Journal of Toxicology最新文献

{"title":"Toxicological Vulnerabilities and Emerging Safety Signals in Modified mRNA Vaccine Technology: A Narrative Review of the COVID-19 Experience.","authors":"Gerry A Quinn, Philipp Bagus, Antonio Sánchez-Bayón, Ronan Connolly, Clare Craig, Paul Frijters, Steven J Hatfill, Anton O'Connor, Daniel Santiago, Ricardo F Savaris, Michaéla C Schippers, Willie Soon, Demetrios A Spandidos, Helmut Sterz, Aristidis M Tsatsakis, Harald Walach","doi":"10.1155/jt/8202757","DOIUrl":"10.1155/jt/8202757","url":null,"abstract":"<p><p>The rapid deployment in early 2021 of modified mRNA (modRNA) as a vaccine platform for the COVID-19 pandemic sparked a wave of optimism for its potential as a preventive medicine. However, this compacted timeframe may not have fully addressed certain toxicological risks associated with this new technology, which would typically require more extensive preclinical testing. Five years postrollout, an accumulating body of postauthorisation evidence has highlighted safety signals that require closer scrutiny, such as those concerning biodistribution, off-target effects and persistent adverse events. Independent analyses of Phase III trial data and pharmacovigilance reports have raised questions regarding benefit-risk balance and potential long-term biological effects. This narrative review examines the evolution of the toxicological understanding of modified RNA as a vaccine technology from platform design through long-term observational data, identifying areas of uncertainty and vulnerability that may inform future development and regulatory evaluation. The review emphasises that fast-tracked decision-making under exceptional uncertainty requires explicit safeguards to prevent premature certainty and to support learning from emerging evidence over time.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8202757"},"PeriodicalIF":2.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216377","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":"90-Day Repeated-Dose Toxicological Assessment of MUVZ in Sprague Dawley Rats: Subchronic Study.","authors":"Devanand Shanmugasundaram","doi":"10.1155/jt/9540593","DOIUrl":"https://doi.org/10.1155/jt/9540593","url":null,"abstract":"<p><strong>Objectives: </strong><i>Vitex negundo</i> and <i>Zingiber officinale</i> are predominantly used in day-to-day life as food or supplements. Both are being reported individually for therapeutic properties. A food supplement consisting of leaves and twigs of <i>Vitex negundo</i> and rhizome of <i>Zingiber officinale</i>, the first-of-a-kind proprietary blend extract (MUVZ), was developed for joint health.</p><p><strong>Methods: </strong>As part of the safety profile, a subchronic toxicity study was performed in Sprague Dawley rats under compliance with Good Laboratory Practice (GLP). The study aimed to determine the potential toxicity of MUVZ following oral (gavage) administration by following Organisation for Economic Co-operation and Development (OECD) Guideline 408. MUVZ was administered for 90 days, with a recovery period of 28 days. MUVZ was administered at 0 (G1), 1000 (G2), 2000 (G3) and 3000 (G4) mg.kg^-1 body weight (<i>n</i> = 10/sex/group); vehicle control (G1R) and high-dose recovery groups 3000 mg.kg^-1·b.w (G4R) (<i>n</i> = 5/sex/group).</p><p><strong>Results: </strong>No MUVZ-related effects were observed in mortality, morbidity, detailed clinical signs, body weight and feed consumption. Statistical significance was found in levels of clinical pathology parameters; however, there was no dose dependency, and further correlative histopathological findings were observed. At the end of the experimental trial, no test article-induced gross and microscopic pathological lesions were observed across the treatment groups.</p><p><strong>Conclusions: </strong>Based on the findings, no toxicologically significant findings were derived at the highest dose of 3000 mg.kg^-1 body weight.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"9540593"},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182744","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":"Chronic Lead Exposure and Tauopathies: Molecular Mechanisms of Neurotoxicity and Emerging Nanotherapeutic Strategies.","authors":"Maryam Ebrahimi, Mahsa Javan, Mahdi Alijanianzadeh","doi":"10.1155/jt/3248563","DOIUrl":"https://doi.org/10.1155/jt/3248563","url":null,"abstract":"<p><p>Chronic exposure to lead (Pb) remains a critical global public health challenge, extending beyond its established neurotoxic effects to its emerging role in the pathogenesis of neurodegenerative disorders, particularly tauopathies. Accumulating evidence indicates that prolonged Pb exposure disrupts neuronal homeostasis through multiple interconnected mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, epigenetic alterations, and dysregulation of tau phosphorylation. These molecular perturbations contribute to synaptic impairment, neuronal loss, and progressive cognitive decline. Current therapeutic strategies primarily rely on metal chelation and antioxidant interventions; however, their clinical efficacy is limited by poor blood-brain barrier penetration, nonselective metal removal, and systemic adverse effects. Recent advances in nanotechnology offer promising alternatives for targeted neuroprotection. Nanocarrier systems, including dendrimers, liposomes, polymeric nanoparticles, and micelles, enable enhanced brain delivery, controlled drug release, and reduced systemic toxicity. This review synthesizes current knowledge on the molecular mechanisms linking Pb exposure to tau-related neurodegeneration and critically evaluates existing therapeutic approaches. Furthermore, it highlights the potential of nano-based delivery systems to overcome the limitations of conventional therapies and outlines future directions for translational research in Pb-associated neurodegenerative disorders.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"3248563"},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182739","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":"In Vivo Acute and Subchronic Toxicity of <i>Stereospermum acuminatissimum</i> Stem Bark Aqueous Extract.","authors":"Fabrice Mba Medou, Lucienne Armelle Brooks, Nyemb Nyunaï, Leonel Ntepe Mbah, Esther Ngo Lemba Tom, Theodora Kowa Kopa, Rosette Megnekou","doi":"10.1155/jt/8985688","DOIUrl":"10.1155/jt/8985688","url":null,"abstract":"<p><strong>Background: </strong>Despite its traditional use in Africa for weight management, the safety profile of the aqueous stem bark extract of <i>Stereospermum acuminatissimum</i> remains undocumented. This study evaluated its acute and subchronic toxicity in <i>Wistar</i> rats.</p><p><strong>Methods: </strong>Acute toxicity was assessed according to OECD Guideline 425 using a single oral dose of 5000 mg/kg. Subchronic toxicity was evaluated over 56 days at doses of 150, 300 and 600 mg/kg/day. Satellite groups (the control and the 600 mg/kg/day group) were maintained for an additional 14 days to observe the reversibility of any treatment-related effects. Parameters studied included body/organ weights, haematological, biochemical, lipid and histopathological profiles.</p><p><strong>Results: </strong>No mortalities or signs of acute toxicity were observed during the 14 days following extract administration. Subchronic administration did not affect survival or relative organ weights, although the 600 mg/kg dose induced minor structural alterations in affected organs. The extract significantly reduced body weight gain. At 150 mg/kg, the extract sex-specifically improved lipid profiles by lowering triglycerides in males and increasing HDL cholesterol in females. Haematological assessment revealed a dose-dependent increase in platelet counts in male rats at 600 mg/kg, which returned to baseline levels after the 14-day recovery period. Elevated AST and ALT fully reversed in females post-recovery; however, elevated ALT persisted at 600 mg/kg in males. Creatinine remained stable or decreased, and minor variations in urea concentrations in both sexes returned to baseline during recovery.</p><p><strong>Conclusion: </strong><i>S. acuminatissimum</i> aqueous extract reduces body weight gain and improves lipid profiles at low-to-moderate doses (150-300 mg/kg), providing its traditional use. However, the persistence of elevated ALT levels and focal leucocyte infiltration in males at 600 mg/kg indicates high-dose hepatotoxicity, highlighting a narrow therapeutic window and the need for careful liver function monitoring during prolonged exposure.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8985688"},"PeriodicalIF":2.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111459","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":"Glycoalkaloids Affect the Animal Nervous System: A Review.","authors":"Gracjan Dudek, Aleksandra Jaworska, Paweł Marciniak","doi":"10.1155/jt/1380303","DOIUrl":"https://doi.org/10.1155/jt/1380303","url":null,"abstract":"<p><p>Glycoalkaloids (GAs) are plant secondary metabolites produced mainly by species of the <i>Solanaceae</i> family, such as the tomato <i>Solanum lycopersicum</i> L. Although traditionally associated with toxicity, recent research highlights their diverse biological activities, including anti-inflammatory, anticancer, antimicrobial, and neuroprotective effects. These properties arise from their ability to interact with cell membranes, modulate key signaling pathways, and influence immune responses. Selected GAs, such as solasonine, solamargine, and α-tomatine, have demonstrated the potential to regulate inflammation, induce apoptosis in cancer cells, affect the tumor microenvironment, and modulate microglial activity in the nervous system. Moreover, their toxicity remains an important limitation, emphasizing the need for further studies on structure-activity relationships and strategies to reduce adverse effects while preserving therapeutic potential. Overall, GAs represent promising candidates for future research aimed at developing novel therapeutic approaches, provided that their safety profiles are thoroughly characterized.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"1380303"},"PeriodicalIF":2.8,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111417","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":"Effect of Herbal Extracts on Antituberculosis Drug-Induced Hepatotoxicity: A Systematic Review.","authors":"Surthi M Ravedar, Kranthi Kiran Akula, Kalesh M Karun, Flemin Felix, Kamran Zaman, Jyothi Bhat, Subarna Roy","doi":"10.1155/jt/6698835","DOIUrl":"10.1155/jt/6698835","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a major global health challenge. While effective, first-line antitubercular drugs such as isoniazid and rifampicin often cause hepatotoxicity, limiting treatment safety. Herbal extracts with antioxidant and hepatoprotective properties may help mitigate this liver damage. This systematic review evaluates the protective effects of plant extracts against antitubercular drug-induced hepatotoxicity, aiming to inform potential adjuvant strategies.</p><p><strong>Methods: </strong>Following PRISMA-P guidelines, PubMed, Scopus, and Google Scholar were searched for \"in vivo studies assessing plant extracts against hepatotoxicity caused by anti-TB drugs.\" Two independent reviewers screened and extracted data. Study quality was evaluated using SYRCLE's risk of bias tool.</p><p><strong>Results: </strong>Sixty-eight in vivo studies were included. Overall, plant extracts demonstrated variable hepatoprotective efficacy, with some showing significant improvement in certain species-<i>Luffa acutangula</i> L.<i>, Lawsonia inermis</i> L., and <i>Cucumis trigonus</i> Roxb. showed the highest reduction in serum liver enzymes: aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) in U/L, and total bilirubin (TBil) and antioxidant parameters glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), suggesting hepatoprotective potential.</p><p><strong>Conclusion: </strong>Medicinal plants demonstrate variable hepatoprotective effects in animal models of anti-TB drug-induced liver injury, though their mechanisms of oxidative stress remain unclear. Among them, the extracts from <i>Luffa acutangula</i> L., <i>Lawsonia inermis</i> L., and <i>Cucumis trigonus</i> Roxb. showed promising hepatoprotective effects. These effects are likely associated with antioxidant and cytoprotective mechanisms. However, further well-designed preclinical and clinical research are required to establish their dosage, safety, and efficacy before integration into TB therapy. <b>Trial Registration:</b> PROSPERO: CRD42024563060.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"6698835"},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080534","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":"Morphological and Cytotoxic Effects of Metal Salts on Osteoblast Cells in Three-Dimensional Spheroidal Cultures.","authors":"Misael Vargas-López, José Luis Castrejón-Flores, Ángel Ernesto Bañuelos-Hernández, Fernando Gómez-Chávez, Ricardo García-Ruiz, Ma Lourdes Rojas-Morales, Elizabeth Pérez-Hernández, Nury Pérez-Hernández","doi":"10.1155/jt/1047932","DOIUrl":"10.1155/jt/1047932","url":null,"abstract":"<p><p>The skeleton provides structural support, organ protection, and mineral storage, making the long-term biocompatibility of orthopedic implants essential. Although stainless steel and cobalt-based alloys are widely used in these devices, corrosion can release metal ions that induce inflammatory and cytotoxic responses in surrounding bone tissue. Because most in vitro studies rely on conventional two-dimensional (2D) cultures, three-dimensional (3D) spheroids offer a more physiologically relevant model for evaluating metal ion toxicity. In this study, human fetal osteoblast (hFOB) spheroids were exposed to CrCl₃, CoCl₂, or NiCl₂ at 100 or 500 μM for 12 days. Morphological alterations were evaluated by scanning electron microscopy and histology, while cytotoxicity and apoptosis were assessed using resazurin, live/dead fluorescence, and annexin V/propidium iodide staining. CrCl₃ caused minimal effects at 100 μM and only moderate cytotoxicity at 500 μM. In contrast, CoCl₂ and especially NiCl₂ significantly reduced spheroid growth, induced retraction of cytoplasmic extensions, membrane damage, and increased apoptosis, with the most severe effects observed at 500 μM. Fluorescence and Annexin V staining confirmed a higher abundance of apoptotic bodies after CoCl₂ and NiCl₂ exposure than after CrCl₃ treatment. These findings demonstrate that 3D osteo-spheroids provide a physiologically relevant platform for investigating the biological effects of metal ions released from orthopedic implants and reveal that nickel and cobalt ions exert substantially greater cytotoxicity than chromium under prolonged exposure conditions.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"1047932"},"PeriodicalIF":2.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062182","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":"Clinical, Biochemical, and Electrocardiographic Predictors of Mortality in Acute Aluminum Phosphide Poisoning.","authors":"Raghda H Deraz, Omar Saafan, Laila M E Sabik, Shymaa M N Abdulrhman","doi":"10.1155/jt/4876498","DOIUrl":"https://doi.org/10.1155/jt/4876498","url":null,"abstract":"<p><strong>Background: </strong>Aluminum phosphide (AlP) poisoning is among the deadliest pesticide poisonings, particularly in developing agricultural communities, with multiorgan involvement significantly affecting the poisoned patient's outcome.</p><p><strong>Objective: </strong>To evaluate the prognostic significance of arterial blood gas (ABG), serum troponin I, cortisol, renin, early ECG abnormalities, and the Simplified Acute Physiology Score II (SAPS II) in predicting the outcome of acute AlP poisoning during the first 24 h postingestion.</p><p><strong>Methods: </strong>A prospective cohort study was conducted on 42 patients with confirmed acute AlP ingestion who met the inclusion criteria at Zagazig University Hospitals. All patients underwent thorough history-taking, clinical assessment, routine laboratory investigations, and selected specific tests, including ECG assessment, measurement of serum troponin I, cortisol, and renin, ABG analysis, and finally SAPS II scoring. Patients were categorized as survivors or nonsurvivors. The predictive ability of several parameters for mortality was assessed using the <i>t</i>-test and ROC curve analysis.</p><p><strong>Results: </strong>Mortality rate was 59.5%. Abnormal ECGs were significantly more common in nonsurvivors (<i>p</i> < 0.001). Renin (AUC = 0.81) and cortisol (AUC = 0.69) demonstrated fair-to-good predictive accuracy, whereas troponin I showed poor prognostic value (AUC = 0.48). SAPS II demonstrated very high discriminatory performance (AUC = 1.00). SAPS II also correlated positively with serum cortisol and renin, and negatively with pH, bicarbonate, and base excess.</p><p><strong>Conclusion: </strong>SAPS II had the highest validity as a mortality predictor for AlP poisoning, followed by bicarbonate, base excess, renin, pH, and cortisol, arranged in descending order according to their AUC. ECG evaluation is also a reliable early predictor of mortality. These parameters can aid early risk stratification and guide timely intensive management.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"4876498"},"PeriodicalIF":2.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039293","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":"Adverse Effects of Airborne Heavy Metals on Human Skin Cells: Insights From Sebum Analysis of Indoor and Outdoor Workers.","authors":"Hye-Won Na, Nari Cha, Eun Joo Kim, Sanghun Kim, Won-Seok Park, Hyoung-June Kim","doi":"10.1155/jt/7925949","DOIUrl":"10.1155/jt/7925949","url":null,"abstract":"<p><p>Heavy metals in particulate matter (PM) contribute to oxidative stress, DNA damage, and inflammatory responses in skin cells. This study aimed to investigate the toxic effects of airborne heavy metals on human sebocytes, keratinocytes, and ex vivo skin. To this end, we collected sebum samples from indoor (<i>n</i> = 62) and outdoor (<i>n</i> = 40) workers in Shanghai and quantified the concentrations of 24 metals using inductively coupled plasma mass spectrometry (ICP-MS). Outdoor workers exhibited higher levels of cobalt (0.0004 vs. 0.39 mg/kg, 924.7-fold), arsenic (0.11 vs. 14.15 mg/kg, 134.7-fold), barium (0.70 vs. 20.24 mg/kg, 28.8-fold), and manganese (0.86 vs. 14.93 mg/kg, 17.3-fold) than indoor workers. Sebum-mimicking metal mixtures (SMMs), formulated to reflect the specific heavy metal profiles identified in the workers' sebum, were applied to human epidermal keratinocytes and sebocytes. Outdoor SMMs significantly reduced cell viability, increased lipid peroxidation, and induced DNA damage, as evidenced by the phosphorylation of histone H2AX (γH2AX) foci formation. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) analysis revealed upregulated <i>IL1A, IL1B, TNFA, IL6,</i> and <i>PTGS2</i> mRNA, primarily after treatment with outdoor SMMs. Further activation of the NF-κB and MAPK signaling pathways was also identified. This was corroborated in human scalp skin models, in which exposure to outdoor SMMs increased the expression of proinflammatory cytokines, including interleukin-1β (IL-1β) and IL-6, and decreased the expression of keratin 10. These findings highlight the detrimental effects of environmental heavy metals on skin homeostasis, providing a scientific basis for the development of antipollution skincare formulations.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"7925949"},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874353","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":"Subacute Oral Toxicity Evaluation of Red Pine Oil in Sprague-Dawley Rats: Safety Profiling for Potential Therapeutic Use.","authors":"Sriwidodo Sriwidodo, Iyan Sopyan, Gofarana Wilar, Cecep Suhandi, Bayu Febram Prasetyo, Mawar Subangkit","doi":"10.1155/jt/5376656","DOIUrl":"10.1155/jt/5376656","url":null,"abstract":"<p><p>Red pine oil (<i>Pinus densiflora</i>) is a monoterpene-rich essential oil with antimicrobial, antioxidant, and anti-inflammatory activities. While commonly used topically, its systemic safety following oral use remains underexplored, limiting its development as an oral therapeutic or supplement. This research aims to evaluate the subacute oral toxicity of red pine oil in Sprague-Dawley rats over 28 days, followed by a 14-day recovery phase. Male and female rats were assigned to six groups (<i>n</i> = 10/group) and administered red pine oil at 90, 270, or 1000 mg/kg body weight/day by oral gavage. All test preparations were diluted in fish oil; control groups received fish oil alone. Parameters evaluated included clinical signs, body weight, hematology, serum biochemistry, organ weights, and histopathology of major organs. Satellite groups assessed reversibility. No mortality, behavioral changes, or clinical signs of toxicity were observed. Red pine oil significantly increased hemoglobin, hematocrit, erythrocyte count, lymphocytes, and platelets in male rats, with values returning to baseline after recovery. Triglyceride levels were reduced in males at mid and high doses. Minor increases in AST and urea in high-dose females were not accompanied by histological abnormalities. Organ weights and tissue structures remained within normal limits. All observed effects were noncumulative and reversible. Red pine oil was well-tolerated at doses up to 1000 mg/kg/day, with no systemic or organ-specific toxicity. The established NOAEL was 1000 mg/kg BW. These findings support its safety for oral use and provide a scientific basis for further pharmacological studies.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"5376656"},"PeriodicalIF":2.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818813","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}