Journal Description
Toxics
Toxics
is an international, peer-reviewed, open access journal on all aspects of the toxic chemicals and materials, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q2 (Chemical Health and Safety)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.7 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.6 (2022);
5-Year Impact Factor:
4.8 (2022)
Latest Articles
Biotransformation of Chlorpyrifos Shewanella oneidensis MR-1 in the Presence of Goethite: Experimental Optimization and Degradation Products
Toxics 2024, 12(6), 402; https://doi.org/10.3390/toxics12060402 - 31 May 2024
Abstract
In this study, the degradation system of Shewanella oneidensis MR-1 and goethite was constructed with chlorpyrifos as the target contaminant. The effects of initial pH, contaminant concentration, and temperature on the removal rate of chlorpyrifos during the degradation process were investigated. The experimental
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In this study, the degradation system of Shewanella oneidensis MR-1 and goethite was constructed with chlorpyrifos as the target contaminant. The effects of initial pH, contaminant concentration, and temperature on the removal rate of chlorpyrifos during the degradation process were investigated. The experimental conditions were optimized by response surface methodology with a Box–Behnken design (BBD). The results show that the removal rate of chlorpyrifos is 75.71% at pH = 6.86, an initial concentration of 19.18 mg·L−1, and a temperature of 30.71 °C. LC-MS/MS analyses showed that the degradation products were C4H11O3PS, C7H7Cl3NO4P, C9H11Cl2NO3PS, C7H7Cl3NO3PS, C9H11Cl3NO4P, C4H11O2PS, and C5H2Cl3NO. Presumably, the degradation pathways involved are: enzymatic degradation, hydrolysis, dealkylation, desulfur hydrolysis, and dechlorination. The findings of this study demonstrate the efficacy of the goethite/S. oneidensis MR-1 complex system in the removal of chlorpyrifos from water. Consequently, this research contributes to the establishment of a theoretical framework for the microbial remediation of organophosphorus pesticides in aqueous environments.
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(This article belongs to the Topic Removal of Hazardous Substances from Water Resources)
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An In Vitro Human Skin Test for Predicting Skin Sensitization and Adverse Immune Reactions to Biologics
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Shaheda Sameena Ahmed, Mohammed Mahid Ahmed, Abbas Ishaq, Matthew Freer, Richard Stebbings and Anne Mary Dickinson
Toxics 2024, 12(6), 401; https://doi.org/10.3390/toxics12060401 - 30 May 2024
Abstract
Biologics, including monoclonal antibodies (mAb), have proved to be effective and successful therapeutic agents, particularly in the treatment of cancer and immune-inflammatory conditions, as well as allergies and infections. However, their use carries an inherent risk of an immune-mediated adverse drug reaction. In
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Biologics, including monoclonal antibodies (mAb), have proved to be effective and successful therapeutic agents, particularly in the treatment of cancer and immune-inflammatory conditions, as well as allergies and infections. However, their use carries an inherent risk of an immune-mediated adverse drug reaction. In this study, we describe the use of a novel pre-clinical human in vitro skin explant test for predicting skin sensitization and adverse immune reactions. The skin explant test was used to investigate the effects of therapeutic antibodies, which are known to cause a limited reaction in a small number of patients or more severe reactions. Material and Methods: Immune responses were determined by T cell proliferation and multiplex cytokine analysis, as well as histopathological analysis of skin damage (grades I–IV in increasing severity), predicting a negative (grade I) or positive (grade ≥ II) response for an adverse skin sensitization effect. Results: T cell proliferation responses were significantly increased in the positive group (p < 0.004). Multiplex cytokine analysis showed significantly increased levels of IFNγ, TNFα, IL-10, IL-12, IL-13, IL-1β, and IL-4 in the positive response group compared with the negative response group (p < 0.0001, p < 0.0001, p < 0.002, p < 0.01, p < 0.04, p < 0.006, and p < 0.004, respectively). Conclusions: Overall, the skin explant test correctly predicted the clinical outcome of 13 out of 16 therapeutic monoclonal antibodies with a correlation coefficient of 0.770 (p = 0.0001). This assay therefore provides a valuable pre-clinical test for predicting adverse immune reactions, including T cell proliferation and cytokine release, both associated with skin sensitization to monoclonal antibodies.
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(This article belongs to the Special Issue Skin Sensitization Testing Using New Approach Methodologies)
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The Easily Overlooked Effect of Global Warming: Diffusion of Heavy Metals
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Wenqi Xiao, Yunfeng Zhang, Xiaodie Chen, Ajia Sha, Zhuang Xiong, Yingyong Luo, Lianxin Peng, Liang Zou, Changsong Zhao and Qiang Li
Toxics 2024, 12(6), 400; https://doi.org/10.3390/toxics12060400 - 30 May 2024
Abstract
Since industrialization, global temperatures have continued to rise. Human activities have resulted in heavy metals being freed from their original, fixed locations. Because of global warming, glaciers are melting, carbon dioxide concentrations are increasing, weather patterns are shifting, and various environmental forces are
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Since industrialization, global temperatures have continued to rise. Human activities have resulted in heavy metals being freed from their original, fixed locations. Because of global warming, glaciers are melting, carbon dioxide concentrations are increasing, weather patterns are shifting, and various environmental forces are at play, resulting in the movement of heavy metals and alteration of their forms. In this general context, the impact of heavy metals on ecosystems and organisms has changed accordingly. For most ecosystems, the levels of heavy metals are on the rise, and this rise can have a negative impact on the ecosystem as a whole. Numerous studies have been conducted to analyze the combined impacts of climate change and heavy metals. However, the summary of the current studies is not perfect. Therefore, this review discusses how heavy metals affect ecosystems during the process of climate change from multiple perspectives, providing some references for addressing the impact of climate warming on environmental heavy metals.
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(This article belongs to the Section Metals and Radioactive Substances)
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Multi-Omics Analysis Reveals the Toxicity of Polyvinyl Chloride Microplastics toward BEAS-2B Cells
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Chengzhi Liu, Shuang Chen, Jiangliang Chu, Yifan Yang, Beilei Yuan and Huazhong Zhang
Toxics 2024, 12(6), 399; https://doi.org/10.3390/toxics12060399 - 30 May 2024
Abstract
Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B
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Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-β signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.
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(This article belongs to the Special Issue State-of-the-Art Environmental Chemicals Exposomics and Metabolomics)
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Association of Prenatal Dietary Toxicants and Inorganic Arsenic Exposure with Children’s Emotional and Behavioral Problems: ECLIPSES Study
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Xiruo Kou, Josefa Canals, Monica Bulló, Nerea Becerra-Tomás, Cristina Jardí and Victoria Arija
Toxics 2024, 12(6), 398; https://doi.org/10.3390/toxics12060398 - 29 May 2024
Abstract
Prenatal exposure to dietary toxicants is linked to neurocognitive issues, but its effect on early emotional and behavioral development in children is less clear. To explore the relationship between prenatal intake of As, iAs, Cd, MeHg, Pb, PCDD/Fs, DL-PCBs, and NDL-PCBs and emotional
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Prenatal exposure to dietary toxicants is linked to neurocognitive issues, but its effect on early emotional and behavioral development in children is less clear. To explore the relationship between prenatal intake of As, iAs, Cd, MeHg, Pb, PCDD/Fs, DL-PCBs, and NDL-PCBs and emotional and behavioral issues in four-year-old children. This study included 192 mother–child pairs from the ECLIPSES study, assessing prenatal dietary toxicant exposure through a food-frequency questionnaire and Catalan Food Safety Agency data. Children’s emotional and behavioral scores were evaluated using the Child Behavior Checklist for ages 1.5–5 years. Multivariable regression and logistic models were used, focusing on iAs after finding significant preliminary associations. Increased prenatal dietary intake of iAs was associated with internalizing, externalizing, and attention-deficit/hyperactivity problems. Higher iAs levels (>4.16 μg/day) significantly increased the risk of total problems (OR = 2.94) and specific issues like anxious/depressed (OR = 4.88), anxiety (OR = 3.27), and oppositional defiant problems (OR = 4.30). High iAs consumption correlated with the intake of meat, eggs, cereals, tubers, fruits, and pulses Prenatal dietary iAs exposure is associated with various emotional and behavioral problems in children. Monitoring and reducing iAs levels in food are crucial for public health.
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(This article belongs to the Special Issue Toxicology Research of Foodborne Contaminants)
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A Review of Remediation Strategies for Diphenyl Ether Herbicide Contamination
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Qingqing Fan, Yi Shen, Yong Yang and Qingming Zhang
Toxics 2024, 12(6), 397; https://doi.org/10.3390/toxics12060397 - 29 May 2024
Abstract
In agriculture, diphenyl ether herbicides are a broad-spectrum family of pesticides mainly used to control annual weeds in agriculture. Although diphenyl ether herbicides have a long-lasting effect in weed control, they can also be harmful to succeeding crops, as well as to the
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In agriculture, diphenyl ether herbicides are a broad-spectrum family of pesticides mainly used to control annual weeds in agriculture. Although diphenyl ether herbicides have a long-lasting effect in weed control, they can also be harmful to succeeding crops, as well as to the water and soil environment. Residual herbicides can also harm a large number of non-target organisms, leading to the death of pest predators and other beneficial organisms. Therefore, it is of great significance to control and remediate the contamination caused by diphenyl ether herbicide residues for the sake of environmental, nutritional, and biological safety. This review provides an overview of the techniques used for remediating diphenyl ether herbicide contamination, including biological, physical, and chemical remediation. Among these techniques, bioremediation, particularly microbial biodegradation technology, is extensively employed. The mechanisms and influencing factors of different remediation techniques in eliminating diphenyl ether herbicide contamination are discussed, together with a prospect for future development directions. This review serves as a scientific reference for the efficient remediation of residual contamination from diphenyl ether herbicides.
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(This article belongs to the Special Issue Ecotoxicity Induced by Pesticides Exposure Volume II)
Open AccessArticle
miR-21-Mediated Endothelial Senescence and Dysfunction Are Involved in Cigarette Smoke-Induced Pulmonary Hypertension through Activation of PI3K/AKT/mTOR Signaling
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Bin He, Binxia Shao, Cheng Cheng, Zitong Ye, Yi Yang, Bowen Fan, Haibo Xia, Hao Wu, Qizhan Liu and Jinsong Zhang
Toxics 2024, 12(6), 396; https://doi.org/10.3390/toxics12060396 - 29 May 2024
Abstract
Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the
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Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.
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(This article belongs to the Section Human Toxicology and Epidemiology)
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High-Coverage UHPLC-MS/MS Analysis of 67 Mycotoxins in Plasma for Male Infertility Exposure Studies
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Xiao Ning, Lulu Wang, Jia-Sheng Wang, Jian Ji, Shaoming Jin, Jiadi Sun, Yongli Ye, Shenghui Mei, Yinzhi Zhang, Jin Cao and Xiulan Sun
Toxics 2024, 12(6), 395; https://doi.org/10.3390/toxics12060395 - 28 May 2024
Abstract
Mycotoxins are a class of exogenous metabolites that are major contributors to foodborne diseases and pose a potential threat to human health. However, little attention has been paid to trace mycotoxin co-exposure situations in vivo. To address this, we devised a novel analytical
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Mycotoxins are a class of exogenous metabolites that are major contributors to foodborne diseases and pose a potential threat to human health. However, little attention has been paid to trace mycotoxin co-exposure situations in vivo. To address this, we devised a novel analytical strategy, both highly sensitive and comprehensive, for quantifying 67 mycotoxins in human plasma samples. This method employs isotope dilution mass spectrometry (IDMS) for approximately 40% of the analytes and utilizes internal standard quantification for the rest. The mycotoxins were classified into three categories according to their physicochemical properties, facilitating the optimization of extraction and detection parameters to improve analytical performance. The lowest limits of detection and quantitation were 0.001–0.5 μg/L and 0.002–1 μg/L, respectively, the intra-day precision ranged from 1.8% to 11.9% RSD, and the intra-day trueness ranged from 82.7–116.6% for all mycotoxins except Ecl, DH-LYS, PCA, and EnA (66.4–129.8%), showing good analytical performance of the method for biomonitoring. A total of 40 mycotoxins (including 24 emerging mycotoxins) were detected in 184 plasma samples (89 from infertile males and 95 from healthy males) using the proposed method, emphasizing the widespread exposure of humans to both traditional and emerging mycotoxins. The most frequently detected mycotoxins were ochratoxin A, ochratoxin B, enniatin B, and citrinin. The incidence of exposure to multiple mycotoxins was significantly higher in infertile males than in healthy subjects, particularly levels of ochratoxin A, ochratoxin B, and citrinin, which were significantly increased. It is necessary to carry out more extensive biological monitoring to provide data support for further study of the relationship between mycotoxins and male infertility.
Full article
(This article belongs to the Special Issue State-of-the-Art Environmental Chemicals Exposomics and Metabolomics)
Open AccessPerspective
A Review of N-(1,3-Dimethylbutyl)-N′-phenyl-p-Phenylenediamine (6PPD) and Its Derivative 6PPD-Quinone in the Environment
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Yi Li, Jingjing Zeng, Yongjin Liang, Yanlong Zhao, Shujun Zhang, Zhongyan Chen, Jiawen Zhang, Xingze Shen, Jiabin Wang, Ying Zhang and Yuxin Sun
Toxics 2024, 12(6), 394; https://doi.org/10.3390/toxics12060394 - 28 May 2024
Abstract
As an antioxidant and antiozonant, N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is predominantly used in the rubber industry to prevent degradation. However, 6PPD can be ozonated to generate a highly toxic transformation product called N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-quinone),
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As an antioxidant and antiozonant, N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is predominantly used in the rubber industry to prevent degradation. However, 6PPD can be ozonated to generate a highly toxic transformation product called N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-quinone), which is toxic to aquatic and terrestrial organisms. Thus, 6PPD and 6PPD-quinone, two emerging contaminants, have attracted extensive attention recently. This review discussed the levels and distribution of 6PPD and 6PPD-quinone in the environment and investigated their toxic effects on a series of organisms. 6PPD and 6PPD-quinone have been widely found in air, water, and dust, while data on soil, sediment, and biota are scarce. 6PPD-quinone can cause teratogenic, developmental, reproductive, neuronal, and genetic toxicity for organisms, at environmentally relevant concentrations. Future research should pay more attention to the bioaccumulation, biomagnification, transformation, and toxic mechanisms of 6PPD and 6PPD-quinone.
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(This article belongs to the Section Emerging Contaminants)
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The Association between Short-Term Exposure to PM1 and Daily Hospital Admission and Related Expenditures in Beijing
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Jingwen Xu, Yan Chen, Feng Lu, Lili Chen and Zhaomin Dong
Toxics 2024, 12(6), 393; https://doi.org/10.3390/toxics12060393 - 28 May 2024
Abstract
Ambient particulate matter (PM) pollution is a leading environmental health threat worldwide. PM with an aerodynamic diameter ≤ 1.0 μm, also known as PM1, has been implicated in the morbidity and mortality of several cardiorespiratory and cerebrovascular diseases. However, previous studies
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Ambient particulate matter (PM) pollution is a leading environmental health threat worldwide. PM with an aerodynamic diameter ≤ 1.0 μm, also known as PM1, has been implicated in the morbidity and mortality of several cardiorespiratory and cerebrovascular diseases. However, previous studies have mostly focused on analyzing fine PM (PM2.5) associated with disease metrics, such as emergency department visits and mortality, rather than ultrafine PM, including PM1. This study aimed to evaluate the association between short-term PM1 exposure and hospital admissions (HAs) for all-cause diseases, chronic obstructive pulmonary disease (COPD), and respiratory infections (RIs), as well as the associated expenditures, using Beijing as a case study. Here, based on air pollution and hospital admission data in Beijing from 2015 to 2017, we performed a time-series analysis and meta-analysis. It was found that a 10 μg/m3 increase in the PM1 concentration significantly increased all-cause disease HAs by 0.07% (95% Confidence Interval (CI): [0, 0.14%]) in Beijing between 2015 and 2017, while the COPD and RI-related HAs were not significantly associated with short-term PM1 exposure. Meanwhile, we estimated the attributable number of HAs and hospital expenditures related to all-cause diseases. This study revealed that an average of 6644 (95% CI: [351, 12,917]) cases of HAs were attributable to ambient PM1, which was estimated to be associated with a 106 million CNY increase in hospital expenditure annually (95% CI: [5.6, 207]), accounting for 0.32% (95% CI: [0.02, 0.62%]) of the annual total expenses. The findings reported here highlight the underlying impact of ambient PM pollution on health risks and economic burden to society and indicate the need for further policy actions on public health.
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(This article belongs to the Special Issue Association between Ambient Fine Particulate Matter Exposures and Human Health Risk)
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Associations of Insecticide Exposure with Childhood Asthma and Wheezing: A Population-Based Cross-Sectional Study in Sanya, China
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Yabin Hu, Guiyan Yang, Dan Wang, Wangyang Gu, Dan Xie, Tingyue Huang, Peng Xue, Jingyi Tang, Hui Wei, Shenghui Li, Shilu Tong and Shijian Liu
Toxics 2024, 12(6), 392; https://doi.org/10.3390/toxics12060392 - 27 May 2024
Abstract
Insecticide exposure may affect childhood asthma/wheezing, but evidence is scarce in low- and middle-income countries. We conducted a population-based cross-sectional study in Sanya, China. Generalized linear models were adopted to assess the associations of insecticide exposure with childhood asthma/wheezing, reported as odds ratios
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Insecticide exposure may affect childhood asthma/wheezing, but evidence is scarce in low- and middle-income countries. We conducted a population-based cross-sectional study in Sanya, China. Generalized linear models were adopted to assess the associations of insecticide exposure with childhood asthma/wheezing, reported as odds ratios (ORs) and 95% confidence intervals (CIs). A subgroup analysis was performed to explore the possible effects of sociodemographic and environmental factors on these associations. The median age of the 9754 children was 6.7 years, and 5345 (54.8%) were boys. The prevalences of ever asthma (EA), ever wheezing (EW), and current wheezing (CW) were 7.4%, 5.3%, and 2.9%, respectively. We found a greater prevalence of childhood EA with insecticide exposure (OR = 1.18, 95% CI: 1.00, 1.38). Outdoor insecticide exposure was associated with elevated ORs for EA (1.24, 95% CI: 1.03, 1.50), EW (1.27, 95% CI: 1.03, 1.57), and CW (1.38, 95% CI: 1.04, 1.81). The p for the trend in insecticide exposure frequency was significant for EA (p = 0.001) and CW (p = 0.034). These adverse impacts were pronounced in girls who were exposed to low temperatures. Our findings suggest adverse effects of insecticide use, especially outdoors, on childhood asthma/wheezing. Further studies are warranted to verify this association and develop tailored prevention measures.
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(This article belongs to the Special Issue Air Pollutant Exposure and Respiratory Diseases)
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Open AccessReview
Global Trends and Hotspots in Research on the Health Risks of Organophosphate Flame Retardants: A Bibliometric and Visual Analysis
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Zhiyuan Du, Yuanyuan Ruan, Jiabin Chen, Jian Fang, Shuo Xiao, Yewen Shi and Weiwei Zheng
Toxics 2024, 12(6), 391; https://doi.org/10.3390/toxics12060391 - 27 May 2024
Abstract
Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in
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Background: Organophosphate flame retardants (OPFRs) are compounds with a wide range of industrial and commercial applications and are mainly used as flame retardants and plasticizers. The global consumption of OPFRs has risen rapidly in recent decades, and they have been widely detected in environmental media. Unfortunately, OPFRs have been associated with many adverse health outcomes. The issue of the health risks of OPFRs is attracting increasing attention. Therefore, there is a need to review the current state of research and trends in this field to help researchers and policymakers quickly understand the field, identify new research directions, and allocate appropriate resources for further development of the OPFR health risk research field. Methods: This study statistically analyzed 1162 relevant publications included in the Web of Science Core Collection from 2003–2023. The internal and external features of the literature, such as publication trends, countries, authors, journals, and keywords, were quantitatively analyzed and visually presented to identify the research hotspots, compositions, and paradigms of the field and to horizontally and vertically analyze the development trends and structural evolution of the field. Results: The development of the field can be divided into three stages, and the field entered a period of rapid development in 2016. China (649 papers) is the most prolific country, followed by the United States (188 papers). The authors STAPLETON HM and WANG Y have the highest combined impact. International collaboration between countries and researchers still needs to be strengthened. Science of The Total Environment is the most frequently published journal (162 papers), and Environmental Science and Technology is the most frequently cited journal (5285 citations). Endocrine disruption, developmental toxicity, and neurotoxicity are the health effects of greatest interest. Conclusions: Future research is expected to be multidisciplinary, and research hotspots may involve a comprehensive assessment of OPFR exposure in the population, exploration of the mechanisms of endocrine-disrupting effects and in vivo metabolic processes, and examination of the health effects of OPFR metabolites.
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(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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Temporal and Spatial Variation of Toxic Metal Concentrations in Cultivated Soil in Jiaxing, Zhejiang Province, China: Characteristics and Mechanisms
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Mengzhuo Cao, Yanbo Jia, Xin Lu, Jinfa Huang, Yanlai Yao, Leidong Hong, Weijing Zhu, Weiping Wang, Fengxiang Zhu and Chunlai Hong
Toxics 2024, 12(6), 390; https://doi.org/10.3390/toxics12060390 - 26 May 2024
Abstract
The toxic metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) pollution in 250 agricultural soil samples representing the urban area of Jiaxing was studied to investigate the temporal and spatial variations. Compared to the early 1990s, the pollution level has increased.
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The toxic metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) pollution in 250 agricultural soil samples representing the urban area of Jiaxing was studied to investigate the temporal and spatial variations. Compared to the early 1990s, the pollution level has increased. Industry and urbanization were the main factors causing toxic metal pollution on temporal variation, especially the use of feed containing toxic metals. The soil types and crop cultivation methods are the main factors causing toxic metal pollution on spatial variation. Although the single-factor pollution indices of all the toxic metals were within the safe limits, as per the National Soil Environmental Quality Standard (risk screening value), if the background values of soil elements in Jiaxing City are used as the standard, the pollution index of all the elements surveyed exceeds 1.0, reaching a level of mild pollution. The soil samples investigated were heavily contaminated with toxic metal compounds, and their levels increased over time. This situation poses potential ecological and health risks.
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(This article belongs to the Special Issue Safe Utilization and Ecological Restoration of Heavy Metal Polluted Farmland)
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Open AccessArticle
Effects of 6PPD-Quinone on Human Liver Cell Lines as Revealed with Cell Viability Assay and Metabolomics Analysis
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Yunqing Qi, Aiqing Qiu, Xinyue Wei, Yiting Huang, Qing Huang and Wei Huang
Toxics 2024, 12(6), 389; https://doi.org/10.3390/toxics12060389 - 26 May 2024
Abstract
N-(1,3-Dimethyl butyl)-N′-phenyl-phenylenediamine-quinone (6PPD-Q) is a derivative of the widely used rubber tire antioxidant 6PPD, which was first found to be acutely toxic to coho salmon. Subsequent studies showed that 6PPD-Q had species-specific acute toxicity in fishes and potential hepatotoxicity in
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N-(1,3-Dimethyl butyl)-N′-phenyl-phenylenediamine-quinone (6PPD-Q) is a derivative of the widely used rubber tire antioxidant 6PPD, which was first found to be acutely toxic to coho salmon. Subsequent studies showed that 6PPD-Q had species-specific acute toxicity in fishes and potential hepatotoxicity in mice. In addition, 6PPD-Q has been reported in human urine, demonstrating the potential widespread exposure of humans to this chemical. However, whether 6PPD-Q poses a higher risk to humans than its parent compound, 6PPD, and could cause adverse effects in humans is still unclear. In this study, we utilized two human liver cell models (the human proto-hepatocyte model L02 and the human hepatocellular carcinoma cell line HepG2) to investigate the potentially differential effects of these two chemicals. Cell viability curve analysis showed that 6PPD-Q had lower IC50 values than 6PPD for both liver cell lines, suggesting higher toxicity of 6PPD-Q to human liver cells than 6PPD. In addition, L02 cells are more sensitive to 6PPD-Q exposure, which might be derived from its weaker metabolic transformation of 6PPD-Q, since significantly lower levels of phase I and phase II metabolites were detected in 6PPD-Q-exposed L02 cell culture medium. Furthermore, pathway analysis showed that 6PPD-Q exposure induced changes in phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism pathways in L02 cells, which might be the mechanism underlying its liver cell toxicity. Gene expression analysis revealed that exposure to 6PPD-Q induced excessive ROS production in L02 cells. Our results further supported the higher risk of 6PPD-Q than 6PPD and provided insights for understanding the effects of 6PPD-Q on human health.
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(This article belongs to the Special Issue Environmental Contaminants and Human Health)
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Open AccessReview
Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health
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Fei Qu and Weiwei Zheng
Toxics 2024, 12(6), 388; https://doi.org/10.3390/toxics12060388 - 26 May 2024
Abstract
Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling
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Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd’s impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications.
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(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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A Rapid In Vivo Toxicity Assessment Method for Antimicrobial Peptides
by
Yulang Chi, Yunhui Peng, Shikun Zhang, Sijia Tang, Wenzhou Zhang, Congjie Dai and Shouping Ji
Toxics 2024, 12(6), 387; https://doi.org/10.3390/toxics12060387 - 25 May 2024
Abstract
Antimicrobial peptides (AMPs) represent a promising antibiotic alternative to overcome drug-resistant bacteria by inserting into the membrane of bacteria, resulting in cell lysis. However, therapeutic applications of AMPs have been hindered by their ability to lyse eukaryotic cells. GF-17 is a truncated peptide
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Antimicrobial peptides (AMPs) represent a promising antibiotic alternative to overcome drug-resistant bacteria by inserting into the membrane of bacteria, resulting in cell lysis. However, therapeutic applications of AMPs have been hindered by their ability to lyse eukaryotic cells. GF-17 is a truncated peptide of LL-37, which has perfect amphipathicity and a higher hydrophobicity, resulting in higher haemolytic activity. However, there is no significant difference in the cytotoxicity against human lung epithelial cells between the GF-17 and LL-37 groups, indicating that there are significant differences in the sensitivity of different human cells to GF-17. In this study, LL-37 and GF-17 were administered to mouse lungs via intranasal inoculation. Blood routine examination results showed that LL-37 did not affect the red blood cells, platelet, white blood cells and neutrophil counts, but GF-17 decreased the white blood cells and neutrophil counts with the increasing concentration of peptides. GF-17-treated mice suffer a body weight loss of about 2.3 g on average in 24 h, indicating that GF-17 is highly toxic to mice. The total cell counts in the bronchoalveolar lavage fluid from GF-17-treated mice were 4.66-fold that in the untreated group, suggesting that GF-17 treatment leads to inflammation in the lungs of mice. Similarly, the histological results showed the infiltration of neutrophils in the lungs of GF-17-treated mice. The results suggest that the administration of GF-17 in the lungs of mice does not affect the red blood cells and platelet counts in the blood but promotes neutrophil infiltration in the lungs, leading to an inflammatory response. Therefore, we established a mouse acute lung injury model to preliminarily evaluate the in vivo toxicity of AMPs. For AMPs with a clinical application value, systematic research is still needed to evaluate their acute and long-term toxicity.
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(This article belongs to the Section Human Toxicology and Epidemiology)
Open AccessArticle
miR–122–5p Promotes Cowshed Particulate Matter2.5-Induced Apoptosis in NR8383 by Targeting COL4A1
by
Yize Sun, Ke Sun, Zhenhua Ma, Xiqing Zhang, Xiaohui Du, Yunna Jia, Yanbin Zhu, Muhammad Inam, Yunhang Gao and Wangdui Basang
Toxics 2024, 12(6), 386; https://doi.org/10.3390/toxics12060386 - 25 May 2024
Abstract
It is well known that Particulate Matter2.5 (PM2.5) has a major adverse effect on the organism. However, the health hazards of livestock farm PM2.5 to humans and animals are not yet known, and the role of miRNAs in the cellular
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It is well known that Particulate Matter2.5 (PM2.5) has a major adverse effect on the organism. However, the health hazards of livestock farm PM2.5 to humans and animals are not yet known, and the role of miRNAs in the cellular damage induced by livestock farm PM2.5 is also unclear. Therefore, our study used cowshed PM2.5 to stimulate rat alveolar macrophage NR8383 to construct an in vitro injury model to investigate the effect of miR–122–5p on PM2.5-induced apoptosis in the NR8383. The level of apoptosis was quantified by flow cytometry and Hoechst 33342/PI double staining. Furthermore, the potential target gene Collagen type IV alpha (COL4A1) of miR–122–5p was identified through the use of bioinformatics methods. The results demonstrated a decline in cell viability and an increase in apoptosis with rising PM2.5 concentrations and exposure durations. The transfection of miR–122–5p mimics resulted in an upregulation of the pro-apoptotic protein Bcl–xL/Bcl–2 and activation of cleaved caspase–3 while inhibiting the anti-apoptotic protein B–cell lymphoma–2. The experimental data indicate that miR–122–5p is involved in the apoptotic process by targeting COL4A1. Furthermore, the overexpression of COL4A1 was observed to enhance the PM2.5-activated PI3K/AKT/NF–κB signaling pathway, which contributed to the inhibition of apoptosis. This finding offers a promising avenue for the development of therapeutic strategies aimed at mitigating cellular damage induced by PM2.5 exposure.
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(This article belongs to the Section Air Pollution and Health)
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Open AccessArticle
Machine Learning to Predict Drug-Induced Liver Injury and Its Validation on Failed Drug Candidates in Development
by
Fahad Mostafa, Victoria Howle and Minjun Chen
Toxics 2024, 12(6), 385; https://doi.org/10.3390/toxics12060385 - 24 May 2024
Abstract
Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and
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Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and procedures to enhance the accuracy of DILI risk prediction for drug candidates under development. In this study, we leveraged a large human dataset to develop machine learning models for assessing DILI risk. The performance of these prediction models was rigorously evaluated using a 10-fold cross-validation approach and an external test set. Notably, the random forest (RF) and multilayer perceptron (MLP) models emerged as the most effective in predicting DILI. During cross-validation, RF achieved an average prediction accuracy of 0.631, while MLP achieved the highest Matthews Correlation Coefficient (MCC) of 0.245. To validate the models externally, we applied them to a set of drug candidates that had failed in clinical development due to hepatotoxicity. Both RF and MLP accurately predicted the toxic drug candidates in this external validation. Our findings suggest that in silico machine learning approaches hold promise for identifying DILI liabilities associated with drug candidates during development.
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(This article belongs to the Collection Predictive Toxicology)
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Open AccessArticle
GC/MS-Based Metabolomic Analysis of A549 Cells Exposed to Emerging Organophosphate Flame Retardants
by
Mengyao Sun, Xiao Chang, Ying Gao, Sisi Zou, Shaomin Wang and Hongmin Liu
Toxics 2024, 12(6), 384; https://doi.org/10.3390/toxics12060384 - 24 May 2024
Abstract
Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological
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Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological studies of the above eOPFRs, especially their information on the perturbation of cellular metabolism, which is, thus far, marginally understood. Our research initially assessed the cytotoxicity of eOPFRs, which include compounds like cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), triallyl phosphate (TAP), and pentaerythritol phosphate alcohol (PEPA). This evaluation was conducted using the methyl thiazolyl tetrazolium (MTT) assay. Subsequently, we utilized a gas chromatography/mass spectrometry (GC/MS)-based metabolomic approach to investigate the metabolic disruptions induced by these four eOPFRs in A549 cells. The MTT results showed that, at high concentrations of 1 mM, their cytotoxicity was ranked as CDP > TAP > RDP > PEPA. In addition, metabolic studies at low concentrations of 10 μM showed that the metabolic interference of CDP, TAP, and PEPA focuses on oxidative stress, amino acid metabolism, and energy metabolism, while RDP mainly affects energy metabolism—galactose metabolism and gluconeogenesis. Therefore, from the perspective of cytotoxicity and metabolic analysis, RDP may be a more promising alternative. Our experiments provide important insights into the possible metabolic effects of potential toxic substances and complement the evidence on the human health risks of eOPFRs.
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(This article belongs to the Section Emerging Contaminants)
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Open AccessArticle
A Simple, Ecofriendly, and Fast Method for Nitrate Quantification in Bottled Water Using Visible Spectrophotometry
by
Wellington Diego da Ascenção, Caroline Cristine Augusto, Vitor Hugo Soares de Melo and Bruno Lemos Batista
Toxics 2024, 12(6), 383; https://doi.org/10.3390/toxics12060383 - 23 May 2024
Abstract
There are many works associating the presence of nitrate in water and the occurrence of cancer in humans. The most common method for quantifying nitrate in water is based on the use of toxic cadmium as a reductant. In this work, a new
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There are many works associating the presence of nitrate in water and the occurrence of cancer in humans. The most common method for quantifying nitrate in water is based on the use of toxic cadmium as a reductant. In this work, a new approach was developed for the quantification of nitrate in bottled water with indirect spectrophotometry using Zn0 as a reductant. Nitrate is reduced to nitrite using Zn0 in a buffered medium (acetate/acetic acid) and quantified with visible spectrophotometry using the Griess reaction between sulfanilamide and N-(1-naphthyl)-ethylenediamine. The influence of pH, buffer solution (constitution and concentration), Zn0 (mass and granulometry), and agitation time on the efficiency of nitrite generation was evaluated. The optimal conditions were an acetate–acetic acid buffer solution with a concentration and pH of 0.75 mol L−1 and 6.00, respectively, and a Zn0 particle size of 20 MESH and Zn0 mass of 300 mg. The limits of detection and quantification (LoD and LoQ) were 0.024 and 0.08 mg L−1, respectively. The method’s accuracy and precision were evaluated using the analysis of commercial bottled water. In conclusion, the use of Zn0 instead of cadmium provided a green method with excellent LoD/LoQ. Further, the method proved to be simple and easy to apply during outdoor analysis.
Full article
(This article belongs to the Section Novel Methods in Toxicology Research)
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