Frontiers in toxicology最新文献

{"title":"Editorial: Emerging talents in toxicology.","authors":"Takamitsu A Kato","doi":"10.3389/ftox.2024.1369297","DOIUrl":"https://doi.org/10.3389/ftox.2024.1369297","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1369297"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of <i>in vitro</i> methodology to investigate phthalate effects on the differentiation of seminiferous tubule-associated stem cells to form Leydig cells and on the Leydig cells derived from the stem cells.","authors":"Kassim Traore, Barry Zirkin","doi":"10.3389/ftox.2024.1352294","DOIUrl":"10.3389/ftox.2024.1352294","url":null,"abstract":"<p><p><b>Introduction:</b> Leydig cells isolated from the testis are able to sustain high levels of testosterone production <i>in vitro</i>, but only for up to 3 days. Such cells are valuable for addressing the acute effects of chemicals on steroidogenic function, but not for repeated or chronic effects. Methodology is now available by which adult Leydig cells can be derived <i>in vitro</i> from seminiferous tubule-associated stem cells. In contrast to isolated Leydig cells, the Leydig cells derived in this way can synthesize and secrete high levels of testosterone for months. Herein, we asked whether this system might be used to address the effect of mono-(2-ethylhexyl) phthalate (MEHP) exposure on the formation of Leydig cells from tubule-associated stem cells, and on the Leydig cells after their formation. <b>Methods:</b> Adult Brown Norway rats received an intraperitoneal injection of ethane dimethanesulfonate (EDS) to eliminate the existing Leydig cells. Seminiferous tubules then were isolated and cultured in medium containing Insulin-Transferrin- Selenium (ITS), Smoothened Agonist (SAG), and luteinizing hormone (LH). <b>Results:</b> Culture of the tubules for 8 weeks resulted in the formation of cells on the surfaces of the tubules that stained for CYP11A1 and STAR and produced high levels of testosterone. When the tubules were cultured in medium containing increasing concentrations of MEHP, concentration-dependent effects on Leydig cell formation occurred. To determine the effect of MEHP on newly produced Leydig cells, tubules were cultured for 8 weeks in the absence of MEHP, resulting in the formation of adult Leydig cells, and then in medium containing increasing concentrations of MEHP. Concentration-dependent decreases in testosterone production by the adult Leydig cells were seen, and these decreases proved to be reversible. <b>Discussion:</b> The use of this new system should make it possible to determine the mechanisms by which acute, repeated, or chronic exposures to increasing concentrations of MEHP and/or exposure to other chemicals affect the formation of Leydig cells from stem cells, as well as the steroidogenic function of adult Leydig cells.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1352294"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10867263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Vaccinium uliginosum</i> L. (bog bilberry) and the search for its alleged toxicity: a review.","authors":"Zuzana Vaneková, Patricia Holloway, Judith M Rollinger","doi":"10.3389/ftox.2024.1358840","DOIUrl":"10.3389/ftox.2024.1358840","url":null,"abstract":"<p><p>Bog bilberry (<i>Vaccinium uliginosum</i> L.) is a wild-growing berry native to all circumboreal regions. There is however a significant discrepancy in the uses of bog bilberry fruits around the world. There exists a strong prejudice against the use of these berries in many European countries as well as a few incidences of poisoning reported between 1906 and 1944. In Asia and North America, this fear is completely absent from the local knowledge and the bog bilberry is valued as an excellent food and medicinal plant. There has been a lack of research on the topic in the last 50 years and thus the presumed toxicity remains unproven. This review aims to gather the conflicting information from all regions where bog bilberry grows and present them in a critical way to elucidate the possible explanations for the discrepancies. There are several possible explanations for the alleged toxicity of the bog bilberry, including a fungal infection of the fruits, individual intolerance or accidental poisoning by a different plant species; the local names meaning \"drunk, inebriating, vomit-inducing berry\" may be related to the alcoholic drinks made from them. This review highlights the gap in knowledge and serves as a theoretical framework for future research.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1358840"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139737090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid application dosing alters the physiology of air-liquid interface (ALI) primary human bronchial epithelial cell/lung fibroblast co-cultures and <i>in vitro</i> testing relevant endpoints.","authors":"Nicholas M Mallek, Elizabeth M Martin, Lisa A Dailey, Shaun D McCullough","doi":"10.3389/ftox.2023.1264331","DOIUrl":"10.3389/ftox.2023.1264331","url":null,"abstract":"<p><p>Differentiated primary human bronchial epithelial cell (dpHBEC) cultures grown under air-liquid interface (ALI) conditions exhibit key features of the human respiratory tract and are thus critical for respiratory research as well as efficacy and toxicity testing of inhaled substances (<i>e.g.</i>, consumer products, industrial chemicals, and pharmaceuticals). Many inhalable substances (<i>e.g.</i>, particles, aerosols, hydrophobic substances, reactive substances) have physiochemical properties that challenge their evaluation under ALI conditions <i>in vitro</i>. Evaluation of the effects of these methodologically challenging chemicals (MCCs) <i>in vitro</i> is typically conducted by \"liquid application,\" involving the direct application of a solution containing the test substance to the apical, air-exposed surface of dpHBEC-ALI cultures. We report that the application of liquid to the apical surface of a dpHBEC-ALI co-culture model results in significant reprogramming of the dpHBEC transcriptome and biological pathway activity, alternative regulation of cellular signaling pathways, increased secretion of pro-inflammatory cytokines and growth factors, and decreased epithelial barrier integrity. Given the prevalence of liquid application in the delivery of test substances to ALI systems, understanding its effects provides critical infrastructure for the use of <i>in vitro</i> systems in respiratory research as well as in the safety and efficacy testing of inhalable substances.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1264331"},"PeriodicalIF":3.6,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-derived neurotrophic factor (BDNF): an effect biomarker of neurodevelopment in human biomonitoring programs","authors":"A. Rodríguez-Carrillo, V. Verheyen, Alexander L. N. Van Nuijs, Mariana F. Fernández, Sylvie Remy","doi":"10.3389/ftox.2023.1319788","DOIUrl":"https://doi.org/10.3389/ftox.2023.1319788","url":null,"abstract":"The present narrative review summarizes recent findings focusing on the role of brain-derived neurotrophic factor (BDNF) as a biomarker of effect for neurodevelopmental alterations during adolescence, based on health effects of exposure to environmental chemical pollutants. To this end, information was gathered from the PubMed database and the results obtained in the European project Human Biomonitoring for Europe (HBM4EU), in which BDNF was measured at two levels of biological organization: total BDNF protein (serum) and BDNF gene DNA methylation (whole blood) levels. The obtained information is organized as follows. First, human biomonitoring, biomarkers of effect and the current state of the art on neurodevelopmental alterations in the population are presented. Second, BDNF secretion and mechanisms of action are briefly explained. Third, previous studies using BDNF as an effect biomarker were consulted in PubMed database and summarized. Finally, the impact of bisphenol A (BPA), metals, and non-persistent pesticide metabolites on BDNF secretion patterns and its mediation role with behavioral outcomes are addressed and discussed. These findings were obtained from three pilot studies conducted in HBM4EU project. Published findings suggested that exposure to some chemical pollutants such as fine particle matter (PM), PFAS, heavy metals, bisphenols, and non-persistent pesticides may alter circulating BDNF levels in healthy population. Therefore, BDNF could be used as a valuable effect biomarker to investigate developmental neurotoxicity of some chemical pollutants.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte DNA damage and response upon acute exposure to ethanol and corticosterone","authors":"Ana Laura Reyes-Ábalos, Magdalena Álvarez-Zabaleta, Silvia Olivera-Bravo, M. D. Di Tomaso","doi":"10.3389/ftox.2023.1277047","DOIUrl":"https://doi.org/10.3389/ftox.2023.1277047","url":null,"abstract":"Introduction: Astrocytes are the glial cells responsible for brain homeostasis, but if injured, they could damage neural cells even deadly. Genetic damage, DNA damage response (DDR), and its downstream cascades are dramatic events poorly studied in astrocytes.Hypothesis and methods: We propose that 1 h of 400 mmol/L ethanol and/or 1 μmol/L corticosterone exposure of cultured hippocampal astrocytes damages DNA, activating the DDR and eliciting functional changes. Immunolabeling against γH2AX (chromatin DNA damage sites), cyclin D1 (cell cycle control), nuclear (base excision repair, BER), and cytoplasmic (anti-inflammatory functions) APE1, ribosomal nucleolus proteins together with GFAP and S100β plus scanning electron microscopy studies of the astrocyte surface were carried out.Results: Data obtained indicate significant DNA damage, immediate cell cycle arrest, and BER activation. Changes in the cytoplasmic signals of cyclin D1 and APE1, nucleolus number, and membrane-attached vesicles strongly suggest a reactivity like astrocyte response without significant morphological changes.Discussion: Obtained results uncover astrocyte genome immediate vulnerability and DDR activation, plus a functional response that might in part, be signaled through extracellular vesicles, evidencing the complex influence that astrocytes may have on the CNS even upon short-term aggressions.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"37 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139446347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The “Big Three” in biocompatibility testing of medical devices: implementation of alternatives to animal experimentation—are we there yet?","authors":"H. Kanďárová, P. Pôbiš","doi":"10.3389/ftox.2023.1337468","DOIUrl":"https://doi.org/10.3389/ftox.2023.1337468","url":null,"abstract":"Biocompatibility testing ensures the safety of medical devices by assessing their compatibility with biological systems and their potential to cause harm or adverse reactions. Thus, it is a critical part of the overall safety evaluation process for medical devices. Three primary types of biocompatibility tests—cytotoxicity, irritation, and sensitisation assessment—are standard for nearly all medical devices. However, additional biocompatibility tests, such as genotoxicity, systemic toxicity, hemocompatibility, and implantation studies, may also be necessary, depending on the device’s nature and intended use. The testing is partly conducted in vitro, but the industry still heavily relies on animal experiments. Compared to other industrial sectors, implementing alternatives in medical device biocompatibility testing has been notably slower. This delay can be attributed to the absence of specific validation processes tailored to medical devices and the resulting hesitation regarding the predictive capacity of these alternative methods despite their successful applications in other domains. This review focuses on the progress and obstacles to implementing new approach methodologies in the areas of cytotoxicity, irritation and sensitisation testing of medical devices. While challenges persist in adopting these innovative methods, the trend towards embracing alternatives remains robust. This trend is driven by technological advancements, ethical considerations, and growing industrial interest and support, all collectively contributing to advancing safer and more effective medical devices.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"46 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139448291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenolic compounds occurrence and human health risk assessment in potable and treated waters in Western Cape, South Africa","authors":"Nkosiyenzile Londiwe Mhlongo, M. O. Akharame, O. Pereao, I. Human, B. Opeolu","doi":"10.3389/ftox.2023.1269601","DOIUrl":"https://doi.org/10.3389/ftox.2023.1269601","url":null,"abstract":"Phenolic pollutants from industrial and agricultural activities pose a major threat to the world’s potable water supply. The persistent micro-pollutants often find their way into drinking water sources with possible adverse human health implications. In this study, bottled water, tap water, and wastewater treatment plant (WWTP) effluent samples from the Boland region of the Western Cape, South Africa were assessed to determine 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP) levels using HPLC/DAD instrumentation. The selected area is known for its vast agricultural ventures and wineries. Evaluation of the human health risk (cancer risk) for the pollutants was conducted using the hazard quotient (HQ). The Ames mutagenicity test was also conducted using the Salmonella typhimurium T98 and T100 strains and the S9 activation enzyme. Trace levels of the phenolics were detected in the samples with a range of 9.32 × 10−7—1.15 × 10−4 mg/L obtained for 4-CP, and 8.80 × 10−7—1.72 × 10−4 mg/L recorded for 2,4-DCP. Both compounds had levels below the limit of 0.01 mg/L prescribed by South African legislation. The assessed HQ for the phenolic concentrations indicates a low level of potential ecological risk and none of the samples had a cancer risk value that exceeded the regulatory limit. The possibility of the analyzed samples causing cancer is unlikely, but non-carcinogenic adverse effects were found. Strong mutagenicity was observed for the T98 strains with a potential ability to cause mutation toward the insertion or deletion of a nucleotide. The T100 bacterial strain showed very slight mutagenicity potential, however, it is unlikely to cause any mutation. The levels of phenolics in the potable water samples may pose a significant threat to human health. Hence, screening persistent organic chemicals in potable water sources and evaluating their potential human health effects is pertinent to prevent associated health challenges.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"34 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Development of skin diseases following systemic exposure: example of dioxins.","authors":"Olivier Sorg, Jean-Hilaire Saurat","doi":"10.3389/ftox.2023.1323294","DOIUrl":"https://doi.org/10.3389/ftox.2023.1323294","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2023.1243192.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1323294"},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10777835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolites in the regulatory risk assessment of pesticides in the EU","authors":"O. Pelkonen, K. Abass, Juan Manuel Parra Morte, Martina Panzarea, Emanuela Testai, Serge Rudaz, J. Louisse, Ursula Gundert-Remy, Gerrit Wolterink, Dorne Jean-Lou CM, Sandra Coecke, C. Bernasconi","doi":"10.3389/ftox.2023.1304885","DOIUrl":"https://doi.org/10.3389/ftox.2023.1304885","url":null,"abstract":"A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities. This is of particular relevance to pesticide metabolites that are unique to humans in comparison with metabolites found in in vitro or in vivo animal studies, but also to disproportionate metabolites (quantitative differences) between humans and mammalian species. Presence of unique or disproportionate metabolites may underlie potential toxicological concerns. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for hazard and risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":" 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138962160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}