Toxicology最新文献

{"title":"Substance depletion of volatile monoterpenes – A confounding factor for toxicity testing in the Ames fluctuation test","authors":"Tobias Karl Jochum,&nbsp;Simone Stegmüller,&nbsp;Elke Richling","doi":"10.1016/j.tox.2024.153993","DOIUrl":"10.1016/j.tox.2024.153993","url":null,"abstract":"<div><div>In <em>in vitro</em> toxicology, reported test results are typically based on nominal concentrations, i.e., the calculated amounts of a substance added to a defined volume of the test system. Consequently, if a test system does not respond to a certain endpoint, the assay is interpreted as negative and the test substance is deemed to exert no toxicity at the tested nominal concentration. However, depending on the physicochemical properties of the test substance and assay setup, the actual exposure may differ widely from nominal concentrations due to different depletion processes. (<em>R</em>)-(+)-Limonene (<em>R</em>LIM), β-myrcene (βMYR) and linalool (LIN) are naturally occurring terpenes that are permitted as flavoring agents in the European Union without limitations based on their low toxicity. Nevertheless, their hydrophobicity and high volatility classifies them as difficult to test chemicals, which has not been considered in previous <em>in vitro</em> tests. To exclude possible false negative results, in the present study, we assessed the cytotoxic and mutagenic potential of the latter substances toward <em>Salmonella Typhimurium</em> in the Ames fluctuation test using different incubation setups to minimize possible substance losses due to sorption or volatilization. Actual substance concentrations during incubation were verified analytically at different time points via headspace gas chromatography-mass spectrometry (HS-GC-MS). Possible substance depletion due to sorption to well-plate material or volatilization was minimized using a polystyrene-free and headspace-free incubation setup, respectively. The results showed complete volatilization of the monoterpenes <em>R</em>LIM and βMYR in the conventional Ames fluctuation test, which may confound mutagenicity testing. The headspace-free incubation setup greatly improved substance exposure and showed cytotoxicity in low micromolar concentrations, but no signs of mutagenicity were observed.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153993"},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628706","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":"Bisphenol A and its metabolites promote white adipogenesis and impair brown adipogenesis in vitro","authors":"Mengyuan Chen,&nbsp;Sijia Yang,&nbsp;Di Yang,&nbsp;Xinbiao Guo","doi":"10.1016/j.tox.2024.153995","DOIUrl":"10.1016/j.tox.2024.153995","url":null,"abstract":"<div><div>Bisphenol A (BPA), an obesogen, can disrupt adipogenesis <em>in vitro</em>, but these studies did not distinguish adipocytes as white or brown. BPA can be metabolized into BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). These metabolites are not completely inactive in the body, but the related studies remain limited. In this study, preadipocytes isolated from mouse white and brown adipose tissues were treated with 0.1, 1, and 10 μM of BPA and its metabolites for 6 days, which are equivalent to the exposure level of general and occupational populations, to investigate and compare the effects of BPA and its metabolites on white and brown adipogenesis. The results showed that BPA and BPA-G increased lipid accumulation during white adipogenesis, whereas only BPA induced this same effect during brown adipogenesis. Moreover, BPA and its metabolites upregulated the expression of pan-adipogenic markers, such as peroxisome proliferator-activated receptor gamma (PPARγ), during white adipogenesis, whereas they downregulated that of PPARγ during brown adipogenesis. Additionally, BPA also inhibited the mRNA and protein expression of brown fat-specific markers (e.g., PPARγ coactivator 1–1alpha (PGC1-α) and uncoupling protein 1 (UCP1)), and mitochondrial activity during brown adipogenesis, and BPA-G also reduced the mRNA expression levels of <em>Pgc1-α</em> and <em>Ucp1</em>. These findings indicated that BPA induced different effects on white and brown adipogenesis, enhancing the former and hindering the latter. Despite less potent than BPA, BPA-G and BPA-S might also affect white and brown adipogenesis. This research provides in-depth insights into the obesogenic effects of BPA and the biological activities of its metabolites.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153995"},"PeriodicalIF":4.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628708","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":"Potential antiandrogenic effects of parabens and benzophenone-type UV-filters by inhibition of 3α-hydroxysteroid dehydrogenases","authors":"Manuel Kley ,&nbsp;Simon Stücheli ,&nbsp;Pamela Ruffiner ,&nbsp;Veronika Temml ,&nbsp;Stéphanie Boudon ,&nbsp;Daniela Schuster ,&nbsp;Alex Odermatt","doi":"10.1016/j.tox.2024.153997","DOIUrl":"10.1016/j.tox.2024.153997","url":null,"abstract":"<div><div>Parabens and UV-filters are frequently used additives in cosmetics and body care products that prolong shelf-life. They are assessed for potential endocrine disrupting properties. Antiandrogenic effects of parabens and benzophenone-type UV-filters by blocking androgen receptor (AR) activity have been reported. Effects on local androgen formation received little attention. Local 5α-dihydrotestosterone (DHT) production with subsequent AR activation is required for male external genitalia formation during embryogenesis. We investigated whether parabens and benzophenone-type UV-filters might cause potential antiandrogenic effects by inhibiting oxidative 3α-hydroxysteroid dehydrogenases (3α-HSDs) involved in the backdoor pathway of DHT formation. Five different 3α-HSDs were assessed for their efficiency to catalyze the 3α-oxidation reaction to form DHT and activate AR. 17β-hydroxysteroid dehydrogenase type 6 (HSD17B6), retinol dehydrogenases type 5 and 16 were further assessed using a radiometric <em>in vitro</em> activity assay to determine the conversion of 5α-androstane-3α-ol-17-one to 5α-androstane-3,17-dione in lysates of overexpressing HEK-293 cells. All parabens tested, except <em>p</em>-hydroxybenzoic acid (a main metabolite) inhibited HSD17B6 activity. Hexyl- and heptylparaben, as well as benzophenone (BP)-1 and BP-2, showed the highest inhibitory potencies, with nanomolar IC₅₀ values. Molecular modeling predicted binding modes for the inhibitory parabens and BPs and provided an explanation for the observed structure-activity-relationship. Our results propose a novel mechanism of antiandrogenic action for commercially used parabens and BP UV-filters by inhibiting HSD17B6 and lowering DHT synthesis. Follow-up studies should assess BP-3 metabolism after topical application and whether the identified inhibitors reach concentrations in liver, testis, or prostate to inhibit HSD17B6, thereby causing antiandrogenic effects.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153997"},"PeriodicalIF":4.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628710","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":"Chronic exposure to polystyrene microplastics induces renal fibrosis via ferroptosis","authors":"Runyang Hong ,&nbsp;Yujie Shi ,&nbsp;Zhencheng Fan ,&nbsp;Yajie Gao ,&nbsp;Hao Chen ,&nbsp;Chun Pan","doi":"10.1016/j.tox.2024.153996","DOIUrl":"10.1016/j.tox.2024.153996","url":null,"abstract":"<div><div>With the increasing prevalence of microplastics (MPs) in the environment, human health has become a growing concern. After entering the human body, MPs accumulate in the kidneys, indicating that the kidneys are their major target organs. This study investigated nephrotoxicity associated with MPs, with a specific focus on polystyrene (PS) MPs and amino-functionalized polystyrene (PS-NH₂) MPs. Although previous studies have documented the nephrotoxic effects associated with short-term exposure to MPs, the mechanisms of kidney toxicity caused by chronic long-term exposure to MPs remain largely unclear. In animal models, mice were exposed to MPs (10 mg/L) at concentrations that are accessible to humans, administered via drinking water over a period of six months. These findings indicate that MPs can induce renal fibrosis by facilitating the onset of inflammation and accumulation of a substantial number of inflammatory cells. Our <em>in vitro</em> study showed that long-term exposure to MPs (60 μg/mL) induced ferroptosis in renal tubular epithelial cells via ferritinophagy and secreted TGF-β1, leading to renal fibroblast activation. Conversely, the application of Fer-1, a ferroptosis inhibitor, prevents ferroptosis in renal epithelial cells and reverses the activation of renal fibroblasts. Our study identified a novel toxicity mechanism for renal fibrosis induced by MPs exposure, offering new insights into the detrimental effects of environmental MPs on human health.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153996"},"PeriodicalIF":4.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628685","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":"Bisphenol A disrupts the neuronal F-actin cytoskeleton by activating the RhoA/ROCK/LIMK pathway in Neuro-2a cells","authors":"Yi Guo ,&nbsp;Yuxin Wang ,&nbsp;Qian Li ,&nbsp;Qiling Liu ,&nbsp;Xuyuan Zhang ,&nbsp;Jiajia Ren ,&nbsp;Chong Wang","doi":"10.1016/j.tox.2024.153994","DOIUrl":"10.1016/j.tox.2024.153994","url":null,"abstract":"<div><div>Bisphenol A (BPA) is an environmental endocrine disruptor that is widely present in the environment and has been reported to affect neuronal cytoskeleton and neural function. However, the exact molecular mechanisms remain unclear. In the present study, the effects of BPA on cytoskeleton rearrangement were examined, and the associated signaling pathways, which were influenced by the RhoA/ROCK/LIMK pathway in Neuro-2a cells in vitro, were identified. Specifically, Neuro-2a cells were exposed to BPA, and the effects of BPA exposure on the cytoskeleton of neuronal cells and on the activation or nonactivation of the RhoA/ROCK signaling pathway were evaluated using Cell Counting Kit-8 (CCK8), phalloidin staining, western blot, and real-time PCR. A RhoA inhibitor (Rhosin hydrochloride) and a ROCK inhibitor (Y-27632) were then used to elucidate the precise function of the pathway. The results demonstrated that 50–100 μM BPA exposure inhibited Neuro-2a cell viability and caused the formation of aberrantly polymerized F-actin and stress fibers. In addition, the RhoA/ROCK pathway was activated, and the expression levels of the pathway-related molecules—RhoA, ROCK2, LIMK1, Cofilin, Profilin, p-MLC2, and F-actin were dramatically elevated. The addition of Rhosin and Y-27632 resulted in a decrease in F-actin polymerization in the Neuro-2a cells, the disassembly of stress fibers, and a noteworthy drop in the levels of molecular proteins related to the RhoA/ROCK pathway affected by BPA. Together, these new findings indicated that BPA exposure thus activated the RhoA/ROCK signaling pathway and caused an abnormal accumulation of F-actin in the Neuro-2a cells, in turn altering the microfilament cytoskeleton. F-actin was restored when the RhoA/ROCK pathway was inhibited, suggesting that the process of BPA-induced neuronal cytoskeletal degradation is linked to the RhoA/ROCK signaling cascade.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153994"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628684","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":"Corrigendum to \"Inhibitory effects of parabens on human and rat 17β-hydroxysteroid dehydrogenase 1: Mechanisms of action and impact on hormone synthesis\" Toxicology 506 (August) (2024) 153873.","authors":"Zhuoqi Chen, Chaochao Gong, Yunbing Tang, Yang Zhu, Shaowei Wang, Ren-Shan Ge, Yingfen Ying","doi":"10.1016/j.tox.2024.153991","DOIUrl":"https://doi.org/10.1016/j.tox.2024.153991","url":null,"abstract":"","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"153991"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628691","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":"Sex-specific transcriptomic effects of low-dose inorganic arsenic exposure on bone marrow-derived macrophages","authors":"Emily J. Illingworth ,&nbsp;Kristal A. Rychlik ,&nbsp;Alexandra Maertens ,&nbsp;Fenna C.M. Sillé","doi":"10.1016/j.tox.2024.153988","DOIUrl":"10.1016/j.tox.2024.153988","url":null,"abstract":"<div><div>Both tissue-resident macrophages and monocytes recruited from the bone marrow that transform into tissue-resident cells play critical roles in mediating homeostasis as well as in the pathology of inflammatory diseases. Inorganic arsenic (iAs) is the most common drinking water contaminant worldwide and represents a major public health concern. There are numerous diseases caused by iAs exposure in which macrophages are involved, including cardiovascular disease, cancer, and increased risk of (respiratory) infectious diseases. Notably, prenatal iAs exposure is also associated with negative birth outcomes and developmental immunotoxicity (DIT) contributing to long-term adverse outcomes of these immune-related diseases. Therefore, understanding the effects of iAs exposure on macrophages, particularly during immune development or tissue injury and inflammation, can help us better grasp the full range of arsenic immunotoxicity and better design therapeutic targets for iAs-induced diseases particularly in exposed populations. In contrast to prior published studies which often only focused on the effect of iAs on mature macrophages <em>after</em> development, in this study, we analyzed the transcriptome of M0-, M1- and M2-polarized male and female murine bone marrow-derived macrophages (BMDMs) which were exposed to iAs <em>during</em> the differentiation phase, as a model to study iAs (developmental) immunotoxicity. We identified differentially expressed genes by iAs in a sex- and stimulation-dependent manner and used bioinformatics tools to predict protein-protein interactions, transcriptional regulatory networks, and associated biological processes. Overall, our data suggest that M1-stimulated, especially female-derived, BMDMs are most susceptible to iAs exposure during differentiation. Most notably, we observed significant downregulation of major proinflammatory transcription factors, like IRF8, and its downstream targets, as well as genes encoding proteins involved in pattern recognition and antigen presentation, such as TLR7, TLR8, and H2-D1, potentially providing causal insight regarding the role of (early-life) arsenic exposure in perturbing immune responses to infectious diseases. We also observed significant downregulation of genes involved in processes crucial to coordinating a proinflammatory response including leukocyte migration, differentiation, and cytokine and chemokine production and response. Finally, we discovered that 24 X-linked genes were dysregulated in iAs-exposed female stimulation groups compared to only 3 across the iAs-exposed male stimulation groups. These findings elucidate the potential mechanisms underlying the sex-differential iAs-associated immune-related disease risk.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"510 ","pages":"Article 153988"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628692","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 polybrominated diphenyl ethers (PBDEs) as potential substrates of various human CYP enzymes and laboratory test of BDE-99 for its metabolism-activated mutagenicity","authors":"Lin Wang ,&nbsp;Nyame Mustapha Murtala ,&nbsp;Keqi Hu ,&nbsp;Yijing Chen ,&nbsp;Manxin Chen ,&nbsp;Haiting Sun ,&nbsp;Yungang Liu","doi":"10.1016/j.tox.2024.153992","DOIUrl":"10.1016/j.tox.2024.153992","url":null,"abstract":"<div><div>Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, of which BDE-47 could be activated by human cytochrome P450s (CYPs) for chromosome-damaging effects. However, the metabolic activation and mutagenicity of other PBDEs remain unknown. In this study, 14 representative PBDEs were analyzed by molecular docking as potential substrates for several human CYPs. The results showed negative free energies for each pair of binding, however, different CYPs demonstrated largely varied frequencies of binding conformations favoring a substrate potential: CYP2E1, 3A4, and 2B6 being suitable for all/most compounds. Using BDE-99 (5 ∼ 40 μM) as a model compound (exposing for 2 cell cycles), it did not induce micronucleus in a human hepatoma HepG2 cell line, however, positive result was observed in C3A cells (derived from HepG2 but with enhanced expression of CYPs). Pretreatment of HepG2 cells with each of bisphenol A (1 μM, inducer of CYPs) and CITCO (10 μM, inducer of CYP2B6) led to micronucleus formation by BDE-99, while the effect of BDE-99 in C3A cells was abolished by 1-aminobenzotriazole (60 μM, inhibitor of CYPs). In a V79-derived cell line genetically engineered for expressing human CYP2B6 BDE-99 induced micronucleus, while it was negative in V79-Mz and its derivatives expressing several other human CYPs. The micronuclei formed in HepG2 cells pretreated with BPA and CITCO were free of centromere protein B immunofluorescence staining. Finally, BDE-99 weakly induced PIG-A gene mutations in C3A, while negative in HepG2 cells. In conclusion, our study suggest that BDE-99 may be activated by human CYP2B6 for chromosome-breaking effects.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153992"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628712","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":"Role of the ROS/NLRP3/caspase-1 pathway in NiSO4-induced cellular pyroptosis and apoptosis in H9c2 cells","authors":"Xinrui Zhao ,&nbsp;Yuxian Yun ,&nbsp;Danni Zhou ,&nbsp;Yuanyuan Ma ,&nbsp;Xianfeng Luo ,&nbsp;Benzhong Zhang","doi":"10.1016/j.tox.2024.153989","DOIUrl":"10.1016/j.tox.2024.153989","url":null,"abstract":"<div><div>According to comprehensive research, the cardiovascular system is damaged by nickel exposure. The present study selected rat cardiomyocytes (H9c2 cells) and subjected them to varying doses of sodium nickel sulfate (NiSO₄) for 24 hours to better understand the mechanism of cardiovascular damage caused by NiSO₄ exposure. The relevant indicators were detected employing biochemical analysis, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot, and flow cytometry was used to detect the cell apoptosis rate. The study revealed that the survival rate of H9c2 cells fell significantly when the concentration of NiSO₄ exposure rose. Moreover, it caused oxidative stress in H9c2 cells by raising the expression of reactive oxygen species and the concentration of LDH in the cell supernatants. After NiSO₄ exposure, the levels of ASC, NLRP3, gasdermin D, and caspase-1 in H9c2 cells increased, suggesting that H9c2 cells underwent pyroptosis induced by NiSO₄. In addition, NiSO₄ exposure also led to inflammation, with increased levels of interleukin [IL]-18, IL-1β. After adding the antioxidant N-Acetyl-L-cysteine (NAC), the level of ROS indicated that the oxidative stress level in H9c2 cells was reduced, western blot inhibited inflammation, the level of pyroptosis was reduced, and the activity of the NLRP3/caspase1 signaling pathway was reduced. To examine the connection between pyroptosis and apoptosis, the cells were treated with the caspase1 inhibitor Z-YVAD-Fluoromethyl Ketone (Z-YVAD-FMK, YVAD), which resulted in a significant decrease in the rate of cell apoptosis as well as a reduction in the activity of the related protein in the signaling pathway, which in turn decreased the level of pyroptosis. NiSO₄ could induce pyroptosis in H9c2 cells through the ROS/NLRP3/caspase-1 axis. Furthermore, NiSO₄-induced apoptosis and pyroptosis were found to be reduced by the addition of the caspase-1 inhibitor.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153989"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628733","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":"Investigation of a broad diversity of nanoparticles, including their processes, as well as toxicity testing in diverse organs and systems","authors":"Azhar U. Khan ,&nbsp;Mohammad Qutob ,&nbsp;Amel Gacem ,&nbsp;Mohd. Rafatullah ,&nbsp;Krishna Kumar Yadav ,&nbsp;Pankaj Kumar ,&nbsp;Javed Khan Bhutto ,&nbsp;Meenal Rehman ,&nbsp;Sudhakar Bansoid ,&nbsp;Lienda Bashier Eltayeb ,&nbsp;Nazia Malik ,&nbsp;Mohammed Azam Ali ,&nbsp;Maha Awjan Alreshidi ,&nbsp;Mir Waqas Alam","doi":"10.1016/j.tox.2024.153985","DOIUrl":"10.1016/j.tox.2024.153985","url":null,"abstract":"<div><div>Nanotechnology arising in wide-ranging areas, covers extensively different ranges of approaches attained from fields such as biology, chemistry, physics, and medicine engineering. Nanoparticles are a necessary part of nanotechnology effectually applied in the cure of a number of diseases. Nanoparticles have gained significant importance due to their unique properties, which differ from their bulk counterparts. These distinct properties of nanoparticles are primarily influenced by their morphology, size, and size distribution. At the nanoscale, nanoparticles exhibit behaviours that can enhance therapeutic efficacy and reduce drug toxicity. Their small size and large surface area make them promising candidates for applications such as targeted drug delivery, where they can improve treatment outcomes while minimizing adverse effects. The harmful effects of nanoparticles on the environment were critically investigated to obtain appropriate results and reduce the risk by incorporating the materials. Nanoparticles tend to penetrate the human body, clear the biological barriers to reach sensitive organs and are easily incorporated into human tissue, as well as dispersing to the hepatic tissues, heart tissues, encephalum, and GI tract. This study aims to examine a wide variety of nanoparticles, focusing on their manufacturing methods, functional characteristics, and interactions within biological systems. Particular attention will be directed towards assessing the toxicity of nanoparticles in different organs and physiological systems, yielding a thorough comprehension of their potential health hazards and the processes that drive nanoparticle-induced toxicity. This analysis will also emphasize recent developments in nanoparticle applications and safety assessment methodologies.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"509 ","pages":"Article 153985"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605910","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}