Current Research in Toxicology最新文献

{"title":"RhoA/ROCK2 signaling pathway regulates Mn-induced alterations in tight junction proteins leading to cognitive dysfunction in mice","authors":"Yan Ma ,&nbsp;Honggang Chen ,&nbsp;Yuxin Jiang ,&nbsp;Diya Wang ,&nbsp;Michael Aschner ,&nbsp;Wenjing Luo ,&nbsp;Peng Su","doi":"10.1016/j.crtox.2024.100207","DOIUrl":"10.1016/j.crtox.2024.100207","url":null,"abstract":"<div><div>Elevated manganese (Mn) exposure has been implicated in a broad spectrum of neurological disorders, including motor dysfunction and cognitive deficits. Previous studies have demonstrated that Mn induces neurotoxicity by disrupting the integrity of the blood–brain barrier (BBB), a critical regulator in maintaining central nervous system homeostasis and a contributing factor in the pathogenesis of numerous neurological disorders. However, the precise molecular mechanisms underlying Mn-induced BBB disruption and its role in facilitating neurotoxicity remain incompletely understood. The primary objectives of this study were to elucidate the mechanisms underlying the relationship between Mn exposure and BBB tight junction proteins (TJPs), and to further investigate potential neuroprotective strategies for mitigating Mn-induced cognitive impairments. In this investigation, we developed Mn exposure models utilizing both murine subjects and cell culture systems to elucidate the mechanisms underlying TJPs involvement and to assess the potential neuroprotective effects of gastrodin (GAS), a bioactive compound extracted from traditional Chinese medicine. Our findings revealed a significant reduction in TJPs expression, both <em>in vivo</em> and <em>in vitro</em>, in Mn-induced BBB disruption. The overexpression of Occludin (OCLN), a crucial component of TJPs, mitigated Mn-induced BBB damage. GAS administration effectively attenuated Mn-induced disruption of the BBB, enhanced the expression of TJPs, and mitigated Mn-induced cognitive dysfunctions, potentially through the modulation of the RhoA/ROCK2 signaling pathway. This research sought to advance our understanding of the molecular pathways involved in Mn-mediated BBB disruption and to identify novel therapeutic approaches for mitigating the deleterious effects of Mn exposure on cognitive function.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100207"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001342","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":"Efficacy of a hydrogen–oxygen generator in treating cigarette smoke–induced chronic obstructive pulmonary disease in rats","authors":"Wan-Ting Huang ,&nbsp;Tzong-Jih Cheng ,&nbsp;Lin-Hsiang Huang ,&nbsp;Yung-Te Hou","doi":"10.1016/j.crtox.2024.100214","DOIUrl":"10.1016/j.crtox.2024.100214","url":null,"abstract":"<div><div>Current treatments for chronic obstructive pulmonary disease (COPD), a common respiratory condition, include oxygen therapy and steroids for temporary relief. In this study, we established a rat model of cigarette smoke (CS)–induced COPD and investigated the benefits of a hydrogen–oxygen generator in this model. CS–exposed rats were treated using either a hydrogen–oxygen generator or a steroid. A hydrogen–oxygen generator reduced the neutrophil, lymphocyte, and eosinophil counts compared to natural recovery, whereas steroid treatment increased the total white blood cell, neutrophil, lymphocyte, monocyte and eosinophil counts. Furthermore, the mean linear intercept and the mean alveolar number were 59.8%, and 188.3%, respectively, after treatment with the generator, compared to the values observed with natural recovery. Finally, the generator increased the tricuspid annular plane systolic excursion values by 113.1% compared with the values in natural recovery. Our findings indicate successful establishment of a rat model of CS–induced COPD and demonstrate the potential benefits of using a hydrogen–oxygen generator for COPD patients.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100214"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001850","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":"Community-based insights into the connection between endocrine-disrupting chemicals and depressive symptoms","authors":"Yun-An Liu ,&nbsp;Heng-Jung Hsu ,&nbsp;Heng-Chih Pan ,&nbsp;Chiao-Yin Sun ,&nbsp;Yih-Ting Chen ,&nbsp;Chin-Chan Lee ,&nbsp;Feng-Chieh Su ,&nbsp;Yi-Chia Wei ,&nbsp;Cheng-Kai Hsu ,&nbsp;Chun-Yu Chen","doi":"10.1016/j.crtox.2025.100225","DOIUrl":"10.1016/j.crtox.2025.100225","url":null,"abstract":"<div><h3>Background</h3><div>The rising prevalence of depressive disorders has sparked concerns regarding environmental risk factors, particularly exposure to endocrine-disrupting chemicals (EDCs). However, the link between EDC exposure and depressive symptoms remains largely unexplored.</div></div><div><h3>Methods</h3><div>The Chang Gung Community Medicine Research Center carried out a cross-sectional study across four regions in northeastern Taiwan. Out of 887 participants, 120 subjects were chosen according to their EDC exposure scores. These participants underwent urinary EDC analysis and were evaluated for depressive symptoms through the standardized Hospital Anxiety and Depression Scale − Depression subscale (HADS-D) questionnaire.</div></div><div><h3>Results</h3><div>Participants with HADS-D scores ≥ 8 exhibited significantly higher EDC exposure score compared to those with lower scores. The correlation analyses identified a notible positive association between urinary monobenzyl phthalate (MBzP) levels and HADS-D scores (<em>r</em> = 0.244, <em>p</em> = 0.007). Multiple regression analysis revealed that MBzP was independently linked to increased HADS-D scores in a positive manner (β ± SE: 0.139 ± 0.050, <em>p</em> = 0.006). Multivariable logistic regression indicated that higher MBzP (OR: 1.150, 95 % CI: 1.036–1.278, <em>p</em> = 0.009) and methylparaben (MP) levels (OR: 1.008, 95 % CI: 1.003–1.013, p &lt; 0.001) showed a significant correlation with the likelihood of HADS-D scores ≥ 8. Receiver operating characteristic curve analysis demonstrated that elevated levels of MBzP, MP and the EDCs exposure score were associated with a greater likelihood of depressive symptoms.</div></div><div><h3>Conclusion</h3><div>Exposure to EDCs, particularly MBzP and MP, could be associated with a heightened risk of depressive symptoms.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100225"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511085","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":"A simple, reliable and easily generalizable cell-based assay for screening potential drugs that inhibit lipid accumulation","authors":"Weili Yang,&nbsp;Qiuyue Pan,&nbsp;Qi Li,&nbsp;Sirui Zhou,&nbsp;Xi Cao","doi":"10.1016/j.crtox.2024.100213","DOIUrl":"10.1016/j.crtox.2024.100213","url":null,"abstract":"<div><div>Ectopic lipid deposition in the hepatocyte plays an important role in the development of nonalcoholic fatty liver disease (NAFLD), which has become one of the most common causes of chronic liver disease worldwide yet no approved drugs are currently available. In this study, a cell-based method was developed to screen potential drugs with low toxicity that inhibit lipid accumulation. In the same 96-well plate, cytotoxicity was measured using CCK8 assay, followed by lipid content detection using BODIPY 493/503 via fluorometry assay, a lipid droplet-specific fluorescent dye commonly used in microscopy and flow cytometry, but not previously reported in fluorometry. Lipid content was normalized to DAPI staining to control for cell number. The results of this assay were highly consistent with the fluorescence microscopy, with significantly lower intra-group variability in detecting lipid accumulation induced by free fatty acids in Huh7 cells. Validation was conducted using 10 well documented steatotic compounds and 5 negative controls, all of which were correctly identified by the assay. In addition, the inhibitory effect of ML261, a well-known inhibitor of hepatic lipid droplets formation, was also confirmed by the assay both in AML12 cells and Hepa1-6 cells. To our knowledge, this study is the first to quantify lipid droplets using BODIPY 493/503 by fluorometry assay, and to demonstrate that CCK8 does not interfere with subsequent BODIPY 493/503 staining, both of which will reduce the cost and increase the efficiency. In conclusion, the method is simple, reliable, efficient and does not rely on expensive instruments, making it an easily generalizable approach to identify potential drug candidates for NAFLD treatment.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100213"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001848","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":"Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice","authors":"Monica Ridlon,&nbsp;Audrey Spiegelhoff,&nbsp;Conner L Kennedy,&nbsp;Thomas Lavery,&nbsp;Kathy Wang,&nbsp;Julia Tlapa,&nbsp;Tamryn Jordan,&nbsp;Lindsey Felth Tanaka,&nbsp;Kimberly Keil Stietz","doi":"10.1016/j.crtox.2025.100227","DOIUrl":"10.1016/j.crtox.2025.100227","url":null,"abstract":"<div><div>Polychlorinated biphenyls (PCBs) are toxicants present in the environment, foodstuff, animal and human tissues. PCBs are linked to numerous adverse health effects; however, impacts of developmental PCB exposure on lower urinary tract function are a comparatively newer area of interest. We have previously found developmental exposure (<em>in utero</em> and lactational) to a human-relevant PCB mixture in mice leads to sex- and dose- dependent changes to urinary voiding physiology at 6 weeks of age. This study expands upon previous findings to investigate if developmental PCB-induced urinary voiding phenotypes persist or shift as mice age to 12 weeks of age. Urinary voiding physiology testing through void spot assays, uroflowmetry, and cystometry demonstrated several sex- and dose- dependent effects of PCB exposure at 12 weeks of age. Further, patterns of dysfunction were either maintained, newly acquired, or reversed compared to those from younger adult mice in a previous study. Here, developmental PCB exposure decreased number of small urine spots in adult male and female mice in a dose dependent manner, and female mice had more frequent voiding events assessed by anesthetized cystometry. Mice also had PCB dose-dependent changes to urinary voiding physiology when challenged with intravesical capsaicin infusion to target transient receptor potential cation channel subfamily V member 1 (TRPV1)-mediated pathways. PCBs either blocked or exacerbated capsaicin induced responses depending on the endpoint examined, suggesting this pathway may play a role in PCB-dependent changes in voiding. PCBs also had subtle impacts on prostate wet weight, with high PCB doses reducing tissue mass compared to low PCB doses, while none differed from vehicle. This study demonstrates developmental exposure to PCBs continues to impact lower urinary tract function in adulthood to at least 12 weeks of age both during homeostatic conditions and upon challenge of capsaicin. Better understanding of how early life stressors like PCBs contribute to aging-associated voiding dysfunction are imperative as these findings may help mitigate risk or improve treatment strategies for patients suffering from lower urinary tract symptoms.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100227"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628828","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":"The impact of in utero tobacco exposure on smoking behaviors, cardiovascular disease risk and all-cause mortality in adulthood: A UK Biobank study","authors":"Yanxu Zheng ,&nbsp;Xinyu Xiong ,&nbsp;Jing Bao ,&nbsp;Jingyu Liu ,&nbsp;Jin Wang ,&nbsp;Fang Zou ,&nbsp;Zixi Chen ,&nbsp;Yang Guo ,&nbsp;Qingyao Wang ,&nbsp;Yixuan Qiu ,&nbsp;Zhaowei Zhu","doi":"10.1016/j.crtox.2025.100226","DOIUrl":"10.1016/j.crtox.2025.100226","url":null,"abstract":"<div><div>The knowledge regarding the negative impacts of in utero tobacco exposure (IUTE) on cardiovascular disease (CVD) was incomplete. This study aims to assess the association between IUTE and the risks of CVD incidence and all-cause mortality, discuss the inter-group difference based on genetic susceptibility and smoking behaviors after birth, and explore the potential mediating factors. Utilizing a total of 375,024 participants from the UK Biobank, the outcomes include myocardial infarction, stroke, chronic ischemic heart disease, nonrheumatic aortic valve disorders, cardiomyopathy, heart failure, atherosclerosis, aortic aneurysm and dissection, and all-cause mortality. During a median follow-up period of 14.6 years, 50,434 cases of CVD were recorded. IUTE was significantly associated with increased CVD incidence (HR 1.10, 95 % CI 1.08–1.12) and all-cause mortality (HR 1.11, 95 % CI 1.09–1.14). Interaction effects between IUTE, smoking behaviors after birth, and genetic risk scores for CVD were observed significant (P for interaction &lt; 0.005). The results of the cross-sectional study revealed a significant positive association between IUTE and smoking behaviors after birth (OR 1.08, 95 % CI 1.06–1.09). Mediation analysis indicated that smoking behaviors (Proportion = 12.40 %, P &lt; 0.001) and HDL-c levels (Proportion = 14.20 %, P &lt; 0.001) partially mediated the IUTE-CVD relationship. This study demonstrated that individuals with IUTE have a higher risk of developing CVD, and smoking behaviors after birth have multifaceted influence on this correlation. These findings underscore the importance of mothers avoiding smoking during pregnancy to mitigate adverse effects on their offspring.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100226"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511086","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":"Assessing placental transfer and in utero reproductive effects in rats of a short-chained paraffin with in vitro endocrine disrupting properties","authors":"Mikala Melchiors ,&nbsp;Anna Kjerstine Rosenmai ,&nbsp;Ronan Cariou ,&nbsp;Mikael Pedersen ,&nbsp;Sofie Christiansen ,&nbsp;Terje Svingen","doi":"10.1016/j.crtox.2025.100237","DOIUrl":"10.1016/j.crtox.2025.100237","url":null,"abstract":"<div><div>Chlorinated paraffins (CPs) are industrial chemicals detected widely in the environment and human tissues, raising concerns due to their persistence, bioaccumulation, and potential health risks. CPs with lower chlorination or shorter carbon chain lengths can cross the placenta and have been detected in breast milk, indicating fetal and early postnatal exposure. Both <em>in vitro</em> and <em>in vivo</em> studies suggest that CPs exhibit endocrine-disrupting properties, particularly affecting reproductive development. This study investigates the developmental effects and placental transfer of 1,2,9,10-tetrachlorodecane (T₄C₁₀), a short-chained CP congener, by exposing pregnant rats from gestation days 7 to 21. T₄C₁₀ concentrations were measured in fetal and maternal blood, fetal steroid hormone levels were measured, and targeted gene expression was analyzed in the fetal genital tubercle. Despite prior <em>in vitro</em> evidence of endocrine-disrupting activity<em>, in vivo</em> exposure to T₄C₁₀ did not significantly affect reproductive parameters, including the anogenital distance (AGD), fetal steroid hormone profiles, or expression of androgen- and estrogen-regulated genes in the developing genital tubercle. The low systemic T₄C₁₀ levels in maternal and fetal blood suggest rapid metabolism or sequestration in adipose tissue, supported by increased liver weight in the exposed dams. These findings suggest that while T₄C₁₀ can cross the placenta, its bioavailability <em>in vivo</em> may be insufficient to elicit measurable endocrine-disrupting effects on reproductive development. This study underscores the importance of accounting for toxicokinetics when extrapolating <em>in vitro</em> findings to <em>in vivo</em> endpoints.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100237"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring transcriptomic databases to identify and experimentally validate tissue-specific consensus reference gene for gene expression normalization in BALB/c mice acutely exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin","authors":"Nour Hammoudeh ,&nbsp;Reem Hasan ,&nbsp;Mohammad Deeb ,&nbsp;Zuher Radwan ,&nbsp;Omar Ayoubi ,&nbsp;Roaa Alendary ,&nbsp;Mouayad Youssef ,&nbsp;Abdulfattah Kazan ,&nbsp;Rasil Alsahli ,&nbsp;Walaa Faiad ,&nbsp;Nour Aldeli ,&nbsp;Abdulsamie Hanano","doi":"10.1016/j.crtox.2025.100234","DOIUrl":"10.1016/j.crtox.2025.100234","url":null,"abstract":"<div><div>2,3,7,8-Tetrachlorodibenzo-<em>p</em>-dioxin (TCDD) is a toxic compound affecting organs like the liver, kidney, lung, and reproductive systems in mammals. This study outlines a strategy for choosing appropriate HKGs for tissue-specific gene expression analysis in TCDD toxicity, including four steps: i) identifying candidate HKGs from literature and databases; ii) defining primers from literature or designing new ones; iii) validating primer efficiency and specificity; iv) experimentally assessing candidate HKGs’ stability in various tissues of TCDD-exposed mice.</div><div>Based on this strategy, a total of 40 potential HKGs was selected, further filtered based on their database sources and ranked according to their frequency of use or expression stability. Ultimately, we identified a final set of 15 HKGs (<em>Rps18</em>, <em>Calr</em>, <em>Polr2b</em>, <em>Brms1l</em>, <em>P4hb</em>, <em>Esd</em>, <em>Hdgf</em>, <em>Gapdh</em>, <em>Mlec</em>, <em>Tbp</em>, <em>Rn18s</em>, <em>Sdha</em>, <em>B2m</em>, <em>Actr3</em> and <em>Actb</em>) with typical efficiencies for further evaluation. Then, the stability of the selected HKGs was determined in the liver, kidney, lung, ovary and testis of TCDD-exposed mouse compared to the control group using the [log (2^ΔCt)] and statistically analyzed using Pearson correlation coefficient (<em>r</em>) by BestKeeper algorithm. Our data analysis revealed that <em>Actb</em>, <em>Rps18</em>, and <em>Polr2b</em> were the most stable HKGs for normalizing gene expression in the liver, while <em>Sdha</em>, <em>Actb</em>, and <em>Gapdh</em> were suitable for kidney tissue. In the lung, <em>Tbp</em>, <em>Sdha</em>, and <em>Rps18</em> showed stability, while <em>Tbp</em>, <em>B2m</em>, and <em>Actb</em> were most stable in ovary. Lastly, <em>Actb</em>, <em>B2m</em>, and <em>Tbp</em> were accurately stable in the testis of TCDD-exposed mice. Our study identifies stable HKGs, improving TCDD toxicity research accuracy and reliability.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100234"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fit for purpose testing and independent GMP validation of the monocyte activation test","authors":"Ruth Daniels ,&nbsp;Wim Van der Elst ,&nbsp;Chi K. So ,&nbsp;Liesbeth Voeten ,&nbsp;Philip Breugelmans ,&nbsp;Marijke W.A. Molenaar-de Backer ,&nbsp;Stephen Poole ,&nbsp;Mehul Patel","doi":"10.1016/j.crtox.2024.100206","DOIUrl":"10.1016/j.crtox.2024.100206","url":null,"abstract":"<div><div>The present study describes the “fit for purpose” testing and the independent product-specific GMP validation of the monocyte activation test (MAT) to detect pyrogenic and pro-inflammatory contaminants, MAT Method A, Quantitative Test (<span><span>European Pharmacopoeia, Ph. Eur. chapter 2.6.30, 2017</span></span>). A fit for purpose study was carried out to ensure that the chosen MAT set-up (cryopreserved PBMC, IL-6 detection) can reliably discriminate between batches of product containing pyrogenic contaminants below the contaminants limit concentration, CLC, from batches containing pyrogenic contaminants above the CLC. Such testing is carried out once, before the chosen MAT set-up is used for subsequent product testing to show that the incidence of false positives (pyrogen-negative (&lt;CLC) batches testing as pyrogen-positive (&gt;CLC) batches) and – especially – false negatives (pyrogen-positive (&gt;CLC) testing as pyrogen-negative (&lt;CLC)) is low. This study also afforded the opportunity to collect an independent body of validation data for comparison with that obtained previously (<span><span>Daniels et al., 2022</span></span>) to evaluate the robustness of MAT Method A and its fitness to replace the rabbit pyrogen test (RPT) where this has not already happened.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100206"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970094","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":"A Review of the Applications, Benefits, and Challenges of Generative AI for Sustainable Toxicology","authors":"Furqan Alam ,&nbsp;Tahani Saleh Mohammed Alnazzawi ,&nbsp;Rashid Mehmood ,&nbsp;Ahmed Al-maghthawi","doi":"10.1016/j.crtox.2025.100232","DOIUrl":"10.1016/j.crtox.2025.100232","url":null,"abstract":"<div><div>Sustainable toxicology is vital for living species and the environment because it guarantees the safety, efficacy, and regulatory compliance of drugs, treatments, vaccines, and chemicals in living organisms and the environment. Conventional toxicological methods often lack sustainability as they are costly, time-consuming, and sometimes inaccurate. It means delays in producing new drugs, vaccines, and treatments and understanding the adverse effects of the chemicals on the environment. To address these challenges, the healthcare sector must leverage the power of the Generative-AI (GenAI) paradigm. This paper aims to help understand how the healthcare field can be revolutionized in multiple ways by using GenAI to facilitate sustainable toxicological developments. This paper first reviews the present literature and identifies the possible classes of GenAI that can be applied to toxicology. A generalized and holistic visualization of various toxicological processes powered by GenAI is presented in tandem. The paper discussed toxicological risk assessment and management, spotlighting how global agencies and organizations are forming policies to standardize and regulate AI-related development, such as GenAI, in these fields. The paper identifies and discusses the advantages and challenges of GenAI in toxicology. Further, the paper outlines how GenAI empowers Conversational-AI, which will be critical for highly tailored toxicological solutions. This review will help to develop a comprehensive understanding of the impacts and future potential of GenAI in the field of toxicology. The knowledge gained can be applied to create sustainable GenAI applications for various problems in toxicology, ultimately benefiting our societies and the environment.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100232"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}