{"title":"Novel synthesized, characterization and <i>in vitro</i> toxicological evaluation of amino acid-based-cerium oxide nanoparticles (CeO<sub>2</sub> NPs).","authors":"Sedanur Güngör, Buket Bakan","doi":"10.1080/01480545.2025.2484461","DOIUrl":"10.1080/01480545.2025.2484461","url":null,"abstract":"<p><p>Surface modifications improve the properties of nanomaterials and make them more appropriate for various applications. Various materials are used for surface modification of cerium nanoparticles (CeO<sub>2</sub> NPs); however, there is no modification process of cerium with glutamic acid. This study focused on the preparation of L-glutamic acid-coated CeO<sub>2</sub> NPs and reveal its potential toxicity depending on the characteristic properties. Characterization analysis was performed by Transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), ZETA sizer/potential and X-ray diffraction (XRD). <i>In vitro</i> toxicities of CeO<sub>2</sub> NPs and Glu-CeO<sub>2</sub> NPs were investigated by using WST-1 (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), hemolysis and HET-CAM (Hen's egg-chorioallantoic membrane) tests. Both NPs-group were determined to be non- cytotoxic on L929 and MCF-10A cell lines, but slightly decrease the viability of A549 and MCF-7 cells after 24 exposure. Glu-CeO<sub>2</sub> NPs increased cell migration in MCF-10A cell line but inhibited in A549 cells. In contrast to CeO<sub>2</sub> NPs, Glu-CeO<sub>2</sub> NPs reduced oxidative stress and hemolysis rate. CeO<sub>2</sub> NP was caused lysis after 0.5nd min, while Glu-CeO<sub>2</sub> NPs didn't exhibit any irritation effect. This is the first report on the synthesis of Glu-CeO<sub>2</sub> NPs. This formulation may be used in drug delivery systems due to its potential to reduce toxicity of CeO<sub>2</sub> NPs.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"697-708"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonio Zandona, Matea Jurić, Ludovic Jean, Pierre-Yves Renard, Maja Katalinić
{"title":"Assessment of cytotoxic properties of tetrahydroisoquinoline oximes in breast, prostate and glioblastoma cancer cells.","authors":"Antonio Zandona, Matea Jurić, Ludovic Jean, Pierre-Yves Renard, Maja Katalinić","doi":"10.1080/01480545.2025.2491534","DOIUrl":"10.1080/01480545.2025.2491534","url":null,"abstract":"<p><p>Tetrahydroisoquinoline (THIQ) oximes have been investigated as antidotes for poisoning by toxic organophosphorus compounds. Recent studies have shown that some THIQ oximes induce cytotoxic effects and trigger apoptosis in various cell types. Since this pathway activation is desirable for anticancer drugs, we further explored the effects of three selected THIQ oximes on well-known cancer cell models: breast (MDA-MB-231 and MCF-7), prostate (PC-3) cancer and malignant glioblastoma (U251). The tested THIQ oximes were cytotoxic to breast cancer cells and, to a lesser extent, to glioblastoma cells, but not to PC-3 cells at concentrations up to 200 µM within a 24-h exposure period. The MCF-7 cells exhibited the highest sensitivity, with all three oximes affecting it in a time-dependent manner (IC<sub>50</sub> from 7-74 µM). While the membrane integrity of affected cells was maintained after treatment with the tested THIQ oximes, they disrupted mitochondrial membrane potential and activated caspase 9 indicating triggering of the mitochondria-mediated apoptosis. Overall, these findings suggest that the THIQ oxime scaffold could be a foundation for developing targeted therapies, especially for breast cancer, and other derivatives may be worthier of exploration.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"856-863"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effects of alumina and polystyrene nanoparticles on global DNA methylation, antimicrobial peptides and intergenerational inheritance of <i>Galleria mellonella</i>.","authors":"Zülbiye Demirtürk, Fevzi Uçkan","doi":"10.1080/01480545.2025.2483970","DOIUrl":"10.1080/01480545.2025.2483970","url":null,"abstract":"<p><p>The epigenetic and immunological effects of nanoparticles (NPs), which have started to be described as nano-pollutants today, are of great interest in living organisms. Particularly alumina (Al) and polystyrene (PS) are among the most produced NPs. <i>Galleria mellonella</i> larvae, an ideal model for the multi-generational effects of these NPs on global DNA methylation and the immune system, were used in the experiments. Al-NPs were bought, and PS-NPs were produced by the single emulsion solvent evaporation method. Al and PS-NPs were administered to larvae at different concentrations by changing only the water content in the diet. Global DNA methylation levels in the first and second generations were determined by HPLC. The expression levels of β-actin, transferrin, galiomycin, and p38 MAPK genes which constitute antimicrobial peptides, one of the humoral immune responses, were determined by RT-qPCR in two generations. The data obtained revealed that Al and PS-NPs increased global DNA methylation, and partially suppressed humoral immune responses. Furthermore, changes in genomic DNA methylation and immune-related gene expression levels induced by NPs in first generation larvae were found to be inherited by the next generation. Considering the importance of multigenerational epigenetic effects and changes in the immune system, our study results contribute to the literature and reveal the importance of such studies.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"729-742"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In silico</i> molecular docking and <i>in vitro</i> analysis of atomoxetine.","authors":"Nurullah Bolat, Merve Meliha Hız-Çelikliyurt, Erhan Akıncı, Gülsüm Akkuş, Melih Günay, Şükrü Alperen Korkmaz","doi":"10.1080/01480545.2025.2452859","DOIUrl":"10.1080/01480545.2025.2452859","url":null,"abstract":"<p><p>Although atomoxetine, a selective norepinephrine reuptake inhibitor, is widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is limited data on its cytogenetic effects. This study aimed to investigate the cytotoxicity and genotoxicity of atomoxetine <i>in vitro</i> and <i>silico</i>. Chromosome aberration and micronucleus assays were used to analyze the genotoxic effect of atomoxetine in human peripheral blood lymphocytes under culture conditions. The mitotic index was assessed for cytotoxic potential. For the docking analysis, DNA receptor (1BNA) was prepared with ChimeraX, and the Atomoxetine molecule was optimized by Avogadro2.0 software. <i>In silico</i> molecular docking analysis was carried out utilizing SwissDock online platform. The results obtained were visualized using ChimeraX and Pymol software. Atomoxetine doses of 9.6 µg/mL (equal to about 1.2 mg/kg as a maintenance dose), 14.4 µg/mL (equal about to 1.8 mg/kg as the highest dose systematically tested), 48.0 µg/mL (equal about to 6 mg/kg as five times the maintenance dose) and 96.0 µg/mL (equal about to 12 mg/kg as ten times the maintenance dose) were analyzed. The findings clearly indicate that atomoxetine has no genotoxic effect at the therapeutic dose. However, we observed genotoxic effects at 48.0 and 96.0 µg/mL doses. No strong binding affinity occurs <i>in silico</i> analyses. As one of the initial inquiries into the <i>in silico</i> and <i>in vitro</i> appraisal of atomoxetine's genotoxic impacts, the research has established that atomoxetine does not significantly affect the frequency of chromosomal damage or micronucleus formation. Genotoxic effects should be kept in mind at doses above clinical practice.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"758-766"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nevin Çankaya, Mehmet Hanifi Kebiroglu, Cengiz Soykan
{"title":"Computational and experimental study of terpolymers: spectroscopic, thermal, thermochemical, molecular property, and <i>in silico</i> toxicity analysis.","authors":"Nevin Çankaya, Mehmet Hanifi Kebiroglu, Cengiz Soykan","doi":"10.1080/01480545.2025.2468924","DOIUrl":"10.1080/01480545.2025.2468924","url":null,"abstract":"<p><p>In this study, a comprehensive analysis of the CMA2OEM-co-DVB-co-AMPS (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-2-acrylamido-2-methyl-1-propanesulfonic acid) and CMA2OEM-co-DVB-co-VIM (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-vinylimidazole) terpolymers was conducted. The structural and chemical properties of the terpolymers were examined using Fourier transform infrared (FT-IR) spectroscopy, frontier molecular orbital analysis, molecular electrostatic potential (MEP) maps, <sup>1</sup>H, and <sup>13</sup>C NMR spectroscopy, thermochemistry surface maps (TCSM), toxicity assessments, physical properties, electron localization function (ELF), and total electrostatic potential (ESP) analyses. <i>In silico</i> toxicity analyses, a quantitative structure-activity relationship (QSAR) model was used for Toxicity Estimation Software Tool (TEST) and ProTox 3.0, a web-based virtual toxicity laboratory, was used for oral toxicity prediction. Toxicity estimates using TEST showed that both terpolymers exhibited low toxicity profiles. Oral toxicity prediction emphasizes that CMA2OEM-co-DVB-co-VIM may pose a greater risk compared to CMA2OEM-co-DVB-co-AMPS. In addition, experimental thermal characterization of these terpolymers was also performed. These comprehensive analyses have provided significant insights into the potential applications and functional properties of the terpolymers.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"767-783"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raquel Cordeiro de Oliveira, Abdênego Rodrigues da Silva, Robson Raion de Vasconcelos Alves, Matheus Cavalcanti de Barros, Talita Giselly Dos Santos Souza, Alisson Macário de Oliveira, Leydianne Leite de Siqueira Patriota, Patrícia Maria Guedes Paiva, Fernanda das Chagas Ângelo Mendes Tenório, Paulo Euzébio Cabral Filho, Adriana Fontes, Thiago Henrique Napoleão, Mércia Liane de Oliveira, Elvis Joacir de França
{"title":"Acute toxicity and biodistribution assessment of quantum dots conjugated to lectins from <i>Schinus terebinthifolia</i> leaves (SteLL) and <i>Punica granatum</i> sarcotesta (PgTeL).","authors":"Raquel Cordeiro de Oliveira, Abdênego Rodrigues da Silva, Robson Raion de Vasconcelos Alves, Matheus Cavalcanti de Barros, Talita Giselly Dos Santos Souza, Alisson Macário de Oliveira, Leydianne Leite de Siqueira Patriota, Patrícia Maria Guedes Paiva, Fernanda das Chagas Ângelo Mendes Tenório, Paulo Euzébio Cabral Filho, Adriana Fontes, Thiago Henrique Napoleão, Mércia Liane de Oliveira, Elvis Joacir de França","doi":"10.1080/01480545.2024.2433074","DOIUrl":"10.1080/01480545.2024.2433074","url":null,"abstract":"<p><p>This work reports the <i>in vivo</i> investigation of telluride cadmium quantum dots (CdTe QDs) conjugated to plant lectins from <i>Schinus terebinthifolia</i> (SteLL) and <i>Punica granatum</i> (PgTeL) for acute toxicity and genotoxicity in healthy mice and 24-h biodistribution in sarcoma 180-bearing animals. Acute toxicity data indicated their safety, despite some histopathological alterations. Comet assay revealed that the QDs-PgTeL group presented a higher damage index and frequency of damage than the negative control. The micronucleus test did not reveal a genotoxic effect. The 24-h biodistribution study showed a major uptake of cadmium by the liver, spleen, and kidneys. A greater accumulation of cadmium was found in tumors of the QDs-SteLL group. In conclusion, the biodistribution study showed no influence of the studied lectins in the absorption of QDs by different organs and that the conjugation of SteLL resulted in increased targeting of QDs to sarcoma 180 cells, suggesting a potential theranostic application in cancer.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"709-719"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NO-mediated DNA damage induced by polystyrene nanoparticles triggers program cell death in mesenchymal stem cells.","authors":"Vesna Matovic, Biljana Ljujic, Marina Miletic Kovacevic, Olivera Milosevic-Djordjevic, Nevena Milivojevic, Sandra Nikolic, Marina Gazdic Jankovic","doi":"10.1080/01480545.2025.2453580","DOIUrl":"10.1080/01480545.2025.2453580","url":null,"abstract":"<p><p>Daily contact with considerable amounts of polystyrene nanoparticles (PSNPs) may cause harmful effects on the living organisms, through mechanisms that are not fully understood. The study aimed to evaluate the cytotoxic and genotoxic effects of PSNPs (size 200 nm and 40 nm) in mesenchymal stem cells (MSCs). In order to estimate cellular uptake and retention of nanoplastics, PSNP-treated cells have been analyzed by transmission electron microscopy. For assessing morphology and viability of MSCs after PSNP treatment at two environmentally relevant doses (0.47 and 4.7 μl/ml) for 24 hours, HE and Giemsa staining were performed. Annexin V‑FITC/PI assay was used to quantify PSNPs-mediated cell death. Genotoxicity of PSNPs was evaluated by Comet test. The capacity of PSNPs to trigger the production of free radicals in MSCs was also evaluated. TEM confirmed endocytosis of PSNPs. Decreased cell volume, nuclear hyperchromatism, edge aggregation, and formation of densely stained apoptotic bodies, indicated that PSNP-treated MSCs undergo apoptosis. The presented data showed that both concentration of PS particles significantly increased early apoptotic cell death in comparison to untreated cells. Moreover, both doses of PSNPs significantly increased the genetic damage index in MSCs in dose-dependent manner. In conclusion, PSNPs penetrate, accumulate and induce cytotoxic and genotoxic damage in MSCs.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"720-728"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective effect of Leuco-methylene blue against acetaminophen-induced liver injury: an experimental study.","authors":"Majid Efati, Amirhossein Sahebkar, Shima Tavallaei, Soodeh Alidadi, Hossein Hosseini, Daryoush Hamidi-Alamdari","doi":"10.1080/01480545.2025.2485347","DOIUrl":"10.1080/01480545.2025.2485347","url":null,"abstract":"<p><p>Acetaminophen is a commonly used drug for mild to moderate pain relief; however, acetaminophen toxicity due to the formation of toxic metabolites is a major cause of drug-induced liver injury. Methylene blue is an FDA-approved drug for the treatment of methemoglobinemia and has potential applications in the treatment of carbon monoxide and cyanide poisoning. Leuco-methylene blue, a colorless form of methylene blue, is more effective in entering cells and counteracting oxidative stress, making it a valuable option in regulating mitochondrial function and ATP production. In this study, we aimed to evaluate the effect of LMB on liver damage caused by acetaminophen toxicity. Thirty-six rats were divided into six groups: control, APAP, NAC, LMB, MB, and NAC+LMB. All groups except the control received acetaminophen (1500 mg/kg), followed by treatments with NAC (100 mg/kg), LMB (5 mg/kg), MB (5 mg/kg), and NAC+LMB after 3 hours. The rats were sacrificed 24 hours post-acetaminophen administration. LMB significantly reduced serum levels of liver enzymes (ALT, AST, and ALP) and increased the expression of genes involved in mitochondrial biogenesis and antioxidant defense (PGC-1, Nrf2, and Tfam). Additionally, LMB significantly increased total antioxidant capacity and glutathione reductase levels, decreased the prooxidant-antioxidant balance (PAB), and reduced the expression of inflammatory cytokines (IL-6 and TNF-α) in the liver tissue. LMB effectively reduced the severity of acetaminophen-induced liver damage through antioxidant and anti-inflammatory effects. LMB can effectively ameliorate APAP-induced toxicity in rats, with comparable efficacy to N-acetylcysteine with respect to most complications of acetaminophen-induced toxicity in rats.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"888-900"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicological evaluation of LivLonga<sup>®</sup>, a polyherbal combination, in rodents.","authors":"Anju Majeed, Anjali Pandey, Smitha Thazhathidath, Sarang Bani","doi":"10.1080/01480545.2024.2420729","DOIUrl":"10.1080/01480545.2024.2420729","url":null,"abstract":"<p><p>There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about <i>Curcuma longa</i>, <i>Garcinia indica</i> and <i>Piper nigrum</i> which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga<sup>®</sup> is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga<sup>®</sup> using <i>in vivo</i> models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga<sup>®</sup> showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"828-841"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pamella Patricia Fuzzer Figueiredo, Laura Cé da Silva, Júlia Menezes, Joana Oliveira Machado, Roberta Rodrigues Zorzo, Mariana Arend Schmitt, Gabriela Endres da Rocha Pompeo, Solange Cristina Garcia, Simone Gasparin Verza, Gunther Gehlen, Natália Brucker, Mariele Feiffer Charão
{"title":"Synergistic toxicity of glyphosate- and 2,4-Dichlorophenoxyacetic acid-based formulations on <i>Caenorhabditis elegans</i>.","authors":"Pamella Patricia Fuzzer Figueiredo, Laura Cé da Silva, Júlia Menezes, Joana Oliveira Machado, Roberta Rodrigues Zorzo, Mariana Arend Schmitt, Gabriela Endres da Rocha Pompeo, Solange Cristina Garcia, Simone Gasparin Verza, Gunther Gehlen, Natália Brucker, Mariele Feiffer Charão","doi":"10.1080/01480545.2025.2486542","DOIUrl":"10.1080/01480545.2025.2486542","url":null,"abstract":"<p><p>The use and marketing of herbicides are increasing worldwide. Glyphosate and 2,4 dichlorophenoxyacetic acid (2,4D) are the most prominent herbicides in this progression, used alone and in combination. There are few reports on the effects of these herbicides in combination. The <i>Caenorhabditis elegans (C. elegans)</i> experimental model has a complete system and is easy to manipulate and maintain. This study evaluated the toxicity of glyphosate and 2,4D alone and in combination with the parameters of survival, development, and reproduction in <i>C. elegans</i> at 4 different concentrations of the herbicides (0.115-0.925 mg/mL for glyphosate and from 1.046 to 8.375 mg/mL for 2,4D). The nature herbicides' interaction was evaluated using SynergyFinder software with the Highest Single Agent (HSA) probabilistic model. The survival results indicated an LC50 (Lethal Concentration 50) of 0.66 mg/mL for glyphosate alone and 0.164 mg/mL when combined with 2,4D. The LC50 for 2,4D alone was 9.41 mg/mL and 3.011 mg/mL when combined with glyphosate. There was a significant reduction in nematode development and reproduction as well as greater herbicide toxicity when combined (<i>p</i> < 0.05). The HSA indicated synergistic effects at different concentrations of the mixture, demonstrating greater toxicity of these herbicides in combination. This is the first time that the synergistic effect of glyphosate and 2,4D on <i>C. elegans</i> has been reported in the literature. This highlights the importance of further studies to understand the impact of using these herbicides alone and in combination, as they are widely used and can affect populations and ecosystems.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"818-827"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}