Chemical Research in Toxicology最新文献

{"title":"Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC–MS/MS Analysis","authors":"Fabian Pilz,&nbsp;Therese Burkhardt,&nbsp;Gerhard Scherer,&nbsp;Max Scherer and Nikola Pluym*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0025810.1021/acs.chemrestox.4c00258","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00258https://doi.org/10.1021/acs.chemrestox.4c00258","url":null,"abstract":"<p >Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC–MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjects̀ compliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 11","pages":"1884–1902 1884–1902"},"PeriodicalIF":3.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142671733","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":"Activity Variations of CYP2B6 Determine the Metabolic Stratification of Efavirenz","authors":"Xin-yue Li,&nbsp;Qian Liu,&nbsp;Xiao-yu Xu,&nbsp;Jing Wang,&nbsp;Yun-shan Zhong,&nbsp;Le-hao Jin,&nbsp;Jing Yuan,&nbsp;Jian-chang Qian* and Xiao-dan Zhang*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0023010.1021/acs.chemrestox.4c00230","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00230https://doi.org/10.1021/acs.chemrestox.4c00230","url":null,"abstract":"<p >Purpose: To investigate the effects of hepatic enzyme activity variations and CYP2B6 gene polymorphisms on the <i>in vivo</i> and <i>in vitro</i> metabolism of efavirenz. Main methods: In vitro enzyme systems using rat and human liver microsomes (RLM/HLM) were established, with in vivo studies conducted on Sprague–Dawley rats. Metabolite detection was performed via LC-MS/MS. Human recombinant CYP2B6 microsomes were prepared using a baculovirus-insect cell system and ultracentrifugation, with efavirenz serving as the substrate to study enzyme kinetics. Results: Isavuconazole exhibited an IC₅₀ of 21.14 ± 0.57 μM in RLM, indicating a mixed competitive and noncompetitive mechanism, and an IC₅₀ of 40.44 ± 4.23 μM in HLM, suggesting an anticompetitive mechanism. In rats, coadministration of efavirenz and isavuconazole significantly increased the AUC, <i>T</i>_max, and <i>C</i>_max of efavirenz. Co-administration of efavirenz and rifampicin significantly elevated the AUC, <i>T</i>_max, and <i>C</i>_max of 8-OH-efavirenz. The activity of CYP2B6.4, 6, and 7 increased significantly compared to CYP2B6.1, with relative clearance ranging from 158.34% to 212.72%. Conversely, the activity of CYP2B6.3, 8, 10, 11, 13–15, 18–21, 23–27, 31–33, and 37 was markedly reduced, ranging from 4.30% to 79.89%. Conclusion: Variations in liver enzyme activity and CYP2B6 genetic polymorphisms can significantly alter the metabolism of efavirenz. It provides laboratory-based data for the precise application of efavirenz and other CYP2B6 substrate drugs.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"37 11","pages":"1867–1875 1867–1875"},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142671829","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":"Near-Infrared Fluorescent Turn-On Probe for Selective Detection of Hypochlorite in Aqueous Medium and Live Cell Imaging","authors":"Anwesha Maiti, Saikat Kumar Manna, Satyajit Halder, Rajdeep Ganguly, Anirban Karak, Pintu Ghosh, Kuladip Jana, Ajit Kumar Mahapatra","doi":"10.1021/acs.chemrestox.4c00222","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00222","url":null,"abstract":"Hypochlorite, as an important reactive oxygen species (ROS), plays a vital role in many physiological and pathological processes, but an excess concentration of hypochlorite (ClO^–) may become toxic to humans and cause disease. Hence, the selective and rapid detection of hypochlorite (ClO^–) is necessary for human safety. Here, we report a novel near-infrared (NIR) fluorescence “turn-on” and highly selective benzophenoxazinium chloride-based fluorescent probe, <b>BPH</b> (benzophenoxazinium dihydroxy benzaldehyde), for hypochlorite detection. Due to hypochlorite-induced vicinal diol oxidation to the corresponding ortho benzoquinone derivative, the photoinduced electron transfer (PET) process, which was operating from vicinal diol to the benzophenoxazinium chloride receptor moiety, was suddenly inhibited, as a result of which strong NIR fluorescence “turn-on” emission was observed. The detection limit of <b>BPH</b> was found to be 2.39 × 10^–10 M, or 0.23 nM. <b>BPH</b> was successfully applied for exogenous and endogenous hypochlorite detection in live MDA-MB 231 cells.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"157 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260484","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":"Sensitive Detection of Histones and γ-H2AX by Immunoblotting: Problems and Solutions.","authors":"Casey Krawic, Michal W Luczak, Anatoly Zhitkovich","doi":"10.1021/acs.chemrestox.4c00307","DOIUrl":"10.1021/acs.chemrestox.4c00307","url":null,"abstract":"<p><p>Histones and their posttranslational modifications (PTMs) are critical regulators of gene expression. Differentiation, environmental stressors, xenobiotics, and major human diseases cause significant changes in histone variants and PTMs. Western blotting is the mainstay methodology for detection of histones and their PTMs in the majority of studies. Surprisingly, despite their high abundance in cells, immunoblotting of histones typically involves loading of large protein amounts that are normally used for detection of sparse cellular proteins. We systematically examined technical factors in the Western-blotting-based detection of human histones with >30 antibodies. We found that under multiple protein transfer conditions, many histone epitopes on polyvinylidene fluoride (PVDF) membranes had a very low antibody accessibility, which was dramatically increased by the addition of a simple denaturation step. Denaturation of membrane-bound proteins also enhanced the specificity of some histone antibodies. In comparison to standard PVDF membranes, the sensitivity of histone detection on standard nitrocellulose membranes was typically much higher, which was further increased by the inclusion of the same denaturation step. Optimized protocols increased by >100-times detection sensitivity for the genotoxic marker γ-H2AX with two monoclonal antibodies. The impact of denaturation and nitrocellulose use varied for different histones, but for each histone, it was generally similar for antibodies targeting N-terminal and C-terminal regions. In summary, denaturation of membrane-bound histones strongly improves their detection by Westerns, resulting in more accurate measurements and permitting analyses with small biological samples.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1588-1597"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138561","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":"Photosensitized Oxidation of Free and Peptide Tryptophan to <i>N</i>-Formylkynurenine.","authors":"Jesuán J Farías, M Laura Dántola, Andrés H Thomas","doi":"10.1021/acs.chemrestox.4c00229","DOIUrl":"10.1021/acs.chemrestox.4c00229","url":null,"abstract":"<p><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":" ","pages":"1562-1573"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892263","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":"Effect of Butyrate on Food-Grade Titanium Dioxide Toxicity in Different Intestinal In Vitro Models.","authors":"Janine M Becht, Hendrik Kohlleppel, Roel P F Schins, Angela A M Kämpfer","doi":"10.1021/acs.chemrestox.4c00086","DOIUrl":"10.1021/acs.chemrestox.4c00086","url":null,"abstract":"<p><p>Short-chain fatty acids (SCFA) are an important energy source for colonocytes and crucial messenger molecules both locally in the intestine and systemically. Butyrate, one of the most prominent and best-studied SCFA, was demonstrated to exert anti-inflammatory effects, improve barrier integrity, enhance mucus synthesis in the intestine, and promote cell differentiation of intestinal epithelial cells in vitro. While the physiological relevance is undisputed, it remains unclear if and to what extent butyrate can influence the effects of xenobiotics, such as food-grade titanium dioxide (E171, _fgTiO₂), in the intestine. TiO₂ has been controversially discussed for its DNA-damaging potential and banned as a food additive within the European Union (EU) since 2022. First, we used enterocyte Caco-2 monocultures to test if butyrate affects the cytotoxicity and inflammatory potential of _fgTiO₂ in a pristine state or following pretreatment under simulated gastric and intestinal pH conditions. We then investigated pretreated _fgTiO₂ in intestinal triple cultures of Caco-2, HT29-MTX-E12, and THP-1 cells in homeostatic and inflamed-like state for cytotoxicity, barrier integrity, cytokine release as well as gene expression of mucins, oxidative stress markers, and DNA repair. In Caco-2 monocultures, butyrate had an ambivalent role: pretreated but not pristine _fgTiO₂ induced cytotoxicity in Caco-2 cells, which was not observed in the presence of butyrate. Conversely, _fgTiO₂ induced the release of interleukin 8 in the presence but not in the absence of butyrate. In the advanced in vitro models, butyrate did not affect the characteristics of the healthy or inflamed states and caused negligible effects in the investigated end points following _fgTiO₂ exposure. Taken together, the effects of _fgTiO₂ strongly depend on the applied testing approach. Our findings underline the importance of the experimental setup, including the choice of in vitro model and the physiological relevance of the exposure scenario, for the hazard testing of food-grade pigments like TiO₂.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1501-1514"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102163","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":"Toward an Explainable Large Language Model for the Automatic Identification of the Drug-Induced Liver Injury Literature.","authors":"Chunwei Ma, Russell D Wolfinger","doi":"10.1021/acs.chemrestox.4c00134","DOIUrl":"10.1021/acs.chemrestox.4c00134","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) stands as a significant concern in drug safety, representing the primary cause of acute liver failure. Identifying the scientific literature related to DILI is crucial for monitoring, investigating, and conducting meta-analyses of drug safety issues. Given the intricate and often obscure nature of drug interactions, simple keyword searching can be insufficient for the exhaustive retrieval of the DILI-relevant literature. Manual curation of DILI-related publications demands pharmaceutical expertise and is susceptible to errors, severely limiting throughput. Despite numerous efforts utilizing cutting-edge natural language processing and deep learning techniques to automatically identify the DILI-related literature, their performance remains suboptimal for real-world applications in clinical research and regulatory contexts. In the past year, large language models (LLMs) such as ChatGPT and its open-source counterpart LLaMA have achieved groundbreaking progress in natural language understanding and question answering, paving the way for the automated, high-throughput identification of the DILI-related literature and subsequent analysis. Leveraging a large-scale public dataset comprising 14 203 training publications from the CAMDA 2022 literature AI challenge, we have developed what we believe to be the first LLM specialized in DILI analysis based on LLaMA-2. In comparison with other smaller language models such as BERT, GPT, and their variants, LLaMA-2 exhibits an enhanced out-of-fold accuracy of 97.19% and area under the ROC curve of 0.9947 using 3-fold cross-validation on the training set. Despite LLMs' initial design for dialogue systems, our study illustrates their successful adaptation into accurate classifiers for automated identification of the DILI-related literature from vast collections of documents. This work is a step toward unleashing the potential of LLMs in the context of regulatory science and facilitating the regulatory review process.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1524-1534"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071265","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":"Novel Dual PPAR δ/γ Partial Agonist Induces Hepatic Lipid Accumulation through Direct Binding and Inhibition of AKT1 Phosphorylation, Mediating CD36 Upregulation.","authors":"Xiaotong Cai, Qin Zhang, Jiwei Wang, Yingying Miao, Yuqing Sun, Ziyin Xia, Luyong Zhang, Qinwei Yu, Zhenzhou Jiang","doi":"10.1021/acs.chemrestox.4c00268","DOIUrl":"10.1021/acs.chemrestox.4c00268","url":null,"abstract":"<p><p>ZLY06 is a dual agonist of peroxisome proliferator-activated receptor (PPAR) δ/γ, showing potential therapeutic effects on metabolic syndrome. However, our research has revealed that ZLY06 exhibits hepatotoxicity in normal C57BL/6J mice, though the precise mechanism remains unclear. This study aims to investigate the manifestations and mechanisms of ZLY06-induced hepatotoxicity. We administered ZLY06 via oral gavage to C57BL/6J mice (once daily for six weeks) and monitored various indicators to preliminarily explore its hepatotoxicity. Additionally, we further investigate the specific mechanisms of ZLY06-induced hepatotoxicity using PPAR inhibitors (GW9662 and GSK0660) and the Protein kinase B (AKT) activator (SC79). Results showed that ZLY06 led to increased serum ALP, ALT and AST, as well as elevated liver index and hepatic lipid levels. There was upregulation in the gene and protein expression of lipid metabolism-related molecules <i>Acc</i>, <i>Scd1</i>, <i>Cd36</i>, <i>Fabp1</i> and <i>Fabp2</i> in hepatocytes, with <i>Cd36</i> showing the most significant change. Furthermore, cotreatment with SC79 significantly reduced ZLY06-induced hepatotoxicity in AML12 cells, evidenced by decreased intracellular TG levels and downregulation of CD36 expression. Specific knockdown of CD36 also mitigated ZLY06-induced hepatotoxicity. The study found that ZLY06 may bind to AKT1, inhibiting its phosphorylation activation, with the downregulation of p-AKT1 preceding the upregulation of CD36. In summary, ZLY06 mediates the upregulation of CD36 by potentially binding to and inhibiting the phosphorylation of AKT1, leading to hepatic lipid metabolism disorder and inducing liver toxicity.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1574-1587"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131154","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":"Targeting Glioblastoma: Efficacy of Ruthenium-Based Drugs.","authors":"Puthiyavalappil Rasin, Sravan Sangeeth Surendran, Karthik K S, Jebiti Haribabu, Anandaram Sreekanth","doi":"10.1021/acs.chemrestox.4c00188","DOIUrl":"10.1021/acs.chemrestox.4c00188","url":null,"abstract":"<p><p>Ruthenium compounds offer improved selectivity and fewer side effects compared to platinum-based drugs in glioblastoma treatment. Insights into their interactions with transferrin suggest targeted drug delivery, while photoactivated chemotherapy is a novel cytotoxic approach in tumor tissues.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1453-1455"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007841","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":"Prediction of Cytochrome P450 Substrates Using the Explainable Multitask Deep Learning Models.","authors":"Jiaojiao Fang, Yan Tang, Changda Gong, Zejun Huang, Yanjun Feng, Guixia Liu, Yun Tang, Weihua Li","doi":"10.1021/acs.chemrestox.4c00199","DOIUrl":"10.1021/acs.chemrestox.4c00199","url":null,"abstract":"<p><p>Cytochromes P450 (P450s or CYPs) are the most important phase I metabolic enzymes in the human body and are responsible for metabolizing ∼75% of the clinically used drugs. P450-mediated metabolism is also closely associated with the formation of toxic metabolites and drug-drug interactions. Therefore, it is of high importance to predict if a compound is the substrate of a given P450 in the early stage of drug development. In this study, we built the multitask learning models to simultaneously predict the substrates of five major drug-metabolizing P450 enzymes, namely, CYP3A4, 2C9, 2C19, 2D6, and 1A2, based on the collected substrate data sets. Compared to the single-task model and conventional machine learning models, the multitask fingerprints and graph neural networks model achieved superior performance with the average AUC values of 90.8% on the test set. Notably, the multitask model demonstrated its good performance on the small amount of substrate data sets such as CYP1A2, 2C9, and 2C19. In addition, the Shapley additive explanation and the attention mechanism were used to reveal specific substructures associated with P450 substrates, which were further confirmed and complemented by the substructure mining tool and the literature.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1535-1548"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085842","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}