Journal of Applied Toxicology最新文献

{"title":"Evaluating the Genotoxicity and Mutagenicity of Food Contaminants: Acrylamide, Penitrem A, and 3-Acetyldeoxynivalenol in Individual and Combined Exposure In Vitro.","authors":"Luna Bridgeman, Cristina Juan, Houda Berrada, Isabelle Severin, Ana Juan-García","doi":"10.1002/jat.4805","DOIUrl":"https://doi.org/10.1002/jat.4805","url":null,"abstract":"<p><p>This study aimed to evaluate the genotoxic effects of food contaminants exposure in human neuroblastoma SH-SY5Y cells using the micronucleus (MN) assay and Ames test. Acrylamide (AA), penitrem A (PEN A), and 3-acetyldeoxynivalenol (3-ADON) were tested both individually and in combination. Since humans are likely to be exposed to these substances simultaneously through diet, it is crucial to investigate their combined effects of the compounds rather than just their individual toxicities. The results demonstrated significant increases in MN frequency for all individual treatments and in a dose-dependent manner for AA and 3-ADON. Combined treatments also resulted in higher MN frequencies, particularly for AA + 3-ADON and PEN A + 3-ADON respect to the control. However, the Ames test revealed no mutagenic potential for any of the individual or combined treatments, consistent with previous studies. These findings suggest that while food contaminants induce chromosomal damage (MN induction), they do not cause gene mutations. Nonetheless, the lack of single mutations activity does not exclude the potential health risks of combined mycotoxin exposure, especially given the observed genotoxicity due to the DNA damage through chromosomal aberrations. Future studies focused on the mechanism of action should investigate the combined effects of food contaminants in more detail to better assess their potential health risks.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyriproxyfen Disrupts the Ongoing Spermatogenesis Wave in Danio rerio Potentially Mediated by Voltage-Dependent Calcium Channels and Protein Kinase C.","authors":"Bruna Antunes Zaniboni, Vanessa Staldoni de Oliveira, Gabriel Adan Araujo Leite, Valdelúcia Maria Alves de Souza Grinevicius, Rozangela Curi Pedrosa, Fátima Regina Mena Barreto Silva","doi":"10.1002/jat.4801","DOIUrl":"https://doi.org/10.1002/jat.4801","url":null,"abstract":"<p><p>Pyriproxyfen (PPX) is an analog of the juvenile hormone from insects. Following our previous studies, for the ex vivo short-term effect, we chose 10^-9 M pyriproxyfen to analyze the morphology of spermatogenesis wave cells. In silico docking and ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) studies were carried out to preliminarily predict possible interaction modes between PPX and the T-type voltage-dependent calcium channel (T-VDCC), as well as with protein kinase C (PKC), as we previously reported by using pharmacological approach. The in silico ADMET evaluations revealed that PPX demonstrates notable lipophilicity. Moreover, PPX is predicted to inhibit the enzymatic activity of CYP1A2, CYP2C19, CYP2C9, and CYP2D6. Furthermore, in silico molecular docking analyses revealed that PPX has the potential to interact with the T-VDCC through hydrogen bonds with Gln1653 and hydrophobic interactions with Leu291, Phe322, Phe1607, and Leu1656. Possible interactions of PPX with PKC involve ionic bonding with Lys463, hydrogen bonds with His592, and hydrophobic interactions with Lys463, Val596, Gly591, Phe593, Lys611, Asp711, and Leu714 reinforcing these both targets to PPX. In summary, short-term PPX exposure influenced the morphology of testicular cells (spermatids, spermatozoa, and Leydig cells) through interactions with molecular targets. Findings reveal the bimodal effects (on morphology and signaling) of this compound on specific cells within the spermatogenic wave, endocrine cells, and signal transduction proteins. This interference may impair reproduction and lead to male infertility. In addition, the prediction from both molecular docking and ADMET supported our in vitro mechanistic analysis firstly reported in the testis of Danio rerio.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TabNet and TabTransformer: Novel Deep Learning Models for Chemical Toxicity Prediction in Comparison With Machine Learning.","authors":"Firas Mahmood Mustafa, Ali Fawzi Al-Hussainy, Hardik Doshi, Anupam Yadav, M M Rekha, Mayank Kundlas, A Sabarivani, Aziz Kubaev, Sada Ghalib Taher, Mariem Alwan, Mahmood Jawad, Hiba Mushtaq, Bagher Farhood","doi":"10.1002/jat.4803","DOIUrl":"https://doi.org/10.1002/jat.4803","url":null,"abstract":"<p><p>The prediction of chemical toxicity is crucial for applications in drug discovery, environmental safety, and regulatory assessments. This study aims to evaluate the performance of advanced deep learning architectures, TabNet and TabTransformer, in comparison to traditional machine learning methods, for predicting the toxicity of chemical compounds across 12 toxicological endpoints. The dataset consisted of 12,228 training and 3057 test samples, each characterized by 801 molecular descriptors representing chemical and structural features. Traditional machine learning models, including XGBoost, CatBoost, SVM, and a voting classifier, were paired with feature selection techniques such as principal component analysis (PCA), recursive feature elimination (RFE), and mutual information (MI). Advanced architectures, TabNet and TabTransformer, were trained directly on the full feature set without dimensionality reduction. Model performance was assessed using accuracy, F1-score, AUC-ROC, AUPR, and Matthews correlation coefficient (MCC), alongside SHAP analysis to interpret feature importance and enhance model transparency under class imbalance conditions. Cross-validation and test set evaluations ensured robust comparisons across all models and toxicological endpoints. TabNet and TabTransformer consistently outperformed traditional classifiers, achieving AUC-ROC values up to 96% for endpoints such as SR.ARE and SR.p53. TabTransformer showed the highest performance on complex labels, benefiting from self-attention mechanisms that captured intricate feature relationships, while TabNet achieved competitive outcomes with an efficient, dynamic feature selection. In addition to standard metrics, we reported AUPR and MCC to better evaluate model performance under class imbalance, with both models maintaining high scores across endpoints. Although traditional classifiers, particularly the voting classifier, performed well when combined with feature selection-achieving up to 94% AUC-ROC on SR.p53-they lagged behind the deep learning models in generalizability and feature interaction modeling. SHAP analysis further highlighted the interpretability of the proposed architectures by identifying influential descriptors such as VSAEstate6 and MoRSEE8. This study highlights the superiority of TabNet and TabTransformer in predicting chemical toxicity while ensuring interpretability through SHAP analysis. These models offer a promising alternative to traditional in vitro and in vivo approaches, paving the way for cost-effective and ethical toxicity assessments.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukemia Inhibitory Factor via JAK-STAT Signaling Drives Beryllium Sulfate-Induced Epithelial-Mesenchymal Transition in 16HBE Cells.","authors":"Yaqi Li, Zhanbing Sun, Yuqi Tong, Chenxi Yan, Lian Huang, Zhaohui Zhang","doi":"10.1002/jat.4802","DOIUrl":"https://doi.org/10.1002/jat.4802","url":null,"abstract":"<p><p>Beryllium and its compounds are classified as carcinogens, and prolonged exposure can trigger chronic beryllium disease. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is known to play a critical role in the development and progression of numerous diseases. Leukemia inhibitory factor (LIF), a key upstream cytokine of the JAK-STAT pathway, has been implicated in regulating inflammatory responses and epithelial-mesenchymal transition (EMT) in various diseases. However, the specific involvement of the JAK-STAT pathway and LIF in beryllium sulfate (BeSO₄)-induced EMT in human bronchial epithelial (16HBE) cells remains unclear. To investigate the regulatory mechanisms, we examined the effects of BeSO₄ on 16HBE cells and targeted the JAK-STAT pathway using both pharmacological inhibition (niclosamide) and genetic silencing of LIF. Subsequently, we assessed cell morphology, proliferative capacity, inflammatory protein levels, and EMT marker expression. Our findings demonstrated that BeSO₄ exposure inhibited 16HBE cell proliferation and activated the JAK-STAT pathway. Pretreatment with niclosamide significantly mitigated cellular inflammation and the EMT process induced by BeSO₄. Additionally, silencing LIF markedly reduced JAK-STAT pathway activation and decreased the expression of EMT markers. This study uncovers a novel mechanism underlying BeSO₄-induced EMT in 16HBE cells, providing valuable insights into the molecular mechanisms of toxicity induced by beryllium and its compounds.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Polyethylene Terephthalate Microplastic Induces Mouse Liver Fibrosis Through Oxidative Stress and p38 MAPK/p65 NF-κB Signaling Pathway.","authors":"Rihao Ji, Yanfang Yang, Bohao Bian, Yafeng Zhang, Feifei Wang, Yuqiao Jia","doi":"10.1002/jat.4797","DOIUrl":"https://doi.org/10.1002/jat.4797","url":null,"abstract":"<p><p>Microplastic (MP) pollution has garnered attention due to its potential impact on living organisms. Among these, polyethylene terephthalate microplastics (PET-MPs) are frequently detected in both environmental samples and human tissues. Despite this, the effects of PET-MPs on liver damage and fibrosis in mammals remain insufficiently understood. This study demonstrated that oral exposure to PET-MPs at doses of 1 mg/day (with a diameter of 1 μm) over 42 days resulted in inhibited weight gain and altered organ coefficients in male mice, suggesting possible liver damage. Using HE and Masson staining revealed pathological changes in the livers of exposed mice, such as hepatocyte swelling, inflammatory cell infiltration, and collagen deposition. Liver function tests confirmed elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Further, the elevated levels of oxidative stress markers, along with the enhanced expression of proteins related to the p38 MAPK/p65 NF-κB signaling pathway as revealed by western blot analysis, both of which are strongly associated with liver damage and fibrosis. To further elucidate these mechanisms, experiments involving N-acetylcysteine (NAC) to counteract oxidative stress and SB203580 to inhibit p38 MAPK activation demonstrated that both interventions effectively mitigated liver fibrosis. Exposure to PET-MPs may trigger liver injury and fibrosis in mice. During this process, oxidative stress and the p38 MAPK/p65 NF-κB signaling pathway may play significant mediating roles.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Cytogenotoxicity of Iohexol in Bronchial Epithelial Cells and In Silico DNA and BCL-XL Affinity Studies.","authors":"Ibrahim Halil Kenger, Batuhan Bilgin","doi":"10.1002/jat.4800","DOIUrl":"https://doi.org/10.1002/jat.4800","url":null,"abstract":"<p><p>Iohexol is a nonionic contrast agent used in x-ray imaging but can sometimes cause anaphylactic reactions. The mechanism of anaphylaxis-induced fatal respiratory symptoms remains unclear. The aim of this study was to investigate the effects of iohexol on cytotoxicity and DNA damage in bronchial epithelial cells (BEAS-2B). BEAS-2B cells were treated with Iohexol (1.5, 15, 75, and 150 mg I/mL) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The IC₅₀ value of iohexol was determined and the DNA damage effect of iohexol (12.4, 24.9, 49.9, and 99.9 mM) on BEAS-2B cells was investigated by Comet assay. Molecular docking analysis was also performed to determine the binding affinity to DNA and the antiapoptotic protein BCL-XL. Iohexol 15 mg I/mL, iohexol 75 mg I/mL, and iohexol 150 mg I/mL groups significantly decreased cell viability compared to the control group (p < 0.0001). Iohexol (12.4, 24.9, 49.9, and 99.9 mM) did not significantly alter genotoxicity in BEAS-2B cells compared to the control group (p > 0.05). In silico study showed that iohexol binds with high affinity to BCL-XL but low affinity to DNA. Our results show that iohexol causes cytotoxicity in BEAS-2B cells and binds strongly to BCL-XL. Our results suggest that the safety of iohexol needs further detailed studies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melissa officinalis Attenuates Diclofenac-Induced Hepatorenal Toxicity via AMPK/SIRT1 and STAT3/Nrf2 Pathways","authors":"Alyaa R. Salama,&nbsp;Neveen R. Ashoura,&nbsp;Kariman A. Esmail,&nbsp;Hossam G. Tohamy,&nbsp;Mustafa Shukry,&nbsp;Badriyah S. Alotaibi,&nbsp;Asmaa A. Aboushouk","doi":"10.1002/jat.4799","DOIUrl":"10.1002/jat.4799","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to assess whether <i>Melissa officinalis</i> (MO) or lemon balm could counteract the detrimental effects of diclofenac (DIC) on the liver and kidneys in male albino rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty adult male Wistar rats were randomly assigned to four groups (<i>n</i> = 10 per group): control, DIC (10 mg/kg intraperitoneally), DIC + MO (10 mg/kg DIC IP + 200 mg/kg lemon balm orally), and MO only (200 mg/kg orally) for 28 days. Biochemical, molecular, and histopathological evaluations were conducted to assess organ function and tissue integrity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DIC significantly impaired hepatic and renal function (<i>p</i> &lt; 0.05), evidenced by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP). Oxidative stress increased, as shown by higher malondialdehyde levels and reduced antioxidants, including glutathione and catalase (CAT). Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were also elevated. Histopathological analysis indicated severe tissue damage and cell death in the liver and kidneys from DIC. However, adding MO alongside DIC mitigated these effects, improving both biochemical and histopathological parameters in the liver and kidneys. Gene expression analysis revealed upregulation of STAT3 and TNF-α and downregulation of AMP-activated protein kinase (<i>AMPK</i>), sirtuin 1 (<i>SIRT1</i>), and nuclear factor erythroid 2–related factor 2 (<i>Nrf2</i>). Coadministration of MO significantly reversed these alterations (<i>p</i> &lt; 0.05), improved tissue architecture, and restored antioxidant and anti-inflammatory balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MO provided substantial protection against oxidative damage and functional disturbances induced by DIC in liver and kidney tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 8","pages":"1649-1663"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) Induces Ferroptosis in Rat Cortical Neurons via p53-SLC7A11-ALOX12/p53-SAT1-ALOX15 Pathways","authors":"Chaoli Zhou,&nbsp;Zhaomeng Xu,&nbsp;Shihan Ding,&nbsp;Xiaohui Li,&nbsp;Hui Wang,&nbsp;Hui He,&nbsp;Hongyu Sun,&nbsp;Xiaomin Tong,&nbsp;Tingyu Ji,&nbsp;Yi Lyu,&nbsp;Jinping Zheng","doi":"10.1002/jat.4798","DOIUrl":"10.1002/jat.4798","url":null,"abstract":"<div>\u0000 \u0000 <p>Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the ultimate metabolite of benzo(a)pyrene, has been implicated in the induction of neuronal cell death. Our previous research established that BPDE initiates ferroptosis in neuroblastoma SH-SY5Y cells; however, the underlying mechanisms remain elusive. This study examines BPDE-induced ferroptosis in rat primary cortical neurons, revealing a significant increase in intracellular reactive oxygen species (ROS) and Fe²⁺ concentrations. Following exposure to 0.5 μM BPDE, distinctive morphological changes in mitochondria, indicative of ferroptosis, were observed. An upregulation of malondialdehyde (MDA) expression was observed, alongside a downregulation of glutathione (GSH) levels, glutathione peroxidase (GSH-PX) activity, and superoxide dismutase (SOD) activity postexposure. Additionally, there was an increase in the expression of ferroptosis-associated proteins ACSL4 and COX2, whereas the levels of SLC7A11 and GPX4 were reduced. Notably, the application of lipid peroxidation inhibitors and iron chelators, such as deferoxamine (DFO) and ferrostatin-1 (Fer-1), partially mitigated these effects. These findings suggest that BPDE is capable of inducing ferroptosis in primary rat neurons. Mechanistically, exposure to BPDE resulted in the upregulation of p53 expression, a reduction in SLC7A11 levels, and the promotion of ALOX12, SAT1, and ALOX15. In contrast, treatment with the p53-specific inhibitor Pifithrin-μ led to an increase in SLC7A11 levels and a significant decrease in ALOX12, SAT1, and ALOX15 levels, thereby mitigating BPDE-induced ferroptosis. In summary, these findings indicate that BPDE induces ferroptosis in primary rat cortical neurons via the p53-SLC7A11-ALOX12 and p53-SAT1-ALOX15 pathways.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 8","pages":"1637-1648"},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allergenicity, Genotoxicity and Subchronic Toxicity Assessment of IgG Binding Protein LT Produced From Aspergillus oryzae","authors":"Kirt R. Phipps,&nbsp;Sachin Patel,&nbsp;Kevin Scaife,&nbsp;Toby Holmes,&nbsp;Alica Šoltésová,&nbsp;Sandra Wingaard Thrane,&nbsp;Louise Kristine Vigsnæs,&nbsp;Nigel Baldwin,&nbsp;Christel Jørgensen","doi":"10.1002/jat.4787","DOIUrl":"10.1002/jat.4787","url":null,"abstract":"<p>Gastrointestinal health is one of the fastest growing areas in the food and beverage industry, as its importance to overall health and well-being is becoming increasingly recognized. Immunoglobulins play a key role in protecting the gastrointestinal tract, and nonbovine sources of immunoglobulins (including camel milk, which has a long history of consumption in East Africa and Asia) are increasing in popularity in Western countries as functional foods, particularly for individuals with allergies or intolerances to cow's milk. The physiological benefits of consuming certain heavy-chain immunoglobulins from camel milk relate to the binding domains of camelid single-domain antibodies; thus, a novel binding protein termed “immunoglobulin G (IgG) binding protein LT” (a dimer of two camelid single-domain antibody protein sequences) has been developed for use in food and beverage products, to provide some of the physiological benefits attributed to consuming camel milk, on an industrial scale. To support the safety of IgG binding protein LT for such use, a comprehensive safety assessment (in silico allergenicity assessment, in vitro genotoxicity studies [bacterial reverse mutation test and in vitro mammalian cell micronucleus test], and a 90-day gavage toxicity study in rats) was conducted. The in silico allergenicity assessment results demonstrate that IgG binding protein LT is highly unlikely to pose a risk of allergenic cross-reactivity, and there was no evidence of genotoxicity in vitro. There were no test article–related effects in the 90-day toxicity study. These data demonstrate the safety of IgG binding protein LT for its intended uses in foods and beverages.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 8","pages":"1614-1636"},"PeriodicalIF":2.7,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Holistic Healing of Cancer: German New Medicine (GNM) and Homeopathic Treatment Beyond Traditional Therapies.","authors":"Ramalakshmi Devi Konudula, Chandra Sekhara Rao Gorantla, Ramesh Athe","doi":"10.1002/jat.4796","DOIUrl":"https://doi.org/10.1002/jat.4796","url":null,"abstract":"<p><p>The study delves into the convergence of German new medicine (GNM) and homeopathy, examining their potential to enhance treatment strategies when considered together such that GNM posits a link between emotional trauma and physical manifestations of disease, providing a specific lens through which one can examine the origins of conditions such as cancer. Homeopathy, with its holistic and individualized approach, considers a vast array of symptoms and patient aspects. The present study debates the merits of integrating the detailed emotional analyses of GNM into the wide-ranging, symptom-based approach of homeopathy. Integration efforts are aimed at augmenting the depth of patient assessments, especially concerning the emotional etiology of diseases. The study indicated that while GNM can provide valuable insights, it should supplement rather than overshadow the comprehensive methodologies of homeopathic treatment. Future research avenues are proposed to evaluate the impact of combined GNM and homeopathic practices on patient outcomes, particularly in the domain of cancer, to uphold and possibly enhance the tradition of holistic and personalized patient care.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}