Toxicology in Vitro最新文献

{"title":"Validation of a new 3D epidermis model for the SENS-IS assay to evaluate skin sensitization potency of chemicals","authors":"Françoise Cottrez,&nbsp;Elodie Boitel,&nbsp;Essia Sahli,&nbsp;Hervé Groux","doi":"10.1016/j.tiv.2025.106039","DOIUrl":"10.1016/j.tiv.2025.106039","url":null,"abstract":"<div><div>In vitro methods for evaluating skin sensitization are advancing as ethical alternatives to animal testing. The SENS-IS assay, based on genomic profiling, relies on robust biological models like 3D reconstructed human epidermis (RHE). The Rhe model from Episkin was typically used to performed the SENS-IS assay. This study validates the Skin+ model as an alternative to the established Episkin model in the SENS-IS assay.</div><div>We tested 19 proficiency chemicals categorized by human and LLNA potency and compared results between Skin+ and Episkin. The Skin+ model demonstrated over 93 % intra- and inter-batch reproducibility, closely matching Episkin's performance. Additionally, barrier function tests and gene expression analyses confirmed the consistency of the Skin+ model in response to SLS, TNBS, and DMSO treatments.</div><div>The Skin+ model proved to be a reliable and reproducible alternative to the EpiSkin model, maintaining strong barrier integrity and delivering comparable sensitization predictions. This validation broadens the options for laboratories and industries seeking versatile 3D RHE models for in vitro skin sensitization testing, supporting the transition to more ethical and precise methods.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106039"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) induce antimicrobial properties and apoptosis in gastric cancer cells.","authors":"Murugan Alwarkurichi Munusamy, Muruganantham Bharathi, Abdullah A Alarfaj, Samer Hasan Hussein-Al-Ali, Ravichandran Nagaiya, Sarathbabu Subbarayan","doi":"10.1016/j.tiv.2025.106037","DOIUrl":"https://doi.org/10.1016/j.tiv.2025.106037","url":null,"abstract":"<p><p>An assessment of the anticancer activity of Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) against gastric cancer cells was the purpose of this study. The increasing prevalence of gastric cancer and the limitations of conventional therapies necessitate novel approaches that combine targeted drug delivery with therapeutic efficacy. Several techniques were used to characterize the synthesized GNANPs, including UV-visible spectroscopy, X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), and photoluminescence (PL). They were evaluated for their antimicrobial properties, cytotoxicity, ROS accumulation, apoptotic activity, and oxidative stress markers against AGS cells. The characterization analyses indicated the existence of Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles with an oval-shaped morphology and an average particle size of 127.80 nm. The existence of several elements and functional groups in the GNANPs was also detected using EDX and FT-IR analyses, respectively. The synthesized GNANPs have shown exceptional antibacterial activities by effectively inhibiting the growth of several infections. The treatment of GNANPs efficiently inhibited the growth of AGS cells. Fluorescence staining studies showed increased apoptosis and oxidative stress markers in AGS cells treated with synthesized Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles, indicating their potential as a viable cancer treatment option.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"106037"},"PeriodicalIF":2.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of culture media on gene expression in reconstructed human epidermis and THP-1 monocytes for skin sensitization evaluation in co-culture systems","authors":"Y. Sugimoto-Sawada ,&nbsp;M. Yamashiro ,&nbsp;M. Kono ,&nbsp;H. Ikeda ,&nbsp;H. Itagaki ,&nbsp;K. Iijima","doi":"10.1016/j.tiv.2025.106035","DOIUrl":"10.1016/j.tiv.2025.106035","url":null,"abstract":"<div><div>Co-culture with reconstituted epidermis formed by normal human epidermal keratinocytes (RhE) increases the expression of the skin sensitization markers CD54 and CD86 on the human monocytic leukemia cell line THP-1 without chemicals. Therefore, we investigated the effects of culture media [RPMI1640 for RhE; keratinization induction (KI) medium for THP-1], co-culture, and the responses to the skin sensitizer 2,4-dinitrochlorobenzene (DNCB) on gene expression in mono- and cocultures of RhE and THP-1 cells. Microarray and pathway analyses revealed that in mono-RhE, RPMI medium induced epidermal differentiation-related genes, whereas in monoculture THP-1 cells, KI medium upregulated inflammation-related genes. Surprisingly, the medium composition had a more significant impact than co-culture in both cells. However, crosstalk between RhE and THP-1 cells was observed upon DNCB exposure by comparing the differentially expressed gene sets. DNCB-treated THP-1 cells showed increased expression of <em>NR4A1</em>, <em>NR4A2</em>, <em>NR4A3</em>, <em>SIK1</em>, and <em>HMOX1</em> in co-culture than in monoculture, and these gene expression patterns were confirmed by real-time RT-PCR. It has been suggested that danger signals from RhE, in response to DNCB, enhance the expression of these genes in THP-1 cells. We clarified the effects of the medium and co-culture and proposed these five genes as potential markers for skin sensitization evaluation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106035"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-species comparisons of plasma binding and considerations for data evaluation","authors":"Scott G. Lynn ,&nbsp;Irvin R. Schultz ,&nbsp;Sharlene R. Matten ,&nbsp;Purvi R. Patel ,&nbsp;Scott L. Watson ,&nbsp;Yun Lan Yueh ,&nbsp;Sherry R. Black ,&nbsp;Barbara A. Wetmore","doi":"10.1016/j.tiv.2025.106036","DOIUrl":"10.1016/j.tiv.2025.106036","url":null,"abstract":"<div><div>The US Environmental Protection Agency is increasingly employing new approach methods (NAMs), including in vitro plasma binding and hepatocyte clearance experiments to collect chemical-species specific data. This paper presents data from plasma binding experiments using rapid equilibrium dialysis (RED) devices and plasma from humans, rats, and rainbow trout with a 4-h incubation time. A total of 54 chemicals, utilizing two concentrations, were tested across the three species resulting in 238 chemical-species specific datasets. Mass balance controls for chemical plasma stability and dialysis system recovery were used to evaluate the datasets and almost 40 % of the datasets (92/238 datasets) produced quantitative measurements. Cross-species comparisons and evaluations of the impact of physicochemical properties on chemical-assay performance were also evaluated. Comparisons of human-rat plasma binding revealed rat plasma generally demonstrated higher <em>f</em>_<em>up</em> values for chemicals than human. While <em>f</em>_<em>up</em> values in trout plasma were frequently lower than rat or human plasma. A comparison with literature data was performed and correlations between plasma binding, expressed as fraction unbound in plasma (<em>f</em>_<em>up</em>), and log K_ow across all three species indicate that the strongest relationship occurs at log K_ow values between 1.5 and 4. The obtained datasets exhibited a wide range of behaviors, emphasizing the need for a robust approach to data quality assessment. The broader analysis of <em>f</em>_<em>up</em> values indicates that chemicals with log K_ow &gt; 4.5 will be highly bound (<em>f</em>_<em>up</em> ≤ 0.0001), difficult to measure, and have low reproducibility across laboratories, suggesting that use of different methods may be needed across different physicochemical properties.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106036"},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reexamining the acute toxicity of chloropicrin: Comprehensive estimation using in silico methods","authors":"Maciej Noga ,&nbsp;Kamil Jurowski","doi":"10.1016/j.tiv.2025.106033","DOIUrl":"10.1016/j.tiv.2025.106033","url":null,"abstract":"<div><div>Chloropicrin, historically infamous as a chemical warfare agent during World War I, has recently resurfaced in global conflicts, prompting a reevaluation of its acute toxicological significance. This study addresses the historical knowledge gap surrounding chloropicrin by employing <em>in silico</em> toxicology methods to estimate toxicophores and predict acute toxicity across various exposure routes. Allegations of its use in recent conflicts necessitate a deeper understanding of its toxicological profile, particularly in modern warfare scenarios. Qualitative analysis (STopTox and admetSAR) revealed chloropicrin to be toxic for oral, dermal, and inhalation administration, with the nitro group attached to the carbon atom identified as a significant contributor to its toxic profile. Quantitative <em>in silico</em> estimates, using multiple methods (TEST, ProTox-II, ADMETlab, ACD/Labs Percepta and QSAR Toolbox), indicated t-LD₅₀ values of 48.71 mg/kg bw for oral exposure, 130.16 mg/kg bw for dermal exposure, and an inhalation t-LC₅₀ of 0.022 mg/L. However, method inconsistencies and variability in dose conversion guidance highlight the importance of a cautious approach to interpreting results. Furthermore, the study explores the potential of <em>in silico</em> methods to reduce reliance on animal testing, providing a more efficient and humane alternative for toxicity assessments. The findings contribute to a comprehensive understanding of chloropicrin's acute toxicity, emphasising the relevance of <em>in silico</em> methods in guiding future toxicological studies and informing safety assessments in agricultural and wartime scenarios.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106033"},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A perfused iPSC-derived proximal tubule model for predicting drug-induced kidney injury","authors":"Michelle Lechtenberg ,&nbsp;Coraline Chéneau ,&nbsp;Kevin Riquin ,&nbsp;Leopold Koenig ,&nbsp;Carlos Mota ,&nbsp;Franck Halary ,&nbsp;Eva-Maria Dehne","doi":"10.1016/j.tiv.2025.106038","DOIUrl":"10.1016/j.tiv.2025.106038","url":null,"abstract":"<div><div>The kidney is frequently exposed to high levels of drugs and their metabolites, which can injure the kidney and the proximal tubule (PT) in particular. In order to detect nephrotoxicity early during drug development, relevant <em>in vitro</em> models are essential. Here, we introduce a robust and versatile cell culture insert-based iPSC-derived PT model, which can be maintained in a microphysiological system for at least ten days. We demonstrate the model's ability to predict drug-induced PT injury using polymyxin B, cyclosporin A, and cisplatin, and observe that perfusion distinctly impacts our model's response to xenobiotics. We observe that the upregulation of metallothioneins that is described <em>in vivo</em> after treatment with these drugs is reliably detected in dynamic, but not static <em>in vitro</em> PT models. Finally, we use our model to alleviate polymyxin-induced nephrotoxicity by supplementing the antioxidant curcumin. Together, these findings illustrate that our perfused iPSC-derived PT model is versatile and well-suited for <em>in vitro</em> studies investigating nephrotoxicity and its prevention. Reliable and user-friendly <em>in vitro</em> models like this enable the early detection of nephrotoxic potential, thereby minimizing adverse effects and reducing drug attrition.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106038"},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interdisciplinary approach to assessing the toxicity reduction of cerium oxide nanoparticles coated with polyethylene glycol and polyvinylpyrrolidone polymers: An in vitro study","authors":"Mohadeseh Soltani ,&nbsp;Motahareh Soltani ,&nbsp;Somayyeh Karami-Mohajeri ,&nbsp;Alireza Mohadesi ,&nbsp;Mehdi Ranjbar ,&nbsp;Zohreh Oghabian ,&nbsp;Omid Mehrpour ,&nbsp;Farshid Khosravi","doi":"10.1016/j.tiv.2025.106022","DOIUrl":"10.1016/j.tiv.2025.106022","url":null,"abstract":"<div><h3>Objective</h3><div>This study combines toxicology, analytical chemistry, and nanotechnology to develop cerium oxide nanoparticles, both uncoated and coated with Polyethylene Glycol and Polyvinylpyrrolidone polymers. The objective is to assess their toxicity reduction using cell-based assays.</div></div><div><h3>Methods</h3><div>Nanoparticles were synthesized using the co-precipitation technique. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were employed to characterize their properties. The MTT assay evaluated cell viability, whereas reactive oxygen species and LPO assays were used to quantify oxidative stress.</div></div><div><h3>Findings</h3><div>The chemical analysis of nanoparticles of the study revealed that cerium oxide nanoparticles exhibited better and more regular morphological characteristics compared to nanoparticles coated with PEG and PVP polymers in terms of size. In addition, cerium oxide nanoparticles combined with PVP polymer did not retain the morphology at the nano level. Toxicological studies demonstrated a reduction in the toxicity of cerium oxide nanoparticles when coated with PEG and PVP polymers.</div></div><div><h3>Discussion and conclusion</h3><div>The study found that PEG coating significantly reduces the cytotoxicity of cerium oxide nanoparticles more effectively than PVP coating by mitigating oxidative stress. This approach presents a promising strategy for developing safer cerium oxide-based products for pharmaceutical and medical applications.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106022"},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applicability of the SENS-IS assay to assess skin sensitization of medical devices according the technical specification ISO/TS11796","authors":"Françoise Cottrez ,&nbsp;Elodie Boitel ,&nbsp;Essia Sahli ,&nbsp;Christian Pellevoisin ,&nbsp;Hervé Groux","doi":"10.1016/j.tiv.2025.106032","DOIUrl":"10.1016/j.tiv.2025.106032","url":null,"abstract":"<div><div>Assessing skin sensitization is critical in the development of medical devices, and the SENS-IS assay provides a reliable <em>in vitro</em> alternative to traditional animal models. By utilizing reconstructed human epidermis (RHE), which closely mimics human skin, the assay allows testing with both saline and sesame oil under conditions similar to <em>in vivo</em> models, facilitating a smoother transition to non-animal testing. This study evaluated the efficacy of the SENS-IS assay according to ISO/TS 11796, testing 14 sensitizers and 3 non-sensitizers during the prevalidation phase, as well as the 8 sensitizers and 4 non-sensitizers recommended in an interlaboratory study using MED-2000 silicone extracts spiked with ISO-specified chemicals at LLNA EC3 concentrations.</div><div>The assay successfully identified 20 out of 22 sensitizers tested at EC3 concentrations. Two chemicals, poorly soluble in the vehicles used,—TPO (EC3 = 27) and Isopropyl Myristate (EC3 = 44)—were detected at slightly higher concentrations, with TPO detected at 50 % and Isopropyl Myristate at 75 % of their EC3 values. All 7 non-sensitizers were accurately classified. These results confirm the sensitivity of the SENS-IS assay and underscore its potential for medical device development, advancing the use of non-animal testing methods.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106032"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6:2 fluorotelomer sulfonate as a safer alternative to PFOS: Comparative cytotoxicity and oxidative stress mechanisms in pancreatic β-cells (INS-1 model)","authors":"Xiao-Min Ren,&nbsp;Jianying Wang,&nbsp;Fenqing Zhao,&nbsp;Pingping Zhang,&nbsp;Zhenghuan Zhang,&nbsp;Zhongneng Yang,&nbsp;Huan He,&nbsp;Zhixiang Xu,&nbsp;Bin Huang,&nbsp;Xuejun Pan","doi":"10.1016/j.tiv.2025.106034","DOIUrl":"10.1016/j.tiv.2025.106034","url":null,"abstract":"<div><div>Previous studies suggest that 6:2 fluorotelomer sulfonate (6:2 FTSA) exhibits lower hepatotoxicity and reduced reproductive and developmental toxicity compared to perfluorooctane sulfonate (PFOS), indicating it may offer a safer alternative. This study aimed to investigate whether 6:2 FTSA is safer than PFOS in terms of its cytotoxic effects on pancreatic β-cells. Using rat insulinoma cells (INS-1) as a model of pancreatic β-cells, we compared the effects of 6:2 FTSA and PFOS in both their acid (6:2 FTSA-H, PFOS-H) and potassium salt forms (6:2 FTSA-K, PFOS-K) on cell viability through Cell Counting Kit-8 (CCK-8) assays, Trypan Blue staining, and apoptosis assays. Results indicated that 6:2 FTSA was less toxic to INS-1 cells than PFOS (6:2 FTSA-H &lt; PFOS-H; 6:2 FTSA-K &lt; PFOS-K), the LOECs of 6:2 FTSA-H, 6:2 FTSA-K, PFOS-H, and PFOS-K were 150 μM, 150 μM, 20 μM, and 10 μM under FBS free conditions, respectively. To further explore whether these compounds induce cell death via oxidative stress, we measured intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels. All four compounds induced oxidative stress in INS-1 cells, with oxidative stress levels corresponding to cytotoxicity, suggesting β-cell death may occur via an oxidative stress mechanism. In conclusion, this study supports the notion that 6:2 FTSA is a safer alternative to PFOS, particularly regarding risks related to pancreatic β-cell cytotoxic effects. While the in vitro experiments in this study provide valuable preliminary information on the compounds' effects on cells and their mechanisms, they cannot fully capture the complexity of the in vivo environment. Therefore, future research should include in vivo experiments to validate the findings from the in vitro studies and comprehensively evaluate the actual effects of the compounds in living organisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106034"},"PeriodicalIF":2.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A group of novel polyfluoroether substances affects lipid metabolism in human hepatocyte HepaRG cells less than classic perfluoroalkyl compounds","authors":"Faezeh Sadrabadi,&nbsp;Wiebke Alker,&nbsp;Heike Sprenger,&nbsp;Albert Braeuning,&nbsp;Thorsten Buhrke","doi":"10.1016/j.tiv.2025.106024","DOIUrl":"10.1016/j.tiv.2025.106024","url":null,"abstract":"<div><div>Per<em>-</em> and polyfluoroalkyl substances (PFAS) are used for numerous industrial applications including the production of fluorosurfactants. Some prominent PFAS, e.g., perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), are non-degradable and therefore persist in the environment. They display various toxic properties including dysregulation of hepatic lipid metabolism. At the molecular level, these effects are mainly based on a PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). A group of novel, degradable polyfluoroether compounds has been designed as building blocks for the production of alternative, degradable fluorosurfactants. In the present study, we examined the capacity of four of these novel polyfluoroether compounds to induce PPARα activation, increase intracellular triglyceride accumulation, and produce a cytotoxic response. In contrast to some classic PFAS including PFOA and PFOS, the novel compounds neither activated PPARα in a transactivation assay, nor did they induce expression of selected PPARα-dependent target genes in differentiated HepaRG cells, a model for human hepatocytes. They also did not induce triglyceride accumulation in HepaRG cells. The in vitro data indicate that the polyfluoroether compounds tested in the present study are not PPARα agonists. Since PPARα agonist activity is often associated with toxic responses, it can be assumed that these substances are less toxic than classic PFAS such as PFOA and PFOS, at least with respect to PPARα-dependent toxicity mechanisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106024"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}