Chemical Research in Toxicology最新文献

{"title":"Conditions Leading to Ketene Formation in Vaping Devices and Implications for Public Health.","authors":"Ping Wang, Peyton Jacob, Zhong-Min Wang, Jefferson Fowles, Donal F O'Shea, Jeff Wagner, Kazukiyo Kumagai","doi":"10.1021/acs.chemrestox.4c00190","DOIUrl":"10.1021/acs.chemrestox.4c00190","url":null,"abstract":"<p><p>The outbreak of e-cigarette or vaping use-associated lung injury (EVALI) in the United States in 2019 led to a total of 2807 hospitalizations with 68 deaths. While the exact causes of this vaping-related lung illness are still being debated, laboratory analyses of products from victims of EVALI have shown that vitamin E acetate (VEA), an additive in some tetrahydrocannabinol (THC)-containing products, is strongly linked to the EVALI outbreak. Because of its similar appearance and viscosity to pure THC oil, VEA was used as a diluent agent in cannabis oils in illicit markets. A potential mechanism for EVALI may involve VEA's thermal decomposition product, ketene, a highly poisonous gas, being generated under vaping conditions. In this study, a novel approach was developed to evaluate ketene production from VEA vaping under measurable temperature conditions in real-world devices. Ketene in generated aerosols was captured by two different chemical agents and analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method takes advantage of the high sensitivity and specificity of tandem mass spectrometry and appears to be more suitable than GC-MS for the analysis of large batches of samples. Our results confirmed the formation of ketene when VEA was vaped. The production of ketene increased with repeat puffs and showed a correlation to temperatures (200 to 500 °C) measured within vaping devices. Device battery power strength, which affects the heating temperature, plays an important role in ketene formation. In addition to ketene, the organic oxidant duroquinone was also obtained as another thermal degradation product of VEA. Ketene was not detected when vitamin E was vaped under the same conditions, confirming the importance of the acetate group for its generation.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1415-1427"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854141","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":"Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids.","authors":"Trevor Harris","doi":"10.1021/acs.chemrestox.4c00073","DOIUrl":"10.1021/acs.chemrestox.4c00073","url":null,"abstract":"<p><p>Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1315-1328"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791184","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":"Mechanisms Mediating the Combined Toxicity of Paraquat and Maneb in SH-SY5Y Neuroblastoma Cells.","authors":"Suzana da Silva, Carolina de Lima da Costa, Aline Aita Naime, Danúbia Bonfanti Santos, Marcelo Farina, Dirleise Colle","doi":"10.1021/acs.chemrestox.3c00389","DOIUrl":"10.1021/acs.chemrestox.3c00389","url":null,"abstract":"<p><p>Epidemiological and experimental studies have demonstrated that combined exposure to the pesticides paraquat (PQ) and maneb (MB) increases the risk of developing Parkinson's disease. However, the mechanisms mediating the toxicity induced by combined exposure to these pesticides are not well understood. The aim of this study was to investigate the mechanism(s) of neurotoxicity induced by exposure to the pesticides PQ and MB isolated or in association (PQ + MB) in SH-SY5Y neuroblastoma cells. PQ + MB exposure for 24 and 48 h decreased cell viability and disrupted cell membrane integrity. In addition, PQ + MB exposure for 12 h decreased the mitochondrial membrane potential. PQ alone increased reactive oxygen species (ROS) and superoxide anion generation and decreased the activity of mitochondrial complexes I and II at 12 h of exposure. MB alone increased ROS generation and depleted intracellular glutathione (GSH) within 6 h of exposure. In contrast, MB exposure for 12 h increased the GSH levels, the glutamate cysteine ligase (GCL, the rate-limiting enzyme in the GSH synthesis pathway) activity, and increased nuclear Nrf2 staining. Pretreatment with buthionine sulfoximine (BSO, a GCL inhibitor) abolished the MB-mediated GSH increase, indicating that MB increases GSH synthesis by upregulating GCL, probably by the activation of the Nrf2/ARE pathway. BSO pretreatment, which did not modify cell viability per se, rendered cells more sensitive to MB-induced toxicity. In contrast, treatment with the antioxidant <i>N</i>-acetylcysteine protected cells from MB-induced toxicity. These findings show that the combined exposure of SH-SY5Y cells to PQ and MB induced a cytotoxic effect higher than that observed when cells were subjected to individual exposures. Such a higher effect seems to be related to additive toxic events resulting from PQ and MB exposures. Thus, our study contributes to a better understanding of the toxicity of PQ and MB in combined exposures.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1269-1282"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755643","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":"Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes.","authors":"Esther E Omaiye, Wentai Luo, Kevin J McWhirter, Prue Talbot","doi":"10.1021/acs.chemrestox.4c00085","DOIUrl":"10.1021/acs.chemrestox.4c00085","url":null,"abstract":"<p><p>Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants (\"Blueberry Ice,\" \"Watermelon Ice,\" \"Green Mint,\" and \"Polar Mint\") were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescence microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13-19 mg/mL) were lower than many fourth generation e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44-100%. SURGE fluids and aerosols had four dominant flavor chemicals (>1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were <100 based on consumption of 1-2 SURGE u-cigarettes/day. Replacing the heating coil with a sonicator did not eliminate chemicals, including aldehydes, in aerosols or diminish toxicity in comparisons between SURGE and other e-cigarette pod products. The high concentrations of nicotine, WS-23, flavor chemicals, and aldehydes and the cytotoxicity of SURGE aerosols do not support the hypothesis that aerosols from u-cigarettes are less harmful than those from e-cigarettes.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1329-1343"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755644","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":"Induction of Thymus Atrophy and Disruption of Thymocyte Development by Fipronil through Dysregulation of IL-7-Associated Genes","authors":"Jui-Fang Kuo,&nbsp;Hsin-Ying Wu,&nbsp;Chun-Wei Tung,&nbsp;Wei-Hsiang Huang,&nbsp;Chen-Si Lin and Chia-Chi Wang*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0006010.1021/acs.chemrestox.4c00060","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00060https://doi.org/10.1021/acs.chemrestox.4c00060","url":null,"abstract":"<p >The susceptibility of the immune system to immunotoxic chemicals is evident, particularly in the thymus, a vital primary immune organ prone to atrophy due to exposure to toxicants. Fipronil (FPN), a widely used insecticide, is of concern due to its potential neurotoxicity, hepatotoxicity, and immunotoxicity. Our previous study showed that FPN disturbed the antigen-specific T-cell functionality <i>in vivo</i>. As T-cell lineage commitment and thymopoiesis are closely interconnected with the normal function of the T-cell-mediated immune responses, this study aims to further examine the toxic effects of FPN on thymocyte development. In this study, 4-week-old BALB/c mice received seven doses of FPN (1, 5, 10 mg/kg) by gavage. Thymus size, medulla/cortex ratio, total thymocyte counts, double-positive thymocyte population, and IL-7-positive cells decreased dose-dependently. IL-7 aids the differentiation of early T-cell precursors into mature T cells, and several essential genes contribute to the maturation of T cells in the thymus. <i>Foxn</i>1 ensures that the thymic microenvironment is suitable for the maturation of T-cell precursors. <i>Lyl</i>1 is involved in specifying lymphoid cells and maintaining T-cell development in the thymus. The <i>c-Kit/SCF</i> collaboration fosters a supportive thymic milieu to promote the formation of functional T cells. The expression of <i>IL-</i>7, <i>IL-</i>7<i>R</i>, <i>c-Kit</i>, <i>SCF</i>, <i>Foxn</i>1, and <i>Lyl</i>1 genes in the thymus was significantly diminished in FPN-treated groups with the concordance with the reduction of IL-7 signaling proteins (IL-7, IL-7R, c-KIT, SCF, LYL1, FOXO3A, and GABPA), suggesting that the dysregulation of T-cell lineage-related genes may contribute to the thymic atrophy induced by FPN. In addition, FPN disturbed the functionality of thymocytes with an increase of IL-4 and IFN-γ production and a decrease of IL-2 secretion after T-cell mitogen stimulation <i>ex vivo</i>. Collectively, FPN significantly deregulated genes related to T-cell progenitor differentiation, survival, and expansion, potentially leading to impaired thymopoiesis.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 9","pages":"1488–1500 1488–1500"},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234593","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":"Toxicity of Bromo-DragonFLY as a New Psychoactive Substance: Application of In Silico Methods for the Prediction of Key Toxicological Parameters Important to Clinical and Forensic Toxicology","authors":"Maciej Noga,&nbsp; and ,&nbsp;Kamil Jurowski*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0010510.1021/acs.chemrestox.4c00105","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00105https://doi.org/10.1021/acs.chemrestox.4c00105","url":null,"abstract":"<p >Bromo-DragonFLY is a synthetic new psychoactive substance (NPS) that has gained attention due to its powerful and long-lasting hallucinogenic effects, legal status, and widespread availability. This study aimed to use various <i>in silico</i> toxicology methods to predict key toxicological parameters for Bromo-DragonFLY, including acute toxicity (LD₅₀), genotoxicity, cardiotoxicity, health effects, and the potential for endocrine disruption. The results indicate significant acute toxicity with noticeable variations across different species, a low likelihood of genotoxic potential suggesting potential DNA damage, and a notable risk of cardiotoxicity associated with inhibition of the hERG channel. Evaluation of endocrine disruption suggests a low probability of Bromo-DragonFLY interacting with the estrogen receptor α (ER-α), indicating minimal estrogenic activity. These insights from <i>in silico</i> investigations are important for advancing our understanding of this NPS in forensic and clinical toxicology. These initial toxicological examinations establish a foundation for future research efforts and contribute to developing risk assessment and management strategies for using and misusing NPS.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 11","pages":"1821–1842 1821–1842"},"PeriodicalIF":3.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665660","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":"Photosensitized Oxidation of Free and Peptide Tryptophan to N-Formylkynurenine","authors":"Jesuán J. Farías,&nbsp;M. Laura Dántola and Andrés H. Thomas*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0022910.1021/acs.chemrestox.4c00229","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00229https://doi.org/10.1021/acs.chemrestox.4c00229","url":null,"abstract":"<p >The oxidation of proteins and, in particular, of tryptophan (Trp) residues leads to chemical modifications that can affect the structure and function. The oxidative damage to proteins in photochemical processes is relevant in the skin and eyes and is related to a series of pathologies triggered by exposure to electromagnetic radiation. In this work, we studied the photosensitized formation of <i>N</i>-formylkynurenine (NFKyn) from Trp in different reaction systems. We used two substrates: free Trp and a peptide of nine amino acid residues, with Trp being the only oxidizable residue. Two different photosensitizers were employed: Rose Bengal (RB) and pterin (Ptr). The former is a typical type II photosensitizer [acts by producing singlet oxygen (¹O₂)]. Ptr is the parent compound of oxidized or aromatic pterins, natural photosensitizers that accumulate in human skin under certain pathological conditions and act mainly through type I mechanisms (generation of radicals). Experimental data were collected in steady photolysis, and the irradiated solutions were analyzed by chromatography (HPLC). Results indicate that the reaction of Trp with ¹O₂ initiates the process leading to NFKyn, but different competitive pathways take place depending on the photosensitizer and the substrate. In Ptr-photosensitization, a type I mechanism is involved in secondary reactions accelerating the formation of NFKyn when free Trp is the substrate.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 9","pages":"1562–1573 1562–1573"},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234528","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":"Cheminformatic Read-Across Approach Revealed Ultraviolet Filter Cinoxate as an Obesogenic Peroxisome Proliferator-Activated Receptor γ Agonist","authors":"Seungchan An,&nbsp;In Guk Park,&nbsp;Seok Young Hwang,&nbsp;Junpyo Gong,&nbsp;Yeonjin Lee,&nbsp;Sungjin Ahn and Minsoo Noh*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0009110.1021/acs.chemrestox.4c00091","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00091https://doi.org/10.1021/acs.chemrestox.4c00091","url":null,"abstract":"<p >This study introduces a novel cheminformatic read-across approach designed to identify potential environmental obesogens, substances capable of disrupting metabolism and inducing obesity by mainly influencing nuclear hormone receptors (NRs). Leveraging real-valued two-dimensional features derived from chemical fingerprints of 8435 Tox21 compounds, cluster analysis and subsequent statistical testing revealed 385 clusters enriched with compounds associated with specific NR targets. Notably, one cluster exhibited selective enrichment in peroxisome proliferator-activated receptor γ (PPARγ) agonist activity, prominently featuring methoxy cinnamate ultraviolet (UV) filters and obesogen-related compounds. Experimental validation confirmed that 2-ethoxyethyl 4-methoxycinnamate, an organic UV filter cinoxate, could selectively bind to PPARγ (<i>K</i>_i = 18.0 μM), eliciting an obesogenic phenotype in human bone marrow-derived mesenchymal stem cells during adipogenic differentiation. Molecular docking and further experiments identified cinoxate as a potent PPARγ full agonist, demonstrating a preference for coactivator SRC3 recruitment. Moreover, cinoxate upregulated transcription levels of genes encoding lipid metabolic enzymes in normal human epidermal keratinocytes as primary cells exposed during clinical usage. This study provides compelling evidence for the efficacy of cheminformatic read-across analysis in prioritizing potential obesogens, showcasing its utility in unveiling cinoxate as an obesogenic PPARγ agonist.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 8","pages":"1344–1355 1344–1355"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001797","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":"Use of Structural Alerts for Reactive Metabolites in the Application SpotRM","authors":"Alf Claesson*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0020510.1021/acs.chemrestox.4c00205","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00205https://doi.org/10.1021/acs.chemrestox.4c00205","url":null,"abstract":"<p >Reactive metabolite (RM) formation is widely accepted as playing a crucial role in causing idiosyncratic adverse drug reactions (IADRs), where the liver is most affected. An important goal of drug design is to avoid selection of drug candidates giving rise to RMs and therefore risk causing problems later on involving IADRs. The simplest, initial approach is to avoid test structures that have substructures known or strongly suspected to be associated with IADRs. However, as is evident from the many case reports of IADRs, in most cases a clear association with any (bio)chemical mechanism is lacking, which makes it hard to establish any structure-toxicity relationship. Separate studies of RM formation, in vitro and in vivo, have led to likely evidence and to establishing many structural alerts (SAs) that can be used for fast selection/deselection of planned test compounds. As a background to a discussion of the concept, 25 kinase inhibitor drugs with known problems of hepatotoxicity were probed against a set of SAs contained in the application SpotRM. A clear majority of the probed drugs show liabilities as evident by being flagged by more than one of the fairly established types of SAs. At the same time, no clear SAs were found in three drugs, which is discussed in the broader context of usefulness and selection tactics of SAs in drug design.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 8","pages":"1231–1245 1231–1245"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001782","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":"Physical and Chemical Characterization of Aerosols Produced from Experimentally Designed Nicotine Salt-Based E-Liquids","authors":"Trevor Harris*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0007310.1021/acs.chemrestox.4c00073","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00073https://doi.org/10.1021/acs.chemrestox.4c00073","url":null,"abstract":"<p >Nicotine salt-based e-liquids deliver nicotine more rapidly and efficiently to electronic nicotine delivery system (ENDS) users than freebase nicotine formulations. Nicotine salt-based products represent a substantial majority of the United States ENDS market. Despite the popularity of nicotine salt formulations, the chemical and physical characteristics of aerosols produced by nicotine salt e-liquids are still not well understood. To address this, this study reports the harmful and potentially harmful constituents (HPHCs) and particle sizes of aerosols produced by laboratory-made freebase nicotine and nicotine salt e-liquids. The nicotine salt e-liquids were formulated with benzoic acid, citric acid, lactic acid, malic acid, or oxalic acid. The nicotine salt aerosols had different HPHC profiles than the freebase nicotine aerosols, indicating that the carboxylic acids were not innocent bystanders. The polycarboxylic acid e-liquids containing citric acid, malic acid, or oxalic acid produced higher acrolein yields than the monocarboxylic acid e-liquids containing benzoic acid or lactic acid. Across most PG:VG ratios, nicotine benzoate or nicotine lactate aerosols contained the highest nicotine quantities (in %) and the highest nicotine yields (per milligram of aerosol). Additionally, the nicotine benzoate and nicotine lactate e-liquids produced the highest carboxylic acid yields under all tested conditions. The lower acid yields of the citric, malic, and oxalic acid formulations are potentially due to a combination of factors such as lower transfer efficiencies, lower thermostabilities, and greater susceptibility to side reactions because of their additional carboxyl groups serving as new sites for reactivity. For all nicotine formulations, the particle size characteristics were primarily controlled by the e-liquid solvent ratios, and there were no clear trends between nicotine salt and freebase nicotine aerosols that indicated nicotine protonation affected particle size. The carboxylic acids impacted aerosol output, nicotine delivery, and HPHC yields in distinct ways such that interchanging them in ENDS can potentially cause downstream effects.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 8","pages":"1315–1328 1315–1328"},"PeriodicalIF":3.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001741","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}