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Toxic Mode of Action, Toxicity Testing, and Health Risks of...
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Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Exposome Analysis and Risk Assessment".

Deadline for manuscript submissions: closed (30 August 2024) | Viewed by 10355

Special Issue Editors

Prof. Dr. Weiwei Zheng

E-Mail Website
Guest Editor
School of Public Health, Fudan University, Shanghai 200433, China
Interests: drinking water; risk assessment; environmental epidemiology; public health; health policy; environment pollution; endocrine disrupting chemicals; chemical mixture
Prof. Dr. Yuanyuan Ruan

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Interests: tumor glycobiology; signaling transduction; protein translation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Based on the new concepts and methods of toxicology in the 21st century, this issue aims to conduct research on the metabolic transformation, toxicity pathways, epigenetic regulation, biomarkers and toxicity mechanisms of a low-dose exposure to environmental pollutants at multiple levels, including molecular, cellular, animal and human levels. Moreover, it aims to conduct a systematic safety assessment study on the potential health hazards and mechanisms of action of new environmental pollutants in China, study the biological effects of potential hazardous substances such as new environmental pollutants, and explore the concepts and strategies for toxicological safety assessment and safety risk assessment.

Prof. Dr. Weiwei Zheng
Prof. Dr. Yuanyuan Ruan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mode of action
  • toxicity testing
  • health risks
  • risk assessment
  • environmental pollutants

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Published Papers (4 papers)

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Research

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12 pages, 3697 KiB  
Article
Molecular Characteristics of Aberrant Gene Mutations and Expression Profiles Induced by Benzo(a)pyrene in Hepatocellular Carcinoma Cells
by Xinyi Cao, Ying Zhu, Shujun Cheng, Kunxiao Zhang, Hui Wang and Qian Ba
Toxics 2024, 12(7), 499; https://doi.org/10.3390/toxics12070499 - 9 Jul 2024
Viewed by 981
Abstract
Benzo(a)pyrene (BaP) is a prevalent food and environmental carcinogen. Chronic low-dose BaP exposure can promote the migratory and invasive capacities of human hepatocellular carcinoma (HCC) cells, yet its intricate molecular mechanisms remain elusive. Utilizing the established BaP-exposed HCC cell model, we analyzed the [...] Read more.
Benzo(a)pyrene (BaP) is a prevalent food and environmental carcinogen. Chronic low-dose BaP exposure can promote the migratory and invasive capacities of human hepatocellular carcinoma (HCC) cells, yet its intricate molecular mechanisms remain elusive. Utilizing the established BaP-exposed HCC cell model, we analyzed the gene expression alteration, exosomal RNA cargo, and genetic variants induced by BaP through transcriptomic and whole-genome sequencing. Transcriptomic analysis revealed significant dysregulation in genes and pathways associated with tumor metastasis, particularly those involved in steroidal lipid metabolism and cell migration. BaP exposure enriched PI3K-AKT, mTOR, and NF-κB signaling pathways and disrupted genes implicated in cellular secretory processes, suggesting the potential involvement of exosomes in metastasis. Exosome analysis depicted the RNA profiling in exosomes of HCC cells altered by BaP, and the exosomal circRNA-miRNA-mRNA interaction network was constructed. Finally, whole-genome sequencing delineated BaP-induced gene mutations and genomic instability in HCC cells. In summary, prolonged low-dose BaP exposure induces intricate molecular alterations in gene mutation and expression profiles in HCC cells, notably those secreted in exosomes, which may potentially remodel the tumor microenvironment and foster HCC metastasis. Our findings offer new insights into the molecular underpinnings of BaP-induced HCC metastasis, thereby advancing the comprehensive understanding of BaP toxicity. Full article
(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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17 pages, 7292 KiB  
Article
Natural Pyrethrin-Induced Oxidative Damage in Human Liver Cells through Nrf-2 Signaling Pathway
by Yun Yang, Xiaoyi Wei, Mengchao Ying, Haiyan Huang, Yijie Sha, Xinyu Hong, Ping Xiao and Gonghua Tao
Toxics 2024, 12(4), 258; https://doi.org/10.3390/toxics12040258 - 30 Mar 2024
Viewed by 1322
Abstract
Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and [...] Read more.
Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs’ induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration. Full article
(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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Review

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20 pages, 12157 KiB  
Review
Global Trends and Hotspots in Research on the Health Risks of Organophosphate Flame Retardants: A Bibliometric and Visual Analysis
by 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
Viewed by 1675
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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15 pages, 1791 KiB  
Review
Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health
by Fei Qu and Weiwei Zheng
Toxics 2024, 12(6), 388; https://doi.org/10.3390/toxics12060388 - 26 May 2024
Cited by 13 | Viewed by 5754
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Toxic Mode of Action, Toxicity Testing, and Health Risks of Environmental Pollutants)
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