Journal of ToxicologyPub Date : 2026-04-28eCollection Date: 2026-01-01DOI: 10.1155/jt/7171333
Ana Elisa Maehashi, Emily de Moura Galdino, Edson Araujo de Almeida, Diego Espirito Santo, Carmem Lúcia Henrich, Bianca da Cruz, Elisângela Dusman, Danielle Cristina da Silva de Oliveira, Gideã Taques Tractz, Regiane da Silva Gonzalez, Osvaldo Valarini Junior, C A Downs, Ana Paula Peron
{"title":"Cellular and Systemic Toxicity Induced by Sunscreen and Paraben Mixtures and the Implications for Root Development in Cultivated Plants.","authors":"Ana Elisa Maehashi, Emily de Moura Galdino, Edson Araujo de Almeida, Diego Espirito Santo, Carmem Lúcia Henrich, Bianca da Cruz, Elisângela Dusman, Danielle Cristina da Silva de Oliveira, Gideã Taques Tractz, Regiane da Silva Gonzalez, Osvaldo Valarini Junior, C A Downs, Ana Paula Peron","doi":"10.1155/jt/7171333","DOIUrl":"https://doi.org/10.1155/jt/7171333","url":null,"abstract":"<p><p>Sunscreens and parabens contaminate agricultural areas worldwide; however, the effects of these micropollutants in mixture on cultivated plants have not yet been reported. This study evaluated the cellular and systemic toxicity induced by octocrylene (OC), methylparaben (MeP), and butylparaben (BuP), individually at concentrations of 10, 50, 100, and 500 ng·L<sup>-1</sup>, as well as by equimolar binary mixtures (1:1) of OC with MeP and OC with BuP, in seeds of <i>Cucumis sativus</i> L. and <i>Lycopersicum esculentum</i> L., and in roots of <i>Allium cepa</i> L. bulbs. The OC + MeP mixtures induced H<sub>2</sub>O<sub>2</sub> accumulation, whereas the OC + BuP mixtures promoted lipid peroxidation in the root meristems of <i>A. cepa</i>, resulting in significant mitodepressive, aneugenic, and clastogenic effects. The OC + BuP combination markedly reduced root growth in the three evaluated species and, in onion, caused mitotic indices below 50% compared to the control, demonstrating severe cytotoxicity to the meristems. In contrast, the OC + MeP combination stimulated root growth in cucumber, tomato, and onion. However, although significantly longer, the formed roots exhibited greater susceptibility to breakage than the control, indicating that growth predominantly associated with cell elongation, without concomitant cell proliferation. The interaction between the compounds was characterized as synergistic for OC + MeP and additive for OC + BuP, with BuP being the main determinant of mixture toxicity. Thus, mixtures of OC + MeP and OC + BuP may impair the early establishment of crops by affecting root system functionality, delaying or inhibiting root development, and altering root structural stability. These effects indicate that the presence of these micropollutant mixtures in contaminated agricultural soils may negatively influence plant development and the agronomic performance of cultivated plants.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"7171333"},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816869","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":"Nonclinical Safety Evaluation of Renogrit: In Vitro Nonmutagenicity (OECD 471) and 28-Day Repeated Oral Dose Toxicity (OECD 407) in Sprague Dawley Rats.","authors":"Acharya Balkrishna, Aakanksha Tiwari, Himanshu Jangid, Kamaraj Mani, Savita Lochab, Sandeep Sinha, Anurag Varshney","doi":"10.1155/jt/5905101","DOIUrl":"https://doi.org/10.1155/jt/5905101","url":null,"abstract":"<p><p>Renogrit is a prescription medicine developed by employing the traditional knowledge of Ayurveda for the management of kidney disorders. To support its extensive clinical investigations, Renogrit requires robust nonclinical safety assessments. Accordingly, in this study, in vitro mutagenicity assay and in vivo subacute toxicity were conducted as per the Organization for Economic Co-operation and Development (OECD) guidelines. Mutagenic potential of Renogrit was tested using <i>Salmonella typhimurium</i> and <i>Escherichia coli uvrA</i> tester strains in the presence and absence of metabolic activation. DMSO stock solution of Renogrit was assessed at 0.05, 0.15, 0.5, 1.5, and 5.0 mg/plate concentrations, in triplicates, along with the vehicle (DMSO) control and respective positive controls. The revertant colonies were counted after 64- to 72-h incubation period at 37°C. Renogrit was administered to Sprague Dawley (SD) rats by oral route for 28 consecutive days, at the dose levels of 100, 300, and 1000 mg/kg/day. Animals were monitored for all major toxicological parameters, such as morbidity and mortality, clinical signs, body weight, feed consumption, ophthalmological examinations, and functional observational battery (FOB) assessments during the live phase of the study. At study termination, all animals were subjected to hematological analysis, clinical chemistry analysis, examination of organs for gross pathology, and histopathological investigations. The revertant colonies counted in the Renogrit-incubated plates were not significantly increased when compared to vehicle-treated plates, thereby signifying its nonmutagenic potential. Additionally, the subacute toxicity study revealed no toxicologically significant changes attributable to Renogrit administration up to a dose of 1000 mg/kg/day. In conclusion, Renogrit was found to be a nonmutagenic at the evaluated concentrations, and its No Observed Adverse Effect Level (NOAEL) was determined to be 1000 mg/kg/day. The study outcomes provide future nonclinical safety assessments of Renogrit and its detailed clinical evaluation.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"5905101"},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775099","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}
Journal of ToxicologyPub Date : 2026-04-23eCollection Date: 2026-01-01DOI: 10.1155/jt/8893441
Samuel Arsène Ntyam Mendo, Séverin Tchameni Nguemezi, Laure Brigitte Kouitcheu Mabeku, Modeste Lambert Sameza, Rosalie Anne Ngono Ngane
{"title":"Safety Assessment of <i>Pseudomonas fluorescens</i> DS17R Chloroform Extract: Low Acute But Dose-Dependent Subacute Oral Toxicity in Rats.","authors":"Samuel Arsène Ntyam Mendo, Séverin Tchameni Nguemezi, Laure Brigitte Kouitcheu Mabeku, Modeste Lambert Sameza, Rosalie Anne Ngono Ngane","doi":"10.1155/jt/8893441","DOIUrl":"https://doi.org/10.1155/jt/8893441","url":null,"abstract":"<p><p>The present study evaluated the acute and subacute oral toxicities of a chloroform extract from <i>Pseudomonas fluorescens</i> DS17R in Wistar rats to support its safe application as a biocontrol agent. For acute toxicity assessment following OECD Guideline 423, female Wistar rats (<i>n</i> = 3 per step) received single oral doses of 300, 2000, or 5000 mg/kg body weight (bw) and were observed for 14 days. For subacute toxicity, female rats (<i>n</i> = 5 per group) received daily oral doses of 0 (control), 57.5, 115, 230, or 460 mg/kg bw for 28 days, after which hematological, biochemical, and histopathological analyses were performed. Acute toxicity testing revealed no mortality at 300 or 2000 mg/kg bw, but 50% mortality at 5000 mg/kg bw, yielding a median lethal dose (LD<sub>50</sub>) of 4574 mg/kg bw, classifying the extract as practically nontoxic (OECD Category 5). Subacute 28-day oral exposure induced dose- and time-dependent physiological and biochemical responses. Body weight showed a biphasic pattern, with a significant increase at 57.5 mg/kg bw and reductions at ≥ 115 mg/kg bw, while feed intake was transiently suppressed. Hepatic enlargement was observed at 115-460 mg/kg bw, accompanied by elevated alkaline phosphatase and mild AST increase; histology revealed sinusoidal dilation and leukocyte infiltration. Splenomegaly, lymphopenia at 230 and 460 mg/kg bw, microcytosis, anisocytosis, and thrombocytosis reflected hematopoietic and immune modulation. Renal stress was evidenced by hyponatremia, hypokalemia, hypochloremia, hypercalcemia, and decreased phosphate at doses ≥ 57.5 mg/kg bw, with mild tubular alterations. Lipid remodeling included increased triglycerides and HDL, with decreased LDL at doses ≥ 115 mg/kg bw. Overall, the extract induced adaptive metabolic and redox-mediated responses without irreversible organ damage, supporting its potential safe use as a microbial biocontrol agent under the tested conditions.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8893441"},"PeriodicalIF":3.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775129","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}
Journal of ToxicologyPub Date : 2026-04-12eCollection Date: 2026-01-01DOI: 10.1155/jt/6989296
Devanand Shanmugasundaram, Richard Anthony Wang
{"title":"90-Day Subchronic Toxicological Evaluation of a Zylaria in Sprague Dawley Rats.","authors":"Devanand Shanmugasundaram, Richard Anthony Wang","doi":"10.1155/jt/6989296","DOIUrl":"https://doi.org/10.1155/jt/6989296","url":null,"abstract":"<p><strong>Objective: </strong>Zylaria comprises a blend of botanical components, including <i>Xylaria Nigripes</i> (mycelium), <i>Cuscuta Chinensis</i> (seed) and <i>Panax Notoginseng</i> (root). This study aimed to evaluate the potential toxicity of Zylaria when administered orally (via gavage) to Sprague Dawley (SD) rats for 90 days continuously and examine any delayed toxicity after a minimum recovery period of 28 days post-treatment cessation.</p><p><strong>Methods: </strong>One hundred SD rats of both sexes were divided into six study groups: four main groups with 10 rats of each sex receiving different doses of Zylaria (0, 1000, 2750 and 4500 mg/kg body weight per day) and two recovery groups with five rats of each sex receiving either the vehicle control (Milli-Q water) or high-dose Zylaria. Throughout the study, animals were monitored daily for general behaviour, body weight fluctuations and clinical signs. Upon completion of the treatment period, haematological, coagulation, clinical chemistry, thyroid hormone analyses and histopathological examination of organs were conducted.</p><p><strong>Results: </strong>Oral administration of Zylaria at tested concentrations did not induce any adverse events on general health, body weight, relative organ weights, or haematological, coagulation, clinical chemistry, and thyroid hormone parameters. Histopathological examination demonstrated no significant structural alterations in organs, even in animals treated with high doses of Zylaria. No test item-related effects were observed during the 28-day recovery period after cessation of the treatment.</p><p><strong>Conclusion: </strong>The study concluded that Zylaria treatment for 90 days does not lead to toxicity, even at doses up to 4500 mg/kg bw/day, indicating its safety for use.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"6989296"},"PeriodicalIF":3.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690759","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}
Journal of ToxicologyPub Date : 2026-04-11eCollection Date: 2026-01-01DOI: 10.1155/jt/2022957
Cheng-Hsin Lu, Chun-Hsien Wu, Pei-Fang Hsieh, Richard Chen-Yu Wu, Hsing-Chia Mai, Wei-Lun Huang, Sih-Han Chen, Chien-Ming Lai, Victor C Lin, Chiang-Ting Wang
{"title":"Phillyrin Modulates AMPK-Associated Cellular Responses and Migration in PC3 Prostate Cancer Cells.","authors":"Cheng-Hsin Lu, Chun-Hsien Wu, Pei-Fang Hsieh, Richard Chen-Yu Wu, Hsing-Chia Mai, Wei-Lun Huang, Sih-Han Chen, Chien-Ming Lai, Victor C Lin, Chiang-Ting Wang","doi":"10.1155/jt/2022957","DOIUrl":"https://doi.org/10.1155/jt/2022957","url":null,"abstract":"<p><p>Males with prostate cancer exhibit substantial mortality and metastasis; however, few effective treatment strategies are available for advanced prostate cancer. Phillyrins (PHNs) are lignan glycosides that have been reported to exhibit diverse biological activities, including potential anticancer effects. We aimed (1) to assess the effect of PHN on PC3 prostate cancer cells and (2) to examine cellular responses associated with its activity. To assess the effects of PHN, it was exposed to various concentrations of PHN (1, 2.5, and 5 μM) for 24 h. A wound-healing assay was performed to evaluate cell migration. Western blotting and immunofluorescence were used to investigate the expression of adenosine monophosphate-activated protein kinase (AMPK)-associated proteins and transcription factors involved in epithelial-mesenchymal transition (EMT). PHN exposure was associated with reduced migratory capacity of PC3 cells under noncytotoxic conditions. PHN exposure was associated with decreased α-smooth muscle actin, Snail, and Slug expression while increasing E-cadherin expression. Sirtuin 1 (SIRT1) and nuclear respiratory factor 1 (NRF1) protein levels were upregulated in PHN-treated cells, accompanied by changes in AMPK protein expression. Pharmacological inhibition with Compound C attenuated PHN-associated changes in EMT-related marker expression in PC3 cells. Thus, PHN exposure may influence EMT-associated phenotypes in PC3 cells, potentially involving AMPK-associated signaling.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"2022957"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674639","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":"Tracing Toxicity: A Scientometric Perspective on Three Decades of Metallic Pollutants Research.","authors":"Prasanna Devi Balachandran, Rajeswari Shanmugam, Vijayalakshmi Varadarajan, Brindha Rethinam, Sankar Ganesh Palani","doi":"10.1155/jt/8884503","DOIUrl":"https://doi.org/10.1155/jt/8884503","url":null,"abstract":"<p><p>Rapid industrialization and urbanization have led to the unchecked discharge of toxic metals, posing serious threats to ecosystems and public health. This study analyses scientometric data on toxic metal pollutants, covering publications from 1992 to 2024. About 220 documents (183 research articles and 37 reviews) were extracted from Web of Science using BibExcel and VOSviewer to explore global research trends on metal toxicity, focusing on lead (Pb), mercury (Hg), cadmium (Cd), arsenic (As), chromium (Cr), scandium (Sc), beryllium (Be), and aluminum (Al). A notable rise in research since 2000 reflects growing awareness of metal-related risks. China leads in publication output, while the United Kingdom ranks highest in citation impact. The National Natural Science Foundation of China (NSFC) played a key role in advancing high-impact studies. It prioritizes funding for research in environmental toxicology and health effects of pollutants, environmental exposure and health effects of emerging toxic substances, toxicology of micro-/nanomaterials, toxicological mechanisms and health impacts of atmospheric fine particulate matter (PM<sub>2</sub>.<sub>5</sub>), and prevention and control of hazardous chemicals. Keyword co-occurrence and cluster analysis highlight themes such as bioremediation, nanomaterials, and detection technologies. Key research gaps include limited data on rare earth metal toxicity and the effects of chronic low-dose exposures. This study underscores the need for integrated global efforts in detecting, remediating, and mitigating risks.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8884503"},"PeriodicalIF":3.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645423","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":"Microplastics Induced Dysfunctions in Physiology and Behavior of Fish: A Comprehensive Review.","authors":"Md Asad Ud Zahan Siddique, Md Sayem Sheikh, Md Shahjahan, Md Al-Emran","doi":"10.1155/jt/4669316","DOIUrl":"https://doi.org/10.1155/jt/4669316","url":null,"abstract":"<p><p>Microplastics (MPs) pollution is a global concern due to their widespread persistence, occurrence, and toxicity to aquatic organisms. Fish are most vulnerable to MPs due to their feeding habits and ecological niches. This review critically synthesizes current evidences on MPs induced disruptions of key physiological functions and behavioral patterns in fish, with an emphasis on the underlying mechanistic pathways and biological consequences. MPs originate from various sources, entering aquatic systems and being ingested by fish directly or via trophic transfer. A prominent effect is growth inhibition commonly caused by gastrointestinal damage, impaired nutrient absorption, and metabolic stress. Moreover, it causes several hematobiochemical disruptions including anemia, leukocyte fluctuations, and biochemical and enzymatic imbalances that are connected to oxidative stress and immunosuppression. MPs also disrupt reproductive performances of fish through altering gonadosomatic index, inducing endocrine disruptions, dysregulating hypothalamic-pituitary-gonadal axis genes, and reducing fertilization and hatching success, with several transgenerational effects. Furthermore, MPs can induce oxidative stress through overproduction of reactive oxygen species (ROS) and modulation of antioxidant enzymes, along with dysregulation of immune and inflammatory responses. Behavioral alterations include reduced swimming performance and changes in feeding and reproductive behavior, which are linked to neurotoxicity and impairment of energy metabolism. Although a limited number of studies suggest species-specific effects, most studies highlight significant adverse impacts on fish health. Hence, this review and meta-analysis indicates that MPs substantially compromise fish physiology manifesting as poor growth, altered blood and metabolic profiles, impaired reproduction, and behavioral patterns. By integrating sources and transport pathways to physiological and behavioral outcomes, this review provides a comprehensive summary to inform ecological risk assessment and management of MPs in fisheries and aquatic ecosystems.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"4669316"},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639247","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":"Protective Effects of <i>Luffa cylindrica</i> Leaf Infusion Against Cisplatin and CCl<sub>4</sub>-Induced Hepatorenal Toxicity in Rats: Biochemical, Histopathological, and Molecular Docking Analysis.","authors":"Takoua Ben Hlel, Anouar Feriani, Nadia Khelifi, Zouhaier Abbes, Issam Smaali","doi":"10.1155/jt/8845909","DOIUrl":"https://doi.org/10.1155/jt/8845909","url":null,"abstract":"<p><p>This study demonstrated the antioxidant potential of <i>Luffa cylindrica</i> leaf infusion (LLI) in alleviating oxidative damage induced by cisplatin and carbon tetrachloride (CCl<sub>4</sub>) in Wistar rats. Phytochemical analysis confirmed the presence of bioactive compounds, such as protocatechuic acid (PCA; 5.83 mg/g DW), naringenin (5.54 mg/g DW), chlorogenic acid (CA; 4.90 mg/g DW), and ascorbic acid (4.87 mg/g DW). In vivo results showed that LLI administration by gavage significantly improved kidney and liver functions, particularly at a dose of 40 mg/kg, as evidenced by serum biochemical markers for both organs. Furthermore, LLI pretreatment restored superoxide dismutase (SOD) and CAT activity while reducing MDA levels, indicating a protective effect against oxidative stress. Histopathological analysis revealed that LLI treatment reduced structural damage in liver and kidney tissues, confirming its protective capacity. Molecular docking studies revealed that naringenin, PCA, and CA exhibit strong binding affinities to SOD, potentially enhancing its activity synergistically. These findings suggest that LLI, rich in natural antioxidants, may serve as a promising therapeutic candidate for mitigating oxidative stress-induced organ damage, warranting further investigation in clinical settings.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8845909"},"PeriodicalIF":3.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633927","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}
Journal of ToxicologyPub Date : 2026-04-01eCollection Date: 2026-01-01DOI: 10.1155/jt/1785323
Domenico Britti, Romano Marabelli, Luigino Calzetta
{"title":"Centripetal Axonal Transport as a Gateway to the CNS for Veterinary Antiparasitics: Bypassing the Blood-Brain Barrier, Clinical Impact in Vulnerable Age Groups, and the Potential Facilitating Role of PFAS.","authors":"Domenico Britti, Romano Marabelli, Luigino Calzetta","doi":"10.1155/jt/1785323","DOIUrl":"https://doi.org/10.1155/jt/1785323","url":null,"abstract":"<p><p>The widespread use of veterinary antiparasitics, including neonicotinoids, isoxazolines, avermectins, and pyrethroids, is essential for canine health but raises concerns regarding potential neurotoxicity, particularly in young and geriatric animals. While the blood-brain barrier (BBB) offers significant protection, this review confronts a central \"Safety Paradox\": how can a drug class with a demonstrated high therapeutic index in conventional safety studies be associated with a significant and persistent number of real-world neurological adverse events? We propose that centripetal (retrograde) axonal transport represents a critical, underappreciated pathway for these compounds to access the central nervous system (CNS) from peripheral nerve terminals, offering a mechanistic solution to this paradox. This mechanism, well documented for various toxins and pathogens, could allow antiparasitics to bypass the BBB, leading to direct neuronal effects and contributing to clinical signs such as tremors. We review the neurotoxic mechanisms of these common antiparasitics, the established principles of retrograde axonal transport, and the chemical properties that make them candidates for such transport. Furthermore, we introduce the expanded hypothesis that per- and polyfluoroalkyl substances (PFASs)-present not only as \"inert\" ingredients or contaminants but, as recent regulatory findings reveal, also as active ingredients themselves-could act as both facilitators of transport for other neurotoxicants and as direct, cotransported neurotoxic agents. This review synthesizes existing and recent evidence to build a compelling case for axonal transport as a significant contributor to antiparasitic neurotoxicity, discusses its potential for differential clinical impact in young and old dogs, and highlights the urgent need for research into this pathway and the complex toxicological role of formulation components like PFAS.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"1785323"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609191","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}
Journal of ToxicologyPub Date : 2026-04-01eCollection Date: 2026-01-01DOI: 10.1155/jt/4227246
Mary-Ann Archer, Kwabena Ofori-Kwakye, Raphael Johnson, Ernest Amponsah Asiamah, Wisdom Ahlidja, Mustapha Abubakar Ahmed, Isaac Tabiri Henneh
{"title":"Assessment of the Safety Profile of Purified <i>Pentadesma butyracea (Clusiaceae)</i> Gum Intended as a Pharmaceutical Excipient.","authors":"Mary-Ann Archer, Kwabena Ofori-Kwakye, Raphael Johnson, Ernest Amponsah Asiamah, Wisdom Ahlidja, Mustapha Abubakar Ahmed, Isaac Tabiri Henneh","doi":"10.1155/jt/4227246","DOIUrl":"https://doi.org/10.1155/jt/4227246","url":null,"abstract":"<p><p><i>Pentadesma butyracea</i> (family <i>Clusiaceae</i>) bark is widely used in traditional medicine across sub-Saharan Africa. However, the investigation of the safety profile of the gum exudate obtained from the stem bark of the plant is undocumented. This study evaluated the acute and subacute toxicity of the purified <i>Pentadesma butyracea</i> gum (PBG) in 36 male Sprague Dawley rats (8-10 weeks old; 100-182.08 g) to determine its safety profile for potential use as a pharmaceutical excipient. Acute toxicity was assessed using a single oral dose of 2000 mg/kg PBG, while subacute toxicity involved daily administration of 250, 500, and 1000 mg/kg PBG for 28 days. In the acute toxicity study, no mortality or significant adverse effects on behavior, body weight, relative organ weight, or histological features were observed, suggesting an LD<sub>50</sub> greater than 2000 mg/kg PBG. Hematological and biochemical analyses revealed no harmful deviations, supporting the safety of PBG in acute exposure. In the subacute study, no mortality occurred across all doses, and body weight changes were minimal. Relative organ weights of the kidneys, heart, and lungs increased at higher doses, indicating potential dose-dependent effects. Biochemical analyses revealed no significant alterations in liver enzymes (AST, ALT, and ALP) or markers of kidney function (urea and creatinine) at lower doses; however, slight elevations in bilirubin and creatinine were observed at 1000 mg/kg PBG, suggesting mild hepatic and renal stress. Histopathological analysis confirmed the absence of severe pathological changes, with only mild and reversible alterations at higher doses. Overall, PBG demonstrated a favorable safety profile at doses below 1000 mg/kg, supporting its potential use as a pharmaceutical excipient. The preliminary phytochemical screening also showed the presence of tannins, glycosides, coumarins, sterols, and triterpenoids. Further studies, including chronic toxicity and pharmacokinetic assessments, are recommended to establish the long-term safety of PBG.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"4227246"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609173","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}