Chemical Research in Toxicology最新文献

{"title":"Goniodomic Acid, a Transient Oxirane Intermediate in the Conversion of the Macrolide Algal Toxin Goniodomin A to Seco Acids.","authors":"Constance M Harris, Bernd Krock, Thomas M Harris","doi":"10.1021/acs.chemrestox.4c00390","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00390","url":null,"abstract":"<p><p>The algal macrolide goniodomin A (GDA) undergoes ring-cleavage under unusually mild, alkaline conditions to form mixtures of stereoisomers of seco acids GDA-sa and iso-GDA-sa. In the primary fragmentation pathway, opening of the macrolide ring occurs by displacement of the carboxyl group by a base-catalyzed attack of the C32 hemiketal hydroxy group on C31, yielding an oxirane-carboxylic acid, named goniodomic acid. The oxirane ring is unstable, undergoing solvolytic opening to form mainly GDA-sa. Experimental support for this pathway obtained by carrying out the ring-opening reaction in H₂¹⁸O resulted in incorporation of the isotopic label at C32 of the seco acid. Collision-induced dissociation (CID) mass spectrometry of Na⁺ and NH₄⁺ ion adducts was employed to establish that ring-opening of the macrolide ring occurred by alkyl-O cleavage. Fragmentation was dominated by Grob-Wharton decarboxylation and retro-Diels-Alder reactions of the labeled seco acids. Direct observation of goniodomic acid was achieved when the ring-opening reaction was carried out under anhydrous conditions. A minor alkyl-O cleavage pathway gives rise to iso-GDA-sa by allylic attack at C29 of GDA or of the oxirane. In the formation of both GDA-sa and iso-GDA-sa, ring-opening is likely to be catalyzed by Na⁺ and NH₄⁺. Reversal of GDA-sa formation can occur in the mass spectrometer. CID fragmentation of the ¹⁸O-labeled GDA-sa restores the oxirane ring but causes preferential loss of the ¹⁸O label from C32.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875480","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":"Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.","authors":"Timothy R Smyth, Stephanie Brocke, Yong Ho Kim, Cara Christianson, Kasey D Kovalcik, Joseph Patrick Pancras, Michael D Hays, Weidong Wu, Zhen An, Ilona Jaspers","doi":"10.1021/acs.chemrestox.4c00291","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00291","url":null,"abstract":"<p><p>Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality. However, limited work has considered the impact of the initial macrophage polarization state on subsequent responses to PM exposure. PM composition can demonstrate seasonality-specific compositional changes based on differences in seasonal weather patterns and energy needs, introducing the need to consider the seasonality-specific effects of airborne PM when investigating its impact on human health. This study sought to determine the impact of airborne PM collected during different seasons of the year in Xinxiang, China, on macrophage function in a polarization state-dependent manner. Macrophages were differentiated using the macrophage colony-stimulating factor (M-CSF) on CD14+CD16- monocytes isolated from the blood of healthy human volunteers. The resulting macrophages were polarized into indicated states using well-characterized polarization methods and assessed for phagocytic function, bioenergetic properties, and secretory profile following exposure to PM collected during a single day during each season of the year. Macrophages demonstrated clear polarization state-dependent phagocytic, bioenergetic, and secretory properties at the baseline and following PM exposure. Specific PM seasonality had a minimal impact on phagocytic function and a minor effect on bioenergetic properties but had clear impacts on the secretory profile as demonstrated by the enriched secretion of well-characterized mediator clusters by particle season. Together, these data suggest that both particle seasonality and macrophage polarization state must be considered when investigating the impact of PM on macrophage function. These factors may contribute to the negative outcomes linked to PM exposure during respiratory infections.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862522","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":"Elucidating the Metabolism of Chiral PCB95 in Wildtype and Transgenic Mouse Models with Altered Cytochrome P450 Enzymes Using Intestinal Content Screening.","authors":"Xueshu Li, Amanda J Bullert, Binita Gautam, Weiguo Han, Weizhu Yang, Qing-Yu Zhang, Xinxin Ding, Hans-Joachim Lehmler","doi":"10.1021/acs.chemrestox.4c00350","DOIUrl":"10.1021/acs.chemrestox.4c00350","url":null,"abstract":"<p><p>Polychlorinated biphenyls (PCBs), such as 2,2',3,5',6-pentachlorobiphenyl (PCB95), are persistent organic pollutants associated with adverse health outcomes, including developmental neurotoxicity. PCB95 is a chiral neurotoxic PCB congener atropselectively metabolized to potentially neurotoxic metabolites in vivo. However, the metabolic pathways of most PCB congeners, including PCB95, remain unknown. To address this knowledge gap, we analyzed the intestinal contents of mice exposed to PCB95 to elucidate the PCB95 metabolism pathway and assess if genetic manipulation of hepatic drug-metabolizing enzymes affects PCB95 metabolism. Our study exposed male and female wildtype (WT), <i>Cyp2abfgs</i>-null (KO), and CYP2A6-transgenic/<i>Cyp2abfgs-null</i> (KI) mice orally to 1.0 mg/kg body weight of PCB95. Intestinal content was collected 24 h after PCB administration. aS-PCB95 was enriched in all intestinal content samples, irrespective of sex and genotype. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analyses identified 5 mono- (OH-PCB95) and 4 dihydroxylated PCB (diOH-PCB95) metabolites. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) identified 15 polar hydroxylated, methoxylated, and sulfated PCB95 metabolites, including 3 dechlorinated metabolites. A sex difference in the relative OH-PCB95 levels was observed only for KO in the LC-HRMS analysis. Genotype-dependent differences were observed for female, but not male, mice, with OH-PCB95 levels in female KO (F_KO) mice tending to be lower than those in female WT (F_WT) and KI (F_KI) mice. Based on the GC-MS/MS analysis, these differences are due to the unknown PCB95 metabolites, X1-95 and Y1-95. These findings demonstrate that combining GC-MS/MS analyses and LC-HRMS subject screening of the intestinal content of PCB95-exposed mice can significantly advance our understanding of PCB95 metabolism in vivo.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1989-2002"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674414","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":"Melatonin Vapes Contain Potential Contaminants and Alter the Human Bronchial Epithelial Transcriptome.","authors":"Kevin D Schichlein, Hye-Young H Kim, Charlotte A Love, Tara N Guhr Lee, Charles R Esther, Ned A Porter, Meghan E Rebuli, Brandie M Ehrmann, Phillip W Clapp, Ilona Jaspers","doi":"10.1021/acs.chemrestox.4c00295","DOIUrl":"10.1021/acs.chemrestox.4c00295","url":null,"abstract":"<p><p>Melatonin vaping products, touted for their faster absorption than oral melatonin supplements, have been gaining popularity among adolescents as sleep aid. Here, we elucidated the response of human bronchial epithelial cells (hBECs) to high levels of melatonin from vaped aerosols, investigated the uptake of melatonin by hBECs <i>in vitro</i>, and characterized the chemical composition of three commercially available melatonin vapes. Melatonin vape exposure decreased the secretion of chemokines and produced an immunosuppressive gene expression signature. The tested devices contained potential contaminants, including pharmaceuticals and industrial chemicals. Further investigation is needed for melatonin vapes to determine their local and systemic toxicity.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1919-1923"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612683","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":"Oxidative Deformylation of the Predominant DNA Lesion 5-Formyl-2'-deoxyuridine.","authors":"Gabriel Robert, Charlotte Sabourin, J Richard Wagner","doi":"10.1021/acs.chemrestox.4c00410","DOIUrl":"10.1021/acs.chemrestox.4c00410","url":null,"abstract":"<p><p>Radical oxidation of DNA gives rise to potentially deleterious lesions such as strand breaks and various nucleobase modifications including 5-formyl-2'-deoxyuridine (5-fo-dU), a prevalent product derived from the oxidation of the C5-methyl group of thymidine. The present study investigates the unusual transformation of 5-fo-dU into 5-hydroxy-2'-deoxyuridine (5-oh-dU) and 5,6-dihydroxy-5,6-dihydro-2'-deoxuridine (gly-dU), two products typically associated with the oxidation of 2'-deoxycytidine. Detailed mechanistic analyses reveal that hydrogen peroxide, either generated as a byproduct of ascorbate autoxidation or added exogenously, mediates the formation of these oxidatively induced C5-dealkylated products. We show that the major product 5-oh-dU results from a Baeyer-Villiger rearrangement of the formyl functionality of 5-fo-dU while the minor product gly-dU derives from α,β-oxidation of the enal portion followed by deformylation. These reactions were observed in both 2'-deoxynucleoside monomers as well as isolated DNA. Our findings further clarify the oxidation chemistry of thymidine and highlight a novel oxidative decomposition pathway that can help understand the fate of certain types of DNA damage. Furthermore, our results underscore the pro-oxidant properties of ascorbate <i>in vitro</i> that can lead to the adventitious oxidation of substrates via the reduction of trace metals ions and generation of hydrogen peroxide.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"2032-2039"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764623","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":"Zebrafish Larvae as a Predictive Model for the Risk of Chemical-Induced Cholestasis: Phenotypic Evaluation and Nomogram Formation.","authors":"Si-Tong Qian, Liang-Min Chen, Ming-Fang He, Hui-Jun Li","doi":"10.1021/acs.chemrestox.4c00324","DOIUrl":"10.1021/acs.chemrestox.4c00324","url":null,"abstract":"<p><p>Chemical-induced cholestasis (CIC) has become a concern in chemical safety risk assessment in pharmaceutical, food, cosmetic, and industrial manufacturing. Currently, known animal and <i>in vitro</i> liver models are unsuitable as high-throughput screening tools due to their high cost, time-consuming, or poor screening accuracy. Herein, a cohort of chemicals validated as cholestatic hepatotoxic in humans, rodents, and <i>in vitro</i> liver models was established for testing. The accuracy and reliability of the detection of CIC in zebrafish larvae were assessed by liver phenotype, bile flow inhibition rate, bile acid distribution, biochemical indices, and RT-qPCR. In addition, the nomogram prediction model was constructed using binomial logistic regression analysis. The model was constructed with three variables: aspartate aminotransferase (AST.FC) level, total bile acid (TBA.FC) level, and fold change in the number of bile acid nodes per unit of bile ducts in the zebrafish liver (NPL.FC), which showed high predictive power (areas under the ROC curve: 0.983). Furthermore, this study demonstrated that zebrafish larvae have some model specificity for CIC risk assessment of estrogen endocrine disruptors and that testing after 10 dpf provides more scientific results. Overall, combining zebrafish larval phenotyping and nomograms is an efficient and powerful tool for CIC risk monitoring of chemicals.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1976-1988"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680018","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":"Photosensitizing Properties of the Topical Retinoid Drug Adapalene.","authors":"Juan A Soler-Orenes, Gemma M Rodríguez-Muñiz, Javier Hernández-Gil, Miguel A Miranda, Inmaculada Andreu, Virginie Lhiaubet-Vallet","doi":"10.1021/acs.chemrestox.4c00384","DOIUrl":"10.1021/acs.chemrestox.4c00384","url":null,"abstract":"<p><p>Photoreactivity is an important issue for topical drugs especially when these are applied on the sun-exposed skin area. In this context, third-generation retinoids are of special interest due to their conjugated chemical structure and their use in the treatment of acne. Herein, the phototoxic potential of one of these drugs, adapalene, is established using an in vitro 3T3 Neutral Red Uptake (NRU) test. Photophysical studies demonstrate the involvement of a Type II process with an efficient formation of singlet oxygen. Interestingly, quenching of the adapalene singlet manifold by oxygen leads to an increased production of this reactive oxygen species through the tagged O₂-enhanced intersystem crossing process. Taken together, these results are relevant from a toxicological point of view as adapalene could be considered as a double-edged sword: it can be at the origin of undesired skin photosensitivity reactions or be considered as a candidate for topical photodynamic therapy.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"2013-2021"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764625","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":"Quantitative Structure-Activity Relationship Models to Predict Cardiac Adverse Effects.","authors":"Zhongyu Mou, Patra Volarath, Rebecca Racz, Kevin P Cross, Mounika Girireddy, Suman Chakravarti, Lidiya Stavitskaya","doi":"10.1021/acs.chemrestox.4c00186","DOIUrl":"10.1021/acs.chemrestox.4c00186","url":null,"abstract":"<p><p>Drug-induced cardiotoxicity represents one of the most common causes of attrition of drug candidates in preclinical and clinical development. For this reason, the evaluation of cardiac toxicity is essential during drug development and regulatory review. In the present study, drug-induced postmarket adverse event combinations from the FDA Adverse Event Reporting System were extracted for 2002 drugs using 243 cardiac toxicity-related preferred terms (PTs). These PTs were combined into 12 groups based on their clinical relevance to serve as training sets. The optimal classification scheme was determined using a combination of data sources that included drug labeling information, published literature, clinical study data, and postmarket surveillance data. Two commercial QSAR platforms were used to construct 12 models, including general cardiac toxicity, cardiac ischemia, heart failure, cardiac valve disease, myocardial disease, pericardial disease, structural heart disease, cardiac arrhythmia, Torsades de Pointes, long QT syndrome, atrial fibrillation and ventricular arrhythmia, and cardiac arrest. The cross-validated performance for the new models reached a sensitivity of up to 80% and negative predictivity of up to 80%. These new models covering a wide range of cardiac endpoints will provide fast, reliable, and comprehensive predictions of potential cardiotoxic compounds in drug discovery and regulatory safety assessment.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1924-1933"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612685","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":"Plant-Derived and Synthetic Nicotine in E-Cigarettes: Is Differentiation with NMR Spectroscopy Possible?","authors":"Yulia B Monakhova, Klaudia Adels, Bernd W K Diehl","doi":"10.1021/acs.chemrestox.4c00398","DOIUrl":"10.1021/acs.chemrestox.4c00398","url":null,"abstract":"<p><p>To circumvent regulatory frameworks, many producers start to substitute plant-derived nicotine (tobacco-derived nicotine, TDN) by synthetic nicotine (tobacco-free nicotine, TFN) in e-cigarette products. Due to the higher costs of enantiomeric synthesis and purification of TFN, there is a need to develop an analytical method that clearly distinguishes between the two sources. To trace nicotine's origin, its enantiomeric purity can be postulated by ¹H NMR spectroscopy using (<i>R</i>)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNPPA) as a chiral complexing agent. Low-field (LF) NMR conditions were optimized for this purpose even using a small amount of e-liquid sample (limit of quantification 8 mg/mL nicotine). All investigated products were found to contain one isomer (most likely (<i>S</i>)-(-)-nicotine). A direct ¹³C NMR method at natural abundance has been validated to differentiate (<i>S</i>)-TDN and (<i>S</i>)-TFN in e-cigarettes produced using nicotine of different origin. The method is based on calculation of the relative ¹³C content of 10 C-positions of the nicotine molecule with intraday and interday precisions below <0.2%. The method was applied to 12 commercial e-cigarette products labeled as containing TDN and TFN. Principal component analysis (PCA) was applied to the relative peak areas to visualize the difference between studied products. The LF ¹H NMR method is a good alternative to expensive high-field NMR to differentiate between a racemate mixture and single optical isomers, whereas only high-precision ¹³C NMR can be used to distinguish (<i>S</i>)-TDN and (<i>S</i>)-TFN in e-cigarettes after appropriate sample extraction.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"2022-2031"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638018","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":"Chemical Composition of Aerosols from the E-Cigarette Vaping of Natural and Synthetic Cannabinoids.","authors":"Nicholas E Robertson, Jack Connolly, Nikolay Shevchenko, Mark Mascal, Kent E Pinkerton, Sascha C T Nicklisch, Tran B Nguyen","doi":"10.1021/acs.chemrestox.4c00326","DOIUrl":"10.1021/acs.chemrestox.4c00326","url":null,"abstract":"<p><p>Vaping cannabinoids in electronic (e)-cigarette devices is rapidly increasing in popularity, particularly among adolescents, although the chemistry affecting the composition of the vape aerosol is not well understood. This work investigates the formation of aerosol mass, bioactive hydroxyquinones, and harmful or potentially harmful carbonyls from the e-cigarette vaping of natural and synthetic cannabinoids e-liquids in propylene glycol and vegetable glycerin (PG/VG) solvent at a 50 mg/mL concentration in a commercial fourth-generation vaping device. The following cannabinoids were studied: cannabidiol (CBD), 8,9-dihydrocannabidiol (H2CBD), 1,2,8,9-tetrahydrocannabidiol (H4CBD), cannabigerol (CBG), and cannabidiolic acid (CBDA). Quantification of analytes was performed using liquid chromatography coupled to accurate mass spectrometry. The addition of cannabinoids significantly increased aerosol and carbonyl formation compared with the PG/VG solvent alone. All cannabinoids in the study formed hydroxyquinones during vaping (up to ∼1% mass conversion) except for CBDA, which primarily decarboxylated to CBD. Hydroxyquinone formation increased and carbonyl formation decreased, with a decreasing number of double bonds among CBD and its synthetic analogues (H2CBD and H4CBD). During the vaping process, ∼3-6% of the cannabinoid mass can be observed as carbonyls under the study conditions. Oxidation of the terpene moiety on the cannabinoids is proposed as a major contributor to carbonyl formation. CBD produced significantly higher concentrations of formaldehyde, acetaldehyde, acrolein, diacetyl, and methylglyoxal compared with the other cannabinoid samples. CBG produced significantly higher levels of acetone, methacrolein, and methylglyoxal. Conversion of CBD to tetrahydrocannabinol (THC) was not observed under the study conditions. The chemical mechanism basis for these observations is discussed. Compared with other modalities of use for CBD and other cannabinoids, vaping has the potential to adversely impact human health by producing harmful products during the heated aerosolization process.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1965-1975"},"PeriodicalIF":3.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612681","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}