Chemical Research in Toxicology最新文献

{"title":"Uncovering the Dual Effect of Menthol and Nicotine Levels in Electronic Nicotine Delivery Systems on Pulmonary Surfactant Function.","authors":"Youssef Harb, Kawthar El Khatib, Baptiste Rey, Amale Mcheik, Christian George, Nathalie Hayeck","doi":"10.1021/acs.chemrestox.5c00048","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00048","url":null,"abstract":"<p><p>Electronic nicotine delivery systems (ENDS) are now increasingly used, with commercial electronic cigarettes frequently containing high levels of nicotine and menthol, which is a popular flavoring agent. This has raised multiple concerns about the health risks associated with menthol-flavored ENDS. Although menthol and nicotine are known for their individual effects on respiratory health, their combined impact on pulmonary surfactants remains poorly understood. Therefore, this study aimed at understanding the interactions between the primary components of all ENDS liquids (PG and VG), nicotine and menthol flavoring, and the pulmonary surfactant. This in vitro study used 1,2 dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) and a stoichiometric mixture of DPPC/1-palmitoyl-2-Oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC)/2-Oleoyl-1-palmitoyl-<i>sn</i>-glycero-3- phospho-rac-(1-glycerol) sodium salt (POPG)/cholesterol at 48/32/10/10 to mimic the pulmonary surfactant. These systems were probed using a Langmuir-Blodgett Trough and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The results indicate a concentration dependence of the impact of different nicotine concentrations combined with menthol on the surfactant mimics. Our findings also reveal the effect of menthol on the surface pressure. The combination of nicotine and menthol appears to alter the conformational state of the surfactant, proximately altering characteristic vibrational groups. Moreover, different behaviors are unveiled between the two model surfactants, particularly attributed to the complexities of the four surfactants mixture. Further research is suggested to address the mechanisms and implications involved with ENDS flavoring and additives on surfactant molecules in biological systems. Establishing well-informed regulations on ENDS consumption and distribution should be developed.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197373","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":"In Vitro Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclays on Airway Epithelial and Lung Fibroblast Cells.","authors":"Todd A Stueckle, Jake Jensen, Jayme P Coyle, Alixandra Wagner, Raymond Derk, Tiffany G Kornberg, Sherri A Friend, Molly Schreiner, Alexander C Ufelle, Sushant Agarwal, Rakesh K Gupta, Cerasela Zoica Dinu, Liying W Rojanasakul","doi":"10.1021/acs.chemrestox.5c00206","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00206","url":null,"abstract":"<p><p>The use of two-dimensional organomodified nanoclays (ONCs) to improve nanocomposite properties continues to grow. Recent evidence suggests that airborne nanoclays in occupational environments pose an inhalation hazard; however, health risks and the underlying mechanisms remain undefined. In vivo studies evaluating pre- and post-incinerated ONC exposures found that cytotoxicity, inflammation, and fibrotic signaling responses are coating- and incineration status-dependent. We hypothesized that physicochemical property differences associated with coating presence/absence and incineration status of nanoclays will elicit changes in key events (KE) in exposed human small airway epithelial (SAECs) and normal lung fibroblast (NHLF) cells that contribute to pulmonary lung fibrosis. Using multiplex high-throughput screening strategies, SAEC and NHLF cells were acutely exposed (0-20 μg/cm²) to pristine nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS), to evaluate how ONC characteristics influence several KE in the pulmonary fibrosis adverse outcome pathway. In vitro exposure to pre-incinerated nanoclay induced organic coating-dependent cytotoxicity in SAECs. CloisNa caused disruption of mitochondrial membrane potential, which coincided with loss in viability in both cell types. Clois30B exposure caused dose-dependent SAEC cytotoxicity, micronuclei formation, and mitochondrial hyperpolarization in SAECs and NHLFs. Incinerated nanoclays were noncytotoxic but elicited a SAEC mitochondrial radical and pro-inflammatory response. Direct in vitro exposure to NHLFs exhibited particle-dependent increased live cell count, reactive oxygen species production, and α-smooth muscle actin expression. Nanoclay-exposed NHLFs (0.6 μg/cm²) possessed elevated collagen I levels while the same mass dose in vivo (300 μg/lung) favored elevated fibronectin and collagen III deposition for CloisNa and CS. In conclusion, organic coating presence and incineration status influenced nanoclays' effects on cellular interaction, membrane integrity, inflammation, fibroblast activation, and collagen accumulation in exposed cell models. Although pre-incinerated nanoclay exposure promoted collagen accumulation in vitro, it was a poor predictor of in vivo model reticular fiber deposition.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084534","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":"Association between Occupational Cadmium Exposure and Markers of Kidney Injury: A Systematic Review and Meta-Analysis.","authors":"Ravibabu Kalahasthi, Raju Nagaraju, Rakesh Balachandar, Kuldip Upadhyay, Bhavani Shankara Bagepally","doi":"10.1021/acs.chemrestox.5c00099","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00099","url":null,"abstract":"<p><p>Cadmium (Cd)-induced nephrotoxicity is a well-known phenomenon; however, several observational studies have used various biomarkers to monitor kidney injury in occupationally exposed populations. The markers used in these studies are found to be varied in sensitivity and are site-specific, and experts have the opinion that a single marker cannot predict the degree of kidney injury in human biomonitoring studies. Therefore, the current systematic review consolidates existing evidence to identify the association between Cd exposure and markers of potential sites of renal dysfunction/damage. Thirty (30) studies with 1980 chronic Cd exposure by occupations and 1292 unexposed were included in the review. The pooled mean difference of Cd exposure was as follows: blood Cd, 6.45 (5.18 to 7.71) μg/L; urine Cd, 4.52 (3.54 to 5.5) μg/g creatinine. Cd exposure was associated with impaired glomerular function (higher serum creatinine, serum β2 microglobulin, and lower creatinine clearance rate), tubular reabsorption (higher urinary β2 microglobulin and retinol binding protein), and injury (higher urinary <i>N</i>-acetyl-β-d-glucosaminidase and kidney injury molecule-1). However, the included studies exhibited high levels of heterogeneity. From the data, it is highly evident that biomarkers such as urinary <i>N</i>-acetyl-β-d-glucosaminidase, and retinol binding protein are found to be more sensitive than conventional clinical renal functional markers such as serum creatinine, urinary albumin, and protein levels, which are found to be within acceptable limits among the Cd-exposed group. Considering the rising disease burden of chronic kidney disease of unknown origin, Cd exposure-associated renal dysfunction and damage is a public health concern. Therefore, the review also discussed emerging biomarkers with higher sensitivity for early detection that can be adopted in occupational biomonitoring studies as early markers to prevent/delay the progression of kidney disease among the working population. Prospero Registration ID: CRD42022380923.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068645","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":"CYP2A6 Activity and Deuterated 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) Metabolism in Cigarette Smokers.","authors":"Linda B von Weymarn, Nicole M Thomson, Loïc Le Marchand, Sharon E Murphy","doi":"10.1021/acs.chemrestox.5c00310","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00310","url":null,"abstract":"<p><p>Smoking is the leading cause of lung cancer. Differences in CYP2A6-catalyzed nicotine metabolism affect smoking dose and intensity, which, in turn, can affect lung cancer risk. CYP2A6 also catalyzes the bioactivation of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To determine the contribution of CYP2A6 to the metabolic activation of NNK, a group of Japanese American and Native Hawaiian smokers with little or no CYP2A6 activity was recruited to smoke [pyridyl-D₄]-NNK-containing cigarettes for a week. [Pyridyl-D₄]-4-hydroxy-4-(3-pyridyl)butanoic acid (D₄-hydroxy acid), the urinary product of NNK α-hydroxylation, the major bioactivation pathway, was quantified in these individuals and in an equal number of smokers with \"normal\" CYP2A6 activity. In expectation of low D₄-hydroxy acid levels, a sensitive nanoflow LC-MS/MS assay was developed. CYP2A6 activity was measured as the plasma ratio of 3'-hydroxycotinine to cotinine, which is the nicotine metabolite ratio (NMR). The average concentration of D₄-hydroxy acid in 24 h urine samples over 3 days was 20 ± 14 fmol/mL in low NMR (<0.05) smokers (<i>n</i> = 8) <i>versus</i> 33 ± 18 fmol/mL (<i>p</i> = 0.056) in \"normal\" NMR (>0.3) smokers (<i>n</i> = 8). The total D₄-hydroxy acid excreted by the low NMR group was half that of the higher NMR group (29.1 ± 16.8 <i>versus</i> 59.7 ± 45.3 pmol/24h, <i>p</i> = 0.048). These data support the role of CYP2A6 in the metabolic activation of NNK. However, it is unlikely that more modest differences in CYP2A6 activity, for example, as might be seen across smokers of European ancestry, would significantly impact NNK bioactivation. The influence of CYP2A6 activity on nicotine metabolism and the associated carcinogen uptake is likely the primary influence of CYP2A6 activity on a smoker's risk of lung cancer, not a modest effect on the metabolic activation of NNK, one of several lung carcinogens in tobacco smoke.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068608","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":"Quantitation by Liquid Chromatography-Nanoelectrospray Ionization-High Resolution Tandem Mass Spectrometry of Methyl and Ethyl DNA Adducts in Oral Cells from Cigarette Smokers and Nonsmokers of the Shanghai Cohort Study.","authors":"Guang Cheng, Matthew W Luedtke, Renwei Wang, Jian-Min Yuan, Silvia Balbo, Stephen S Hecht","doi":"10.1021/acs.chemrestox.5c00223","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00223","url":null,"abstract":"<p><p>We used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry (LC-NSI-HRMS/MS) to quantify DNA adducts released from human oral cell DNA upon neutral thermal hydrolysis followed by acid hydrolysis. The assay was applied to 80 buccal cell samples selected from those collected in the Shanghai Cohort Study, a prospective epidemiology study of 18,244 Chinese men 45-64 years old who resided in Shanghai, China when the samples were collected in 2001-2003. The DNA adducts quantified were 3-methyladenine (3-Me-Ade), 3-ethyladenine (3-Et-Ade), and 7-ethylguanine (7-Et-Gua). The method used hydrolysis of DNA samples containing the stable isotope labeled internal standards, solid phase extraction for adduct enrichment, and analysis by LC-NSI-HRMS/MS. Accuracy and precision of the analytical method were established with detection limits of 10-20 amol on column. Median levels of 3-Me-Ade -187 adducts/10⁹ nucleotides in smokers and 129 adducts/10⁹ nucleotides in nonsmokers; and 7-Et-Gua -49 adducts/10⁹ nucleotides in smokers and 21 adducts/10⁹ nucleotides in nonsmokers─were significantly higher in smokers than in nonsmokers (both <i>P</i> values <0.01). Levels of 3-Et-Ade -50 adducts/10⁹ nucleotides in smokers and 43 adducts/10⁹ nucleotides in nonsmokers - were not significantly different. These results demonstrate the applicability of a highly sensitive LC-NSI-HRMS/MS method for the analysis of human oral cell DNA for adducts released by neutral thermal and acid hydrolysis and show the significant effects of cigarette smoking on levels of 3-Me-Ade and 7-Et-Gua in this DNA. This is apparently the first study to characterize 3-Me-Ade in intact DNA isolated from any human tissue.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038701","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":"Overview of <i>In Silico</i> Tools to Evaluate Human Health Toxicity, Ecotoxicity, and Toxicokinetic Profiles in the Hazard Assessment of Chemicals Used in Cosmetics.","authors":"Pauline Lancia, Myriam Louazzani, Ludivine Gros, José Ginestar, Elena Fioravanzo, Aurélie Baleydier","doi":"10.1021/acs.chemrestox.4c00534","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00534","url":null,"abstract":"<p><p>The development of alternative methods to animal testing has gained momentum over the years, including the rapid growth of <i>in silico</i> methods, which are faster and more cost-effective. A large number of <i>computational</i> tools have been published, focusing on Read-Across, (quantitative) Structure-Activity Relationship ((Q)SAR) models, and Physiologically Based Pharmacokinetic (PBPK) models. All of these methods play a crucial role in the risk assessment for cosmetics. However, despite the continuous efforts of various working groups, these methods are not always accepted by regulatory authorities around the world due to a lack of standardization and transparency in their development and application. This study aimed to identify <i>in silico</i> tools that can predict key properties relevant to the hazard assessment of cosmetic ingredients, aiming to streamline decision-making and assist toxicologists in efficiently selecting and integrating <i>in silico</i> predictions. Eighty-four <i>in silico</i> tools were identified based on their predictive capabilities, covering physicochemical parameters, toxicological/ecotoxicological endpoints, and toxicokinetic properties using different computational methods, e.g., (Q)SARs; Read-Across. Additional criteria were also considered for QSAR models, helping toxicologists integrate them into risk assessment processes: (1) definition of the Applicability Domain (AD), (2) model performance, and (3) nearest neighbors of the target substance. Based on these criteria, the models were classified as either useful for screening or suitable for a Weight of Evidence (WoE) approach. Finally, this study highlights the growing number of computational tools available for assessing various endpoints relevant to cosmetic safety. The number of tools continues to increase, and regular reviews are necessary. A deeper understanding of these <i>in silico</i> tools will facilitate their use by toxicologists and improve their acceptance for regulatory purposes from different cosmetic authorities.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028599","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":"Temozolomide-Derived AIC Is Incorporated into Purine Synthesis in Glioblastoma.","authors":"Mark L Sowers, Tuvshintugs Baljinnyam, Jason L Herring, Bruce Chang-Gu, Linda C Hackfeld, Hui Tang, Sandra Hatch, Pablo Valdes, Kangling Zhang, Lawrence C Sowers","doi":"10.1021/acs.chemrestox.5c00196","DOIUrl":"10.1021/acs.chemrestox.5c00196","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a lethal brain tumor with limited therapeutic options. Temozolomide (TMZ), a standard-of-care chemotherapeutic agent, exerts its cytotoxicity by alkylating DNA, which triggers a DNA damage response and depletes ATP and NAD⁺. However, TMZ also releases the byproduct 4-amino-5-imidazole carboxamide (AIC), which is believed to be a benign metabolite. We considered the possibility that AIC from TMZ could enter the de novo purine synthesis pathway, contributing to AMP and NAD⁺ synthesis and thus potentially antagonizing the anticancer activity of TMZ. The purpose of this article is to determine if AIC from TMZ can be incorporated into cellular purines. Using mass spectrometry with isotope-labeled TMZ, we demonstrate that the AIC derived from TMZ is incorporated into AMP and NAD⁺ in glioblastoma cell lines. Further, we performed an analysis of publicly available transcriptomic data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Our analyses demonstrate that de novo purine synthesis is upregulated in GBM relative to the normal brain. Collectively, our findings demonstrate that a drug metabolite of TMZ, AIC, can be incorporated into de novo purine synthesis, which is upregulated in GBM.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028515","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":"Ultrasensitive Direct Chemical Analysis of Human Hair Using Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-TOF-MS) for Nontargeted Exposure Profiling.","authors":"Anna C Neville, David A Jarma, Daniel C Blomdahl, Chou-Hsien Lin, Kerry A Kinney, Pawel K Misztal","doi":"10.1021/acs.chemrestox.5c00002","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00002","url":null,"abstract":"<p><p>Exposure to air pollution plays a significant role in human health. Current methods of measuring human exposure are often limited to outdoor measurements, are time intensive, or are unable to accurately measure certain classes of compounds. This study proposes human hair as a promising indicator of pollution exposure. We present a novel method of hair analysis involving thermal extraction and detection of semivolatile organic compounds using a Vocus 2R proton transfer reaction time-of-flight mass spectrometer (Vocus PTR-TOF-MS). The hair samples were subjected to a temperature ramp spanning three different temperatures: 60 °C, 90 °C, and 120 °C. A hierarchical clustering approach was used to create \"clustergrams\", dendrograms comprising chemical fingerprints of the hair samples at each different temperature. Each clustergram grouped the chemicals in the samples by similarity, allowing the determination of potential sources of exposure. Multivariate factor analysis revealed the presence of phthalates and their corresponding metabolites, confirming that this method can detect biomarkers associated with pollution exposure. This method enables the rapid and sensitive detection of a wide spectrum of toxicologically relevant compounds in human hair, providing an initial screening tool for measuring human exposure and assessing health risks.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013477","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":"N-Doped Graphene for Biomedical Applications: A Comparative Biocompatibility Assessment of Green and Chemical Exfoliation","authors":"Eirini Papanikolaou*,&nbsp;Antrea- Maria Athinodorou,&nbsp;Michaela Patila,&nbsp;Panagiota Zygouri,&nbsp;Konstantinos Spyrou,&nbsp;Mohammed Subrati,&nbsp;Christina Alatzoglou,&nbsp;Evangelia Dounousi,&nbsp;Dimitrios P. Gournis,&nbsp;Konstantinos T. Kotoulas,&nbsp;Ming Xie,&nbsp;Andrew D. Burrows,&nbsp;Gareth Cave,&nbsp;Dimitrios Peschos,&nbsp;Konstantinos Tsamis,&nbsp;Lampros Lakkas,&nbsp;Haralambos Stamatis and Yannis V. Simos,&nbsp;","doi":"10.1021/acs.chemrestox.5c00167","DOIUrl":"10.1021/acs.chemrestox.5c00167","url":null,"abstract":"<p >Graphene-based nanomaterials have transformed biomedical applications due to their exceptional physicochemical properties, and nitrogen (N)-doping further enhances the electrocatalytic activity of graphene. Driven by the demand for safer and more sustainable nanomaterials, in this work, we compared eco-friendly produced <i>N</i>- doped graphene (bD) with conventionally synthesized <i>N</i>- doped graphene (cD) in three different cell lines. Across all cell types and assays, cD was more toxic than bD. In NIH/3T3 fibroblast cells, cD activated the Nrf2 signaling pathway, whereas in HaCaT keratinocytes, it triggered oxidative stress responses and increased the apoptotic population. High doses of cD also affected THP-1-derived macrophages by inducing apoptosis and arresting the cell cycle in the G0/G1 phase. Although high doses of bD were also cytotoxic, overall, its effects were milder than cD. Our results confirm that green exfoliation of <i>N</i>- doped graphene retains its desirable biomedical properties while enhancing its biocompatibility, making bD a safer choice for future biomedical applications.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 9","pages":"1509–1523"},"PeriodicalIF":3.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.chemrestox.5c00167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999281","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}

{"title":"Heating Coil Corrosion by E-Liquid Containing Nicotine Lactate Salt and In Vitro and In Vivo Evaluation of Nickel Leachate in E-Liquid and E-Cigarette Aerosol","authors":"Zeyi Dong,&nbsp;Qianqian Pang,&nbsp;Qin Ling,&nbsp;Chao He,&nbsp;Guanlin Wu,&nbsp;Shijing Wei,&nbsp;Wei Deng,&nbsp;Chang Liu,&nbsp;Jiang Qian,&nbsp;Yao Fu,&nbsp;Tao Hai,&nbsp;Zhichao Chen,&nbsp;Liang Yun* and Xianfang Rong*,&nbsp;","doi":"10.1021/acs.chemrestox.5c00178","DOIUrl":"10.1021/acs.chemrestox.5c00178","url":null,"abstract":"<p >Nicotine lactate salt is one of the commonly used nicotine salts in electronic cigarette (e-cigarette) formulations, including products that have received Marketing Granted Orders through the FDA’s Premarket Tobacco Product Application (PMTA) evaluation in the US. However, full-life cycle evaluation on nicotine lactate salt remains limited, especially its leaching reactions with heating elements and the potential to influence aerosol composition. This study investigated the chemical effects of nicotine lactate salt on e-cigarette heating coils and potential toxicological consequences of nickel (Ni) leachates using in vitro cells and animal models. The results showed that immersion of heating coils in e-liquid (PG:VG 6:4) containing 2% nicotine lactate salt resulted in a significant increase in Ni concentration in the e-liquid over a period of 4 weeks, with levels rising over time as compared to the nicotine benzoate group. A commercially available disposable e-cigarette (liquid capacity: 9.4 mL; power output: 11 W) was utilized. Similarly, aerosol generated from the e-liquid containing 2% nicotine lactate salt exhibited elevated Ni levels. In vitro cytotoxicity exposure to the Beas-2B, SH-SY5Y, and HepG2 cell lines indicated that the aerosol generated from 2% nicotine lactate e-liquid showed higher toxicity than that of the 2% nicotine benzoate e-liquid, with more pronounced Ni accumulation in cells. In vivo inhalation using C57BL/6J mice demonstrated significant Ni accumulation in mice exposed to the aerosol produced from nicotine lactate salt, particularly in the liver. The corrosion of heating coils of nicotine lactate salt e-liquid was attributed to combined electrochemical and acidic corrosion mechanisms. In conclusion, our findings provide valuable insights into the material compatibility and potential toxicological implications for nicotine lactate-based e-liquids in electronic nicotine delivery systems. More research is needed to fully assess the implications of these preclinical findings.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 9","pages":"1557–1563"},"PeriodicalIF":3.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999237","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}