{"title":"Human Health Risks Attributable to Tyre-Derived Crumb Rubber-A Literature Review on Artificial Turfs and Playgrounds.","authors":"Federica Ghelli, Giulia Squillacioti, Samar El Sherbiny, Valeria Bellisario, Roberto Bono","doi":"10.3390/jox16050177","DOIUrl":"10.3390/jox16050177","url":null,"abstract":"<p><p>Tyre granule-based artificial turf surfaces are currently a matter of debate. Most of the Agencies involved in environmental and health protection have stated a negligible/virtually negligible risk to health and have issued a general call for caution concerning the possible presence of emerging risks. The concern for the potential detrimental effect, especially in children, has attracted significant resonance since the beginning of the use of these surfaces. This review aims to describe the current knowledge in both scientific and grey literature concerning the possible adverse risks to health due to human exposure to artificial turf or playgrounds with tyre-derived crumb rubber. We included 20 original research articles and 13 reports published between 2006 and 2025. The current knowledge about the topic was revealed to be still highly fragmentary, with stark differences in methodological approaches and theoretical assumptions used in the risk assessment. However, most of the research and reports are consistent in their results, assessing, in the majority of cases, a low/negligible risk for both professional and recreational players, even though some chemicals were able to leach or volatilise and, in some cases, the estimated risk was higher than the reference threshold conventionally applied for the risk assessment method employed.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariachiara Galati, Giuseppe De Marco, Mariano Dara, Giulia La Pusata, Maria Giovanna Parisi, Matteo Cammarata, Maria Maisano, Tiziana Cappello
{"title":"Polylactic Acid Bioplastics (PLA BPs): A Threat to the Reproductive Health of the Mediterranean Mussel <i>Mytilus galloprovincialis</i>.","authors":"Mariachiara Galati, Giuseppe De Marco, Mariano Dara, Giulia La Pusata, Maria Giovanna Parisi, Matteo Cammarata, Maria Maisano, Tiziana Cappello","doi":"10.3390/jox16050176","DOIUrl":"10.3390/jox16050176","url":null,"abstract":"<p><p>In the context of the global transition towards a more sustainable economy, the use of bioplastics (BPs) is rapidly increasing across several sectors, including industry, medicine and cosmetics. Among BPs, polylactic acid (PLA) is the \"polymer of the 21st century\". Because of its wide use and slow degradation capacity, it can be found in various aquatic matrices, causing potential health concerns for biota. This work evaluated the influence of environmental concentrations (0.5 µg/mL) of PLA BPs on the reproductive health of the Mediterranean mussel <i>Mytilus galloprovincialis</i>, following a short-term exposure of 7 days. This resulted in an early spawning event from the gonads of both sexes, accompanied by an intense hemocyte recall, suggesting the onset of a pro-inflammatory condition. Alterations in the bioenergetic pathway affecting glycogen reserves as an adaptive strategy were revealed in both sexes by proton Nuclear Magnetic Resonance (<sup>1</sup>H NMR)-based metabolomics, in addition to disorders in the redox balance. This latter was more evident in males, as confirmed by the increased activity of antioxidant (catalase) and detoxifying (glutathione <i>S</i>-transferase) enzymes, while no lipid peroxidation occurred. Overall, this study highlights the threat of PLA BPs on the reproductive system of non-target organisms, raising further questions on the reproductive fitness and survival of a species with high ecological and economic value.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Abramenko, Vadim Vergun, Julia Jukova, Varvara Topolenko, Sergey Simanovsky, Vera Isaeva, Eugene Krysanov, Leonid Kustov
{"title":"Accumulation and Genotoxicity of UiO-66 Nanoparticles in Freshwater Fish <i>Nothobranchius rachovii</i>.","authors":"Natalia Abramenko, Vadim Vergun, Julia Jukova, Varvara Topolenko, Sergey Simanovsky, Vera Isaeva, Eugene Krysanov, Leonid Kustov","doi":"10.3390/jox16050175","DOIUrl":"10.3390/jox16050175","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) possess remarkable physicochemical properties, making them highly attractive candidates for advanced drug delivery, catalysis, water purification, gas separation, and biomedical application. Thus, it is important to understand its toxic effect on the environment and human health prior to wide practical application. In this study, UiO-66 nanoparticles (Zr<sub>6</sub>O<sub>4</sub>(OH)<sub>4</sub>-octahedral clusters with benzene-1,4-dicarboxylate linkers) were synthesized and characterized by XRD, SEM, and TEM techniques. The genotoxicity and accumulation of UiO-66 were investigated towards freshwater fish, <i>Nothobranchius rachovii</i>, for the first time. To gain a better understanding of the effects of UiO-66 nanoparticles towards <i>N. rachovii</i>, fish were exposed to UiO-66, the linker, and zirconium salts. The genotoxic risk caused by UiO-66 was detected by analyzing the Chromosome Aberrations (CAs), frequencies of Sister Chromatid Exchanges (SCEs), mitotic index, and accumulations of Zr in tissues of fish treated with UiO-66 samples, linker, zirconium salt, and non-exposed control subjects.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cumulative and Interactive Effects of Heavy Metal Mixtures Across Neurodegenerative Diseases: A Comparative Review of Alzheimer, Parkinson, Amyotrophic Lateral Sclerosis and Multiple Sclerosis.","authors":"Ivona Mitu, Ioana-Cezara Caba, Irina Macovei","doi":"10.3390/jox16050174","DOIUrl":"10.3390/jox16050174","url":null,"abstract":"<p><p>Heavy metals and metalloids are persistent environmental contaminants that accumulate in the central nervous system and interact with endogenous essential metals, yet most neurotoxicological research continues to treat metals as independent agents rather than as co-occurring mixtures. This review systematically compares the evidence for cumulative and interactive effects of heavy metal mixtures across four major neurodegenerative diseases-Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)-asking which metal combinations have been directly documented for each disease, and whether these patterns are disease-specific or shared. Following a PubMed search (January 2016-June 2026), 93 unique studies were included (AD: 49; PD: 38; ALS: 19; MS: 18; 31 shared across diseases). Combined exposure to lead, cadmium, arsenic, and mercury is linked to amyloid-beta accumulation and dementia risk in AD; manganese-vanadium co-exposure produces more severe dopaminergic damage in PD than either metal alone, with manganese activating the familial PD gene LRRK2; a multi-metal mixture in ALS was associated with a three-fold higher disease risk independent of genetic susceptibility; and MS showed almost no designed mixture studies despite considerable single-metal data, with conflicting findings across cohorts. Three general mechanisms were identified: competition at shared membrane transporters (notably DMT1), sequestration by metal-binding proteins, and direct synergistic or antagonistic interactions, in which essential elements can modulate toxic-metal handling. Mixture-statistics approaches (WQS, BKMR), already established for AD and PD, should be extended to MS to close this evidence gap.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Antonio Ramírez-Vargas, Cristian Oswaldo Bravo-Nava, Ma Elena Moreno-Godínez, Gerardo Huerta-Beristain, Eugenia Flores-Alfaro, Guillermina Vences-Velázquez, José Ángel Cahua-Pablo
{"title":"Translational Gaps in Assessing the Obesogenic Effects of Herbicides: A Scoping Review.","authors":"Marco Antonio Ramírez-Vargas, Cristian Oswaldo Bravo-Nava, Ma Elena Moreno-Godínez, Gerardo Huerta-Beristain, Eugenia Flores-Alfaro, Guillermina Vences-Velázquez, José Ángel Cahua-Pablo","doi":"10.3390/jox16050173","DOIUrl":"10.3390/jox16050173","url":null,"abstract":"<p><p>Obesity is a disease characterized by excessive accumulation of adipose tissue. It is a multifactorial condition arising from complex interactions among genetic background, lifestyle-related factors (such as physical inactivity, socioeconomic and cultural determinants), and environmental factors, including dietary patterns and exposure to environmental pollutants. In this context, exposure to environmental pollutants has been considered an independent risk factor for the development of obesity. However, the evidence linking herbicide exposure and obesity is limited. Therefore, the present scoping review aimed to map the available evidence regarding the obesogenic effects of herbicides across <i>in vitro</i>, <i>in vivo</i>, and epidemiological models, evaluate their translational concordance, and identify methodological gaps in the available literature. A systematic literature search was conducted in PubMed, Web of Science, and Scopus to identify studies reporting the effect of herbicide exposure and obesity-related endpoints. The search was limited to March 2026. A total of 24 studies fully met our eligibility criteria and were classified into <i>in vitro</i>, <i>in vivo</i>, and epidemiological evidence categories. The findings revealed a substantial disconnect across the different levels of evidence. In both <i>in vitro</i> and <i>in vivo</i> studies, the concentrations and doses tested often did not reflect realistic exposure scenarios, thereby limiting the applicability of these findings to human health risk assessment. In contrast, epidemiological studies frequently relied on obesity indicators with limited sensitivity and specificity, such as body mass index (BMI). Overall, the evidence suggests limited external validity in population-based studies and the arbitrary selection of concentrations and doses in experimental models.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João Simões, Alexandra Bernardo, Luísa Lima Gonçalves, José Brito
{"title":"Air Pollution, Temperature, and Demographic Vulnerability as Determinants of Cause-Specific Mortality in Portugal.","authors":"João Simões, Alexandra Bernardo, Luísa Lima Gonçalves, José Brito","doi":"10.3390/jox16050172","DOIUrl":"10.3390/jox16050172","url":null,"abstract":"<p><p>Air pollution and temperature are important environmental risk factors for mortality, but variation in risks across causes of death, population groups, and co-exposure conditions remains incompletely characterised. This study used nationwide monthly data from Portugal for the period 2010-2022 to estimate cause-specific mortality risks associated with nitrogen dioxide (NO<sub>2</sub>), fine particulate matter (PM<sub>2.5</sub>), and temperature, while evaluating sex-age interaction structures and selected co-exposure patterns. Mortality from malignant tumours, circulatory diseases, and respiratory diseases was modelled using Generalised Estimating Equations to account for temporal correlation and interaction effects. Pollutant exposures were defined as concentrations exceeding the 2021 World Health Organization air quality guideline values. Associations varied by cause of death. Respiratory mortality showed the strongest environmental association, with a 1.4% increase in risk per 1 μg/m<sup>3</sup> increase in NO<sub>2</sub> above the guideline value (RR 1.014, 95% CI 1.009-1.019), and the highest predicted risk was observed among males aged ≥65 years (RR 142.610, 95% CI 142.200-143.020). Circulatory mortality was also associated with NO<sub>2</sub> (RR 1.005, 95% CI 1.001-1.008) and showed a submultiplicative sex-age interaction (RR 0.344, 95% CI 0.343-0.344), indicating attenuation of sex differences at older ages. Malignant tumour mortality showed weaker environmental associations but a greater-than-multiplicative sex-age interaction (RR 1.117) and attenuation of the NO<sub>2</sub> association at higher PM<sub>2.5</sub> levels, although the pollutant-related findings were less robust in sensitivity analyses. These findings indicate that mortality risks are not uniform across causes of death or population groups, supporting the value of locally derived, demographically stratified estimates for environmental health assessment and targeted public health strategies.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrashort-Chain and Short-Chain Per- and Polyfluoroalkyl Substances Are Universal Contaminants in Wines: A Comprehensive Survey of Red, White, Rosé, and Sparkling Samples.","authors":"Shun-Hsin Liang, Justin A Steimling","doi":"10.3390/jox16050171","DOIUrl":"10.3390/jox16050171","url":null,"abstract":"<p><p>Ultrashort-chain (USC) per- and polyfluoroalkyl substances (PFAS) are increasingly detected in environmental and drinking water systems, yet information regarding their occurrence in alcoholic beverages remains limited. The analysis of USC PFAS in wine is particularly challenging because of their high polarity and the complex composition of wine matrices. This study presents a streamlined analytical method for the simultaneous determination of 42 PFAS, including C1-C13 perfluoroalkyl carboxylic and sulfonic acids, in red, white, rosé, and sparkling wines. Chromatographic separation was achieved using a polar-embedded alkyl-phase liquid chromatography column, providing enhanced retention of USC PFAS while maintaining adequate performance for longer-chain analytes. A dilute-and-shoot sample preparation approach combined with 18 isotopically labeled internal standards enabled efficient analysis with minimal sample handling. Method verification using PFAS-spiked wine samples demonstrated satisfactory accuracy (recoveries within ±30% of nominal values) and precision (%RSD < 15%) across analyte-specific calibration ranges of 1-2500 ng/L. Application to commercial wines revealed the widespread occurrence of trifluoroacetic acid (TFA), trifluoromethanesulfonic acid (TFMS), perfluoropropionic acid (PFPrA), and perfluorobutanoic acid (PFBA) across all wine categories examined. These findings demonstrate the feasibility of comprehensive PFAS monitoring in wines and highlight the importance of including USC PFAS in exposure assessments of beverages.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicological Assessment of the Marine-Derived Cyclic Dipeptide Cyclo(Pro-Tyr) Using In Vitro, Zebrafish Embryo, and BALB/c Mouse Models.","authors":"Shana Balachandran, Madan Kumar Arumugam, Rakhee Rathnam Kalari Kandy","doi":"10.3390/jox16050170","DOIUrl":"10.3390/jox16050170","url":null,"abstract":"<p><p>Cyclo(Pro-Tyr), a marine-derived cyclic dipeptide, has demonstrated anticancer activity, but its toxicological profile remains insufficiently characterized. The present study evaluated the preliminary toxicological effects of Cyclo(Pro-Tyr) using complementary in vitro cytotoxicity, zebrafish embryo developmental toxicity, and sub-acute oral toxicity in mice models. Cytotoxicity was assessed in 3T3-L1, HEK293, and HepG2 cells following 24 h exposure to Cyclo(Pro-Tyr) at 0-250 µM. Developmental toxicity was evaluated in zebrafish embryos exposed to 0-1000 µM for up to 96 h post-fertilization. A repeated-dose oral toxicity study was conducted in male and female BALB/c mice administered Cyclo(Pro-Tyr) at 100 or 500 mg/kg/day for 30 consecutive days, followed by hematological, serum biochemical, organ-weight, and histopathological assessments. Cyclo(Pro-Tyr) produced concentration-dependent reductions in cellular viability, with pronounced effects at the upper concentrations tested. In zebrafish embryos, exposure to 750 and 1000 µM was associated with increased mortality, reduced hatchability, developmental malformations, and reduced body length. In mice, repeated oral administration did not produce mortality, overt clinical toxicity, or significant changes in body weight or relative liver and kidney weights. However, dose-dependent alterations in selected hematological and serum biochemical parameters were observed, particularly at 500 mg/kg, accompanied by mild inflammatory and degenerative changes in hepatic and renal tissues. Overall, Cyclo(Pro-Tyr) exhibited concentration-dependent cellular and developmental toxicity at higher exposure concentrations and produced mild systemic alterations following repeated oral administration at the higher tested dose. These findings provide preliminary toxicological information relevant to the further preclinical evaluation of Cyclo(Pro-Tyr) as a marine-derived bioactive compound.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ikhwandi Chandra Nugraha, Ami Febriza, Asdar Tajuddin, Suryani As'ad
{"title":"Empagliflozin Targets NF-κB Signaling Through PTGS2 and TLR4 in Polycystic Ovary Syndrome: A Drug Repurposing Study and Molecular Simulation.","authors":"Ikhwandi Chandra Nugraha, Ami Febriza, Asdar Tajuddin, Suryani As'ad","doi":"10.3390/jox16050169","DOIUrl":"10.3390/jox16050169","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by chronic inflammation, insulin resistance, and reproductive dysfunction. Although empagliflozin, a sodium-glucose cotransporter-2 inhibitor, has demonstrated anti-inflammatory and metabolic benefits, its molecular mechanisms in PCOS remain poorly understood. This study investigated the anti-inflammatory mechanisms of empagliflozin in PCOS using network pharmacology, molecular docking, and molecular dynamics simulations. Potential drug targets were identified using SwissTargetPrediction and SuperPred, while PCOS- and inflammation-related genes were obtained from GeneCards. Overlapping targets were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and hub gene analyses. Molecular docking and 50 ns molecular dynamics simulations were performed to evaluate binding affinity and complex stability. Key inflammatory targets identified included TNF, IL6, IL1B, TLR4, STAT3, and PTGS2, with significant enrichment in cytokine-mediated signaling, TNF signaling, and NF-κB pathways. Empagliflozin showed strong binding affinities for PTGS2 (-9.0 kcal/mol) and TLR4 (-8.8 kcal/mol), while molecular dynamics simulations demonstrated stable protein-ligand complexes throughout the simulation. These findings suggest that empagliflozin may alleviate PCOS-associated inflammation by modulating the TLR4/NF-κB/PTGS2 signaling axis, supporting its potential as a repurposed therapeutic agent for PCOS and providing a foundation for future experimental validation.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gisele de Paula Júlio Garcia, Carolina Silva Schiebel, Maiara Vicentini, Daniele Maria-Ferreira, Izonete Cristina Guiloski
{"title":"Individual and Combined Effects of Commercial Glyphosate and Dicamba-Based Herbicide Formulations on Cytotoxicity, Oxidative Stress and Cell Death on Human Intestinal Caco-2 Cells.","authors":"Gisele de Paula Júlio Garcia, Carolina Silva Schiebel, Maiara Vicentini, Daniele Maria-Ferreira, Izonete Cristina Guiloski","doi":"10.3390/jox16050168","DOIUrl":"10.3390/jox16050168","url":null,"abstract":"<p><p>Pesticide contamination of food and environmental matrices represents a potential risk to human health. This study investigated the toxicological effects of commercial glyphosate and dicamba-based herbicide formulations, individually and in combination, on human intestinal epithelial Caco-2 cells. Cells were exposed to a concentration range of 0.1-10,000 mg/L for 24, 48, and 72 h to determine IC<sub>50</sub> values. Subsequent assays were conducted using concentrations based on the lowest IC<sub>50</sub> obtained and in the limits established by the Environmental Protection Agency for drinking water. After 48 h of exposure, glyphosate at the highest tested concentration, as well as co-exposure to glyphosate and dicamba, induced significant cytotoxicity, modulation of oxidative stress parameters, and alterations in antioxidant defenses, accompanied by increased rates of apoptosis and necrosis. Dicamba exposure alone also resulted in elevated apoptotic and necrotic cell populations. A reduction in N-acetyl-β-D-glucosaminidase activity was observed across most tested concentrations, suggesting impaired inflammatory response capacity. This work identified alterations in Caco-2 that impair cellular homeostasis by cytotoxicity, alterations in oxidative stress, antioxidant response, inflammation, apoptosis and necrosis. Future studies investigating inflammatory pathways, genetic damage, and assays with in vivo and in silico models are important to elucidate the mechanism of the cellular damage caused by exposure to these herbicides.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"16 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}