Frontiers in toxicology最新文献

{"title":"Evaluation of estrogenic and anti-estrogenic activity of endocrine disruptors using breast cancer spheroids: a comparative study of T47D and MCF7 cell lines in 2D and 3D models.","authors":"Katia Barbaro, Elisa Innocenzi, Valentina Monteleone, Daniele Marcoccia, Annalisa Altigeri, Alessia Zepparoni, Daniela Caciolo, Cristian Alimonti, Marta Mollari, Paola Ghisellini, Cristina Rando, Roberto Eggenhöffner, Maria Teresa Scicluna","doi":"10.3389/ftox.2025.1547640","DOIUrl":"10.3389/ftox.2025.1547640","url":null,"abstract":"<p><strong>Introduction: </strong>The estrogenic and anti-estrogenic effects of endocrine disruptors were examined <i>in vitro</i> using two-dimensional 2D and three-dimensional 3D estrogen receptor-positive T47D and MCF7 human breast cancer cells.</p><p><strong>Methods: </strong>The <i>in vitro</i> model system was used to test the plasticizer Bisphenol A (BPA), a known endocrine disruptor (EDs) with estrogen-like action, aga inst 17β-Estradiol (E2), the endogenous nuclear estrogen receptor (nERs) ligand, and the anti-estrogenic drug Fulvestrant (FUL). Spheroid formation and gene expression of estrogen-regulated markers (pS2 and TGFβ3) both in 2D and 3D cultures were used to establish the dose-dependent cellular effects of these substances, evaluated cell viability either by separately treating with the individual substances or in co-treatment.</p><p><strong>Results: </strong>BPA exhibited a dose-dependent estrogenic activity in both 2D and 3D cultures, significantly influencing cell proliferation and gene expression of estrogen-regulated markers (pS2 and TGFβ3). In contrast, FUL displayed anti-estrogenic properties, effectively inhibiting the proliferative effects of E2, thereby highlighting the complex interactions between these compounds and the nERs pathways in human breast cancer cells.</p><p><strong>Discussion: </strong>Our findings indicate that E2 and BPA significantly increase pS2 expression while decreasing TGFβ3, and that FUL co-treatment reverses these effects. Therefore, the <i>in vitro</i> model system could serve to observe the cell-mediated effects caused by the interaction of EDs with nERs. Through the use of these <i>in vitro</i> model systems - 2D and especially 3D, the latter of which allow better emulation of complex physiological and pathological processes occurring <i>in vivo</i>, the effects caused by EDs on nERs pathways can be detected and studied under various conditions. This approach performs as a preliminary screening tool to identify estrogenic substances, offering the potential to reduce reliance on <i>in vivo</i> experiments and contributing to improved environmental and health risk assessments.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1547640"},"PeriodicalIF":3.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588498","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":"Comparing computational times for simulations when using PBPK model template and stand-alone implementations of PBPK models.","authors":"Amanda S Bernstein, Paul M Schlosser, Dustin F Kapraun","doi":"10.3389/ftox.2025.1518769","DOIUrl":"10.3389/ftox.2025.1518769","url":null,"abstract":"<p><strong>Introduction: </strong>We previously developed a PBPK model template that consists of a single model \"superstructure\" with equations and logic found in many physiologically based pharmacokinetic (PBPK) models. Using the template, one can implement PBPK models with different combinations of structures and features.</p><p><strong>Methods: </strong>To identify factors that influence computational time required for PBPK model simulations, we conducted timing experiments using various implementations of PBPK models for dichloromethane and chloroform, including template and stand-alone implementations, and simulating four different exposure scenarios. For each experiment, we measured the required computational time and evaluated the impacts of including various model features (e.g., number of output variables calculated) and incorporating various design choices (e.g., different methods for estimating blood concentrations).</p><p><strong>Results: </strong>We observed that model implementations that treat body weight and dependent quantities as constant (fixed) parameters can result in a 30% time savings compared with options that treat body weight and dependent quantities as time-varying. We also observed that decreasing the number of state variables by 36% in our PBPK model template led to a decrease of 20-35% in computational time. Other factors, such as the number of output variables, the method for implementing conditional statements, and the method for estimating blood concentrations, did not have large impacts on simulation time. In general, simulations with PBPK model template implementations of models required more time than simulations with stand-alone implementations, but the flexibility and (human) time savings in preparing and reviewing a model implemented using the PBPK model template may justify the increases in computational time requirements.</p><p><strong>Conclusion: </strong>Our findings concerning how PBPK model design and implementation decisions impact computational speed can benefit anyone seeking to develop, improve, or apply a PBPK model, with or without the PBPK model template.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1518769"},"PeriodicalIF":3.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568957","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: Model organisms in toxicology.","authors":"Michael Aschner, Asok K Dasmahapatra, Arantza Muriana","doi":"10.3389/ftox.2025.1560492","DOIUrl":"10.3389/ftox.2025.1560492","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1560492"},"PeriodicalIF":3.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560148","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: Leveraging artificial intelligence and open science for toxicological risk assessment.","authors":"Marc Teunis, Thomas Luechtefeld, Thomas Hartung","doi":"10.3389/ftox.2025.1568453","DOIUrl":"10.3389/ftox.2025.1568453","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1568453"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517386","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":"TAME 2.0: expanding and improving online data science training for environmental health research.","authors":"Alexis Payton, Elise Hickman, Jessie Chappel, Kyle Roell, Lauren E Koval, Lauren A Eaves, Chloe K Chou, Allison Spring, Sarah L Miller, Oyemwenosa N Avenbuan, Rebecca Boyles, Paul Kruse, Cynthia V Rider, Grace Patlewicz, Caroline Ring, Cavin Ward-Caviness, David M Reif, Ilona Jaspers, Rebecca C Fry, Julia E Rager","doi":"10.3389/ftox.2025.1535098","DOIUrl":"10.3389/ftox.2025.1535098","url":null,"abstract":"<p><strong>Introduction: </strong>Data science training has the potential to propel environmental health research efforts into territories that remain untapped and holds immense promise to change our understanding of human health and the environment. Though data science training resources are expanding, they are still limited in terms of public accessibility, user friendliness, breadth of content, tangibility through real-world examples, and applicability to the field of environmental health science.</p><p><strong>Methods: </strong>To fill this gap, we developed an environmental health data science training resource, the inTelligence And Machine lEarning (TAME) Toolkit, version 2.0 (TAME 2.0).</p><p><strong>Results: </strong>TAME 2.0 is a publicly available website that includes training modules organized into seven chapters. Training topics were prioritized based upon ongoing engagement with trainees, professional colleague feedback, and emerging topics in the field of environmental health research (e.g., artificial intelligence and machine learning). TAME 2.0 is a significant expansion upon the original TAME training resource pilot. TAME 2.0 specifically includes training organized into the following chapters: (1) Data management to enable scientific collaborations; (2) Coding in R; (3) Basics of data analysis and visualizations; (4) Converting wet lab data into dry lab analyses; (5) Machine learning; (6) Applications in toxicology and exposure science; and (7) Environmental health database mining. Also new to TAME 2.0 are \"Test Your Knowledge\" activities at the end of each training module, in which participants are asked additional module-specific questions about the example datasets and apply skills introduced in the module to answer them. TAME 2.0 effectiveness was evaluated via participant surveys during graduate-level workshops and coursework, as well as undergraduate-level summer research training events, and suggested edits were incorporated while overall metrics of effectiveness were quantified.</p><p><strong>Discussion: </strong>Collectively, TAME 2.0 now serves as a valuable resource to address the growing demand of increased data science training in environmental health research. TAME 2.0 is publicly available at: https://uncsrp.github.io/TAME2/.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1535098"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517392","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":"Development and characterization of a double-crested cormorant hepatic cell line, DCH22, for chemical screening.","authors":"Tasnia Sharin, Doug Crump, Jason M O'Brien","doi":"10.3389/ftox.2025.1482865","DOIUrl":"10.3389/ftox.2025.1482865","url":null,"abstract":"<p><p>There are currently no available cell lines for the ecologically relevant colonial waterbird species, the double-crested cormorant (DCCO). DCCOs are high trophic level aquatic birds that are used for routine contaminant monitoring programs in the Laurentian Great Lakes and marine coasts of Canada. Developing a DCCO cell line for <i>in vitro</i> toxicological screening will ideally provide improved understanding of the effects of environmental chemicals given the large differences in sensitivity between laboratory and wild avian species. In this study, an immortalized DCCO hepatic cell line, DCH22, was established from the liver of a day 22 female embryo as a potential alternative to primary DCCO embryonic hepatocytes (DCEH) for chemical screening. DCH22 cells were cultured for over a year and have hepatocyte-like morphology. Exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB-126), benzo-a-pyrene, ß-napthoflavone and phenacetin induced <i>CYP1A</i> activity and mRNA expression in DCH22 3D spheroids. Induction of <i>CYP3A</i> activity and mRNA expression was observed following exposure to hexabromocyclododecane (HBCD), tris(1,3-dichloroisopropyl)phosphate, carbamazepine, and metyrapone. The phase II metabolism gene, UGT1A1, was upregulated following HBCD exposure and DCH22 spheroids expressed vitellogenin protein after exposure to 17α-ethinylestradiol. Based on these data, the novel DCH22 cell line, cultured as 3D spheroids, has potential use as an alternative to DCEH for chemical screening and will permit the evaluation of avian species differences in sensitivity from an <i>in vitro</i> screening perspective.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1482865"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517380","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 effect of cannabis-derived terpenes on alveolar macrophage function.","authors":"Patrick M Greiss, Jacquelyn D Rich, Geoffrey A McKay, Dao Nguyen, Mark G Lefsrud, David H Eidelman, Carolyn J Baglole","doi":"10.3389/ftox.2024.1504508","DOIUrl":"10.3389/ftox.2024.1504508","url":null,"abstract":"<p><p><i>Cannabis sativa</i> (marijuana) is used by millions of people around the world. <i>C. sativa</i> produces hundreds of secondary metabolites including cannabinoids, flavones and terpenes. Terpenes are a broad class of organic compounds that give cannabis and other plants its aroma. Previous studies have demonstrated that terpenes may exert anti-inflammatory properties on immune cells. However, it is not known whether terpenes derived from cannabis alone or in combination with the cannabinoid ∆⁹-THC impacts the function of alveolar macrophages, a specialized pulmonary innate immune cell that is important in host defense against pathogens. Therefore, we investigated the immunomodulatory properties of two commercially-available cannabis terpene mixtures on the function of MH-S cells, a murine alveolar macrophage cell line. MH-S cells were exposed to terpene mixtures at sublethal doses and to the bacterial product lipopolysaccharide (LPS). We measured inflammatory cytokine levels using qRT-PCR and multiplex ELISA, as well as phagocytosis of opsonized IgG-coated beads or mCherry-expressing <i>Escherichia coli</i> via flow cytometry. Neither terpene mixture affected inflammatory cytokine production by MH-S cells in response to LPS. Terpenes increased MH-S cell uptake of opsonized beads but had no effect on phagocytosis of <i>E. coli</i>. Addition of ∆⁹-THC to terpenes did not potentiate cytotoxicity nor phagocytosis. These results suggest that terpenes from cannabis have minimal impact on the function of alveolar macrophages.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1504508"},"PeriodicalIF":3.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434358","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":"Phytocanabinoids and synthetic cannabinoids: from recreational consumption to potential therapeutic use - a review.","authors":"Helena M Teixeira","doi":"10.3389/ftox.2024.1495547","DOIUrl":"10.3389/ftox.2024.1495547","url":null,"abstract":"<p><p>Cannabinoids are part of the most popular group of illicit substances in the Western world. The word \"cannabinoid\" refers to any chemical substance, regardless of structure or origin, that binds to the body's cannabinoid receptors and that has effects similar to those produced by the Cannabis plant. Regarding their origin, cannabinoids can be classified into endocannabinoids, phytocannabinoids and synthetic cannabinoids. The behavioral and physiological effects of cannabinoids have received particular attention over the last few decades, including sensations of euphoria, relaxation and loss of concentration, with their repeated use being associated with short and long-term side effects, including respiratory and cardiovascular disorders, cognitive changes, psychoses, schizophrenia and mood disorders. On the other hand, recent investigations have proposed a promising therapeutic potential of cannabinoid-based drugs for a wide range of medical situations, including neurological and psychiatric disorders, among other indications. The growing popularity in the use of cannabinoid-based compounds, both for recreational and therapeutic purposes, has been accompanied by an equally continuous and growing evolution of knowledge regarding their potential harmful and beneficial effects. However, there are several open questions and challenges to be answered, which require more and better investigations. This article's main objectives are: i) to understand the importance of the action of cannabinoids in humans; ii) identify the different types of cannabinoids that exist and understand the differences in their action; iii) distinguish the legislative framework for cannabinoid consumption; iv) identify the possible adverse effects of cannabinoid consumption, as well as their potential benefits; v) know the existing medical-scientific evidence in terms of therapeutic potential, particularly in relation to aspects of safety and efficacy; vi) encourage critical thinking about the recreational consumption and therapeutic use of cannabinoids, based both on currently available evidence and gaps in knowledge.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1495547"},"PeriodicalIF":3.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400787","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 neurotoxicity of iodoacetic acid, a byproduct of drinking water disinfection.","authors":"Xu Wang, Chunshu Rong, Ping Niu, Wei Leng, Gaihua Wang, Ziqiao He, Xin Qi, Dexi Zhao, Jinhua Li","doi":"10.3389/ftox.2025.1543374","DOIUrl":"10.3389/ftox.2025.1543374","url":null,"abstract":"<p><p>IAA is a by-product of the water disinfection process and has been found to be neurotoxic. However, the role and mechanism of IAA neurotoxicity remain unclear. In this review, we comprehensively discuss the neurotoxic effects and mechanisms of IAA from the molecular level, cellular level and neurological manifestations. At the molecular level, IAA causes neurotoxicity by reducing mitochondrial membrane potential, aggravating oxidative stress and DNA damage. At the cellular level, IAA causes neurotoxicity by inducing BBB disruption, neuroinflammation, and apoptosis. In neurological manifestations, IAA can lead to neurotransmitter disorders, neurodevelopment dysfunction, and even neurodegenerative diseases. Taken together, our review provides insights into the mechanisms of IAA neurotoxicity that will contribute to future studies of IAA neurotoxicity and its protective strategies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1543374"},"PeriodicalIF":3.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392612","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":"Investigating the research landscape of chlorinated paraffins over the past ten decades.","authors":"Chinemerem Ruth Ohoro, Chijioke Olisah, Victor Wepener","doi":"10.3389/ftox.2024.1533722","DOIUrl":"10.3389/ftox.2024.1533722","url":null,"abstract":"<p><p>Chlorinated paraffins (CPs) are classified as emerging persistent organic pollutants (POPs). Due to their associated environmental and health impacts, these groups of chemicals have been a subject of interest among researchers in the past decades. Here we used a scientometric approach to understand the research landscape of CPs using literature published in the Web of Science and Scopus database. RStudio and VOSviewer programs were employed as scientometric tools to analyze the publication trends in global CP-related research from 1916 to 2024. A total of 1,452 articles were published over this period, with a publication/author and co-author/publication ratio of 0.43 and 5.49, respectively. China ranked first in publication output (n = 556, 43.3%), and the highest total citations (n = 12,007), followed by Sweden (n = 90), Canada (n = 77), and Germany (n = 75). Publications from developing countries were limited, with most contributions from Africa originating from Egypt (n = 7), South Africa (n = 5), and Nigeria (n = 3), primarily through international collaborations. The average annual growth rate of 4.3% suggests a significant future article output. This scientometric analysis allowed us to infer global trends in CPs, identify tendencies and gaps, and contribute to future research. Despite having similar toxicity to short-chain chlorinated paraffin (SCCP), long-chain chlorinated paraffin (LCCP) has received less attention. Therefore, future research should prioritize studying LCCP bioaccumulation and toxicity in diverse food webs, focusing on aquatic species vulnerable to CPs and effective toxicological models. Additionally, collaborative research with developing countries should be encouraged to enhance meeting the Stockholm Convention's demand.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1533722"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257511","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}