Frontiers in toxicology最新文献

筛选
英文 中文
Optimizing Wnt activation in fetal calf serum (FCS)-free organoid expansion media. 优化Wnt在无胎牛血清(FCS)类器官扩增培养基中的激活。
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1504469
Esther J M Liefting, Jeffrey J Bajramovic
{"title":"Optimizing Wnt activation in fetal calf serum (FCS)-free organoid expansion media.","authors":"Esther J M Liefting, Jeffrey J Bajramovic","doi":"10.3389/ftox.2025.1504469","DOIUrl":"10.3389/ftox.2025.1504469","url":null,"abstract":"<p><p>Organoid technology can revolutionize biomedical research by increasing the translational value of experimental results while at the same time reducing the need for experimental animal use. However, in most cases the organoid culture workflow relies on expansion media that contain fetal calf serum (FCS). The production of FCS causes animal suffering, and the use of it is hampered by factors that negatively impact the reproducibility (such as the large inter-batch variation and the undefined composition of FCS), relevance (such as the induction of a non-physiological cellular phenotype), as well as the clinical translatability (such as the potential to cause xeno-immunization or to contain xenogeneic pathogens). There is thus a strong impetus to find animal-free alternatives to the use of FCS. Most contemporary expansion media for organoid culture are not FCS-free. This is mainly contributable to the use of FCS for the recombinant production of the growth factor Wnt3A. Wnt3A-conditioned medium is added to expansion media to induce Wnt signaling, which is necessary for organoid proliferation. In turn, FCS is pivotal to stabilize and solubilize the Wnt3A protein, and not perse for the survival, adhesion or proliferation of cells. This mini-review explores alternative methods to induce Wnt signaling in organoid expansion media, encompassing the use of soluble Wnt mimetics, the use of carriers, and the use of small molecule inhibitors. Ultimately, alternative Wnt activation approaches for different experimental goals are reviewed and discussed.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1504469"},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176005","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}
引用次数: 0
Case report: Treatment of severe phorate poisoning. 病例报告:重度磷中毒的治疗。
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-09 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1581362
Wang Kunlun, Yuan Jun, Xu Shiming, Shen Jie, Gao Mingqiang, Zhang Yuxia, Mo Weichun
{"title":"Case report: Treatment of severe phorate poisoning.","authors":"Wang Kunlun, Yuan Jun, Xu Shiming, Shen Jie, Gao Mingqiang, Zhang Yuxia, Mo Weichun","doi":"10.3389/ftox.2025.1581362","DOIUrl":"10.3389/ftox.2025.1581362","url":null,"abstract":"<p><strong>Background: </strong>Phorate is a highly toxic organophosphorus pesticide. Owing to its low cost and insecticidal potency, it is still widely used in parts of China, resulting in cases of occupational and life poisoning. This article presents the treatment process for phorate poisoning and monitoring the toxic metabolites terminology in the body.</p><p><strong>Case report: </strong>A 23-year-old male patient ingested about 300 mL (180 g) of 60% phorate emulsion 4 h before admission at our hospital. The patient had ingested over 300 times the lethal dose. During hospitalization, the patient's levels of cholinesterase, phorate and its metabolites, atropine and pralidoxime chloride (PAM), were monitored. Phorate was quickly absorbed into the blood, producing five metabolites. Before hemoperfusion (HP), the concentration of phorate in the blood could not be detected. After the first HP we found five metabolites of phorate in the blood (phoratoxon sulfoxide,phoratoxon sulfone, phorate sulfone, phorate sulfoxide, and phoratoxon). In the follow-up treatment, the concentration of five metabolites gradually decreased. The concentration of the phorate sulfoxide and phorate sulfone rebounded with the suspension of HP, but that of the other metabolites did not rebound. It took 20 days for cholinesterase to recover. Treatment included multiple rounds of HP, atropinization, and reactivator of cholinesterase by PAM. The patient recovered after 34 days and was discharged from hospital.</p><p><strong>Conclusion: </strong>Phorate is oxidized and catalyzed into five metabolites, which cause the toxic effects. Phoratoxon sulfoxide has the highest concentration of these metabolites, followed by phoratoxon sulfone, phorate sulfone, phorate sulfoxide, and phoratoxon, respectively. HP treatment significantly lowered the serum levels of the toxic metabolites terminology. If HP treatment is interrupted, the serum levels of phorate sulfoxide and phorate sulfone tend to rise again. It takes a long time for cholinesterase to recover from severe phorate poisoning.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1581362"},"PeriodicalIF":3.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144777","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}
引用次数: 0
Rat embryonic stem cell-based in vitro testing platform for mammalian embryo toxicology at pre- and post-implantation stages. 基于大鼠胚胎干细胞的哺乳动物胚胎着床前后毒理学体外测试平台。
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1561386
Corinne Quadalti, Marzia Moretti, Fabio Ferrazzi, Laura Calzà, Luciana Giardino, Vito Antonio Baldassarro
{"title":"Rat embryonic stem cell-based <i>in vitro</i> testing platform for mammalian embryo toxicology at pre- and post-implantation stages.","authors":"Corinne Quadalti, Marzia Moretti, Fabio Ferrazzi, Laura Calzà, Luciana Giardino, Vito Antonio Baldassarro","doi":"10.3389/ftox.2025.1561386","DOIUrl":"10.3389/ftox.2025.1561386","url":null,"abstract":"<p><strong>Introduction: </strong>The international guidelines outlining the mandatory developmental toxicology studies of new molecules on pre-implantation, post-implantation and organogenesis phases, require a minimum of 60 pregnant female rats for each molecule to be tested. To date, available in vitro methods still have many limitations, resulting in poor translational power.</p><p><strong>Methods: </strong>In the present study, an innovative in vitro platform is proposed, based on rat embryonic stem cells (RESCs), which is easy to use and suitable for wide-scale screening, mimicking two different developmental stages: i) pre-implant model (undifferentiated pluripotent cells), ii) post-implant model (neuroectodermal lineage differentiation).</p><p><strong>Results: </strong>The in vitro platform was validated by testing the toxicity on the pre-implant model of RA itself, as a known teratogen, a member of the environmental pollutant family per- and polyfluoroalkyl substances (PFAS), the perfluorooctanic acid (PFOA), and the endocrine disruptor chemical 2,2',6,6'-tetrabromobisphenol A (TBBPA) as test compound, targeting the thyroid hormone (TH) signal. The post-implant model showed inactivation of the pluripotent markers and activation of the neuroectodermal markers. The preimplant model resulted high responsive and sensitive to the embryotoxic effect of the tested compounds. The TBBPA was selected to test the potential effects of on viability and neuroectodermal differentiation, assessed through colorimetric and cell-based high-content screening methods establishing sub-toxic (20 μM) and toxic (40 μM) doses. A high-throughput gene expression array-based analysis showed a prompt response of the in vitro testing platform to TBBPA treatment. A rescue experiment exploiting a pan-thyroid receptor (pan-TR) inhibitor (1-850) showed that the effects of TBBPA on RESCs was blocked, demonstrating its activity through TRs.</p><p><strong>Discussion: </strong>The RESCs-based platform allowed reproducible, robust and highly predictable results, thanks to the coupling of RESCs with high-throughput technologies. These results support the possible use of RESCs-based models as a screening platform for developmental toxicity testing to reduce the number of animals currently used for this aim.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1561386"},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129693","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}
引用次数: 0
Raising awareness of riverine populations in the Brazilian Amazon about MeHg intoxication in APOE4 carriers: cardiovascular risk and potential benefit of native selenium diets. 提高巴西亚马逊河流域人群对APOE4携带者甲基汞中毒的认识:心血管风险和天然硒饮食的潜在益处
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1571658
Camila G M Carvalho, Patrícia Marçal Da Costa, Luana M Rocha Souza, Vitória K Félix Monteiro, Jacqueline I Alvarez-Leite, Maria Elena Crespo-Lopez, Reinaldo B Oriá
{"title":"Raising awareness of riverine populations in the Brazilian Amazon about MeHg intoxication in <i>APOE</i>4 carriers: cardiovascular risk and potential benefit of native selenium diets.","authors":"Camila G M Carvalho, Patrícia Marçal Da Costa, Luana M Rocha Souza, Vitória K Félix Monteiro, Jacqueline I Alvarez-Leite, Maria Elena Crespo-Lopez, Reinaldo B Oriá","doi":"10.3389/ftox.2025.1571658","DOIUrl":"10.3389/ftox.2025.1571658","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1571658"},"PeriodicalIF":3.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129691","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}
引用次数: 0
Editorial: Women in nanotoxicology 2023-2024. 社论:2023-2024纳米毒理学中的女性。
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-06 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1599767
Iseult Lynch, Ilika Ghosh
{"title":"Editorial: Women in nanotoxicology 2023-2024.","authors":"Iseult Lynch, Ilika Ghosh","doi":"10.3389/ftox.2025.1599767","DOIUrl":"10.3389/ftox.2025.1599767","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1599767"},"PeriodicalIF":3.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112993","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}
引用次数: 0
Nutrients and phytochemicals characterisations, acute and sub-acute oral toxicity studies of BobyGuard C, a polyherbal nutraceutical with anti-breast cancer properties. BobyGuard C是一种具有抗乳腺癌特性的多草药营养保健品,其营养成分和植物化学物质特征、急性和亚急性口服毒性研究。
IF 3.6
Frontiers in toxicology Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1598185
Borelle Mafogang, Roger Ponka, Joseph Ngakou Mukam, Elie Fokou
{"title":"Nutrients and phytochemicals characterisations, acute and sub-acute oral toxicity studies of BobyGuard C, a polyherbal nutraceutical with anti-breast cancer properties.","authors":"Borelle Mafogang, Roger Ponka, Joseph Ngakou Mukam, Elie Fokou","doi":"10.3389/ftox.2025.1598185","DOIUrl":"https://doi.org/10.3389/ftox.2025.1598185","url":null,"abstract":"<p><strong>Background: </strong>In 2022, approximately 2.3 million new cases of female breast cancer and 670,000 related deaths worldwide despite significant advancements in conventional treatments. BobyGuard C (BGC) is a novel polyherbal nutraceutical formulated from five plants, selected for their antioxidant, anticancer, anti-inflammatory and nutritional properties to be used for breast cancer management. This study aimed to characterize its physicochemical, nutritional, and phytochemical properties as well as assess its safety through acute and sub-acute oral toxicity studies in Wistar rats.</p><p><strong>Methods: </strong>Thecomposition of BGC was analyzed for macronutrients, minerals, and phytochemicals using standard methods. Antioxidant activity was assessed through DPPH, TAC and FRAP assays, while antiproliferative activity was evaluated using the MTT assay on MDA-MB 231 and MCF-7 breast cancer cell lines. Acute (single 5,000 mg/kg dose with 14 days observation) and sub-acute oral (daily administration of 784, 1,568, and 3,136 mg/kg for 28 days) toxicity studies in female Wistar rats followed OECD guidelines.</p><p><strong>Results: </strong>BGC was found to be rich in proteins (38.36 g/100 g), carbohydrates (59.70 g/100 g), and essential minerals such as magnesium (60,066.67 µg/100 g), and it was free from toxic heavy metals. Several bioactive compounds, including diosgenin, diosbulbin H, β-carotene, Bafoudiosbulbin G and catechin were identified in BGC. Phytochemical analysis revealed high levels of phenols (9,783.48 mg GAE/100 g), flavonoids (47.72 mg QuE/100 g), and alkaloids (106.14 mg berberine eq/100 g), contributing to its strong antioxidant activity (DPPH inhibition: 90.39%). BGC exhibited significant antiproliferative effects on MDA-MB 231 cells, highlighting its potential anticancer activity. Acute toxicity tests showed no mortality at 5,000 mg/kg, with an LD<sub>50</sub> exceeding this dose. In the sub-acute 28-day repeated-dose oral study, doses up to 3,136 mg/kg/day resulted in some dose dependent hematological and biochemical changes but no histopathological abnormalities were observed indicating its safety at lower doses.</p><p><strong>Conclusion: </strong>BGC is a nutritionally rich formulation with potent antioxidant and anticancer potential, demonstrating a favorable safety profile at lower dose (784 mg/kg).</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1598185"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082537","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}
引用次数: 0
Associations of environmental pollution with pro-oxidant, antioxidant and inflammatory markers in pregnant mothers and newborns. 环境污染与孕妇和新生儿促氧化、抗氧化和炎症标志物的关系。
IF 3.6
Frontiers in toxicology Pub Date : 2025-04-29 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1572486
Antonin Ambroz, Jiri Klema, Andrea Rossnerova, Alena Milcova, Anna Pastorkova, Jana Pulkrabova, Ondrej Parizek, Veronika Gomersall, Tomas Gramblicka, Jaroslav Zelenka, Tomas Ruml, Nikola Vrzackova, Milos Veleminsky, Newroz Hasan, Jan Topinka, Radim J Sram, Pavel Rossner
{"title":"Associations of environmental pollution with pro-oxidant, antioxidant and inflammatory markers in pregnant mothers and newborns.","authors":"Antonin Ambroz, Jiri Klema, Andrea Rossnerova, Alena Milcova, Anna Pastorkova, Jana Pulkrabova, Ondrej Parizek, Veronika Gomersall, Tomas Gramblicka, Jaroslav Zelenka, Tomas Ruml, Nikola Vrzackova, Milos Veleminsky, Newroz Hasan, Jan Topinka, Radim J Sram, Pavel Rossner","doi":"10.3389/ftox.2025.1572486","DOIUrl":"10.3389/ftox.2025.1572486","url":null,"abstract":"<p><p>The aim of the study was to analyze the variables that modify the levels of oxidative DNA damage and lipid peroxidation in non-smoking mothers and their newborns from environmentally distinct localities of the Czech Republic: Ceske Budejovice (CB, an agricultural region) and Karvina (an industrial region). Personal, socio-economic and medical data, concentrations of particulate matter of aerodynamic diameter < 2.5 µm (PM2.5) and benzo[a]pyrene (B[a]P) in the ambient air, the activities of antioxidant mechanisms (superoxide dismutase, catalase, glutathione peroxidase) and antioxidant capacity), the levels of pro-inflammatory cytokines, the concentrations of persistent organic pollutants (POPs) in blood plasma/cord blood plasma and urinary levels of polycyclic aromatic hydrocarbons metabolites (OH-PAHs) were investigated as parameters potentially affecting the markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG) and lipid peroxidation (15-F<sub>2</sub>t-isoprostane, 15-F<sub>2</sub>t-IsoP). Significantly higher levels of POPs were detected in the plasma of mothers/newborns from CB (p < 0.001), while increased external levels of B[a]P and PM2.5, confirmed by analyzing urinary OH-PAHs, were found in Karvina subjects (p < 0.001). In mothers, multivariate analysis showed no significant difference in oxidative stress markers (15-F<sub>2</sub>t-IsoP, 8-oxodG) between the two localities. The analysis further revealed that neither in CB nor, unexpectedly, in Karvina, did PAH exposure affect maternal lipid peroxidation. Significant associations between OH-PAHs and 15-F<sub>2</sub>t-IsoP or 8-oxodG were observed only in newborns. In addition, multivariate analyses revealed a borderline significant association between locality and 8-oxodG in the urine of all newborns (p = 0.05). In conclusion, not only the maternal exposure of PAHs but also some POPs can negatively affect oxidative stress status in the early-life of newborns.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1572486"},"PeriodicalIF":3.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057867","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}
引用次数: 0
Elucidating the mechanistic relationships between peroxisome proliferator-activated receptors and hepatic fibrosis using the ROBOKOP knowledge graph. 利用ROBOKOP知识图谱阐明过氧化物酶体增殖物激活受体与肝纤维化之间的机制关系。
IF 3.6
Frontiers in toxicology Pub Date : 2025-04-22 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1549268
Karamarie Fecho, Nyssa Tucker, Jon-Michael Beasley, Scott S Auerbach, Chris Bizon, Alexander Tropsha
{"title":"Elucidating the mechanistic relationships between peroxisome proliferator-activated receptors and hepatic fibrosis using the ROBOKOP knowledge graph.","authors":"Karamarie Fecho, Nyssa Tucker, Jon-Michael Beasley, Scott S Auerbach, Chris Bizon, Alexander Tropsha","doi":"10.3389/ftox.2025.1549268","DOIUrl":"https://doi.org/10.3389/ftox.2025.1549268","url":null,"abstract":"<p><p>We developed the Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP) application as an open-source knowledge graph system to support evidence-based biomedical discovery and hypothesis generation. This study aimed to apply ROBOKOP to suggest biological mechanisms that might explain the hypothesized relationship between exposure to the herbicide and lipid-lowering drug clofibrate, an activator of peroxisome proliferator-activated receptor-α (PPARA), and hepatic fibrosis. We queried ROBOKOP to first establish that it could demonstrate a relationship between clofibrate and PPARA as a validation test and second to identify intermediary genes and biological processes or activities that might relate the activation of PPARA by clofibrate to hepatic fibrosis. Queries of ROBOKOP returned several paths relating clofibrate, PPARA, and hepatic fibrosis. One path suggested the following: <i>clofibrate - affects / increases_ expression_ of / increases_ activity_ of / increases_ response_ to / decreases_ response_ to / is_ related_ to - PPARA - is_ actively_ involved_ in - cellular response to lipid - actively_ involves - CCL2 - is_ genetically_ associated_ with - hepatic fibrosis</i>. This result established a relationship between clofibrate and PPARA and further suggested that PPARA is actively involved in the cellular response to lipids, which actively involves the chemokine ligand CCL2, a gene genetically associated with hepatic fibrosis; thus, we can infer that PPARA, upon activation by clofibrate, plays a role in hepatic fibrosis. We conclude that ROBOKOP can be used to derive insights into biological mechanisms that might explain relationships between environmental exposures and liver toxicity.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1549268"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057619","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}
引用次数: 0
Critical values for dimensional parameters of mesotheliomagenic mineral fibers: evidence from the dimensions and rigidity of MWCNT. 间皮瘤矿物纤维尺寸参数的临界值:来自MWCNT尺寸和刚性的证据。
IF 3.6
Frontiers in toxicology Pub Date : 2025-04-22 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1568513
Ann G Wylie, Andrey A Korchevskiy
{"title":"Critical values for dimensional parameters of mesotheliomagenic mineral fibers: evidence from the dimensions and rigidity of MWCNT.","authors":"Ann G Wylie, Andrey A Korchevskiy","doi":"10.3389/ftox.2025.1568513","DOIUrl":"https://doi.org/10.3389/ftox.2025.1568513","url":null,"abstract":"<p><p>MWCNT (multi-walled carbon nanotubes) used in 72 animal instillation or inhalation studies were classified by average length, average width, Young's modulus, Rigidity Index (RI), and potency for mesothelioma in animals. The RI is based on the Euler buckling theory. MWCNT that induce mesothelioma have average lengths >2 µm and widths >37 nm, and average RI > 0.05 (µm<sup>2</sup> x GPa x 10<sup>4</sup>). Many noncarcinogenic MWCNT materials have RI < 0.05 and lack biological rigidity. In comparison, Elongate Mineral Particle (EMP) populations with one exception have RI > 0.05. Mineral particles likely to have RI < 0.05 include chrysotile fibrils with lengths >5 μm, amosite and crocidolite fibers with widths <60 nm, and sheet silicate fibers with widths <200 nm. The product of percent EMPA, average RI, and biosolubility among silicates correlates with known mesothelioma potency. The derived models reproduce published values of R<sub>M</sub> with high statistical significance (P < 0.05). Average RI, length, and width are critical parameters for mesotheliomagenicity for both MWCNT and EMPA mineral fiber.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1568513"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022454","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}
引用次数: 0
Developing a predictive model for blood-brain-barrier permeability to explore relevance of in vitro neurotoxicity data for in vivo risk assessment. 建立血脑屏障通透性预测模型,探索体外神经毒性数据与体内风险评估的相关性。
IF 3.6
Frontiers in toxicology Pub Date : 2025-04-17 eCollection Date: 2025-01-01 DOI: 10.3389/ftox.2025.1535112
Siena E Illa, Yumei Feng Earley, Li Li, Dingsheng Li
{"title":"Developing a predictive model for blood-brain-barrier permeability to explore relevance of <i>in vitro</i> neurotoxicity data for <i>in vivo</i> risk assessment.","authors":"Siena E Illa, Yumei Feng Earley, Li Li, Dingsheng Li","doi":"10.3389/ftox.2025.1535112","DOIUrl":"https://doi.org/10.3389/ftox.2025.1535112","url":null,"abstract":"<p><strong>Introduction: </strong>Despite recent rapid advancements in <i>in vitro</i> toxicology, its application to whole-body health outcomes remains limited. Incorporating factors like internal exposure, such as permeability across biomembranes, could improve its relevance. Notably, there is a lack of data and predictive models for blood-brain barrier (BBB) permeability, a proxy for the exposure of target organs to neurotoxicity. We developed a predictive model for BBB permeability to investigate whether it can strengthen the correlation between <i>in vitro</i> and <i>in vivo</i> neurotoxicity data.</p><p><strong>Methods: </strong>We collected permeability data from parallel artificial membrane permeability assays for brain membranes (PAMPA-BBB) for 106 compounds with varied physicochemical properties. This was utilized to develop an empirical model to expand the potential coverage of chemicals. A list of 23 chemicals with available <i>in vivo</i> and <i>in vitro</i> neurotoxicity data from EPA IRIS and ToxCast was curated to analyze the correlation in toxicity rankings with the Spearman correlation coefficient, with and without the consideration of permeability from our predictive model.</p><p><strong>Results: </strong>The PAMPA-BBB predictive model showed promising results, with an R2 of 0.71 (measured vs predicted permeabilities). Considering permeability did not improve the correlation between <i>in vitro</i> and <i>in vivo</i> neurotoxicity (0.01 vs -0.11).</p><p><strong>Discussion: </strong>This weak correlation may stem from model uncertainty and the exclusion of other toxicokinetic processes, along with interspecies toxicodynamics differences. Our results indicate more detailed information on how neurotoxic substances behave inside the body is essential to better utilize the <i>in vitro</i> neurotoxicity data for predicting <i>in vivo</i> toxicity and assessing the risk to the central nervous system.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1535112"},"PeriodicalIF":3.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030000","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信