chemical and biological agents of benzoxonium-like salts offer attractive potential as active components of decontamination mixtures in the case of a terrorist threat or chemical or biological accidents. Full article
(This article belongs to the Special Issue Chemical and Biological Threats, Hazard Potential and Countermeasures)
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12 pages, 839 KiB  
Article
Relationships between Long-Term Ozone Exposure and Allergic Rhinitis and Bronchitic Symptoms in Chinese Children
by Pei-En Zhou, Zhengmin (Min) Qian, Stephen Edward McMillin, Michael G. Vaughn, Zhong-Yue Xie, Yu-Jie Xu, Li-Zi Lin, Li-Wen Hu, Bo-Yi Yang, Xiao-Wen Zeng, Wang-Jian Zhang, Ru-Qing Liu, Gongbo Chen and Guang-Hui Dong
Toxics 2021, 9(9), 221; https://doi.org/10.3390/toxics9090221 - 14 Sep 2021
Cited by 10 | Viewed by 2684
Abstract
Numerous studies have demonstrated that exposure to ambient ozone (O3) could have adverse effects on children’s respiratory health. However, previous studies mainly focused on asthma and wheezing. Evidence for allergic rhinitis and bronchitic symptoms (e.g., persistent cough and phlegm) associated with [...] Read more.
Numerous studies have demonstrated that exposure to ambient ozone (O3) could have adverse effects on children’s respiratory health. However, previous studies mainly focused on asthma and wheezing. Evidence for allergic rhinitis and bronchitic symptoms (e.g., persistent cough and phlegm) associated with O3 is limited, and results from existing studies are inconsistent. This study included a total of 59,754 children from the seven northeastern cities study (SNEC), who were aged 2 to 17 years and from 94 kindergarten, elementary and middle schools. Information on doctor-diagnosed allergic rhinitis (AR), persistent cough, and persistent phlegm was collected during 2012–2013 using a standardized questionnaire developed by the American Thoracic Society (ATS). Information for potential confounders was also collected via questionnaire. Individuals’ exposure to ambient ozone (O3) during the four years before the investigation was estimated using a satellite-based random forest model. A higher level of O3 was significantly associated with increased risk of AR and bronchitic symptoms. After controlling for potential confounders, the OR (95% CI) were 1.13 (1.07–1.18), 1.10 (1.06–1.16), and 1.12 (1.05–1.20) for AR, persistent cough, and persistent phlegm, respectively, associated with each interquartile range (IQR) rise in O3 concentration. Interaction analyses showed stronger adverse effects of O3 on AR in children aged 7–17 years than those aged 2–6 years, while the adverse association of O3 with cough was more prominent in females and children aged 7–12 years than in males and children aged 2–6 and 13–17 years. This study showed that long-term exposure to ambient O3 was significantly associated with higher risk of AR and bronchitic symptoms in children, and the association varies across age and gender. Our findings contribute additional evidence for the importance of controlling O3 pollution and protecting children from O3 exposure. Full article
(This article belongs to the Special Issue Integrated Effects of Air Pollutions and Climate Change on Human Health)
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11 pages, 1847 KiB  
Article
A Glyphosate-Based Formulation but Not Glyphosate Alone Alters Human Placental Integrity
by Christelle Simasotchi, Audrey Chissey, Gérald Jungers, Thierry Fournier, Gilles-Eric Seralini and Sophie Gil
Toxics 2021, 9(9), 220; https://doi.org/10.3390/toxics9090220 - 13 Sep 2021
Cited by 9 | Viewed by 2728
Abstract
Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, [...] Read more.
Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity. Full article
(This article belongs to the Section Toxicology)
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18 pages, 1166 KiB  
Article
Blood Toxic Elements and Effects on Plasma Vitamins and Carotenoids in Two Wild Bird Species: Turdus merula and Columba livia
by Pablo Sánchez-Virosta, José Manuel Zamora-Marín, Mario León-Ortega, Pedro J. Jiménez, Silvia Rivas, Lidia Sánchez-Morales, Pablo R. Camarero, Rafael Mateo, Manuel Zumbado, Octavio P. Luzardo, Tapio Eeva, Antonio J. García-Fernández and Silvia Espín
Toxics 2021, 9(9), 219; https://doi.org/10.3390/toxics9090219 - 11 Sep 2021
Cited by 3 | Viewed by 2538
Abstract
Birds have historically suffered adverse effects by toxic elements, such as As, Pb, Hg, and Cd. However, reports on exposure to a wide range of elements, including rare earth elements and other minor elements of emerging concern, and the potential consequences for wildlife [...] Read more.
Birds have historically suffered adverse effects by toxic elements, such as As, Pb, Hg, and Cd. However, reports on exposure to a wide range of elements, including rare earth elements and other minor elements of emerging concern, and the potential consequences for wildlife are still scarce. This study evaluates blood concentrations of 50 elements and their related effects on lutein and vitamin levels in the Eurasian blackbird (Turdus merula) and wild rock pigeon (Columba livia), inhabiting different scenarios of contaminant exposure. Blood concentrations of As, Cd, and Pb (and Mn in T. merula) were increased in both species captured in the mining area, compared to the control site. T. merula also showed increased As, Cd, and Pb concentrations in blood in the agricultural–urban area, as compared to the control area, together with the highest Hg levels, which could be related to agricultural practices and industrial activities. Decreases of 33 and 38% in the plasma retinol levels in T. merula inhabiting the mining and the agricultural–urban areas, respectively, as compared to the control site, were associated with increased Pb, As, and Cd exposure. This could be due to a metal-driven suppressive effect in retinol metabolism and/or its over-use for coping with metal-related oxidative stress. Full article
(This article belongs to the Special Issue Wildlife Toxicology: An Update on Contaminant Exposure and Effects)
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12 pages, 539 KiB  
Review
Toxicity in Peripheral Nerves: An Overview
by Wolfgang Grisold and Valentina Alda Carozzi
Toxics 2021, 9(9), 218; https://doi.org/10.3390/toxics9090218 - 11 Sep 2021
Cited by 8 | Viewed by 3913
Abstract
Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, [...] Read more.
Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification. Full article
(This article belongs to the Special Issue Toxic Neuropathy: Mechanisms, Causes, Risk Exposure, Diagnosis, Prevention and Therapeutic Options)
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14 pages, 953 KiB  
Article
Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure
by Chung-Yao Hsu, Yao-Chung Chuang, Fang-Chia Chang, Hung-Yi Chuang, Terry Ting-Yu Chiou and Chien-Te Lee
Toxics 2021, 9(9), 217; https://doi.org/10.3390/toxics9090217 - 10 Sep 2021
Cited by 3 | Viewed by 2108
Abstract
Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead [...] Read more.
Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep–wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including rPer1, rPer2, and rBmal1b, were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep–wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of rPer1 and rPer2 and the feedback repression of rBmal1b. We concluded that chronic lead exposure has a negative impact on the sleep–wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus. Full article
(This article belongs to the Special Issue Heavy Metal Exposure and Gene Expression)
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13 pages, 5046 KiB  
Article
Air Phthalate Emitted from Flooring Building Material by the Micro-Chamber Method: Two-Stage Emission Evaluation and Comparison
by Wu-Ting Lin, Chung-Yu Chen, Ching-Chang Lee, Cheng-Chen Chen and Shih-Chi Lo
Toxics 2021, 9(9), 216; https://doi.org/10.3390/toxics9090216 - 09 Sep 2021
Cited by 7 | Viewed by 2359
Abstract
The phthalate and semi-volatile organic compounds (SVOCs) are modern chemical substances and extensively existing in the indoor environment. The European Commission stipulated the “European Unified Test Criteria”, since 2011, for the declared specifications of building products (CEN/TS 16516), based on the “lowest concentrations [...] Read more.
The phthalate and semi-volatile organic compounds (SVOCs) are modern chemical substances and extensively existing in the indoor environment. The European Commission stipulated the “European Unified Test Criteria”, since 2011, for the declared specifications of building products (CEN/TS 16516), based on the “lowest concentrations of interest (LCI)”, the index pollutants, test method, and emission standard of “phthalate” and “SVOC” were specified in detail. The purpose of this study is to use six common indoor floor construction products in Taiwan (regenerated pseudoplastic rubber flooring, healthy pseudoplastic imitation wood floor, regenerated pseudoplastic rubber flooring, PVC floor tile/floor, plastic click floor, composite floor covered with carpet) to detect the changes in the concentration of phthalate emitted to the air. The ISO 16000-25 Indoor air—Part 25: Determination of the emission of semi-volatile organic compounds by building products—micro-chamber method is used to build a DS-BMEMC (glass micro-chamber: volume 630 mL), the SVOC, including phthalate, is collected in two stages, in the stable conditions of temperature 25 °C, relative humidity 50% and air change rate 2 times/h, the Stage 1 emission detection experiment (24 h) is performed, and then the Stage 2 heating-up desorption emission detection experiment (40 min air sampling) is performed, the temperature rises to 200–220 °C, the phthalate and SVOC adsorbed on the glass micro-chamber is desorbed at a high temperature to catch the air substances, the air is caught by Tenax®—TA and Florisil® adsorption tube, and then the GC/MS and LC/MSMS analysis methods are used for qualitative and emission concentration analyses of SVOC of two-stage emission, respectively. The findings show that the floor construction materials emit nine phthalate SVOCs: DEHP, DINP, DNOP, DIDP, BBP, DBP, DIBP, DEP, and DMP, the two-stage emission concentrations are different, Stage 1 (normal temperature) emission concentration of six floor construction materials is 0.01–1.2% of Stage 2 (high temperature) emission concentration, meaning the phthalate SVOC of floor construction materials is unlikely to be volatilized or emitted at normal temperature. An interesting finding is that only S3 was detected DINP 72.6 (μg/m3) in stage 1. Others were detected DINP in stage 2. This might be because S3 has carpet on the surface. This implies that floor material with carpet may have an emission of DINP at normal temperature. The result of this study refers to the limited value evaluation of EU structural material standard emission TSVOC ≤ 0.1 ug/m3, the floor building material emissions are much higher than the evaluation criteria, increasing the health risk of users. The detection method and baseline can be used as the standard for controlling the emission of phthalate SVOC of Taiwan’s green building material labeling system in the future. Full article
(This article belongs to the Special Issue Plasticizer Exposure: Harmful Impact on Human Health)
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23 pages, 4539 KiB  
Article
Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice
by Karen Chiu, Shah Tauseef Bashir, Liying Gao, Jessica Gutierrez, Maria R. C. de Godoy, Jenny Drnevich, Christopher J. Fields, Isaac Cann, Jodi A. Flaws and Romana A. Nowak
Toxics 2021, 9(9), 215; https://doi.org/10.3390/toxics9090215 - 09 Sep 2021
Cited by 5 | Viewed by 2571
Abstract
Di-2-ethylhexyl phthalate (DEHP) is a plasticizer commonly found in polyvinyl chloride, medical equipment, and food packaging. DEHP has been shown to target the reproductive system and alter the gut microbiome in humans and experimental animals. However, very little is known about the impact [...] Read more.
Di-2-ethylhexyl phthalate (DEHP) is a plasticizer commonly found in polyvinyl chloride, medical equipment, and food packaging. DEHP has been shown to target the reproductive system and alter the gut microbiome in humans and experimental animals. However, very little is known about the impact of DEHP-induced microbiome changes and its effects during pregnancy. Thus, the objective of this study was to investigate the effects of DEHP exposure during pregnancy on the cecal microbiome and pregnancy outcomes. Specifically, this study tested the hypothesis that subacute exposure to DEHP during pregnancy alters the cecal microbiome in pregnant mice, leading to changes in birth outcomes. To test this hypothesis, pregnant dams were orally exposed to corn oil vehicle or 20 µg/kg/day DEHP for 10 days and euthanized 21 days after their last dose. Cecal contents were collected for 16S Illumina and shotgun metagenomic sequencing. Fertility studies were also conducted to examine whether DEHP exposure impacted birth outcomes. Subacute exposure to environmentally relevant doses of DEHP in pregnant dams significantly increased alpha diversity and significantly altered beta diversity. Furthermore, DEHP exposure during pregnancy significantly increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes and Deferribacteres compared with controls. The affected taxonomic families included Deferribacteraceae, Lachnospiraceae, and Mucisprillum. In addition to changes in the gut microbiota, DEHP exposure significantly altered 14 functional pathways compared with the control. Finally, DEHP exposure did not significantly impact the fertility and birth outcomes compared with the control. Collectively, these data indicate that DEHP exposure during pregnancy shifts the cecal microbiome, but the shifts do not impact fertility and birth outcomes. Full article
(This article belongs to the Section Toxicology)
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18 pages, 2631 KiB  
Article
The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice
by Conner L. Kennedy, Audrey Spiegelhoff, Kathy Wang, Thomas Lavery, Alexandra Nunez, Robbie Manuel, Lauren Hillers-Ziemer, Lisa M. Arendt and Kimberly P. Keil Stietz
Toxics 2021, 9(9), 214; https://doi.org/10.3390/toxics9090214 - 08 Sep 2021
Cited by 3 | Viewed by 2250
Abstract
Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls [...] Read more.
Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls (PCBs) leads to changes in immune cells within the bladder of young mice. Female mice were exposed to an environmentally relevant mixture of PCBs through gestation and lactation, and bladders were collected from offspring at postnatal day (P) 28–31. We identify several dose- and sex-dependent PCB effects in the bladder. The lowest concentration of PCB (0.1 mg/kg/d) increased CD45+ hematolymphoid immune cells in both sexes. While PCBs had no effect on CD79b+ B cells or CD3+ T cells, PCBs (0.1 mg/kg/d) did increase F4/80+ macrophages particularly in female bladder. Collagen density was also examined to determine whether inflammatory events coincide with changes in the stromal extracellular matrix. PCBs (0.1 mg/kg/d) decreased collagen density in female bladder compared to control. PCBs also increased the number of cells undergoing cell division predominantly in male bladder. These results implicate perturbations to the immune system in relation to PCB effects on the bladder. Future study to define the underlying mechanisms could help understand how environmental factors can be risk factors for lower urinary tract symptoms. Full article
(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)
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20 pages, 1696 KiB  
Article
Potential Environmental Risk Characteristics of PCB Transformation Products in the Environmental Medium
by Minghao Li, Wei He, Hao Yang, Shimei Sun and Yu Li
Toxics 2021, 9(9), 213; https://doi.org/10.3390/toxics9090213 - 07 Sep 2021
Cited by 2 | Viewed by 2085
Abstract
The complementary construction of polychlorinated biphenyl (PCB) phytotoxicity and the biotoxicity 3D-QSAR model, combined with the constructed PCB environmental risk characterization model, was carried out to evaluate the persistent organic pollutant (POP) properties (toxicity (phytotoxicity and biotoxicity), bioconcentration, migration, and persistence) of PCBs [...] Read more.
The complementary construction of polychlorinated biphenyl (PCB) phytotoxicity and the biotoxicity 3D-QSAR model, combined with the constructed PCB environmental risk characterization model, was carried out to evaluate the persistent organic pollutant (POP) properties (toxicity (phytotoxicity and biotoxicity), bioconcentration, migration, and persistence) of PCBs and their corresponding transformation products (phytodegradation, microbial degradation, biometabolism, and photodegradation). The transformation path with a significant increase in environmental risks was analyzed. Some environmentally friendly PCB derivatives, exhibiting a good modification effect, and their parent molecules were selected as precursor molecules. Their transformation processes were simulated and evaluated for assessing the environmental risks. Some transformation products displayed increased environmental risks. The environmental risks of plant degradation products of the PCBs in the environmental media showed the maximum risk, indicating that the potential risks of the transformation products of the PCBs and their environmentally friendly derivatives could not be neglected. It is essential to further improve the ability of plants to degrade their transformation products. The improvement of some degradation products for environmentally friendly PCB derivatives indicates that the theoretical modification of a single environmental feature cannot completely control the potential environmental risks of molecules. In addition, this method can be used to analyze and evaluate environmentally friendly PCB derivatives to avoid and reduce the potential environmental and human health risks caused by environmentally friendly PCB derivatives. Full article
(This article belongs to the Special Issue The Transformation Mechanism and Environmental Effects of Emerging Pollutants)
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13 pages, 2763 KiB  
Article
Elevated IgG Antibody to Aluminum Bound to Human Serum Albumin in Patients with Crohn’s, Celiac and Alzheimer’s Disease
by Aristo Vojdani
Toxics 2021, 9(9), 212; https://doi.org/10.3390/toxics9090212 - 04 Sep 2021
Cited by 3 | Viewed by 2522
Abstract
Aluminum is in our water and food, and is used as an adjuvant in vaccines. About 40% of the ingested dose accumulates within the intestinal mucosa, making the gut the main target of inflammation and autoimmunity; about 1% accumulates in the skeletal system [...] Read more.
Aluminum is in our water and food, and is used as an adjuvant in vaccines. About 40% of the ingested dose accumulates within the intestinal mucosa, making the gut the main target of inflammation and autoimmunity; about 1% accumulates in the skeletal system and brain, inducing the cross-linking of amyloid-β-42 peptide and the formation of amyloid aggregates associated with Alzheimer’s disease. To examine whether the accumulation of aluminum in the gut and brain tissues results in neoantigen formation, we bound aluminum compounds to human serum albumin. We used ELISA to measure IgG antibody in 94 different sera from healthy controls and 47 sera from each group of patients: anti-Saccharomyces cerevisiae antibody-positive (Crohn’s), and positive for deamidated α-gliadin and transglutaminase-2 IgA antibodies (celiac disease), autoimmune disorders associated with intestinal tissue antigens. Because earlier studies have shown that aluminum exposure is linked to Alzheimer’s disease etiology, and high aluminum content is detected in Alzheimer’s patients’ brain tissue, we also measured aluminum antibody in the blood of these patients. Additionally, we measured aluminum antibody in the sera of mixed connective tissue disease patients who were positive for antinuclear antibodies, and used them as disease controls. We found significant IgG antibody elevation against all three aluminum compounds in the sera of patients with Crohn’s, celiac and Alzheimer’s disease, but not in patients with mixed connective tissue disease. We concluded that aluminum ingestion and absorption from the GI tract and brain may contribute to Crohn’s, celiac and Alzheimer’s disease, but not to mixed connective tissue disease. Full article
(This article belongs to the Section Toxicology)
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20 pages, 3662 KiB  
Article
Environmentally Relevant Levels of Depleted Uranium Impacts Dermal Fibroblast Proliferation, Viability, Metabolic Activity, and Scratch Closure
by Nathan Cruz, Robert Buscaglia, Matthew Salanga and Robert Kellar
Toxics 2021, 9(9), 211; https://doi.org/10.3390/toxics9090211 - 03 Sep 2021
Cited by 1 | Viewed by 2287
Abstract
Uranium (U) is a heavy metal used in military and industrial settings, with a large portion being mined from the Southwest region of the United States. Uranium has uses in energy and military weaponry, but the mining process has released U into soil [...] Read more.
Uranium (U) is a heavy metal used in military and industrial settings, with a large portion being mined from the Southwest region of the United States. Uranium has uses in energy and military weaponry, but the mining process has released U into soil and surface waters that may pose threats to human and environmental health. The majority of literature regarding U’s human health concern focuses on outcomes based on unintentional ingestion or inhalation, and limited data are available about its influence via cutaneous contact. Utilizing skin dermis cells, we evaluated U’s topical chemotoxicity. Employing soluble depleted uranium (DU) in the form of uranyl nitrate (UN), we hypothesized that in vitro exposure of UN will have cytotoxic effects on primary dermal fibroblasts by affecting cell viability and metabolic activity and, further, may delay wound healing aspects via altering cell proliferation and migration. Using environmentally relevant levels of U found in water (0.1 μM to 100 μM [UN]; 23.8–23,800 ppb [U]), we quantified cellular mitosis and migration through growth curves and in vitro scratch assays. Cells were exposed from 24 h to 144 h for a time-course evaluation of UN chemical toxicity. The effects of UN were observed at concentrations above and below the Environmental Protection Agency threshold for safe exposure limits. UN exposure resulted in a dose-dependent decrease in the viable cell count; however, it produced an increase in metabolism when corrected for the viable cells present. Furthermore, cellular proliferation, population doubling, and percent closure was hindered at levels ≥10 μM UN. Therefore, inadvertent exposure may exacerbate pre-existing skin diseases in at-risk demographics, and additionally, it may substantially interfere in cutaneous tissue repair processes. Full article
(This article belongs to the Section Toxicology)
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20 pages, 15781 KiB  
Article
A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density
by Yasmin Arezki, Juliette Cornacchia, Mickaël Rapp, Luc Lebeau, Françoise Pons and Carole Ronzani
Toxics 2021, 9(9), 210; https://doi.org/10.3390/toxics9090210 - 31 Aug 2021
Cited by 2 | Viewed by 2763
Abstract
This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as [...] Read more.
This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Qek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = −43.3 mV); CD-PEI600 (Qek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Qek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Qek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges. Full article
(This article belongs to the Special Issue Assessment of the (Eco)Toxicity of Nanomaterials)
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8 pages, 235 KiB  
Article
Ambient Air Pollution and Stillbirths Risk in Sydney, Australia
by Bin Jalaludin, Farhad Salimi, Mahsan Sadeghi, Laura Collie and Geoffrey Morgan
Toxics 2021, 9(9), 209; https://doi.org/10.3390/toxics9090209 - 31 Aug 2021
Cited by 5 | Viewed by 1987
Abstract
We aimed to determine the associations between ambient air pollution, specifically particulate matter less than or equal to 10 microns and 2.5 microns (PM10 and PM2.5 respectively) and ozone (O3), and stillbirths. We analysed all singleton births between 20–42 [...] Read more.
We aimed to determine the associations between ambient air pollution, specifically particulate matter less than or equal to 10 microns and 2.5 microns (PM10 and PM2.5 respectively) and ozone (O3), and stillbirths. We analysed all singleton births between 20–42 weeks gestation in metropolitan Sydney, Australia, from 1997 to 2012. We implemented logistic regression to assess the associations between air pollutants and stillbirth for each trimester and for the entire pregnancy. Over the study period, there were 967,694 live births and 4287 stillbirths. Mean levels of PM10, PM2.5 and O3 for the entire pregnancy were 17.9 µg/m3, 7.1 µg/m3 and 3.2 ppb, respectively. Adjusted odds ratios were generally greater than unity for associations between PM and stillbirths, but none were statistically significant. There were no significant associations between O3 and stillbirths. There was potential effect modification of the PM10 and O3 association by maternal age. We did not find consistent evidence of associations between PM and O3 and stillbirths in Sydney, Australia. More high quality birth cohort studies are required to clarify associations between air pollution and stillbirths. Full article
(This article belongs to the Collection Exposure and Effects of Environmental Pollution on Vulnerable Populations)
15 pages, 2104 KiB  
Article
Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease
by Vivek Vardhan Veerapaneni, Swapna Upadhyay, Tania A. Thimraj, Jayaraj Biligere Siddaiah, Chaya Sindaghatta Krishnarao, Komarla Sundararaja Lokesh, Rajesh Thimmulappa, Lena Palmberg, Koustav Ganguly and Mahesh Padukudru Anand
Toxics 2021, 9(9), 208; https://doi.org/10.3390/toxics9090208 - 31 Aug 2021
Cited by 3 | Viewed by 2313
Abstract
Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD [...] Read more.
Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study (n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air–liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly (p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3–2.4) and TS-COPD (1.8; 1.4–2.5) subjects compared to TS-CONTROL (3.3; 2.9–3.5) and healthy controls (5.1; 4.5–7.2). The levels of SCGB1A1 were positively correlated (r = 0.7–0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly (p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly (p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts. Full article
(This article belongs to the Special Issue Effects of Exposure to Air Pollution on Respiratory Health)
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24 pages, 1410 KiB  
Review
Mechanisms of Neurotoxicity Associated with Exposure to the Herbicide Atrazine
by Sydney C. Stradtman and Jennifer L. Freeman
Toxics 2021, 9(9), 207; https://doi.org/10.3390/toxics9090207 - 31 Aug 2021
Cited by 29 | Viewed by 5978
Abstract
Atrazine is an herbicide commonly used on crops to prevent broadleaf weeds. Atrazine is an endocrine-disrupting chemical mainly targeting the neuroendocrine system and associated axes, especially as a reproductive toxicant through attenuation of the luteinizing hormone (LH). Current regulatory levels for chronic exposure [...] Read more.
Atrazine is an herbicide commonly used on crops to prevent broadleaf weeds. Atrazine is an endocrine-disrupting chemical mainly targeting the neuroendocrine system and associated axes, especially as a reproductive toxicant through attenuation of the luteinizing hormone (LH). Current regulatory levels for chronic exposure are based on no observed adverse effect levels (NOAELs) of these LH alterations in rodent studies. Atrazine has also been studied for its effects on the central nervous system and neurotransmission. The European Union (EU) recognized the health risks of atrazine exposure as a public health concern with no way to contain contamination of drinking water. As such, the EU banned atrazine use in 2003. The United States recently reapproved atrazine’s use in the fall of 2020. Research has shown that there is a wide array of adverse health effects that are seen across multiple models, exposure times, and exposure periods leading to dysfunction in many different systems in the body with most pointing to a neuroendocrine target of toxicity. There is evidence of crosstalk between systems that can be affected by atrazine exposure, causing widespread dysfunction and leading to changes in behavior even with no direct link to the hypothalamus. The hypothetical mechanism of toxicity of atrazine endocrine disruption and neurotoxicity can therefore be described as a web of pathways that are influenced through changes occurring in each and their multiple feedback loops with further research needed to refine NOAELs for neurotoxic outcomes. Full article
(This article belongs to the Collection Xenobiotics in Developmental Neurotoxicity)
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10 pages, 888 KiB  
Communication
Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice
by Karl F. W. Foley, Daniel Barnett, Deborah A. Cory-Slechta and Houhui Xia
Toxics 2021, 9(9), 206; https://doi.org/10.3390/toxics9090206 - 31 Aug 2021
Cited by 3 | Viewed by 1821
Abstract
Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to [...] Read more.
Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to shed light on potential mechanistic underpinnings, including changes in synaptic transmission and plasticity. However, previous studies relied on extended exposure into adulthood, and little is known about the effect of arsenic exposure in early development. Here, we studied the effects of early developmental arsenic exposure in juvenile mice on synaptic transmission and plasticity in the hippocampus. C57BL/6J females were exposed to arsenic (0, 50 ppb, 36 ppm) via drinking water two weeks prior to mating, with continued exposure throughout gestation and parturition. Electrophysiological recordings were then performed on juvenile offspring prior to weaning. In this paradigm, the offspring are exposed to arsenic indirectly, via the mother. We found that high (36 ppm) and relatively low (50 ppb) arsenic exposure both decreased basal synaptic transmission. A compensatory increase in pre-synaptic vesicular release was only observed in the high-exposure group. These results suggest that indirect, ecologically relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies. Full article
(This article belongs to the Special Issue Developmental Exposure to Environmental Contaminants)
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17 pages, 6544 KiB  
Article
Metabolic Response of RAW 264.7 Macrophages to Exposure to Crude Particulate Matter and a Reduced Content of Organic Matter
by Monika Jankowska-Kieltyka, Adam Roman, Magdalena Mikrut, Marta Kowalska, Rudi van Eldik and Irena Nalepa
Toxics 2021, 9(9), 205; https://doi.org/10.3390/toxics9090205 - 30 Aug 2021
Cited by 5 | Viewed by 2252
Abstract
Exposure to air pollution from various airborne particulate matter (PM) is regarded as a potential health risk. Airborne PM penetrates the lungs, where it is taken up by macrophages, what results in macrophage activation and can potentially lead to negative consequences for the [...] Read more.
Exposure to air pollution from various airborne particulate matter (PM) is regarded as a potential health risk. Airborne PM penetrates the lungs, where it is taken up by macrophages, what results in macrophage activation and can potentially lead to negative consequences for the organism. In the present study, we assessed the effects of direct exposure of RAW 264.7 macrophages to crude PM (NIST1648a) and to a reduced content of organic matter (LAp120) for up to 72 h on selected parameters of metabolic activity. These included cell viability and apoptosis, metabolic activity and cell number, ROS synthesis, nitric oxide (NO) release, and oxidative burst. The results indicated that both NIST1648a and LAp120 negatively influenced the parameters of cell viability and metabolic activity due to increased ROS synthesis. The negative effect of PM was concentration-dependent; i.e., it was the most pronounced for the highest concentration applied. The impact of PM also depended on the time of exposure, so at respective time points, PM induced different effects. There were also differences in the impact of NIST1648a and LAp120 on almost all parameters tested. The negative effect of LAp120 was more pronounced, what appeared to be associated with an increased content of metals. Full article
(This article belongs to the Section Toxicology)
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15 pages, 1038 KiB  
Article
Relationship between Occupational Exposure to Airborne Nanoparticles, Nanoparticle Lung Burden and Lung Diseases
by Valérie Forest, Jérémie Pourchez, Carole Pélissier, Sabyne Audignon Durand, Jean-Michel Vergnon and Luc Fontana
Toxics 2021, 9(9), 204; https://doi.org/10.3390/toxics9090204 - 30 Aug 2021
Cited by 13 | Viewed by 3107
Abstract
The biomonitoring of nanoparticles in patients’ broncho-alveolar lavages (BAL) could allow getting insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Our objective was to investigate the relationship between the biomonitoring of nanoparticles in BAL, interstitial lung [...] Read more.
The biomonitoring of nanoparticles in patients’ broncho-alveolar lavages (BAL) could allow getting insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Our objective was to investigate the relationship between the biomonitoring of nanoparticles in BAL, interstitial lung diseases and occupational exposure to these particles released unintentionally. We analyzed data from a cohort of 100 patients suffering from lung diseases (NanoPI clinical trial, ClinicalTrials.gov Identifier: NCT02549248) and observed that most of the patients showed a high probability of exposure to airborne unintentionally released nanoparticles (>50%), suggesting a potential role of inhaled nanoparticles in lung physiopathology. Depending on the respiratory disease, the amount of patients likely exposed to unintentionally released nanoparticles was variable (e.g., from 88% for idiopathic pulmonary fibrosis to 54% for sarcoidosis). These findings are consistent with the previously performed mineralogical analyses of BAL samples that suggested (i) a role of titanium nanoparticles in idiopathic pulmonary fibrosis and (ii) a contribution of silica submicron particles to sarcoidosis. Further investigations are necessary to draw firm conclusions but these first results strengthen the array of presumptions on the contribution of some inhaled particles (from nano to submicron size) to some idiopathic lung diseases. Full article
(This article belongs to the Special Issue Human Biomonitoring in Health Risk Assessment: Current Practices and Recommendations for the Future)
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10 pages, 2150 KiB  
Article
MTF1 Is Essential for the Expression of MT1B, MT1F, MT1G, and MT1H Induced by PHMG, but Not CMIT, in the Human Pulmonary Alveolar Epithelial Cells
by Sang-Hoon Jeong, Cherry Kim, Jaeyoung Kim, Yoon-Jeong Nam, Hong Lee, Ariunaa Togloom, Ja-Young Kang, Jin-Young Choi, Hyejin Lee, Myeong-Ok Song, Eun-Kee Park, Yong-Wook Baek, Ju-Han Lee and Ki-Yeol Lee
Toxics 2021, 9(9), 203; https://doi.org/10.3390/toxics9090203 - 29 Aug 2021
Cited by 8 | Viewed by 2874
Abstract
The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are [...] Read more.
The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are poorly understood. In this study, RNA sequencing (RNA-seq) data showed that the expression levels of metallothionein-1 (MT1) isoforms, including MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X, were increased in human pulmonary alveolar epithelial cells (HPAEpiCs) that were treated with PHMG but not in those treated with CMIT. Moreover, upregulation of MT1B, MT1F, MT1G, and MT1H was observed only in PHMG-treated HPAEpiCs. The protein expression level of metal regulatory transcription factor 1 (MTF1), which binds to the promoters of MT1 isoforms, was increased in PHMG-treated HPAEpiCs but not in CMIT-treated HPAEpiCs. However, the expression of early growth response 1 (EGR1) and nuclear receptor superfamily 3, group C, member 1 (NR3C1), other transcriptional regulators involved in MT1 isomers, were increased regardless of treatment with PHMG or CMIT. These results suggest that MTF1 is an essential transcription factor for the induction of MT1B, MT1F, MT1G, and MT1H by PHMG but not by CMIT. Full article
(This article belongs to the Section Toxicology)
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17 pages, 2556 KiB  
Article
Acute Cd Toxicity, Metal Accumulation, and Ion Loss in Southern Catfish (Silurus meridionalis Chen)
by Wenming Liu, Hanxun Qiu, Yulian Yan and Xiaojun Xie
Toxics 2021, 9(9), 202; https://doi.org/10.3390/toxics9090202 - 29 Aug 2021
Cited by 6 | Viewed by 2326
Abstract
The amounts of cadmium in multiple organs and the amounts of Na+ and Ca2+ in the carcass were measured in dead and surviving southern catfish exposed to different concentrations of Cd. The 96 h median lethal concentration was 6.85 mg/L. The [...] Read more.
The amounts of cadmium in multiple organs and the amounts of Na+ and Ca2+ in the carcass were measured in dead and surviving southern catfish exposed to different concentrations of Cd. The 96 h median lethal concentration was 6.85 mg/L. The Cd content and Cd accumulation rate were positively correlated with Cd exposure concentrations, and there were significant differences between dead and surviving individuals, indicating that both Cd content in tissues and Cd accumulation rates were correlated with mortality. Cd levels in the liver of dead fish were saturated. A lethal threshold for Cd concentration in the whole fish was obtained. Bioconcentration factors for Cd did not decrease with increasing exposure. Acute exposure to waterborne Cd caused a significant decrease in the ion content of the fish carcass. There was a significant difference between the Na+ content of the carcass of dead fish (34.54 μmol/g wet weight) and surviving fish (59.34 μmol/g wet weight), which was not the case with the Ca2+ content, indicating that the lethal toxicity of Cd was probably related to the decrease in Na+ content. Collectively, these results suggest that whole-fish Cd concentration and carcass Na+ content can be useful indicators of fish acutely exposed to Cd. Full article
(This article belongs to the Section Ecotoxicology)
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18 pages, 3237 KiB  
Article
Evaluation of One- and Two-Box Models as Particle Exposure Prediction Tools at Industrial Scale
by Carla Ribalta, Ana López-Lilao, Ana Sofia Fonseca, Alexander Christian Østerskov Jensen, Keld Alstrup Jensen, Eliseo Monfort and Mar Viana
Toxics 2021, 9(9), 201; https://doi.org/10.3390/toxics9090201 - 29 Aug 2021
Cited by 6 | Viewed by 2565
Abstract
One- and two-box models have been pointed out as useful tools for modelling indoor particle exposure. However, model performance still needs further testing if they are to be implemented as trustworthy tools for exposure assessment. The objective of this work is to evaluate [...] Read more.
One- and two-box models have been pointed out as useful tools for modelling indoor particle exposure. However, model performance still needs further testing if they are to be implemented as trustworthy tools for exposure assessment. The objective of this work is to evaluate the performance, applicability and reproducibility of one- and two-box models on real-world industrial scenarios. A study on filling of seven materials in three filling lines with different levels of energy and mitigation strategies was used. Inhalable and respirable mass concentrations were calculated with one- and two-box models. The continuous drop and rotating drum methods were used for emission rate calculation, and ranges from a one-at-a-time methodology were applied for local exhaust ventilation efficiency and inter-zonal air flows. When using both dustiness methods, large differences were observed for modelled inhalable concentrations but not for respirable, which showed the importance to study the linkage between dustiness and processes. Higher model accuracy (ratio modelled vs. measured concentrations 0.5–5) was obtained for the two- (87%) than the one-box model (53%). Large effects on modelled concentrations were seen when local exhausts ventilation and inter-zonal variations where parametrized in the models. However, a certain degree of variation (10–20%) seems acceptable, as similar conclusions are reached. Full article
(This article belongs to the Special Issue Advanced Modeling Tools for Occupational and Consumer Exposure Assessment)
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16 pages, 2508 KiB  
Article
Analysis of Phthalates and Alternative Plasticizers in Gloves by Gas Chromatography–Mass Spectrometry and Liquid Chromatography–UV Detection: A Comparative Study
by Kelly Poitou, Tiphaine Rogez-Florent, Marie Lecoeur, Cécile Danel, Romain Regnault, Philippe Vérité, Christelle Monteil and Catherine Foulon
Toxics 2021, 9(9), 200; https://doi.org/10.3390/toxics9090200 - 28 Aug 2021
Cited by 11 | Viewed by 4790
Abstract
Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, [...] Read more.
Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, including phthalates. The purpose of the present study was to develop two orthogonal methods, GC–MS and HPLC–DAD, for the screening of plasticizers in gloves. Performances of these two methods were compared in terms of ease of use, number of analyzed plasticizers, and sample preparation. The two methods were validated and applied for the identification and quantification of plasticizers in ten gloves made with different materials (vinyl, nitrile, latex, and neoprene). Results revealed the presence of three main ones: DEHP, DEHT, and DINP. Additionally, the contents of plasticizers were extremely variable, depending on the glove material. As expected, the results point out a predominant use of plasticizers in vinyl gloves with an amount that should be of concern. While DEHP is classified as a toxic substance for reproduction 1B, it was, however, quantified in the ten different glove samples studied. This study provides new data regarding the plasticizers’ content in protective gloves, which could be useful for risk assessment. Full article
(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)
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Article
Simulated Wildfire Smoke Significantly Alters Sperm DNA Methylation Patterns in a Murine Model
by Adam Schuller, Chiara Bellini, Timothy G. Jenkins, Matthew Eden, Jacqueline Matz, Jessica Oakes and Luke Montrose
Toxics 2021, 9(9), 199; https://doi.org/10.3390/toxics9090199 - 27 Aug 2021
Cited by 12 | Viewed by 4583
Abstract
Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory [...] Read more.
Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory morbidity due to smoke exposure is a priority, evaluating the molecular underpinnings that explain recent extrapulmonary observations is necessary. Here, we use an Apoe−/− mouse model to investigate the epigenetic impact of paternal exposure to simulated wildfire smoke. We demonstrate that 40 days of exposure to smoke from Douglas fir needles induces sperm DNA methylation changes in adult mice. DNA methylation was measured by reduced representation bisulfite sequencing and varied significantly in 3353 differentially methylated regions, which were subsequently annotated to 2117 genes. The differentially methylated regions were broadly distributed across the mouse genome, but the vast majority (nearly 80%) were hypermethylated. Pathway analyses, using gene-derived and differentially methylated region-derived gene ontology terms, point to a number of developmental processes that may warrant future investigation. Overall, this study of simulated wildfire smoke exposure suggests paternal reproductive risks are possible with prolonged exposure. Full article
(This article belongs to the Special Issue Molecular Basis of Air-Pollution-Induced Disease Risk)
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