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The estimation of acute oral toxicity (LD50) of G-series organophosphorus-based chemical warfare agents using quantitative and qualitative toxicology in silico methods Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-17 Maciej Noga, Agata Michalska, Kamil Jurowski
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Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nano emulsions Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-17 Thiago Guedes Pinto, Barbara dos Anjos Rosario, Andrea Cristina de Moraes Malinverni, Rosana Xavier, Yasmin Alaby Martins Ferreira, Luciana Pellegrini Pisani, Pedro Everson Alexandre de Aquino, Glauce Socorro de Barros Viana, Daniel Vitor de Souza, Milena de Barros Viana, Daniel Araki Ribeiro
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Flavonoids commonly induce hormetic responses Arch. Toxicol. (IF 6.1) Pub Date : 2024-04-01
Abstract The present paper provides a new perspective of previously published findings by Siwak (Food Chem 141:1227–1241, 2013) which showed that 15 structurally diverse flavonoids reduced toxicity (i.e., enhanced cell viability) from hypochlorite using the MTT assay within a pre-conditioning experimental protocol, with each agent showing a similar biphasic concentration response relationship. We use
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Identification of key neuronal mechanisms triggered by dimethyl fumarate in SH-SY5Y human neuroblastoma cells through a metabolomic approach Arch. Toxicol. (IF 6.1) Pub Date : 2024-04-01
Abstract Dimethyl fumarate (DMF) is an old drug used for psoriasis treatment that has recently been repurposed to treat relapse–remitting multiple sclerosis, mostly due to its neuro- and immunomodulatory actions. However, mining of a pharmacovigilance database recently ranked DMF as the second pharmaceutical most associated with cognitive adverse events. To our best knowledge, the signaling mechanisms
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ATF4 in cellular stress, ferroptosis, and cancer Arch. Toxicol. (IF 6.1) Pub Date : 2024-04-01
Abstract Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding (CREB) family, plays a critical role as a stress-induced transcription factor. It orchestrates cellular responses, particularly in the management of endoplasmic reticulum stress, amino acid deprivation, and oxidative challenges. ATF4's primary function lies in regulating gene expression to ensure cell
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Prediction of cytochrome P450-mediated bioactivation using machine learning models and in vitro validation Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-16 Xin-Man Hu, Yan-Yao Hou, Xin-Ru Teng, Yong Liu, Yu Li, Wei Li, Yan Li, Chun-Zhi Ai
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Elevated aerobic glycolysis driven by p62-mTOR axis promotes arsenic-induced oncogenic phenotypes in human mammary epithelial cells Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14 Yongfang Li, Jiao Liu, Dianqi Yao, Zijun Guo, Xuheng Jiang, Chengwen Zhang, Litong Qu, Yuyan Liu, Yuxin Hu, Lanyue Gao, Yi Wang, Yuanyuan Xu
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Toxicokinetics of homosalate in humans after dermal application: applicability of oral-route data for exposure assessment by human biomonitoring Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14 Katharina E. Ebert, Peter Griem, Tobias Weiss, Thomas Brüning, Heiko Hayen, Holger M. Koch, Daniel Bury
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Use of human predictive patch test (HPPT) data for the classification of skin sensitization hazard and potency Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14
Abstract Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation
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Cellular senescence gene TACC3 associated with colorectal cancer risk via genetic and DNA methylated alteration Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14 Hengyang Shen, Yang Chen, Menghuan Xu, Jieyu Zhou, Changzhi Huang, Zhenling Wang, Yu Shao, Hongqiang Zhang, Yunfei Lu, Shuwei Li, Zan Fu
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Combined use of multiparametric high-content-screening and in vitro circadian reporter assays in neurotoxicity evaluation Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14
Abstract Accumulating evidence indicates that chronic circadian rhythm disruption is associated with the development of neurodegenerative diseases induced by exposure to neurotoxic chemicals. Herein, we examined the relationship between cellular circadian rhythm disruption and cytotoxicity in neural cells. Moreover, we evaluated the potential application of an in vitro cellular circadian rhythm assay
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Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-14 Klaudia Jomova, Suliman Y. Alomar, Saleh H. Alwasel, Eugenie Nepovimova, Kamil Kuca, Marian Valko
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Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-13 Melania Maria Serafini, Sara Sepehri, Miriam Midali, Marth Stinckens, Marta Biesiekierska, Anna Wolniakowska, Alexandra Gatzios, Elise Rundén-Pran, Edyta Reszka, Marina Marinovich, Tamara Vanhaecke, Joanna Roszak, Barbara Viviani, Tanima SenGupta
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Involvement of per- and polyfluoroalkyl compounds in tumor development Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-13 Maija Pesonen, Kirsi Vähäkangas
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Acetaminophen overdose causes a breach of the blood–bile barrier in mice but not in rats Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-11
Abstract Acetaminophen (APAP) is known to cause a breach of the blood–bile barrier in mice that, via a mechanism called futile bile acid (BA) cycling, increases BA concentrations in hepatocytes above cytotoxic thresholds. Here, we compared this mechanism in mice and rats, because both species differ massively in their susceptibility to APAP and compared the results to available human data. Dose and
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Future in the past: paternal reprogramming of offspring phenotype and the epigenetic mechanisms Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-09 Di Wu, Kejia Zhang, Kaifeng Guan, Faheem Ahmed Khan, Nuruliarizki Shinta Pandupuspitasari, Windu Negara, Fei Sun, Chunjie Huang
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Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-09 Yong Zhu, Xiaoxiao Meng, Xian Zhu, Jiaxiang Zhang, Hui lv, Feiyao Wang, Jinfeng Wang, Cheng Chen, Mengting Chen, Dapeng Wang, Wei Jin, Rui Tian, Ruilan Wang
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A-series agent A-234: initial in vitro and in vivo characterization Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-06 Martina Hrabinova, Jaroslav Pejchal, Vendula Hepnarova, Lubica Muckova, Lucie Junova, Jakub Opravil, Jana Zdarova Karasova, Tomas Rozsypal, Alzbeta Dlabkova, Helena Rehulkova, Tomas Kucera, Zbyněk Vecera, Filip Caisberger, Monika Schmidt, Ondrej Soukup, Daniel Jun
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YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-05
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The acute toxicity of Novichok's degradation products using quantitative and qualitative toxicology in silico methods Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-05 Maciej Noga, Agata Michalska, Kamil Jurowski
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Genetic variants in m5C modification genes are associated with survival of patients with HBV-related hepatocellular carcinoma Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-04 Bowen Chen, Moqin Qiu, Rongbin Gong, Yingchun Liu, Zihan Zhou, Qiuping Wen, Xiaoxia Wei, Xiumei Liang, Yanji Jiang, Peiqin Chen, Yuying Wei, Qiongguang Huang, Qiuyan Mo, Qiuling Lin, Hongping Yu
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In vitro and in vivo protective potential of quercetin-3-glucuronide against lipopolysaccharide-induced pulmonary injury through dual activation of nuclear factor-erythroid 2 related factor 2 and autophagy Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-04 Pei-Rong Yu, Chiao-Yun Tseng, Cheng-Chin Hsu, Jing-Hsien Chen, Hui-Hsuan Lin
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Integrated data from intravital imaging and HPLC–MS/MS analysis reveal large interspecies differences in AFB1 metabolism in mice and rats Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-04
Abstract Large interspecies differences between rats and mice concerning the hepatotoxicity and carcinogenicity of aflatoxin B1 (AFB1) are known, with mice being more resistant. However, a comprehensive interspecies comparison including subcellular liver tissue compartments has not yet been performed. In this study, we performed spatio-temporal intravital analysis of AFB1 kinetics in the livers of
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Toxicity of particles derived from combustion of Ethiopian traditional biomass fuels in human bronchial and macrophage-like cells Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-01 Sarah McCarrick, Mathilde N. Delaval, Ulrike M. Dauter, Annette M. Krais, Anastasiia Snigireva, Asmamaw Abera, Karin Broberg, Axel C. Eriksson, Christina Isaxon, Anda R. Gliga
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Effect of cell treatment procedures on in vitro genotoxicity assessment Arch. Toxicol. (IF 6.1) Pub Date : 2024-03-01
Abstract So far, the majority of in vitro toxicological experiments are conducted after an acute 24 h treatment that does not represent a realistic human chemical exposure. Recently, new in vitro approaches have been proposed to study the chemical toxicological effect over several days in order to be more predictive of a representative exposure scenario. In this study, we investigated the genotoxic
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Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-18 Mark R. Viant, E. Amstalden, T. Athersuch, M. Bouhifd, S. Camuzeaux, D. M. Crizer, P. Driemert, T. Ebbels, D. Ekman, B. Flick, V. Giri, M. Gómez-Romero, V. Haake, M. Herold, A. Kende, F. Lai, P. E. G. Leonards, P. P. Lim, G. R. Lloyd, J. Mosley, C. Namini, J. R. Rice, S. Romano, C. Sands, M. J. Smith, T. Sobanski, A. D. Southam, L. Swindale, B. van Ravenzwaay, T. Walk, R. J. M. Weber, F. M. Zickgraf
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In vitro and in vivo metabolic activation and hepatotoxicity of chlorzoxazone mediated by CYP3A Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-18 Chen Sun, Mingyu Zhang, Chunjing Guan, Weiwei Li, Ying Peng, Jiang Zheng
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Characterization of pathological changes in the olfactory system of mice exposed to methylmercury Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-17 Yuta Iijima, Ryohei Miki, Nobumasa Takasugi, Masatake Fujimura, Takashi Uehara
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Modular air–liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-10 M. J. Küstner, D. Eckstein, D. Brauer, P. Mai, J. Hampl, F. Weise, B. Schuhmann, G. Hause, F. Glahn, H. Foth, A. Schober
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Investigating the applicability domain of the hiPSC-based PluriLum assay: an embryotoxicity assessment of chemicals and drugs Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-04 Andreas Frederik Treschow, Maria João Valente, Karin Lauschke, Bjørn Holst, Anders Reenberg Andersen, Anne Marie Vinggaard
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Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone Arch. Toxicol. (IF 6.1) Pub Date : 2024-02-02 Shiyue Pan, Donald A. Bruun, Pamela J. Lein, Chao-Yin Chen
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Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-30 Wing-Kee Lee, Stephanie Probst, Bettina Scharner, Timo Deba, Faouzi Dahdouh, Frank Thévenod
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Molecular signatures of angiogenesis inhibitors: a single-embryo untargeted metabolomics approach in zebrafish Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-29 Pia Wilhelmi, Volker Haake, Franziska M. Zickgraf, Varun Giri, Philipp Ternes, Peter Driemert, Julia Nöth, Stefan Scholz, Marta Barenys, Burkhard Flick, Barbara Birk, Hennicke Kamp, Robert Landsiedel, Dorothee Funk-Weyer
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The phosphylated butyrylcholinesterase-derived tetrapeptide GlyGluSerAla proves exposure to organophosphorus agents with enantioselectivity Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-24 Tamara Kranawetvogl, Markus Siegert, Dirk Steinritz, Horst Thiermann, Harald John
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Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-24 Yao Xiang, Xiaohua Song, Dingxin Long
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Utility of in vivo metabolomics to support read-across for UVCB substances under REACH Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-24 H. Kamp, N. Aygun Kocabas, F. Faulhammer, N. Synhaeve, E. Rushton, B. Flick, V. Giri, S. Sperber, L. G. Higgins, M. G. Penman, B. van Ravenzwaay, M. Rooseboom
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The cytotoxicity of microcystin-LR: ultrastructural and functional damage of cells Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-22
Abstract Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function
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Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-21
Abstract Tobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene
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Artificial intelligence (AI)—it’s the end of the tox as we know it (and I feel fine)* Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-20 Nicole Kleinstreuer, Thomas Hartung
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Sex-related differences in delayed doxorubicin-induced cardiac dysfunction in C57BL/6 mice Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-20
Abstract Cancer survivors may experience long-term cardiovascular complications due to chemotherapeutic drugs such as doxorubicin (DOX). The exact mechanism of delayed DOX-induced cardiotoxicity has not been fully elucidated. Sex is an important risk factor for DOX-induced cardiotoxicity. In the current study, we identified sex differences in delayed DOX-induced cardiotoxicity and determined the underlying
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Exposure limits for indoor volatile substances concerning the general population: The role of population-based differences in sensory irritation of the eyes and airways for assessment factors Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-19 Stefan Kleinbeck, Peder Wolkoff
Assessment factors (AFs) are essential in the derivation of occupational exposure limits (OELs) and indoor air quality guidelines. The factors shall accommodate differences in sensitivity between subgroups, i.e., workers, healthy and sick people, and occupational exposure versus life-long exposure for the general population. Derivation of AFs itself is based on empirical knowledge from human and animal
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Probing the hair detectability of prohibited substances in sports: an in vivo-in silico-clinical approach and analytical implications compared with plasma, urine, and faeces Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-15 Shao-Hsin Hung, Hung-Lin Kan, Chun-Wei Tung, Yi-Ching Lin, Ting-Ting Chen, Ciao Tian, William Chih-Wei Chang
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Quantitative determination of the intracellular uptake of silica nanoparticles using asymmetric flow field flow fractionation coupled with ICP mass spectrometry and their cytotoxicity in HepG2 cells Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-14 Yu-ki Tanaka, Yasumitsu Ogra
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Cytotoxicity of Prymnesium parvum extracts and prymnesin analogs on epithelial fish gill cells RTgill-W1 and the human colon cell line HCEC-1CT Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-11 Elisabeth Varga, Hélène-Christine Prause, Matthias Riepl, Nadine Hochmayr, Deniz Berk, Eva Attakpah, Endre Kiss, Nikola Medić, Giorgia Del Favero, Thomas Ostenfeld Larsen, Per Juel Hansen, Doris Marko
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TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-11 Xinyi Shao, Dawei Yang, Liuqun Shan, Xueqin Yan, Di Xu, Lei Li, Yidan Sun, Qiang Yu, Honglei Zhou, Yongbin Ding, Jinhai Tang
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Development of an adverse outcome pathway network for nephrotoxicity Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-10
Abstract Adverse outcome pathways (AOPs) were introduced in modern toxicology to provide evidence-based representations of the events and processes involved in the progression of toxicological effects across varying levels of the biological organisation to better facilitate the safety assessment of chemicals. AOPs offer an opportunity to address knowledge gaps and help to identify novel therapeutic
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Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-08 Linyu Han, Yanfei Huo, Linying Huang, Yanxiu Zheng, Xinyuan Yu, Nasha Zhang, Ming Yang
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The role of ferroptosis in cardio-oncology Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-05 Kai Hou, Lin Liu, Zhi-Hui Fang, Wei-Xing Zong, Daqiang Sun, Zhigang Guo, Lu Cao
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Hepatic glucuronidation of tetrabromobisphenol A and tetrachlorobisphenol A: interspecies differences in humans and laboratory animals and responsible UDP-glucuronosyltransferase isoforms in humans Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-05
Abstract Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA), bisphenol A (BPA) analogs, are endocrine-disrupting chemicals predominantly metabolized into glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in humans and rats. In the present study, TBBPA and TCBPA glucuronidation by the liver microsomes of humans and laboratory animals (monkeys, dogs, minipigs, rats, mice, and hamsters)
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27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-05 Xiaoyan Zhao, Xiaxia Cai, Haiyan Zhu, Qinyu Dang, Qian Yang, Yandi Zhu, Yadi Zhang, Mengling Zhang, Xinyin Jiang, Zhuo Hu, Yuchen Wei, Rong Xiao, Huanling Yu
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Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-05 Brecht Attema, Outi Kummu, Sini Pitkänen, Jonna Weisell, Taina Vuorio, Erika Pennanen, Maria Vorimo, Jaana Rysä, Sander Kersten, Anna-Liisa Levonen, Jukka Hakkola
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In vitro evaluation of the reductive carbonyl idarubicin metabolism to evaluate inhibitors of the formation of cardiotoxic idarubicinol via carbonyl and aldo–keto reductases Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-04 Gzona Bajraktari-Sylejmani, Julia Sophie Oster, Jürgen Burhenne, Walter Emil Haefeli, Max Sauter, Johanna Weiss
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Divinyl sulfone, an oxidative metabolite of sulfur mustard, induces caspase-independent pyroptosis in hepatocytes Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-03 Zhi Li, Bo Ma, Hua Xu, Mengqiang Gong, Pengxia Gao, Lili Wang, Jianwei Xie
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Critical assessment of the endocrine potential of Linalool and Linalyl acetate: proactive testing strategy assessing estrogenic and androgenic activity of Lavender oil main components Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-01 Lars Hareng, Susanne N. Kolle, Caroline Gomes, Steffen Schneider, Markus Wahl
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Caspase-3/GSDME dependent pyroptosis contributes to offspring lung injury induced by gestational PFOS exposure via PERK/ATF4 signaling Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-01 Cong Li, Huishan Zhang, Jiali Mo, Jingye Zuo, Leping Ye
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Evaluation of neurological behavior alterations and metabolic changes in mice under chronic glyphosate exposure Arch. Toxicol. (IF 6.1) Pub Date : 2024-01-01 Yun-Chung Hsiao, Gregory Johnson, Yifei Yang, Chih-Wei Liu, Jiahao Feng, Haoduo Zhao, Sheryl S. Moy, Kathryn M. Harper, Kun Lu
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Impact of plastic-related compounds on the gene expression signature of HepG2 cells transfected with CYP3A4 Arch. Toxicol. (IF 6.1) Pub Date : 2023-12-30 Matteo Rosellini, Ejlal A. Omer, Alicia Schulze, Nadeen T. Ali, Joelle C. Boulos, Federico Marini, Jan-Heiner Küpper, Thomas Efferth
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Medication-related osteonecrosis of the jaw (MRONJ): a review of pathogenesis hypothesis and therapy strategies Arch. Toxicol. (IF 6.1) Pub Date : 2023-12-28
Abstract Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic
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Systematic review and meta-analysis on the efficacy of Indian polyvalent antivenom against the Indian snakes of clinical significance Arch. Toxicol. (IF 6.1) Pub Date : 2023-12-28
Abstract Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country. Antivenom is the primary therapy for snakebite, and its manufacturing techniques have essentially stayed unaltered for over a century. Indian polyvalent antivenom, a scientifically validated medicine for treating the toxic
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Development and validation of a human bronchial epithelial spheroid model to study respiratory toxicity in vitro Arch. Toxicol. (IF 6.1) Pub Date : 2023-12-26
Abstract The use of laboratory animals in research has been extensively criticized. While most of the critique has been centered around the ethical aspect, also the economic and scientific aspects have been frequently mentioned as points of concern. As a result, the use of alternative methods has gradually become more enticing. The most used alternatives to laboratory animals are the 2D monolayer cell