Frontiers in toxicology最新文献

{"title":"An Adverse Outcome Pathway for food nanomaterial-induced intestinal barrier disruption.","authors":"Deborah Stanco, Dorelia Lipsa, Alessia Bogni, Susanne Bremer-Hoffmann, Laure-Alix Clerbaux","doi":"10.3389/ftox.2024.1474397","DOIUrl":"https://doi.org/10.3389/ftox.2024.1474397","url":null,"abstract":"<p><strong>Introduction: </strong>The ingestion of nanomaterials (NMs) may impair the intestinal barrier, but the underlying mechanisms remain evasive, and evidence has not been systematically gathered or produced. A mechanistic-based approach would be instrumental in assessing whether relevant NMs disrupt the intestinal barrier, thereby supporting the NM risk assessment in the food sector.</p><p><strong>Methods: </strong>In this study, we developed an adverse outcome pathway (AOP) based on biological plausibility and by leveraging information from an existing NM-relevant AOP that leads to hepatic outcomes. We then extracted the current evidence from the literature for a targeted selection of NMs with high relevance to the food sector, namely, ZnO, CuO, FeO, SiO₂, and Ag NMs and nanocellulose.</p><p><strong>Results: </strong>We propose a new AOP (AOP 530) that starts with endocytic lysosomal uptake, leading to lysosomal disruption inducing mitochondrial dysfunction. Mitochondrial impairments can lead to cell injury/death and disrupt the intestinal barrier. The evidence collected supports that these food-related NMs can be taken up by intestinal cells and indicates that intestinal barrier disruption may occur due to Ag, CuO, and SiO₂ NMs, while only few studies support this outcome for FeO and ZnO. Lysosomal disruption and mitochondrial dysfunction are rarely evaluated. For nanocellulose, none of the studies report toxicity-related events.</p><p><strong>Conclusion: </strong>The collection of existing scientific evidence supporting our AOP linking NM uptake to intestinal barrier impairments allowed us to highlight current evidence gaps and data inconsistencies. These inconsistencies could be associated with the variety of stressors, biological systems, and key event (KE)-related assays used in different studies. This underscores the need for further harmonized methodologies and the production of mechanistic evidence for the safety regulatory assessment of NMs in the food sector.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1474397"},"PeriodicalIF":3.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959686","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":"Editorial: Reducing animal use in carcinogenicity testing.","authors":"Jan Willem Van der Laan, Joseph Manuppello","doi":"10.3389/ftox.2024.1538905","DOIUrl":"https://doi.org/10.3389/ftox.2024.1538905","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1538905"},"PeriodicalIF":3.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916066","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":"Mineral composition in mussel <i>Mytilus galloprovincialis</i> and clam <i>Tapes decussatus</i> from Faro Lake of Messina: risk assessment for human health.","authors":"Fabio Bruno, Vincenzo Nava, Sebastiano Zappalà, Giovanna Lucrezia Costa, Francesco Fazio, Vincenzo Parrino, Patrizia Licata","doi":"10.3389/ftox.2024.1494977","DOIUrl":"10.3389/ftox.2024.1494977","url":null,"abstract":"<p><p>Bivalve are exposed to a wide range of contaminants, some of which may be toxic to human health. The aim of this study was to detect essential and non-essential elements such as Na, Ca, Mg, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Pb, Hg, Be and Co in water, sediments, and <i>Mytilus galloprovincialis</i> and <i>Tapes decussatus</i> from Faro Lake. It is a lake of marine origin located on the northern coast of Messina (Sicily), where shellfish farming has been practiced for many years. Metals were analysed by a single quadrupole inductively coupled plasma mass spectrometer (ICP-MS), except for Hg, which was quantified using a direct mercury analyser (DMA-80). The study evaluated the nutritional intake of elements through the ingestion of clams and mussels and the potential health risks to consumers. The lead levels found in <i>M. galloprovincialis</i> were below the LOQ, while in <i>T. decussatus</i> the concentrations were below the limit indicated by European Regulation 915/2023. Statistical analysis was carried out on <i>M. galloprovincialis</i> and <i>T. decussatus</i> samples using SPSS 27 and the data showed highly significant differences between the two species (<i>p</i> < 0.001). Cadmium (Cd) and mercury (Hg) concentrations were also below the legal limit in all samples analyzed. This study has shown that clams and mussels are a source of sodium (Na) with a Recommended Dietary Allowance (RDA) of 36% in <i>M. galloprovincialis</i> and 77% in <i>T. decussatus</i>. The percentages obtained for calcium (Ca) and magnesium (Mg) were 17%-19% and 18%-8%, respectively. The RDA of chromium (Cr) was of 191% for <i>M. galloprovincialis</i> and of 405% for <i>T. decussatus.</i> The Fe percentages were 92% and 169% for <i>M. galloprovincialis</i> and <i>T. decussatus</i>, respectively. The concentrations of the other metals observed in the two bivalve species of Lake Faro were generally lower than the Tolerable Weekly Intake (TWI) values estimated as a risk to human health.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1494977"},"PeriodicalIF":3.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904165","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":"Editorial: A Toxic Aging Coin perspective to investigate the intersection of toxicology and aging.","authors":"Rachel M Wise, John P Wise, Julie K Andersen, Michael Aschner","doi":"10.3389/ftox.2024.1527706","DOIUrl":"10.3389/ftox.2024.1527706","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1527706"},"PeriodicalIF":3.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900634","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":"Ah receptor, vitamin B12 and itaconate: how localized decrease of vitamin B12 prevents survival of macrophage-ingested bacteria.","authors":"Karl Walter Bock","doi":"10.3389/ftox.2024.1491184","DOIUrl":"10.3389/ftox.2024.1491184","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1491184"},"PeriodicalIF":3.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900628","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":"Considering future qualification for regulatory science in the early development of microphysiological systems: a case study of microthrombosis in a Vessel-on-Chip.","authors":"Huub J Weener, Heleen H T Middelkamp, Andries D Van der Meer","doi":"10.3389/ftox.2024.1513002","DOIUrl":"10.3389/ftox.2024.1513002","url":null,"abstract":"<p><p>Microphysiological systems (MPS) and Organs-on-Chips (OoCs) hold significant potential for replicating complex human biological processes <i>in vitro</i>. However, their widespread adoption by industry and regulatory bodies depends on effective qualification to demonstrate that these models are fit for purpose. Many models developed in academia are not initially designed with qualification in mind, which limits their future implementation in end-user settings. Here, we explore to which extent aspects of qualification can already be performed during early development stages of MPS and OoCs. Through a case study of our blood-perfused Vessel-on-Chip model, we emphasize key elements such as defining a clear context-of-use, establishing relevant readouts, ensuring model robustness, and addressing inherent limitations. By considering qualification early in development, researchers can streamline the progression of MPS and OoCs, facilitating their adoption in biomedical, pharmaceutical, and toxicological research. In addition, all <i>in vitro</i> methods must be independent of animal-derived materials to be considered fully fit for purpose. Ultimately, early qualification efforts can enhance the availability, reliability, and regulatory as well as ethical acceptance of these emerging New Approach Methodologies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1513002"},"PeriodicalIF":3.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878762","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":"Protective effects of <i>Pelargonium graveolens</i> (geranium) oil against cefotaxime-induced hepato-renal toxicity in rats.","authors":"Shaimaa M Azzam, Heba M A Elsanhory, Ahmed H Abd El-Slam, Marwa S M Diab, Halima Mohamed Ibrahim, Abdalrahman Mohammed Yousef, Fatma Mahmoud Sabry, Ebtihal Y Khojah, Somaiah A Bokhari, Gad Elsayed Mohamed Salem, Marwa Saad Zaghloul","doi":"10.3389/ftox.2024.1489310","DOIUrl":"10.3389/ftox.2024.1489310","url":null,"abstract":"<p><p>Cefotaxime is a broad-spectrum antibiotic targeting Gram-negative bacteria used for diverse infections, but it can be toxic to the stomach, liver, and kidneys. This study explored the protective effects of geranium oil against cefotaxime-induced hepatotoxicity and nephrotoxicity in rats, employing biochemical, histopathological, and immunohistochemical evaluations. Thirty rats were divided into five groups of six animals each one. Group 1 received orally normal saline for 14 days, Group 2 was given orally 2.5% DMSO for 14 days, Group 3 received cefotaxime (200 mg/kg/day IM) for 14 days, Group 4 received with cefotaxime (200 mg/kg/day IM) and geranium oil (67 mg/kg b. w./day orally in DMSO) for 14 days, and Group 5 received geranium oil alone (67 mg/kg b. w./day orally in DMSO) for 14 days. Geranium oil significantly reduced cefotaxime-induced damage, evidenced by lower serum levels of liver enzymes (AST, ALT), renal markers (urea, creatinine), and other indicators (alkaline phosphatase, TNF-alpha, IL-1Beta, MAPK, nitric oxide, MDA). It also increased levels of protective tissue biomarkers such as NrF2, albumin, catalase, Beclin 1, and reduced glutathione (GSH). Histopathological and immunohistochemical analyses revealed significant protective effects in liver and renal tissues in rats treated with Geranium oil. These results suggest that Geranium oil is effective in mitigating cefotaxime-induced hepatotoxicity and renal toxicity.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1489310"},"PeriodicalIF":3.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857103","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":"The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following <i>in utero</i> opioid exposures in mouse fetuses.","authors":"Dustyn Barnette, Amy L Inselman, Pravin Kaldhone, Grace S Lee, Kelly Davis, Sumit Sarkar, Pritpal Malhi, J Edward Fisher, Joseph P Hanig, Richard D Beger, E Ellen Jones","doi":"10.3389/ftox.2024.1452974","DOIUrl":"10.3389/ftox.2024.1452974","url":null,"abstract":"<p><strong>Introduction: </strong>In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a dynamic approach capable of generating 2D ion images to visualize the distribution of an analyte of interest across a tissue section.</p><p><strong>Methods: </strong>Given the importance of lipid metabolism and neurotransmitters in the developing central nervous system, this study incorporates MALDI MSI to assess lipid distributions across mouse gestational day (GD) 18 fetuses, with and without observable NTDs following maternal exposure on GD 8 to morphine (400 mg/kg BW) or the NTD positive control valproic acid (VPA) (500 mg/kg BW).</p><p><strong>Results: </strong>Analysis of whole-body mouse fetuses revealed differential lipid distributions localized mainly in the brain and spinal cord, which included several phosphatidylcholine (PC) species such as PCs 34:1, 34:0, and 36:2 localized to the cortex or hippocampus and lyso PC 16:0 across all brain regions. Overall, differential lipids increased in with maternal morphine and VPA exposure. Neurotransmitter distributions across the brain using FMP-10 derivatizing agent were also assessed, revealing morphine-specific changes.</p><p><strong>Discussion: </strong>The observed differential glycerophospholipid distributions in relation to treatment and NTD development in mouse fetuses provide potential targets for further investigation of molecular mechanisms of opioid-related developmental effects. Overall, these findings support the feasibility of incorporating MALDI MSI to assess non-standard endpoints of opioid exposure during gestation.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1452974"},"PeriodicalIF":3.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848532","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>In vitro</i> toxicological evaluation of pouched portioned oral nicotine products.","authors":"Brian M Keyser, Robert Leverette, Reagan McRae, John Wertman, Tom Shutsky, Ken Szeliga, Patrudu Makena, Kristen G Jordan","doi":"10.3389/ftox.2024.1452274","DOIUrl":"10.3389/ftox.2024.1452274","url":null,"abstract":"<p><strong>Introduction: </strong>Modern oral nicotine pouch products (ONPs) are a category of oral nicotine products which contain pharmaceutical-grade nicotine, flavors, and other food-grade ingredients but no tobacco leaf. Recent reports indicate that ONPs in general do not contain (or only at minimal levels) the harmful and potentially harmful constituents (HPHCs) identified in cigarette smoke, suggesting their potential as alternative products for reducing harm from cigarette smoking.</p><p><strong>Methods: </strong>We assessed <i>in vitro</i> toxicological effects of eight ONPs, designated as modern oral (MO) 1 to 8 along with an ONP, an oral tobacco (snus), and a combustible cigarette market comparator using established regulatory toxicological assays including Ames, <i>in vitro</i> micronucleus (ivMN), and neutral red uptake (NRU) assays.</p><p><strong>Results: </strong>The MO test products 1-7 ZYN wintergreen, and General Snus white mint were negative for mutagenicity (Ames assay), genotoxicity (ivMN), and cytotoxicity (NRU). The combustible cigarette was positive in all three assays. The MO-8 test product was negative for mutagenicity; however, it was positive in the ivMN and NRU assays at concentrations either 42 to 135-fold based on the ivMN i to iv treatment schedule or 60-fold higher, respectively, when compared to combustible cigarettes.</p><p><strong>Discussion: </strong>Thus, the MO test products are likely to be less harmful than combustible cigarettes and are alternatives to cigarettes. However, understanding of long-term effects of ONPs in general requires additional research.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1452274"},"PeriodicalIF":3.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820292","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":"Heterogenous bioluminescence patterns, cell viability, and biofilm formation of <i>Photobacterium leiognathi</i> strains exposed to ground microplastics.","authors":"Rener De Jesus, Sameera Iqbal, Sunil Mundra, Ruwaya AlKendi","doi":"10.3389/ftox.2024.1479549","DOIUrl":"10.3389/ftox.2024.1479549","url":null,"abstract":"<p><p>Microplastics (MPs) have been detected in various aquatic environments and negatively affect organisms, including marine luminous bacteria. This study investigated the differences in bioluminescence patterns, cell viability, and biofilm formation of <i>Photobacterium leiognathi</i> strains (LB01 and LB09) when exposed to various concentrations of ground microplastics (GMPs; 0.25%, 0.50%, 1%, or 2% [w/v] per mL) at 22°C or 30°C for 3.1 days (75 h) and 7 days. The strains exhibited heterogenous responses, including variable bioluminescence patterns, cell viability, and biofilm formation, due to the GMPs having effects such as hormesis and bioluminescence quenching. Moreover, the bioluminescence and cell viability differed between the two strains, possibly involving distinct cellular mechanisms, suggesting that GMPs affect factors that influence quorum sensing. Furthermore, the biofilm formation of LB01 and LB09 was observed following exposure to GMPs. Both strains showed increased biofilm formation at higher GMP concentrations (1% and 2%) after 3.1 days at 30°C and 22°C. However, in the 7-day experiment, LB01 significantly (<i>p</i> < 0.05) increased biofilms at 22°C, while LB09 significantly (<i>p</i> < 0.05) produced biofilms at 30°C. These findings highlight the strain-specific responses of <i>Phb. leiognathi</i> to MP pollutants. Therefore, this study underscores the importance of evaluating MPs as environmental stressors on marine microorganisms and their role in the ecophysiological repercussions of plastic pollution in aquatic environments.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1479549"},"PeriodicalIF":3.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815076","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}