Frontiers in toxicology最新文献

{"title":"Modeling marine microplastic emissions in Life Cycle Assessment: characterization factors for biodegradable polymers and their application in a textile case study.","authors":"Felicitas Pellengahr, Elena Corella-Puertas, Valérie Mattelin, Nadim Saadi, Francesca Bertella, Anne-Marie Boulay, Yvonne van der Meer","doi":"10.3389/ftox.2025.1494220","DOIUrl":"10.3389/ftox.2025.1494220","url":null,"abstract":"<p><strong>Introduction: </strong>With the continuous increase of plastics production, it is imperative to carefully examine their environmental profile through Life Cycle Assessment (LCA). However, current LCA modeling is not considering the potential impacts of plastic emissions on the biosphere. To integrate plastic emissions into LCA, characterization factors are needed that commonly consist of three elements: a fate factor, an exposure factor, and an effect factor. In this context, fate factors quantify the distribution and longevity of plastics in the environment. Research on these fate factors is still limited, especially for biodegradable polymers. Hence, the main objective of this research was to determine the fate factors of biodegradable polymers [poly (lactic acid), poly (butylene succinate), and poly (ε-caprolactam)] based on primary experimental data for the marine environment.</p><p><strong>Methods: </strong>The validity of former research is tested by comparing the degradation evolution of i. macro- and microplastic particles, ii. two different grades of the polymer, and iii. different temperature levels. The degradation data are obtained by monitoring the oxygen consumption over a period of six months in natural seawater. The determined degradation rates are combined with sedimentation, resuspension, and deep burial rates to obtain fate factors. These fate factors are used to develop polymer-specific characterization factors. The resulting characterization factors are tested in an LCA case study of a synthetic sports shirt made from biodegradable polymer fibers. It allows to assess the relative importance of microplastic impacts compared to other life cycle impacts.</p><p><strong>Results and discussion: </strong>Comparing the resulting specific surface degradation rates indicates that microplastic degradation rates could be overestimated when using macroplastic degradation data. Pertaining to the case study, the results show that the impact on ecosystem quality by microplastic emissions could account for up to 30% of the total endpoint category. Overall, this work aims to foster interdisciplinary collaboration to leverage the accuracy of LCA studies and thus provide guidance for novel material development.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1494220"},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775217","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: Global excellence in toxicology: Asia, Australia and New Zealand.","authors":"Yongning Wu","doi":"10.3389/ftox.2025.1584009","DOIUrl":"10.3389/ftox.2025.1584009","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1584009"},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756266","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":"Selection of the critical effect size alters hazard characterization - a retrospective analysis of key studies used for risk assessments of PFAS.","authors":"L Brunken, A Vieira Silva, M Öberg","doi":"10.3389/ftox.2025.1525089","DOIUrl":"10.3389/ftox.2025.1525089","url":null,"abstract":"<p><p>Regulatory values for per- and polyfluoroalkyl substances (PFAS) vary widely across agencies, creating inconsistencies that challenge effective risk management and public health communication. These differences often stem from methodological choices in determining points of departure (PoDs), the selection of critical effect size (CES) and the modeling framework for benchmark dose (BMD) analysis. This study investigates the impact of CES selection on hazard characterization by analyzing how variations in CES influence resulting PoDs and health-based guidance values. A retrospective analysis of key studies from four regulatory PFAS risk assessments was conducted, covering both animal and epidemiological data (thyroid hormone, cholesterol, and vaccine response). CES options compared included 5%, 10%, one standard deviation from background, and a generalized effect size theory, using both frequentist and Bayesian statistics. The findings show that CES selection and statistical approach substantially affect BMD estimates such as the lower bound BMD (BMDL) of the respective confidence interval or credible interval; with larger CES values and Bayesian modeling yielding more biologically relevant, stable results. For instance, Bayesian methods provided narrower credible intervals, compared to frequentist methods at lower CES levels, minimizing overly conservative assessments. However, in comparison to the PoD previously derived by the European Food Safety Authority the results generally suggest lower values. In conclusion, this study supports the use of a flexible, endpoint-specific CES with Bayesian model averaging, which may enhance the accuracy and consistency of PFAS guidance values, offering a more robust foundation for regulatory risk assessments.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1525089"},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756268","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":"Case report: Pesticide-related methemoglobinemia: Tebufenozide and indoxacarb poisoning.","authors":"Jieru Wang, Guangcai Yu, Tianzi Jian, Baotian Kan, Wei Li, Xiangdong Jian","doi":"10.3389/ftox.2025.1557990","DOIUrl":"10.3389/ftox.2025.1557990","url":null,"abstract":"<p><strong>Background: </strong>Methemoglobinemia can be inherited or acquired. Acquired forms are more common due to drugs or poisonous substances that oxidize hemoglobin, and pesticide-related cases are notably rare.</p><p><strong>Case presentation: </strong>We report a 69-year-old woman who ingested 30 mL of tebufenozide and indoxacarb and was asymptomatic for 3 h; however, the patient was admitted to the hospital after 8 h, unconscious, with tachypnea, cyanosis, and 61.9% methemoglobin. The patient was administered methylene blue, mechanically ventilated, and hemoperfused. Subsequently, the patient recovered and was discharged with no discomfort and with normal laboratory test results.</p><p><strong>Conclusion: </strong>Tebufenozide and indoxacarb may cause methemoglobinemia, leading to cyanosis, unconsciousness, and respiratory failure; therefore, they should be handled with care in clinical practice.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1557990"},"PeriodicalIF":3.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627022","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":"Comprehensive overview of the toxicities of small-molecule cryoprotectants for carnivorous spermatozoa: foundation for computational cryobiotechnology.","authors":"Isaac Karimi, Layth Jasim Mohammad, A Suvitha, Zohreh Haidari, Helgi B Schiöth","doi":"10.3389/ftox.2025.1477822","DOIUrl":"10.3389/ftox.2025.1477822","url":null,"abstract":"<p><strong>Background: </strong>The specific and non-specific toxicities of cryoprotective agents (CPAs) for semen or spermatozoa cryopreservation/vitrification (SC/SV) remain challenges to the success of assisted reproductive technologies.</p><p><strong>Objective: </strong>We searched for and integrated the physicochemical and toxicological characteristics of small-molecule CPAs as well as curated the information of all extenders reported for carnivores to provide a foundation for new research avenues and computational cryobiology.</p><p><strong>Methods: </strong>The PubMed database was systematically searched for CPAs reported in SC/SV of carnivores from 1964 to 2024. The physicochemical features, ADMET parameters, toxicity classes, optimized structures, biological activities, thermodynamic equilibrium constants, and kinetic parameters were curated and assessed computationally.</p><p><strong>Results: </strong>Sixty-two relevant papers pertaining to CPAs used in SC/SV were found, and 11 CPAs were selected. Among the properties of CPAs, the molecular weight range (59-758 g/mol), melting point (-60°C to 236°C), XlogP3 (-4.5 to 12.9), topological polar surface area (TPSA; 20-160 Ų), Caco2 permeability (-0.62 to 1.55 log(P<i>app</i>) in 10^-6 cm/s), volume of distribution (-1.04 to 0.19 log L/kg), unbound fraction of a CPA in plasma (0.198-0.895), and <i>Tetrahymena pyriformis</i> toxicity (log µg/L; -2.230 to 0.285) are reported here. Glutathione, dimethyl formamide, methyl formamide, and dimethyl sulfoxide were used as the P-glycoprotein substrates. Ethylene glycol, dimethyl sulfoxide, dimethyl formamide, methyl formamide, glycerol, and soybean lecithin showed Caco2 permeabilities in this order, whereas fructose, glutathione, glutamine, glucose, and citric acid were not Caco2-permeable. The CPAs were distributed in various compartments and could alter the physiological properties of both seminal plasma and spermatozoa. Low volume distributions of all CPAs except glucose indicate high water solubility or high protein binding because higher amounts of the CPAs remain in the seminal plasma.</p><p><strong>Conclusion: </strong>ADMET information of the CPAs and extenders in the bipartite compartments of seminal plasma and intracellular spaces of spermatozoa are very important for systematic definition and integration because the nature of the extenders and seminal plasma could alter the physiology of cryopreserved spermatozoa.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1477822"},"PeriodicalIF":3.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617887","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":"Evaluation of a non-animal toolbox informed by adverse outcome pathways for human inhalation safety.","authors":"Renato Ivan de Ávila, Iris Müller, Hugh Barlow, Alistair Mark Middleton, Mathura Theiventhran, Danilo Basili, Anthony M Bowden, Ouarda Saib, Patrik Engi, Tymoteusz Pietrenko, Joanne Wallace, Bernadett Boda, Samuel Constant, Holger Peter Behrsing, Vivek Patel, Maria Teresa Baltazar","doi":"10.3389/ftox.2025.1426132","DOIUrl":"10.3389/ftox.2025.1426132","url":null,"abstract":"<p><strong>Introduction: </strong>This work evaluated a non-animal toolbox to be used within a next-generation risk assessment (NGRA) framework to assess chemical-induced lung effects using human upper and lower respiratory tract models, namely MucilAir™-HF and EpiAlveolar™ systems, respectively.</p><p><strong>Methods: </strong>A 12-day substance repeated exposure scheme was established to explore potential lung effects through analysis of bioactivity readouts from the tissue integrity and functionality, cytokine/chemokine secretion, and transcriptomics.</p><p><strong>Results: </strong>Eleven benchmark chemicals were tested, including inhaled materials and drugs that may cause lung toxicity following systemic exposure, covering 14 human exposure scenarios classified as low- or high-risk based on historical safety decisions. For calculation of bioactivity exposure ratios (BERs), obtained chemical-induced bioactivity data were used to derive <i>in vitro</i> points of departures (PoDs) using a nonlinear state space model. PoDs were then combined with human exposure estimates, i.e., predicted lung deposition for benchmark inhaled materials using multiple path particle dosimetry (MPPD) exposure computational modeling or literature maximum plasma concentration (C_max) for systemically available benchmark drugs.</p><p><strong>Discussion: </strong>In general, PoDs occurred at higher concentrations than the corresponding human exposure values for the majority of the low-risk chemical-exposure scenarios. For all the high-risk chemical-exposure scenarios, there was a clear overlap between the PoDs and lung deposited mass and C_max for the benchmark inhaled materials and therapeutic drugs, respectively. Our findings suggest that combining computational and <i>in vitro</i> new approach methodologies (NAMs) informed by adverse outcome pathways (AOPs) associated with pulmonary toxicity can provide relevant biological coverage for chemical lung safety assessment.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1426132"},"PeriodicalIF":3.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588496","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":"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}