Chemical Research in Toxicology最新文献

{"title":"Toxicokinetic Characterization of Isopropyl Glycidyl Ether in Rat by a Validated LC-APCI-MS/MS Method Using In-Source Derivatization.","authors":"Aliz Széles, Károly Schöll, Gábor Hirka, Katalin Monostory, Tibor Renkecz","doi":"10.1021/acs.chemrestox.4c00376","DOIUrl":"10.1021/acs.chemrestox.4c00376","url":null,"abstract":"<p><p>Isopropyl glycidyl ether (IPGE) is a member of the large glycidyl ether family frequently used as a reactive diluent during the epoxy resin manufacturing process. Although the toxicity induced by this type of chemical has been investigated in many studies of different aspects (acute, subchronic, genotoxic, reproduction, etc.), there is still little known about their toxicokinetics. To gain information about the attainable systemic concentration, a liquid chromatography─tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of IPGE in rat plasma using its structural analogue <i>tert</i>-butyl glycidyl ether as the internal standard. Two types of atmospheric pressure ionization techniques have been utilized; however, the protonated molecule ion could not be observed in either ionization mode. First, the ammonium adduct form was used for fragmentation, albeit this multiple-reaction monitoring transition proved to be not sensitive enough for real study sample analysis. In order to achieve the desired sensitivity, the Meerwein reaction was applied as an in-source derivatization tool to generate a product by using the ethylnitrilium ion formed from the eluent acetonitrile. This gas-phase reaction enabled us to build up a method with a substantial sensitivity increase (LLOQ of 0.01 μg/mL) compared to that obtained with the ammonium adduct. After method validation, real study samples from a single-dose oral toxicity study were analyzed to evaluate the blood plasma concentration of IPGE at three dose levels. Dose-dependent superproportional systemic exposure was observed in the studied dose range (1000-2000 mg/kg). Additionally, seven metabolites of IPGE were tentatively identified in rat plasma: 3-isopropoxy-2-hydroxy-1-propanol (M1), sulfate-conjugate of IPGE (M3), glucuronide-conjugate of IPGE (M4), 3-isopropoxy-2-hydroxypropionic acid (M5), <i>O</i>-isopropyl-<i>N</i>-acetylserine (M6), <i>O</i>-(2-hydroxy-isopropyl)-<i>N</i>-acetylserine (M7), and glutathione-conjugate of IPGE (M11). Present work may pave the way to other methods that are able to quantify compounds similar to IPGE even in human plasma, which could provide valuable information to assist exposure assessment and biomonitoring in occupational health and safety studies.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"380-391"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555317","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":"Exploring Potential Associations between Benzo[<i>a</i>]pyrene, Nicotine Exposure, and Lung Cancer: Molecular Insights, Prognostic Biomarkers, and Immune Cell Infiltration.","authors":"Xiang Deng, Hui Zhang, Yang Wang, Dongbo Ma, Qiuge Wu","doi":"10.1021/acs.chemrestox.4c00469","DOIUrl":"10.1021/acs.chemrestox.4c00469","url":null,"abstract":"<p><p>Benzo[<i>a</i>]pyrene (BaP) and nicotine exposure have been implicated in lung cancer development. This study aims to elucidate the molecular mechanisms and potential biomarkers associated with this exposure in lung cancer patients. We integrated gene expression data from The Cancer Genome Atlas lung cancer cohort and the Comparative Toxicogenomics Database to identify differentially expressed genes (DEGs) associated with BaP and nicotine exposure. Enrichment analyses, survival analyses, and immune cell infiltration analyses were conducted to interpret the biological significance of these DEGs. A risk score model and a nomogram were constructed for a prognostic evaluation. We identified 163 DEGs related to BaP and nicotine exposure in lung cancer. Enrichment analysis revealed significant biological processes and pathways, including \"IL-17 signaling\", \"cellular senescence\", and \"p53 signaling\". From the DEGs, 34 prognostic genes were identified, with <i>CLDN5</i>, <i>DNASE1L3</i>, and <i>GPR37</i> being independent prognostic factors. A risk score model based on these genes showed significant prognostic value, with high-risk patients exhibiting poorer survival outcomes. Additionally, a nomogram based on these risk scores demonstrated good predictive accuracy and clinical utility. Kaplan-Meier analyses confirmed that high expression of <i>CLDN5</i> and <i>GPR37</i> correlated with poor survival, while high <i>DNASE1L3</i> expression indicated better survival. Single-gene enrichment analyses linked these genes to immune responses, cell adhesion, and DNA methylation. Immune cell infiltration analysis revealed significant correlations between the expression of these genes and the infiltration of various immune cell types. Our findings highlight the significant role of <i>CLDN5</i>, <i>DNASE1L3</i>, and <i>GPR37</i> in lung cancer associated with BaP and nicotine exposure. The constructed risk score model and nomogram provide valuable tools for prognostication, and the identified genes offer potential targets for therapeutic intervention. Understanding the influence of toxic exposure on the tumor-immune microenvironment can guide future research and treatment strategies.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"458-470"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466412","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":"Assessing Modes of Toxic Action of Organic Cations in <i>In Vitro</i> Cell-Based Bioassays: the Critical Role of Partitioning to Cells and Medium Components.","authors":"Eunhye Bae, Stephan Beil, Maria König, Stefan Stolte, Beate I Escher, Marta Markiewicz","doi":"10.1021/acs.chemrestox.4c00527","DOIUrl":"10.1021/acs.chemrestox.4c00527","url":null,"abstract":"<p><p>High-throughput cell-based bioassays can fulfill the growing need to assess the hazards and modes of toxic action (MOA) of ionic liquids (ILs). Although nominal concentrations (<i>C</i>_nom) are typically used in an <i>in vitro</i> bioassay, freely dissolved concentrations (<i>C</i>_free) are considered a more accurate dose metric because they account for chemical partitioning processes and are informative about MOA. We determined the <i>C</i>_free of IL cations in AREc32 and AhR-CALUX assays using both mass balance model (MBM) prediction and experimental quantification. Partition coefficients between membrane lipid-water (<i>K</i>_mw), serum albumin-water (<i>K</i>_albumin/w), and cell-water (<i>K</i>_cell/w) as well as potential confounding factors (binding to a test plate and micelle formation) were determined to improve the MBM prediction. IL cations showed a higher affinity for both cell lines than that predicted by the MBM based on <i>K</i>_mw and <i>K</i>_albumin/w. Their affinity for the AhR-CALUX cells was more than 1 order of magnitude higher than for the AREc32, signifying cell line-specific affinity. The MBM with an experimental <i>K</i>_cell/w accurately predicted <i>C</i>_free. Evaluating cytotoxicity based on <i>C</i>_free eliminated the leveling off of toxicity observed for hydrophobic IL cations (side chain cutoff), suggesting that <i>C</i>_nom underestimates the effects of compounds with high affinity for the assay medium. Cell membrane concentrations calculated from <i>C</i>_free using <i>K</i>_mw were compared to the critical membrane burden to identify whether IL cations act as baseline toxicants. The IL cations carrying 16 carbons in the chain in the AREc32 assay and most of the IL cations in the AhR-CALUX assay were classified as excess toxicants. However, since the reasons for the deviation of experimental <i>K</i>_cell/w from MBM prediction remain unexplained, it is uncertain whether the cell membrane concentrations can be well predicted from <i>K</i>_mw used in this study. Therefore, future studies should aim to uncover the underlying causes of differing cell affinities observed across cell lines and model predictions.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"488-502"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539492","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":"Improving Volatile Organic Compound Exposure Assessment Using Biomonitoring by Relating Exposure Biomarker Levels in Blood and Urine.","authors":"David M Chambers, Blake J Roberson, Carmen A Woodruff, Benjamin C Blount, Deepak Bhandari","doi":"10.1021/acs.chemrestox.4c00485","DOIUrl":"10.1021/acs.chemrestox.4c00485","url":null,"abstract":"<p><p>Exposure assessment of hazardous volatile organic compounds (VOCs) requires accurate quantification of internal dose when establishing limits or identifying significant differences within and among populations. Even though accurate internal dose can be directly measured in blood, it is not always practical or possible to collect a suitable blood specimen. This work studies the relationship between blood and urine levels for certain smoke biomarkers (e.g., tobacco, marijuana) measured in self-reported cigarette smokers. Urine and blood specimens were collected as matched pairs from individuals at the same time. We used our latest specimen collection and VOC analysis protocols to minimize sample collection, handling, and analysis biases. From these analyses, unmetabolized urine benzene, furan, 2,5-dimethylfuran, isobutyronitrile, and benzonitrile levels were found to trend with blood levels. In addition, we measured urine creatinine levels, which were found to be significantly associated with all blood analyte concentrations (<i>p</i>-value ranging from <0.0063 to <0.0001) except for isobutyronitrile (<i>p</i> = 0.3347). For the analytes that were associated with urine creatinine levels, the ratios of urine-to-blood concentrations were substantially higher than those predicted from the urine/blood partition coefficients (<i>K</i>_urine/blood), which should occur if VOCs can freely equilibrate (i.e., passive diffusion) between the blood and urine. The urine isobutyronitrile concentration, which was the only analyte that was not associated with the urine creatinine level, had a urine-to-blood ratio similar to <i>K</i>_urine/blood. These results suggest either that urine VOC levels for certain VOCs do not equilibrate with blood levels in the urinary tract or that there is a conversion of conjugated to free forms, increasing urine VOC levels. Nevertheless, these deviations from partition theory (e.g., Henry's Law) are analyte-specific and require characterization to establish a relationship between blood and urine levels.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"471-477"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466417","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":"Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis","authors":"Amanuel Hailemariam,&nbsp;Srijana Upadhyay,&nbsp;Vinod Srivastava,&nbsp;Zahin Hafiz,&nbsp;Lei Zhang,&nbsp;Wai Ning Tiffany Tsui,&nbsp;Arafat Rahman Oany,&nbsp;Jaileen Rivera-Rodriguez,&nbsp;Robert S. Chapkin,&nbsp;Nicole Riddell,&nbsp;Robert McCrindle,&nbsp;Alan McAlees and Stephen Safe*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0052810.1021/acs.chemrestox.4c00528","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00528https://doi.org/10.1021/acs.chemrestox.4c00528","url":null,"abstract":"<p >Polyfluoroalkyl substances (PFAS) are widely used industrial compounds that have been identified as contaminants in almost every component of the global ecosystem, and in human studies, higher levels of PFAS have been correlated with increased incidence of multiple diseases. Based on the results of human and laboratory animal studies, we hypothesize that the orphan nuclear receptor 4A1 (NR4A1) may be a critical target for some PFAS such as the legacy linear polyfluorooctanesulfonate (PFOS) and other sulfonates. We show that PFOS and related compounds bound the ligand binding domain (LBD) of NR4A1 and induced the growth of several cancer cell lines and enhanced tumor growth in an athymic nude mouse model. Using NR4A1-responsive rhabdomyosarcoma Rh30 cells as a model, PFOS induced NR4A1-dependent cell proliferation and Rh30 cell migration and invasion. Moreover, in Rh30 cells, PFOS also induces several NR4A1-regulated genes including the PAX3-FOXO1 oncogene and downstream gene products, and in a chromatin immunoprecipitation assay, PFOS does not decrease NR4A1 binding to the promoter. These results demonstrate that PFOS is an NR4A1 ligand and enhances tumorigenesis through the activation of this receptor.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"705–716 705–716"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00528","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851229","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":"Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.","authors":"Amanuel Hailemariam, Srijana Upadhyay, Vinod Srivastava, Zahin Hafiz, Lei Zhang, Wai Ning Tiffany Tsui, Arafat Rahman Oany, Jaileen Rivera-Rodriguez, Robert S Chapkin, Nicole Riddell, Robert McCrindle, Alan McAlees, Stephen Safe","doi":"10.1021/acs.chemrestox.4c00528","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00528","url":null,"abstract":"<p><p>Polyfluoroalkyl substances (PFAS) are widely used industrial compounds that have been identified as contaminants in almost every component of the global ecosystem, and in human studies, higher levels of PFAS have been correlated with increased incidence of multiple diseases. Based on the results of human and laboratory animal studies, we hypothesize that the orphan nuclear receptor 4A1 (NR4A1) may be a critical target for some PFAS such as the legacy linear polyfluorooctanesulfonate (PFOS) and other sulfonates. We show that PFOS and related compounds bound the ligand binding domain (LBD) of NR4A1 and induced the growth of several cancer cell lines and enhanced tumor growth in an athymic nude mouse model. Using NR4A1-responsive rhabdomyosarcoma Rh30 cells as a model, PFOS induced NR4A1-dependent cell proliferation and Rh30 cell migration and invasion. Moreover, in Rh30 cells, PFOS also induces several NR4A1-regulated genes including the PAX3-FOXO1 oncogene and downstream gene products, and in a chromatin immunoprecipitation assay, PFOS does not decrease NR4A1 binding to the promoter. These results demonstrate that PFOS is an NR4A1 ligand and enhances tumorigenesis through the activation of this receptor.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603025","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":"Positive Ion Tandem Mass Spectrometry Offers Enhanced Structural Insights for the Discovery of Mercapturic Acids","authors":"Kevin J. Murray,&nbsp;Dylan Mckeon,&nbsp;Chiara Lecchi,&nbsp;Laura Maertens,&nbsp;Peter W. Villalta and Silvia Balbo*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0044610.1021/acs.chemrestox.4c00446","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00446https://doi.org/10.1021/acs.chemrestox.4c00446","url":null,"abstract":"<p >Urinary mercapturic acids represent valuable biological markers of chemical exposure and detoxification mechanisms. Characterization of this class of compound has historically employed LC–MS/MS analytical platforms using negative ion mode. In this study, we report the first application of a UHPLC–MS/MS method using positive ion mode detection for the unbiased characterization of mercapturic acids. A preliminary spectral library of synthetically available mercapturic acids was generated to evaluate fragmentation pathways of mercapturic acids in positive mode. From our findings, we propose a discovery method that utilizes a neutral loss monitoring paradigm based on two diagnostic fragmentation pathways of mercapturic acids. Using a cohort of 20 nonsmokers and 20 smokers, we detected 180 putative mercapturic acid signatures that exhibited a high degree of reproducibility. Following a combination of multivariate and univariate statistics, we found 33 putative mercapturic acids associated with smoking status. The increased structural insights of analytical profiling in positive mode enable more informative annotation of discovery results. Using the latest structural prediction technology, we were able to assign preliminary structural identifications to these features and eliminate likely false positive detections. From our workflow, we discovered a previously unreported mercapturic acid with a strong association with tobacco cigarette usage and putatively identified it as <i>N</i>-acetyl-<i>S</i>-(2-ethyl-3-pyridine)-<span>l</span>-cysteine, a potential metabolite of nicotine pyrolysis product 3-ethenylpyridine.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"635–646 635–646"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851230","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":"Positive Ion Tandem Mass Spectrometry Offers Enhanced Structural Insights for the Discovery of Mercapturic Acids.","authors":"Kevin J Murray, Dylan Mckeon, Chiara Lecchi, Laura Maertens, Peter W Villalta, Silvia Balbo","doi":"10.1021/acs.chemrestox.4c00446","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00446","url":null,"abstract":"<p><p>Urinary mercapturic acids represent valuable biological markers of chemical exposure and detoxification mechanisms. Characterization of this class of compound has historically employed LC-MS/MS analytical platforms using negative ion mode. In this study, we report the first application of a UHPLC-MS/MS method using positive ion mode detection for the unbiased characterization of mercapturic acids. A preliminary spectral library of synthetically available mercapturic acids was generated to evaluate fragmentation pathways of mercapturic acids in positive mode. From our findings, we propose a discovery method that utilizes a neutral loss monitoring paradigm based on two diagnostic fragmentation pathways of mercapturic acids. Using a cohort of 20 nonsmokers and 20 smokers, we detected 180 putative mercapturic acid signatures that exhibited a high degree of reproducibility. Following a combination of multivariate and univariate statistics, we found 33 putative mercapturic acids associated with smoking status. The increased structural insights of analytical profiling in positive mode enable more informative annotation of discovery results. Using the latest structural prediction technology, we were able to assign preliminary structural identifications to these features and eliminate likely false positive detections. From our workflow, we discovered a previously unreported mercapturic acid with a strong association with tobacco cigarette usage and putatively identified it as <i>N</i>-acetyl-<i>S</i>-(2-ethyl-3-pyridine)-l-cysteine, a potential metabolite of nicotine pyrolysis product 3-ethenylpyridine.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595773","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":"Predicting Liver-Related In Vitro Endpoints with Machine Learning to Support Early Detection of Drug-Induced Liver Injury","authors":"Marina Garcia deLomana*,&nbsp;Domenico Gadaleta,&nbsp;Marian Raschke,&nbsp;Robert Fricke and Floriane Montanari,&nbsp;","doi":"10.1021/acs.chemrestox.4c0045310.1021/acs.chemrestox.4c00453","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00453https://doi.org/10.1021/acs.chemrestox.4c00453","url":null,"abstract":"<p >Drug-induced liver injury (DILI) is a major cause of drug development failures and postmarket drug withdrawals, posing significant challenges to public health and pharmaceutical research. The biological mechanisms leading to DILI are highly complex and the adverse reaction is often difficult to foresee. Hence, mechanistic insights into DILI, as well as machine learning models to predict molecular events that trigger adverse outcomes, pharmacokinetics and pharmacodynamics in the liver, are essential tools for understanding and preventing DILI. In this study, we collected a comprehensive data set of 28 in vitro endpoints related to liver toxicity and function, as well as data specific to DILI, to explore the potential of multi-task learning for their prediction. We demonstrate the benefits of ensemble modeling and provide an uncertainty estimation based on the standard deviation of the predictions to define an applicability domain for the models. Available assays at Bayer for two of the endpoints (Bile salt export pump (BSEP) inhibition and phospholipidosis) were run on a set of public compounds and used for further evaluation (data provided in the Supporting Information). Additionally, we conducted an in-depth data analysis of the relationships among the different endpoints, as well as with DILI. The presented models can be used to derive a “Virtual Liver Safety Profile” showcasing the predicted activity of a compound on the selected endpoints to support the prioritization of assays and the elucidation of modes of action.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"656–671 656–671"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851163","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":"Benzo[a]pyrene in the Mainstream Smoke of Little Cigars","authors":"Sandra I. Salido*,&nbsp;Matthew Hassink,&nbsp;Kenneth Taylor,&nbsp;Elizabeth A. Cowan,&nbsp;Morgann S. Woods,&nbsp;Shanga Lee,&nbsp;Oleksii Motorykin,&nbsp;Bryan Hearn,&nbsp;Liza Valentín-Blasini and Clifford H. Watson,&nbsp;","doi":"10.1021/acs.chemrestox.4c0041110.1021/acs.chemrestox.4c00411","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00411https://doi.org/10.1021/acs.chemrestox.4c00411","url":null,"abstract":"<p >Little cigars are similar to cigarettes, with respect to dimensions, filters, and overall appearance. Some smokers also use little cigars as substitutes for cigarettes. Comparison of little cigars with cigarettes is relevant to understanding their respective public health impact. To understand their relative toxicities, mainstream smoke yields of benzo[a]pyrene (B[a]P), a human carcinogen, were measured for 60 commercial little cigars. The little cigars were smoked on a linear smoking machine using the International Organization of Standardization (ISO) nonintense and Canadian Intense (CI) smoking regimens followed by analysis with a validated gas chromatography/mass spectrometry (GC/MS) method. The average analytical quantitative variability of the measured little cigar constituents was lower compared to previously tested commercial cigarettes (%RSD 9.6 vs 14.5, respectively). B[a]P yields ranged from 14.5–44.0 ng/cigar (ISO) and 24.0–65.7 ng/cigar (CI). The mean ISO yield is 25.5 ng/cigar versus the CI yield of 42.2 ng/cigar, which are 2.5- and 2-fold greater, respectively, than the corresponding mean cigarette yields. When normalized to tobacco weight, B[a]P yields of the little cigars are 1.5- (ISO) and 1.3- (CI) fold greater than cigarette yields. B[a]P smoke yields are known to correlate with tobacco weight. The little cigar B[a]P yield correlations to tobacco weight (CI <i>R</i>² = 0.35; ISO <i>R</i>² = 0.24) are similar to cigarette yield correlations (CI <i>R</i>² = 0.31; ISO <i>R</i>² = 0.21). Other physical properties (i.e., filter length, filter ventilation, and packing density) that may impact B[a]P smoke yields for the little cigars had very weak correlations. Except for cigarette packing density, cigars and cigarettes have similar correlations between B[a]P yields and physical design parameters. In summary, the little cigars, although physically similar to cigarettes, differ in smoke chemistry by generating higher B[a]P yields, even when normalized to tobacco weight.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 4","pages":"609–622 609–622"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851162","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}