Frontiers in toxicology最新文献

{"title":"Corrigendum: Applying new approach methodologies to assess next-generation tobacco and nicotine products.","authors":"David Thorne, Damian McHugh, Liam Simms, K Monica Lee, Hitoshi Fujimoto, Sara Moses, Marianna Gaca","doi":"10.3389/ftox.2024.1460271","DOIUrl":"https://doi.org/10.3389/ftox.2024.1460271","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2024.1376118.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891161","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":"Safety of titanium dioxide (E171) as a food additive for humans","authors":"David B. Warheit","doi":"10.3389/ftox.2024.1333746","DOIUrl":"https://doi.org/10.3389/ftox.2024.1333746","url":null,"abstract":"Titanium dioxide (TiO2), also known as E171, is commonly used as a white colorant in food, pharmaceuticals, cosmetics, and toothpaste. However, in May 2021, the European Food Safety Authority (EFSA) expert panel, in evaluating the safety of titanium dioxide (E171) as a food additive, concluded that a concern for genotoxicity could not be ruled out. This occurred several years after EFSA had previously considered titanium dioxide to be safe as a food additive. EFSA based this new interpretation on the results of genotoxicity tests of TiO2 nanomaterials. EFSA noted that available data are insufficient to define threshold doses/concentrations of TiO2 particles below which genotoxicity will not occur in tissues containing these particles. Here, it is argued that EFSA made a manifest error regarding the safety of titanium dioxide (E171) particles as a food additive for humans. First, the notion of particle size distribution of TiO2 particles is explained. Second, the changing opinions from the various EFSA evaluations in 2016, 2018, 2019 vs. 2021 are discussed. Third, the low toxicity of TiO2 particles is described in rats exposed by oral gavage and feeding studies in rats and mice. Fourth, the importance of low absorption rates from the gastrointestinal tract vs. circulation in rats and humans but not in mice is identified. Fifth, other international health scientists have weighed in on the EFSA (EFSA J, 2021, 19 (5), 6585) decision and generally disagreed with EFSA’s opinion on the safety of E171 TiO2. A common theme voiced by the United Kingdom, Canada, Australia, and New Zealand agencies is that it is inappropriate to compare nanoparticle toxicity studies of dispersed/sonicated nanoparticles with the content of E171 TiO2 in foods because the test materials used in key studies considered by EFSA (EFSA J, 2021, 19 (5), 6585) are not representative of E171 TiO2 particles. Finally, a group of experts recently considered the genotoxicity of TiO2 and could not find support for a direct DNA damaging mechanism of TiO2 (nano and other forms). For these reasons, it is suggested that EFSA made a manifest error on the safety of E171 as a food additive.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Per- and poly-fluoroalkyl substances (PFAS) effects on lung health: a perspective on the current literature and future recommendations","authors":"Megan E. Solan, Jin-Ah Park","doi":"10.3389/ftox.2024.1423449","DOIUrl":"https://doi.org/10.3389/ftox.2024.1423449","url":null,"abstract":"Per- and poly-fluoroalkyl substances (PFAS) are a broad class of synthetic compounds widely used in commercial applications. The persistent nature of PFAS in the environment has earned them the epithet “forever chemicals.” Concerns arise from widespread exposure to PFAS from occupational, household, and environmental sources. This widespread use of PFAS is particularly concerning, as emerging epidemiological evidence highlights their adverse effects on lung health. Such adverse impacts include impaired fetal lung development, reduced immune function in children, and potential links to lung cancer. Both in vivo and in vitro studies illuminate potential mechanisms underlying such adverse health outcomes subsequent to PFAS inhalation exposure, which may include immunomodulation, oxidative stress, and disruptions to epithelial barriers. However, evidence-based information focusing on the mechanisms of PFAS-mediated lung injury is lacking. Additionally, the discrepancies between data collected from animal and epidemiological studies highlight the need for improved approaches to better understand the toxicity results of PFAS exposure. To address these gaps, we recommend leveraging route-to-route extrapolation for risk assessment, prioritizing research on understudied PFAS, and adopting physiologically relevant, high-throughput approaches. These strategies are aimed at enhancing our understanding of PFAS inhalation effects, aiding in more informed risk management decisions. In this review, we summarize the current literature on PFAS exposure, emphasizing its adverse effects on lung health, particularly through inhalation. We then discuss the current knowledge on mechanisms underlying tissue- and cellular-level adverse outcomes caused by PFAS.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unleashing the potential of cell painting assays for compound activities and hazards prediction","authors":"Floriane Odje, David Meijer, E. von Coburg, J. V. D. van der Hooft, Sebastian Dunst, M. Medema, Andrea Volkamer","doi":"10.3389/ftox.2024.1401036","DOIUrl":"https://doi.org/10.3389/ftox.2024.1401036","url":null,"abstract":"The cell painting (CP) assay has emerged as a potent imaging-based high-throughput phenotypic profiling (HTPP) tool that provides comprehensive input data for in silico prediction of compound activities and potential hazards in drug discovery and toxicology. CP enables the rapid, multiplexed investigation of various molecular mechanisms for thousands of compounds at the single-cell level. The resulting large volumes of image data provide great opportunities but also pose challenges to image and data analysis routines as well as property prediction models. This review addresses the integration of CP-based phenotypic data together with or in substitute of structural information from compounds into machine (ML) and deep learning (DL) models to predict compound activities for various human-relevant disease endpoints and to identify the underlying modes-of-action (MoA) while avoiding unnecessary animal testing. The successful application of CP in combination with powerful ML/DL models promises further advances in understanding compound responses of cells guiding therapeutic development and risk assessment. Therefore, this review highlights the importance of unlocking the potential of CP assays when combined with molecular fingerprints for compound evaluation and discusses the current challenges that are associated with this approach.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141828531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Next generation chemical risk assessment: integration of advances in toxicology, biology and computation.","authors":"Kan Shao, Chao Ji, Bernard Gadagbui","doi":"10.3389/ftox.2024.1440229","DOIUrl":"https://doi.org/10.3389/ftox.2024.1440229","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629374","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 the immunotoxicity potential of nanomaterials using THP-1 cells.","authors":"Asuka Nishida, Yuka Sawada, Rion Arai, Naoki Ishibashi, Miho Suzuo, Akiko Ohno, Takao Ashikaga, Kazutoshi Iijima","doi":"10.3389/ftox.2024.1293147","DOIUrl":"10.3389/ftox.2024.1293147","url":null,"abstract":"<p><p>With the expansion of nanomaterials (NMs) usage, concerns about their toxicity are increasing, and the wide variety of NMs makes it difficult to assess their toxicity. Therefore, the development of a high-throughput, accurate, and certified method to evaluate the immunotoxicity of NMs is required. In this study, we assessed the immunotoxicity potential of various NMs, such as nanoparticles of silver, silica, and titanium dioxide, using the human Cell Line Activation Test (h-CLAT) at the cellular level. After exposure to silver nanoparticle dispersions, the expression levels of CD86 and CD54 increased, suggesting the activation of antigen-presenting cells (APCs) by silver nanoparticles. Quantification of silver ions eluted from silver nanoparticles and the activation of APCs by silver ions suggested that it was due to the release of silver ions. Silica nanoparticles also increased the expression of CD86 and/or CD54, and their activation ability correlated with the synthesis methods and hydrodynamic diameters. The ability of titanium dioxide to activate APCs differed depending on the crystal type and hydrodynamic diameter. These results suggest a potential method to evaluate the immunotoxicity potential of various NMs based on their ability to activate APCs using human monocytic THP-1 cells. This method will be valuable in assessing the immunotoxicity potential and elucidating the immunotoxic mechanisms of NMs.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621853","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":"Optimisation of an in vitro human cardiovascular model on-a-chip for toxicological assessment of nicotine delivery products","authors":"F. Chapman, Luuk de Haan, Linda Gijzen, Wouter Strijker, E. T. Sticken, S. J. Pour, R. Wieczorek, Florian Haberstroh, Sandra Otte, Thomas Nahde, L. Simms, M. Stevenson","doi":"10.3389/ftox.2024.1395670","DOIUrl":"https://doi.org/10.3389/ftox.2024.1395670","url":null,"abstract":"Smoking cigarettes is a cause of serious diseases in smokers, including cardiovascular disease. Through a pathway of endothelial dysfunction, lipid infiltration, macrophage recruitment and vascular remodeling, atherosclerosis is fundamental in the development of most cardiovascular diseases. There is an increasing number of next-generation products (NGP) which provide potentially reduced harm forms of nicotine delivery to adult smokers. This study aimed to optimise an in vitro cardiovascular model to assess such products. Human Coronary Artery Endothelial Cells (HCAECs) were cultured on an OrganoPlate®2-lane chip (Mimetas BV) combined with THP-1 monocytes under flow conditions.An aqueous aerosol extract from the 1R6F reference cigarette was compared with two categories of NGP, (a heated tobacco product (HTP) and an electronic nicotine delivery system (ENDS)), to assess relative effects on select atherogenic endpoints (oxidative stress, monocyte adhesion, ICAM-1 expression, and inflammatory markers). Following exposure of THP-1 monocytes with the aqueous extracts, the resulting conditioned medium was then added to the HCAEC vessels.1R6F was consistently the most potent test article, eliciting observed responses at 4x lower concentrations than applied for both the HTP and ENDS. The HTP was more potent than the ENDS product across all endpoints, however, all test articles increased monocyte adhesion. ICAM-1 did not appear to be a main driver for monocyte adhesion, however, this could be due to replicate variability. Upon comparison to an extract-only control exposure, THP-1-medium pre-conditioning was an important mediator of the responses observed.In conclusion, the data suggests that the NGP extracts, containing primary aerosol chemical constituents exhibit a marked reduction in biological activity in the early key events associated with atherogenesis when compared to a cigarette, adding to the weight of evidence for the tobacco harm reduction potential of such products.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying new approach methodologies to assess next-generation tobacco and nicotine products","authors":"David Thorne, Damian McHugh, Liam Simms, K. M. Lee, Hitoshi Fujimoto, Sara Moses, M. Gaça","doi":"10.3389/ftox.2024.1376118","DOIUrl":"https://doi.org/10.3389/ftox.2024.1376118","url":null,"abstract":"In vitro toxicology research has accelerated with the use of in silico, computational approaches and human in vitro tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput in vitro cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing in vivo testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of in vitro tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and “roadmaps” to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate in vitro model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing human carcinogenicity risk of agrochemicals without the rodent cancer bioassay","authors":"Amber Goetz, Natalia Ryan, Alaina Sauve-Ciencewicki, Caleb C. Lord, G. Hilton, Douglas C. Wolf","doi":"10.3389/ftox.2024.1394361","DOIUrl":"https://doi.org/10.3389/ftox.2024.1394361","url":null,"abstract":"The rodent cancer bioassays are conducted for agrochemical safety assessment yet they often do not inform regulatory decision-making. As part of a collaborative effort, the Rethinking Carcinogenicity Assessment for Agrochemicals Project (ReCAAP) developed a reporting framework to guide a weight of evidence (WOE)-based carcinogenicity assessment that demonstrates how to fulfill the regulatory requirements for chronic risk estimation without the need to conduct lifetime rodent bioassays. The framework is the result of a multi-stakeholder collaboration that worked through an iterative process of writing case studies (in the form of waivers), technical peer reviews of waivers, and an incorporation of key learnings back into the framework to be tested in subsequent case study development. The example waivers used to develop the framework were written retrospectively for registered agrochemical active substances for which the necessary data and information could be obtained through risk assessment documents or data evaluation records from the US EPA. This exercise was critical to the development of a framework, but it lacked authenticity in that the stakeholders reviewing the waiver already knew the outcome of the rodent cancer bioassay(s). Syngenta expanded the evaluation of the ReCAAP reporting framework by writing waivers for three prospective case studies for new active substances where the data packages had not yet been submitted for registration. The prospective waivers followed the established framework considering ADME, potential exposure, subchronic toxicity, genotoxicity, immunosuppression, hormone perturbation, mode of action (MOA), and all relevant information available for read-across using a WOE assessment. The point of departure was estimated from the available data, excluding the cancer bioassay results, with a proposed use for the chronic dietary risk assessment. The read-across assessments compared data from reliable registered chemical analogues to strengthen the prediction of chronic toxicity and/or tumorigenic potential. The prospective case studies represent a range of scenarios, from a new molecule in a well-established chemical class with a known MOA to a molecule with a new pesticidal MOA (pMOA) and limited read-across to related molecules. This effort represents an important step in establishing criteria for a WOE-based carcinogenicity assessment without the rodent cancer bioassay(s) while ensuring a health protective chronic dietary risk assessment.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141354042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Linking environmental exposure to toxicants and chronic disease","authors":"David R. Wallace, Aleksandra Buha Đorđević","doi":"10.3389/ftox.2024.1430316","DOIUrl":"https://doi.org/10.3389/ftox.2024.1430316","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141375218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}