Journal of Toxicology最新文献

{"title":"Exposure to Heavy Metals Arsenic, Cadmium and Lead Exacerbates Carcinogenic and Noncarcinogenic Health Risks Among Diabetic and Hypertensive Patients.","authors":"Fombat Zenabou Mbebwoh, Muankang Junior Tegha Kum, Choumessi Tchewonpi Aphrodite, Kada Sanda Antoine, Fusi Christian Suh, Manfo Tsague Faustin Pascal, Nantia Akono Edouard","doi":"10.1155/jt/8564316","DOIUrl":"10.1155/jt/8564316","url":null,"abstract":"<p><p>Exposure to toxic metals contributes to the growing burden of noncommunicable diseases (NCDs), yet evidence from sub-Saharan Africa remains limited. This hospital-based cross-sectional study assessed heavy metal (arsenic [As], cadmium [Cd], lead [Pb]) exposure levels and their association with health risks in adult diabetic and hypertensive patients in Cameroon. It involved 178 participants (39 diabetics, 78 hypertensives, 61 comorbid), and the urinary metals were quantified using atomic absorption spectrophotometry and normalized to creatinine. Serum oxidative stress biomarkers including glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and paraoxonase 1 (PON1) were measured. Health risk indices including estimated daily intake (EDI), chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI) and cancer risk (CR), were computed. Proportion contribution trend (PCT), receiver operating characteristic (ROC) and ordinary least squares (OLS) regression were applied for risk and predictive analyses. Diabetic patients exhibited significantly higher (<i>p</i> < 0.05) urinary Cd (5.21 ± 0.83 μg/g creatinine) and Pb (0.66 ± 0.12 μg/g creatinine) levels compared with hypertensive and comorbid patients. GSH levels were markedly lower (<i>p</i> < 0.05) in diabetics than in hypertensives. Although HQs and HIs were < 1, diabetics recorded the highest HI (2.73 × 10^-1 ± 2.27 × 10^-2; <i>p</i> < 0.05), indicating increased chronic exposure risk. CR values for As and Cd exceeded USEPA thresholds (10^-6), with diabetics showing the greatest risk. PCT identified Cd as the dominant contributor to HI across groups. ROC analysis showed that As CDI moderately predicted CR in diabetics (AUC = 0.604; <i>p</i> = 0.047). OLS regression revealed water source and residence as significant determinants of As and Pb exposure. Summarily, diabetic individuals demonstrated disproportionately higher heavy metal exposure and associated carcinogenic risk, largely driven by Cd. Integrating environmental biomonitoring into NCD management is essential to mitigate heavy metal-related health burdens in Cameroon.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8564316"},"PeriodicalIF":2.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361049","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":"Correction to \"Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats\".","authors":"","doi":"10.1155/jt/9868425","DOIUrl":"https://doi.org/10.1155/jt/9868425","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2016/9507563.].</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"9868425"},"PeriodicalIF":2.8,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345741","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":"Combined Effects of Microplastics and Mercury on Growth, Hematology, Tissue Morphology, GH/IGF Axis, and Antioxidant-Immune Responses in Nile Tilapia.","authors":"Md Ruhul Amin, Moshfiq Momtasir Neloy, Tasmia Islam Kanta, Md Mahiuddin Zahangir, Saleha Khan, Md Shahjahan","doi":"10.1155/jt/1847474","DOIUrl":"10.1155/jt/1847474","url":null,"abstract":"<p><p>Microplastics (MPs) and heavy metal mercury (Hg) have drawn global surveillance as major contaminants due to their toxic effects on aquatic organisms. The individual effects of both contaminants have been extensively characterized; however, their coexposure effects remain insufficiently explored. As aquatic organisms are increasingly exposed to multiple pollutants simultaneously in natural environments, this investigation explored the combined effects of polyamide MP (PA-MP) and Hg on Nile tilapia (<i>Oreochromis niloticus</i>) fingerlings, focusing on survival, growth, hematological balance, tissue structure, GH/IGF axis regulation, and immune-antioxidant responses. Over a 42-day trial, 240 Nile tilapia fingerlings were allocated into four triplicated treatments: control (no PA-MP or Hg), PA-MP (10 mg/L), Hg (0.03 mg/L), and PA-MP + Hg (10 mg/L + 0.03 mg/L), with 20 fingerlings per tank. The coexposure group showed increased MP accumulation and mortality, suppressed growth indicators, and substantial shifts in blood physiology, including elevated glucose (126.83 ± 2.40 mg/dL) and lowered hemoglobin (9.45 ± 0.85 g/dL), along with higher cellular and nuclear abnormalities. The histoarchitectural assessment identified severe structural deformities in the gills, intestine, liver, and kidney of coexposed fish compared to control and individual contaminants. At the transcriptional level, the expression of growth hormone-secreting gene (<i>gh</i>) in the pituitary and insulin-like growth factors (<i>igf-1</i> and <i>igf-2</i>) in the liver showed a significant downregulation under coexposure treatment. Moreover, coexposure to PA-MP and Hg induced hepatic oxidative damage by affecting antioxidant defense, as evidenced by altered activity of superoxide dismutase (<i>sod</i>) and catalase (<i>cat</i>), and simultaneously modulated immune responses by significantly upregulating interferon-γ (<i>ifn-γ</i>) and tumor necrosis factor-α (<i>tnf-α</i>) while downregulating interleukin-1β (<i>il-1β</i>), indicating an oxidative-inflammatory response. These outcomes collectively underscore that MP and Hg coexposure aggravates both systemic and molecular impairments in Nile tilapia, resulting in weakened molecular responses, impaired physiological functions, and decreased survivability.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"1847474"},"PeriodicalIF":2.8,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295553","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 Vitro hRPTEC TERT1 Model for Uranium-Induced Nephrotoxicity Pathway Study.","authors":"Marie Frerejacques, Victoria Powell, Sebastien Giraud, Annabelle Manoury, Céline Bouvier-Capely, Thierry Hauet, Clara Steichen, Yann Guéguen","doi":"10.1155/jt/6692188","DOIUrl":"10.1155/jt/6692188","url":null,"abstract":"<p><p>As a heavy metal and alpha emitter, uranium U(VI) presents chemical and radiological toxicity risks. Its toxicity particularly targets the kidneys in the event of intoxication, but the detailed study mechanisms leading to uranium-induced renal failure have not yet been studied based on the adverse outcome pathway (AOP) approach. Using a well-specialized in vitro model of renal proximal tubule epithelial cells (hRPTEC TERT1), this research aims to contribute to the development of the AOP of kidney toxicity. After identifying the U(VI) concentrations that induce deleterious effects (apoptosis and necrosis/cytotoxicity), key events linked to oxidative stress, apoptosis, survival, inflammation, and kidney toxicity are studied at the gene and protein levels. Apoptosis (Caspase 3/7 activity) is induced starting from exposure to 300 μM and necrosis (LDH assay) from 500 μM with a rate of 60%. hRPTEC cells have an IC50 of 420 μM after 48 h U(VI) exposure. Uranium induces an early 2-fold rise in ROS production, and an antioxidant response was observed accordingly. Cell survival signaling appeared to be enhanced at 100 μM, while higher concentrations (> 300 μM) induced a marked inflammatory response, with increased levels of TNFα (6,5-fold), IL-6, and IL-18, leading to a 16% increase in caspase 3/7 at 300 μM and LDH at 500 μM. A slight increase of 22% in the KIM-1 protein level is observed at 500 μM, and limited changes occurred for other nephrotoxicity biomarkers. In conclusion, this exploratory work generated a multiplex panel detailing the key events in the AOP of uranium-induced renal failure (Graphical Abstract). This panel features a human phenotype of renal proximal tubule epithelial cells, the preferential target of uranium in the kidney, while also considering the dose-dependent effects.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"6692188"},"PeriodicalIF":2.8,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13276292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295543","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":"Combined Toxicity Effects and Health Risks of Microplastics and Multiple Pollutants.","authors":"Lizhi Wu, Yuting Zhou, Mingluan Xing, Huixia Niu, Xueqing Li, Zhijian Chen, Xiaoming Lou","doi":"10.1155/jt/3404011","DOIUrl":"10.1155/jt/3404011","url":null,"abstract":"<p><p>Microplastics, as emerging pollutants, are ubiquitously present globally and pose significant threats to both ecosystems and human health. These pollutants not only exert direct toxicity on the environment and living organisms but also influence the toxicity of other pollutants through mechanisms such as adsorption and carrier effects. The health risks of microplastics are multifaceted and complex, involving cellular toxicity, immune dysfunction, and impairments to neurological, endocrine, and reproductive systems. This review summarizes the combined toxic effects of microplastics and heavy metals, organic pollutants, plastic additives, antibiotics, and viruses, exploring their potential mechanisms and influencing factors. The paper suggests that future research should focus on simulating exposure scenarios, examining the long-term effects of exposure, and understanding the health consequences of combined exposures. This will provide new perspectives on the toxic effects of microplastics on the environment and organisms, enhance public awareness of their potential harm, and better address the impact of microplastic pollution on ecosystems.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"3404011"},"PeriodicalIF":2.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252107","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":"Organ-Specific Microplastic Profiling and Polymer Characterization in Freshwater Fish Species of Karnataka.","authors":"Kuruveetil Manikandan Ashitha, Anjali Tamrakar, Gopika Melethil, Anish Kumar Warrier","doi":"10.1155/jt/8854199","DOIUrl":"10.1155/jt/8854199","url":null,"abstract":"<p><p>Microplastic (MP) contamination is an emerging threat to freshwater ecosystems and food security. The objective of this study was to provide a comprehensive baseline assessment of MP abundance, polymer composition, and tissue-specific distribution across five organs (gut, gills, liver, gonads, and muscle) of two economically vital species <i>Labeo rohita</i> and <i>Pangasius pangasius</i>, in Udupi, Karnataka, India. MPs were detected in 100% of specimens, with higher mean (± standard deviation) abundances of 58.27 ± 10.48 particles per individual (particles ind^-1) in <i>L. rohita</i> and 42.40 ± 5.40 particles ind^-1 in <i>P. pangasius</i>. While <i>L. rohita</i> showed preferential accumulation in the gills and gut, in <i>P. pangasius</i>, MPs were more uniformly distributed across organs. Fibers dominated the assemblage (97.68%), with polypropylene and polyester identified as the primary polymers via Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) analysis. We conclude that the pervasive presence of MPs across all tissues, particularly the high accumulation in edible muscle and reproductive gonadal tissue, signals an urgent ecological risk and a direct pathway for human dietary exposure. The detection of MPs in gonadal tissues, while not yet linked to observed physiological impairment, identifies a potential reproductive risk and highlights a critical area for future histological and toxicological investigation. These findings establish a baseline for assessing the long-term health of local fisheries.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"8854199"},"PeriodicalIF":2.8,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199518","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":"Acute (14-Day) and Subchronic (90-Day) Toxicity Evaluation of the Dried Fruit Spice <i>Xylopia aethiopica</i> (Dunal) A. Rich. (Annonaceae) in Male and Female Wistar Rats.","authors":"Merline Ymele Nguedia, Ornella Bernie Kami Nkuimi, Borelle Mafogang, Herve Herve Abaissou Ngatanko, Dieudonne Njamen, Stephane Zingue","doi":"10.1155/jt/2002718","DOIUrl":"10.1155/jt/2002718","url":null,"abstract":"<p><strong>Background: </strong><i>Xylopia aethiopica</i> (XAE) fruit (Ethiopian pepper) is a culinary spice widely used in African countries. It has numerous biological properties including potent anticancer properties; however, there is a lack of data on its safety, which justifies this study.</p><p><strong>Methods: </strong>Animals were administered a unique dose of 2000 mg/kg for the acute (14-day) toxicity and three doses (75, 150, and 300 mg/kg BW) of the subchronic (90-day) oral toxicity of ethanol dry fruit of XAE extract guideline numbers 423 and 408, respectively. Behavioral, morphological (body weight and relative weight of the organs), biochemical, hematological, and histological parameters of toxicological interest were evaluated with organs, such as the lung, liver, kidney, breast, and testes, just to name a few.</p><p><strong>Results: </strong>An LD₅₀ > 2000 mg/kg was found after an acute exposure to XAE in young female rats. After 90 days of administration, XAE induced no significant changes in body weight and relative weights of the organs. In both female and male rats, no significant changes were observed in the tested biochemical parameters (creatinine, total proteins, triglycerides, total cholesterol, HDL, LDL, ALT, AST, and urea), except for the bilirubin levels, which slightly decreased in males at a dose of 300 mg/kg BW. No change was observed in the histological sections of organs of interest in toxicology (spleen, lungs, kidneys, liver, and heart) as well as in the reproductive organs (vagina, uterus, and ovary for females and testes, seminal vesicle, prostate, and epididymis for males). A significant decrease was observed in the level of hematological parameters, such as platelet levels in both female (<i>p</i> ≤ 0.001) and male (<i>p</i> ≤ 0.01) Wistar rats when compared to the control. This decrease in platelet concentration observed in experimental rats suggests that XAE may induce thrombocytopenia, possibly through an adverse effect on thrombopoiesis.</p><p><strong>Conclusion: </strong>Taken altogether, the observations therefore showed that long-term administration of XAE dry fruit extract might induce thrombocytopenia and anemia, particularly at higher doses, warranting caution regarding long-term use.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"2002718"},"PeriodicalIF":2.8,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016176","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":"Effects of Legacy PFAS and Novel Alternatives on Thyroid Function in Mother‒Child Populations: A Systematic Review.","authors":"Lemin Gong, Yuhan Zhou","doi":"10.1155/jt/1578567","DOIUrl":"10.1155/jt/1578567","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are extensively utilized in industrial and consumer applications, such as firefighting foams, textiles, electronics, industrial coatings, food packaging, and household consumer products, due to their excellent chemical stability. However, legacy long-chain PFAS are prohibited because of their endocrine-disrupting properties, bioaccumulative nature, and potential carcinogenicity, followed by the emergence of new alternatives, such as short-chain congeners and novel PFAS alternatives. PFAS are known to disrupt endocrine function, and the thyroid gland, a critical endocrine organ, is particularly vulnerable to their effects. Mother‒child populations are more likely to be affected by PFAS due to their specific physiological characteristics, metabolic differences, and developmental stages. This paper reviews the exposure levels of legacy PFAS and their alternatives in maternal and infant blood and breast milk, and the relationship between PFAS exposure and thyroid hormone (TH) levels. It also examines the similarities and differences in the mechanisms by which different PFAS affect thyroid function. Research has revealed that both legacy and PFAS alternatives have been detected in maternal blood, infant blood, and breast milk. While legacy PFAS exhibit higher exposure levels with notable regional variations, the concentrations of PFAS alternatives, although lower, remain a concern. PFAS exposure affects TH in mothers and infants, with legacy PFAS having a more significant effect. The mechanisms underlying thyroid disruption caused by different PFAS are largely similar. However, PFAS alternatives are characterized by high protein affinity, ability to disrupt fatty acid metabolism, and high hydrophilicity, and may also increase the risk of thyroid cancer (TC). This study provides critical evidence for evaluating the safety of PFAS alternatives and provides a scientific foundation for developing preventive and regulatory measures.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2026 ","pages":"1578567"},"PeriodicalIF":2.8,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963847","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":"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":"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^-1, 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 H₂O₂ 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":2.8,"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":"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":2.8,"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}