NAM journal最新文献

{"title":"Assessment of the toxic effects of parabens, commonly used preservatives in cosmetics, and their halogenated by-products on human skin and endothelial cells.","authors":"Alisha Janiga-MacNelly, Mackenna McGraw, Maria Teresa Fernandez-Luna, Ramon Lavado","doi":"10.1016/j.namjnl.2025.100011","DOIUrl":"10.1016/j.namjnl.2025.100011","url":null,"abstract":"<p><p>Parabens, widely used as preservatives in cosmetics, are increasingly concerning due to potential health risks, while their chlorinated and brominated by-products, found in aquatic environments, pose additional toxicity concerns. This study evaluated the toxic effects of parabens, their metabolite, and three halogenated by-products on human skin and endothelial cells using cytotoxicity and wound healing assays. Human epidermal keratinocytes (HEK001) and human dermal microvascular endothelial cells (HMEC-1) were used as models. In keratinocytes, butylparaben (BuP) and benzylparaben (BeP) were the most cytotoxic, with EC₅₀ values of 1.52 ± 0.51 µM and 3.34 ± 0.97 µM, respectively. Halogenated parabens, such as methyl 3‑chloro-4-hydroxybenzoate (CMeP) and methyl 3,5-dibromo-4-hydroxybenzoate (DBMeP), also showed significant cytotoxicity, with EC₅₀ values of 2.20 ± 0.76 µM and 1.49 ± 0.37 µM. Methylparaben (MeP), ethylparaben (EtP), and the metabolite 4-hydroxybenzoic acid (HBA) showed lower toxicity, with EC₅₀ values ranging from 536 ± 178 µM to 1,313 ± 464 µM. In endothelial cells, MeP, EtP, and HBA had reduced toxicity, and halogenated by-products were less toxic, with EC₅₀ values from 788 ± 140 µM to >10 mM. High concentrations (100 µM) of BuP, BeP, and halogenated by-products significantly inhibited wound healing in both cell types, while halogenated parabens inhibited keratinocyte proliferation at just 1 µM. This research enhances understanding of parabens' impact on wound healing, informing safety assessments for cosmetics and personal care products.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":"100011"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348593","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":"Acute immobilization assay with <i>Daphnia similis</i>: A miniaturized protocol.","authors":"João Gabriel Mesquita Silva, Gabriela Russi de Oliveira, Ádria Caloto de Oliveira, Anjaina Fernandes de Albuquerque, Francine Inforçato Vacchi, Paula Suares-Rocha, Gisela de Aragão Umbuzeiro","doi":"10.1016/j.namjnl.2025.100010","DOIUrl":"10.1016/j.namjnl.2025.100010","url":null,"abstract":"<p><p>To reduce volume of samples, residues, costs and time, ecotoxicologists are seeking for new approach methodologies. Miniaturized versions of already well-established protocols are arising as a promising tool to diminish costs and residues in the laboratory. The aim of this study was to establish and validate a miniaturized protocol of the acute immobilization assay with <i>Daphnia similis,</i> using 96-well microplates. For that, conventional and miniaturized assays were performed, exposing the test organism to organic and inorganic substances and environmental samples, and results compared. The correlation of results obtained with both protocols revealed that they were not influenced by the different volumes of liquid, used in each version. Tests with negative controls confirmed that the reduced volume did not negatively interfere in the fitness of <i>D. similis</i> and were sufficient to perform tests with quality, validating the miniaturized protocol. In addition to the reduction of production of residues from the test and faster scoring, the reduced volume of samples used to perform the miniaturized version is particularly advantageous when low amount of sample is available (<i>i.e.</i>, extracts, synthesized environmental samples, new formulated products), allowing testing of different concentrations and repetitions. These peculiarities make the miniaturized test with <i>D. similis</i> an effective and feasible version of the conventional one and can be used as an alternative protocol in ecotoxicological investigations.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":"100010"},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348450","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 of <i>in silico</i> models that define the applicability domains of binary classifiers: An ITSv2-defined approach for identifying skin sensitization hazards.","authors":"Takaho Asai, Kazuhiko Umeshita, Michiko Sakurai, Shinji Sakane","doi":"10.1016/j.namjnl.2025.100007","DOIUrl":"10.1016/j.namjnl.2025.100007","url":null,"abstract":"<p><p>The applicability domain's definition is important in validating the reliability of toxicity prediction models. However, applicability domains are established in various model formats and situations, and the definition method is still in the research stage. In this study, because predicting the correctness of a binary classifier means correctly identifying the target on which the binary classifier operates, we considered that the correctness prediction model itself functions as a threshold for the applicability domain of the binary classifier and used machine learning to develop <i>in silico</i> models that define applicability domains by predicting the true/false values of the ITSv2-defined approach for identifying skin sensitization hazards of chemical substances. The correctness of the ITSv2 hazard identification was used as the objective variable, and each alternative to animal testing data, molecular descriptors, and similar substances' information were used as an explanatory variable. Because very few data were misclassified, they were very difficult to detect. Therefore, as a different approach, we assumed the distribution of the false data and quantitatively predicted the misclassification risk of the qualitative evaluation. By setting thresholds for the misclassification risk, the true/false values of the ITSv2 hazard identification were judged. With the newly defined applicability domain, the accuracy of the ITSv2 hazard identification improved substantially. In this study, machine learning was used to optimize the method for defining applicability domains according to trends derived from toxicity assessment data.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":"100007"},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348571","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":"A miniaturised method for feeding rate in daphnids-A physiology endpoint for risk assessment.","authors":"Emma Rowan, Flavia Melati Chiappara, Harry Esmonde, Konstantinos Grintzalis","doi":"10.1016/j.namjnl.2025.100009","DOIUrl":"10.1016/j.namjnl.2025.100009","url":null,"abstract":"<p><p>Pollution is monitored in the ecosystem with methods that aim to capture the presence of pollutants. However, risk assessment is more oriented to develop sensitive metrics that rely on Novel Approach Methodologies (NAMs) which can support existing methods and offer mechanistic insight to the action of pollutants. Feeding is a phenotypic endpoint assessed in many organisms to describe changes in their physiology. For daphnids, feeding is usually quantified with assays employing large volumes and long incubation periods or even cumbersome techniques. In this paper we present a more robust and a faster method to assess feeding with simple fluorescence measurements based on the consumption of algae. The optimized protocol has been tested in a range of pollutants and feeding has proved to be a sensitive indicator for non-lethal exposures.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":"100009"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348493","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":"A systematic approach towards long-term, serum-free cultivation of fish cells with the RTgill-W1 cell line as example.","authors":"Barbara Jozef, Zhao Rui Zhang, Hans-Michael Kaltenbach, Kristin Schirmer","doi":"10.1016/j.namjnl.2025.100008","DOIUrl":"10.1016/j.namjnl.2025.100008","url":null,"abstract":"<p><p>Continuous cultures of vertebrate cells, referred to as cell lines, comprise invaluable biological material for a seemingly unlimited range of applications: from basic cell biology to toxicology to biotechnology, to name a few. Cell lines of fish, such as the cold-water fish rainbow trout (<i>Oncorhynchus mykiss</i>), are no exception but are still little tapped into compared to the widely applied mammalian cell lines. Yet, fish cell lines hold promises as alternatives to animal use in, e.g., toxicology and cell-based food production. However, while the number of fish cell lines is growing, a severe bottleneck for their defined and ethical use is lack of a fully described culture medium that supports long-term viability and proliferation, prerequisites to exploit them. More specifically, routine culture of these cells still depends on fetal bovine serum, an undefined, animal-derived component. Here, we report on the first systematically developed, fully defined medium for long-term culture of fish cells, using the rainbow trout gill cell line, RTgill-W1, as example. We first identified components that are apparently provided by serum. A purposefully designed short-term proliferation assay then allowed the screening of the serum replacement components regarding cell viability and proliferation support. Cells were then taken into long-term culture using the designed mix - yielding 35 passages in the fully defined medium thus far. They can be cryopreserved/thawed in this medium; and for the functions tested, they resemble their parent strain. We thus provide impetus to move fish cell line culture to fully defined media for basic research and application.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":"100008"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> assessments of ENDS toxicity in the respiratory tract: Are we there yet?","authors":"Thivanka Muthumalage, Emma Sarles, Qixin Wang, Edward Hensel, Thomas Hill, Irfan Rahman, Risa Robinson, Andrea M Stroup, Krista Thongphanh, Lisa A Miller","doi":"10.1016/j.namjnl.2025.100016","DOIUrl":"10.1016/j.namjnl.2025.100016","url":null,"abstract":"<p><p>Approximately 4.6 % of U.S. adults over the age of 18 use e-cigarettes, which are a type of electronic nicotine delivery system (ENDS). Over 2.5 million U.S. middle and high school students also use both disposable and/or flavored ENDS products. The health impacts of ENDS use by adults and adolescents are considered a controversial topic in the social media partially due to misperceptions surrounding ENDS toxicity compared to that of combustible cigarettes. There is growing evidence that ENDS, particularly their product composition and design, individual and combined ingredients, and produced aerosols, are toxic to human health. Animal studies have been critical for defining the pathophysiologic outcomes resulting from ENDS use. However, <i>in vitro</i> approaches using human cells can measure the potential toxicity of ENDS e-liquids and aerosols on a shorter timeline and are in keeping with recent statements to replace, reduce and refine the use of animals in biomedical research and regulatory decision making. This review examines current research related to cell culture models of the respiratory tract and exposure methodologies for ENDS use and compares known <i>in vivo</i> parameters of injury and inflammation associated with ENDS to different <i>in vitro</i> systems developed to replicate the inhaled toxicant outcomes. The design and interpretation of exposure methodologies and technological gaps in the evaluation of ENDS aerosols are also discussed. Given the ongoing evolution and popularity of ENDS products, <i>in vitro</i> assessments for measuring respiratory tract injury and inflammation resulting from ENDS use provide a critical scientific platform for rapid evaluation of potential inhalation toxicity in tobacco regulatory science.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035199","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":"Sensitivity Analysis of the Inputs for Bioactivity-Exposure Ratio Calculations in a NAM-Based Systemic Safety Toolbox.","authors":"Hsing-Chieh Lin, Maria Teresa Baltazar, Sophie Cable, Lucie C Ford, Alistair Middleton, Beate Nicol, Ans Punt, Joe Reynolds, Ivan Rusyn, Weihsueh A Chiu","doi":"10.1016/j.namjnl.2025.100056","DOIUrl":"10.1016/j.namjnl.2025.100056","url":null,"abstract":"<p><p>To support regulatory decision-making without animal testing, Next-Generation Risk Assessment (NGRA) frameworks leverage New Approach Methodologies (NAM). A widely used strategy in such frameworks is to calculate Bioactivity-Exposure Ratios (BERs), which compare NAM assay-derived points of departure (PODs) and estimated human internal exposures. However, key methodological choices in NGRA, such as toxicokinetic modeling software, POD sources, and adjustments for <i>in vivo</i> and <i>in vitro</i> free concentrations, may introduce uncertainty. To determine the robustness of our previously reported NGRA workflow, we conducted a comprehensive sensitivity analysis of these variables as applied to 35 chemicals covering a range of end uses including consumer, pesticide and pharmaceutical. Physiologically based kinetic (PBK) modeling using both commercial (GastroPlus) and open-source (<i>httk</i>) software was evaluated across three levels of parameterization. The <i>httk</i> model produced individual and population C_max estimates that are comparable to GastroPlus when the chemical-specific input parameters are aligned. BERs were calculated using C_max estimates, previously reported <i>in vitro</i> PODs from human-relevant cell-based assays, ToxCast, and fixed values based on internal threshold of toxicological concern (iTTCs), with and without adjustment for unbound fractions in plasma and media. We found that BERs from human-relevant cell-based PODs and nominal concentrations best matched risk classifications, with improved predictive performance over iTTC or ToxCast-derived PODs. Consideration of population variability in PBK had limited impact on risk prediction. Adjustments for free concentrations did not enhance classification or <i>in vitro/in vivo</i> concordance. These findings support the potential of human-relevant <i>in vitro</i> PODs and nominal dose metrics in NGRA, and demonstrate that accessible, well-parameterized PBK tools can enhance efficiency and reproducibility.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822490","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":"Complement-ARIE: Catalyzing the Development and Adoption of New Approach Methodologies.","authors":"Kristifor Sunderic, Andrew M Wright, Nicole Kleinstreuer, Victoria Ledbetter, Katelynn A Milora, Christine Happel, Daniel Shaughnessy, Chariz P Johnstone, Daniel Anthony Casco, Nikeya Macioce, Jacqui Marzec, Kristin Kano, Margaret J Ochocinska, Danilo A Tagle","doi":"10.1016/j.namjnl.2025.100026","DOIUrl":"10.1016/j.namjnl.2025.100026","url":null,"abstract":"<p><p>New approach methodologies (NAMs) are proving to be invaluable tools in basic and clinical research to better understand human health and disease, elucidate mechanisms, and study the efficacy and toxicity of novel therapeutics that can improve upon and complement animal-based methodologies. Over the last 15 years, the National Institutes of Health (NIH) has increased investment in NAMs, including in chemico, in silico, and in vitro approaches, such as cell-free assay systems, digital twins, and microphysiological systems (MPS). To further catalyze and innovate the use of NAMs, the NIH Common Fund has initiated a new program, Complement Animal Research In Experimentation (Complement-ARIE), which aims to pioneer the development, standardization, validation, and regulatory use of combinatorial NAMs that will more accurately model human biology and disease states. This program specifically aims to 1) better model human health and disease differences in outcomes across populations, 2) develop NAMs that can provide insights into specific biological processes or disease states, 3) validate mature NAMs to support regulatory use and standardization, and 4) complement traditional animal models to make research more efficient and effective. To inform the implementation of Complement-ARIE, the NIH organized strategic planning activities including an inter-agency retreat, public listening sessions, scientific literature landscape analysis, and a challenge prize. Here we discuss the goals and findings of these activities, and how these results helped identify and address scientific and operational opportunities and roadblocks for implementation of the program towards broader acceptance and impact of NAMs. We anticipate these new methods and approaches could transform the way we do basic, translational, and clinical sciences.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791698","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":"HepaRG^™ cell micronucleus assay as a genetic toxicology new approach methodology.","authors":"Leslie Recio, Nimisha Bhatarri, Raymond Samuel, Jamie Scaglione","doi":"10.1016/j.namjnl.2025.100045","DOIUrl":"10.1016/j.namjnl.2025.100045","url":null,"abstract":"<p><p>A significant limitation of the currently validated cell lines used in regulatory genetic toxicology is that these cells lines do not express key xenobiotic metabolizing Phase I and Phase II enzymes. Metabolically competent human HepaRG cells are emerging as human centric genetic toxicology New Approach Methodology cell-based test system for use as a follow up to positive response observed in the regulatory genetic toxicology test battery. Multiple endpoint genetic toxicology assessment in HepaRG cells quantifying the identical in vivo regulatory genotoxicity endpoints integrated with mechanistic transcriptomicshave the potential to reduce reliance on rodent testing to assess the impact of xenobiotics on genome integrity and human relevance. In this study, three direct acting genotoxic compounds that cause chromosomal damage by either DNA adducts ethyl methanesulfonate, cisplatin) or by effecting topoisomerases (etoposide) were positive.Two of three genotoxic compounds that require bioactivation by either CYP1A1 (benzo(a)pyrene) and the most common human CYP450 involved in drug metabolism CYP3A4 (cyclophosphamide, aflatoxin B1) were positive, howeveraflatoxin B1 was cytotoxic but did not induce MN. Two compounds (d-limonene and urea) were negative using the top dose criteria outlined in OECD 487 to assess if cytotoxicity would lead to non-specific genotoxic responses. These data and others indicate that the HepaRG cell MN assay cells meet OECD acceptance criteria and can serve as a genetic toxicology NAM aimed at reducing and replacing reliance on rodent based testing as the only follow up bioassays to positive results from the in vitro genetic toxicology bioassays.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12797121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971586","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":"High-resistance coils in E-cigarettes increase heavy metals leaching into aerosols to cause oxidants generation in human bronchial epithelial cells at air-liquid interface: A unique non-animal methodological approach on vaping studies.","authors":"Felix Effah, Sadiya Bi Shaikh, David Chalupa, Md Imam Faizan, Alison Elder, Irfan Rahman","doi":"10.1016/j.namjnl.2025.100060","DOIUrl":"10.1016/j.namjnl.2025.100060","url":null,"abstract":"<p><p>Electronic cigarettes (e-cigs) use electrical resistance (sub-ohm to above-ohm) to heat coils that vaporize e-liquids for the generation of aerosols, which are inhaled directly. The effect of varying coil resistances on the production of toxicants in e-liquid aerosols remains unclear. In this study, we examined how varying coil resistance (0.6 Ω (sub-Ohm), 0.9 Ω (intermediate-Ohm), or 1.4 Ω (above-Ohm)) affects the physicochemical properties of e-cig aerosols, including mass median aerodynamic diameter (MMAD), size distribution, heavy metals, acellular reactive oxygen species (ROS), and volatile organic compounds (VOCs) in PG/VG, PG/VG with nicotine, and commercially available menthol and tobacco-flavored e-liquids. Further, we examined how varying coil resistance affected cytotoxicity and inflammatory mediator (interleukin-6) release by normal human bronchial epithelial cells (NHBE) that were exposed to e-cig aerosols at the air-liquid interface (ALI), a unique non-animal new methodological approach for vaping studies. Sub-ohm coils led to increased MMAD, while above-ohm coils produced finer particles and contained higher levels of aluminium, lead, chromium, and nickel, depending on the e-liquid formulation. Additionally, above-ohm coils significantly increased ROS generation in aerosols from commercially available flavored e-liquids, which in turn led to greater cellular ROS production in ALI-cultured NHBE. Both sub-ohm and above-ohm coils induced similar interleukin-6 release. Conversely, for cytotoxicity, PG/VG and menthol aerosols from sub- and intermediate-Ohm coils significantly raised LDH release. Overall, sub-ohm coils produce larger aerosols, above-ohm coils contain higher concentrations of heavy metals and ROS, whose toxicological impacts are reflected by the physiologically relevant in vitro lung models at the air-liquid interface.</p>","PeriodicalId":520522,"journal":{"name":"NAM journal","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088716","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}