Frontiers in toxicology最新文献

筛选
英文 中文
Organ-specific bioaccumulation and deterministic health risk assessment of selected heavy metal(loid)s in commercial fish from a southern harbor region (Nagapattinam). 南港口地区(Nagapattinam)商品鱼中选定重金属(loid)的器官特异性生物积累和确定性健康风险评估
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1773891
Suryapratap Ray, Rahul Vashishth
{"title":"Organ-specific bioaccumulation and deterministic health risk assessment of selected heavy metal(loid)s in commercial fish from a southern harbor region (Nagapattinam).","authors":"Suryapratap Ray, Rahul Vashishth","doi":"10.3389/ftox.2026.1773891","DOIUrl":"https://doi.org/10.3389/ftox.2026.1773891","url":null,"abstract":"<p><strong>Introduction: </strong>Heavy metal contamination of coastal waters results in bioaccumulation in fish, posing a significant route of human exposure via seafood consumption. The present study focuses on organ-specific metal distribution and associated health risk indices in three important fish species from the Nagapattinam coast, India.</p><p><strong>Methods: </strong>In the current study, three species of fish (<i>Nemipterus japonicus</i>, <i>Oreochromis mossambicus</i>, and <i>Lates calcarifer</i>) were considered with three biological replicates per species obtained from local fish markets of Nagapattinam, Tamil Nadu, India, during January-February 2024. The HM profiling was performed on three organs: liver, gills, and muscle tissues. HMs, including arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), strontium (Sr), and vanadium (V), were analyzed using inductively coupled plasma mass spectrometry (ICP-MS).</p><p><strong>Results: </strong>The concentrations were found to be in the range of 0.025-21.53 μg kg<sup>-1</sup>. Upon non-carcinogenic risk assessment, the target hazard quotient (THQ) for all species was found to be <1 for both adults and children, indicating low non-carcinogenic risk associated with the consumption of the selected species under the assumed intake scenario. In contrast, the cancer risk (CR) value for chromium in <i>Nemipterus japonicus</i> was found to be elevated (children: 1643.58 × 10<sup>-6</sup> and adults: 939.19 × 10<sup>-6</sup>), assuming a conservative worst-case exposure scenario in which total chromium is considered as Cr(VI), potentially inflating cancer risk estimates.</p><p><strong>Discussion: </strong>Overall, the findings suggest low non-carcinogenic risk under average consumption conditions; however, the estimated carcinogenic risk for chromium exceeded the commonly referenced acceptable threshold under conservative assumptions and should therefore be interpreted with caution. These results highlight the need for further investigation, particularly chromium speciation analysis, to refine risk estimates for fish consumed from the Nagapattinam marketplace.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1773891"},"PeriodicalIF":4.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790988","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}
引用次数: 0
Protective effect of Carica papaya ethanolic leaf extract against lead-induced toxicity in Wistar rats. 番木瓜乙醇叶提取物对Wistar大鼠铅中毒的保护作用。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1762172
Richard Haakonde, Golden Zyambo, Katendi Changula, Roy Mwenechanya, Kaampwe Mayovu Muzandu
{"title":"Protective effect of <i>Carica papaya</i> ethanolic leaf extract against lead-induced toxicity in Wistar rats.","authors":"Richard Haakonde, Golden Zyambo, Katendi Changula, Roy Mwenechanya, Kaampwe Mayovu Muzandu","doi":"10.3389/ftox.2026.1762172","DOIUrl":"https://doi.org/10.3389/ftox.2026.1762172","url":null,"abstract":"<p><strong>Introduction: </strong>Lead poisoning remains a significant public health issue globally, with varied negative health outcomes, particularly in developing countries. Lead is a pervasive environmental pollutant that induces systemic toxicity, largely through oxidative stress resulting from its tissue bioaccumulation and disruption of normal physiological processes in a biological system. Plant-derived chelators and antioxidants may provide low-cost strategies to mitigate Pb-induced damage in both humans and animals. This study was aimed at evaluating the protective effect of <i>Carica papaya</i> leaf ethanolic extract against lead-induced toxicity in Wistar rats.</p><p><strong>Methods: </strong>The protective effect of <i>Carica papaya</i> leaf ethanolic extract was evaluated in Wistar rats exposed to Pb - acetate, 50 mg/kg body weight. Thirty animals were assigned to six groups (n = 5) and treated for 30 days with vehicle - double distilled water, Pb - acetate alone, or Pb - acetate in combination with <i>Carica papaya</i> leaf ethanolic extract (50, 100, 200 and 400 mg/kg body weight). Weekly changes in body weight were monitored across all exposure groups. Lead concentrations were then quantified in blood, liver, kidney, and bone tissues. Additionally, oxidative stress and lipid peroxidation were evaluated by measuring malondialdehyde levels in liver homogenates for all treatment groups.</p><p><strong>Results and discussion: </strong>Pb - acetate exposure led to significant Pb accumulation in blood, liver, kidney, and bone, as well as increased hepatic malondialdehyde levels (<i>p</i><0.05). Co-administration of the extract particularly at doses ≥100 mg/kg BW, showed significant corresponding reduction of Pb accumulation in blood, liver, and kidney, and liver malondialdehyde levels. This study provides preliminary indications that <i>Carica papaya</i> leaf ethanolic extract may provide protection against Pb-induced toxicity, likely through its flavonoid and phenolic chelation and antioxidant activities, coupled with Pb tissue deposition mitigation. These findings suggest Carica papaya leaf ethanolic extract could have potential, to be a low-cost phytotherapeutic candidate for managing Pb poisoning.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1762172"},"PeriodicalIF":4.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790998","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}
引用次数: 0
Towards learning and memory risk assessment with human brain organoids: barriers and opportunities. 用人脑类器官进行学习和记忆风险评估:障碍和机会。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1783893
Ronit Mohapatra, Dowlette-Mary Alam El Din, Hanyu Zhao, Thomas Hartung, Lena Smirnova
{"title":"Towards learning and memory risk assessment with human brain organoids: barriers and opportunities.","authors":"Ronit Mohapatra, Dowlette-Mary Alam El Din, Hanyu Zhao, Thomas Hartung, Lena Smirnova","doi":"10.3389/ftox.2026.1783893","DOIUrl":"https://doi.org/10.3389/ftox.2026.1783893","url":null,"abstract":"<p><p>Neurodevelopmental conditions, including autism spectrum disorder, intellectual disability, and learning disabilities, as well as neurodegenerative disorders, affect millions of people in the United States alone. Both genetic and environmental factors contribute to their onset, yet traditional neurotoxicity testing often fails to identify specific risks or mechanisms underlying cognitive impairment. Human brain organoids (hBOs), also called neural organoids or brain microphysiological systems, are three-dimensional (3D) stem cell-derived models that recapitulate key features of human brain development and offer greater physiological relevance than traditional 2D <i>in vitro</i> or animal models. The emerging field of \"organoid intelligence\" integrates these systems with advanced bioengineering and artificial intelligence to model higher-order neural functions and assess learning and memory-relevant endpoints that were previously less explored <i>in vitro</i>. Despite this promise, we have identified four key barriers that hinder the application of hBOs for the hazard identification phase of functional neurotoxic risk assessments: [1] limited maturity and regional complexity, [2] lack of high-throughput defined procedures for assessing cognitive development and function <i>in vitro</i>, [3] limited standardization for reproducibility, and [4] challenges in translating <i>in vitro</i> results to human health outcomes. Here, we outline current efforts to overcome these challenges, i.e., scientific, technical, and regulatory advances. We also illustrate how hBO-based assays can be applied to advance both mechanistic understanding and the regulatory evaluation of environmental (developmental) neurotoxicants, using heavy metals as a model.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1783893"},"PeriodicalIF":4.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790953","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}
引用次数: 0
An In vitro assessment of the genotoxic potential of short-, medium-, and long-chain triacylglycerides. 短链、中链和长链甘油三酯基因毒性潜能的体外评估。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-08 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1807786
Sydney Schreppler, Nikifar Lazouski, Lars Damen, Roy Hoffmans, Dejan Petrovic, Kathleen C Alexander
{"title":"An <i>In vitro</i> assessment of the genotoxic potential of short-, medium-, and long-chain triacylglycerides.","authors":"Sydney Schreppler, Nikifar Lazouski, Lars Damen, Roy Hoffmans, Dejan Petrovic, Kathleen C Alexander","doi":"10.3389/ftox.2026.1807786","DOIUrl":"https://doi.org/10.3389/ftox.2026.1807786","url":null,"abstract":"<p><p>The genotoxic potential of a mixture of short-, medium-, and long-chain triacylglycerides (SMLCT), a novel synthetic fat intended as a non-animal alternative for food applications, was evaluated using a standard battery of <i>in vitro</i> assays in accordance with OECD Test Guidelines. Studies included a bacterial reverse mutation assay (OECD Test Guideline 471) with <i>Salmonella</i> Typhimurium and <i>Escherichia coli</i> strains at concentrations up to 5000 µg/plate; an <i>in vitro</i> mammalian gene mutation test in L5178Y mouse lymphoma cells (OECD Test Guideline 490) at concentrations up to 31 μg/mL; and an <i>in vitro</i> micronucleus assay in cultured human peripheral blood lymphocytes (OECD Test Guideline 487) at concentrations up to 7.8 μg/mL. Across all assays, SMLCT did not induce biologically relevant increases in revertant colonies, mutant frequencies, or micronucleated binucleated cells. These findings indicate that SMLCT is neither mutagenic nor clastogenic under the conditions of the studies, supporting its safety for use as a dietary fat ingredient in finished food.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1807786"},"PeriodicalIF":4.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790841","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}
引用次数: 0
Correction: In Vitro BBB triculture assay and preliminary computational model development to predict brain exposure. 更正:体外血脑屏障培养试验和初步计算模型开发,以预测脑暴露。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-07 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1836636
Zhuangyan Monica Xu, James P Sluka, Charlie C Zhang, Gregory Knipp
{"title":"Correction: <i>In Vitro</i> BBB triculture assay and preliminary computational model development to predict brain exposure.","authors":"Zhuangyan Monica Xu, James P Sluka, Charlie C Zhang, Gregory Knipp","doi":"10.3389/ftox.2026.1836636","DOIUrl":"https://doi.org/10.3389/ftox.2026.1836636","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ftox.2026.1781588.].</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1836636"},"PeriodicalIF":4.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791006","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}
引用次数: 0
Exposure to manganese during juvenile development increases microglial activation in the hippocampus following systemic infection with A/California/04/2009 Influenza A H1N1 virus. 在幼年期暴露于锰会增加A/California/04/2009甲型H1N1流感病毒全身性感染后海马小胶质细胞的激活。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-02 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1789730
Megan R Hager, Adam J Schuller, Omar A Yanouri, Collin M Bantle, Richard J Smeyne, Ronald B Tjalkens
{"title":"Exposure to manganese during juvenile development increases microglial activation in the hippocampus following systemic infection with A/California/04/2009 Influenza A H1N1 virus.","authors":"Megan R Hager, Adam J Schuller, Omar A Yanouri, Collin M Bantle, Richard J Smeyne, Ronald B Tjalkens","doi":"10.3389/ftox.2026.1789730","DOIUrl":"https://doi.org/10.3389/ftox.2026.1789730","url":null,"abstract":"<p><p>Up to 80% of patients with Parkinson's Disease (PD) develop dementia within 20 years of diagnosis. Although the etiology of PD and related neurodegenerative disorders is poorly understood, risk factors including environmental toxicants and viral infections are linked to disease onset and progression. Exposure to high doses of the essential element, manganese (Mn), causes neurotoxicity associated with parkinsonian symptoms and cognitive impairment in humans. Additionally, epidemiologic studies indicate that viral infections increase risk of developing PD. Previously, our lab demonstrated that mice exposed to Mn during juvenile development showed greater neuroinflammatory changes in microglia within the substantia nigra following systemic infection with H1N1 influenza virus (California/04/09 influenza A) than mice infected without prior exposure to Mn. In the present study, this murine dual-hit model was employed to investigate how juvenile Mn exposure alters H1N1-induced neuropathology and glial morphology in the hippocampus. Mice were exposed to Mn in drinking water from post-natal day 21-51 and then intranasally infected with 10<sup>3</sup> TCID<sub>50</sub> A/California/04/2009 H1N1. To assess histopathology following this exposure paradigm, we performed high-content microscopy and machine learning-based image analysis of H&E and IHC-stained sections spanning the hippocampus to quantify pyknotic neurons and reactive microglia. We report a significant increase in the number of pyknotic neurons in the dentate gyrus as well as morphologic changes in microglia that are consistent with inflammatory activation. Our findings highlight the capacity of combined juvenile manganese exposure and adult viral infection to induce substantial microgliosis in the hippocampus.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1789730"},"PeriodicalIF":4.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700938","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}
引用次数: 0
A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics. 对小分子和生物制剂的临床前物种和人类毒性发现的大规模一致性研究。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-02 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1731947
Xin Liu, Fan Fan
{"title":"A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics.","authors":"Xin Liu, Fan Fan","doi":"10.3389/ftox.2026.1731947","DOIUrl":"https://doi.org/10.3389/ftox.2026.1731947","url":null,"abstract":"<p><p>Translating preclinical safety findings into reliable insights for human risk assessment remains a fundamental challenge in drug development. Prior preclinical-clinical concordance studies have been constrained by limited drug coverage, reliance on identical-term matching for adverse events (AEs), and limited consideration of species, modality, exposure, and biological or mechanistic context. To address these gaps, we assembled a large cross-species concordance dataset, integrating standardized preclinical and clinical safety data for 7,565 marketed and investigational drugs from PharmaPendium and OFF-X. Our framework employs likelihood ratios to reduce prevalence bias and extends concordance assessment beyond identical-term matches to include semantically and mechanistically related AE pairs. Stratified analyses by species, modality, and exposure-matched subsets further refined translational relevance, while integration of on- and off-target annotations supports mechanistic interpretation and potential screening. Using this approach, we identified 850 significant identical-term AEs and 2,833 additional unique endpoints from cross-term associations. To promote reproducibility and transparency in animal research, we provide open access to the analytic code and statistical results via an interactive web application. An accompanying multi-agent AI system (ToxAgents) enables standardized querying and interpretation of concordance results. Together, these resources extend previous foundational efforts and establish a shared, data-driven platform to advance translational safety science, support evidence-based study design aligned with the 3Rs principles, and ultimately contribute to the development of safer medicines to improve human health.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1731947"},"PeriodicalIF":4.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700904","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}
引用次数: 0
Clinical characteristics in Russula subnigricans poisoning: a retrospective study of 103 cases. 黑穗槐中毒103例临床特点回顾性分析。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-02 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1815129
Lei Wu, Congli Yang, Yangshan Fu, Ruiling Zuo, Xingcheng Li, Junyue Hu, Shibiao Fu, Yaowu Chen, Wenfang Zhang, Fenshuang Zheng
{"title":"Clinical characteristics in <i>Russula subnigricans</i> poisoning: a retrospective study of 103 cases.","authors":"Lei Wu, Congli Yang, Yangshan Fu, Ruiling Zuo, Xingcheng Li, Junyue Hu, Shibiao Fu, Yaowu Chen, Wenfang Zhang, Fenshuang Zheng","doi":"10.3389/ftox.2026.1815129","DOIUrl":"https://doi.org/10.3389/ftox.2026.1815129","url":null,"abstract":"<p><strong>Background: </strong>Mushroom poisoning, a form of foodborne intoxication, poses serious life-threatening risks in severe cases. <i>Russula subnigricans</i>, a rare but highly toxic species, warrants particular attention due to its unique symptom profile and clinical manifestations.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 103 patients with confirmed highly suspected Russula subnigricans poisoning admitted to the Affiliated Hospital of Yunnan University between 2020 and 2024. Data encompassed epidemiological characteristics, clinical manifestation, laboratory findings, and treatment outcomes.</p><p><strong>Results: </strong>Patients were predominantly middle-aged (61.2%) and from Yunnan Province (93.2%), with most poisonings (93.2%) resulting from Self-picking. Symptom onset was rapid (median latency, 2.4 h), primarily featuring gastrointestinal, cardiovascular, and rhabdomyolysis-related manifestations. Laboratory findings revealed high rates of hepatotoxicity (97.1%) and myocardial injury (85.4%). A combination of conventional therapy and blood purification was employed in 60.2% of cases, yielding favorable outcomes. After treatment at Yunnan University Affiliated Hospital, the final clinical outcomes were as follows: 91 patients (88.3%) recovered and were discharged.</p><p><strong>Conclusion: </strong><i>Russula subnigricans</i> poisoning is characterized by severe multi-organ toxicity. The adjunctive application of blood purification in combination with conventional therapy appears associated with improved clinical outcomes, although no specific antidote exists. Future research should focus on elucidating toxin mechanisms and toxicokinetics to guide targeted treatment and prevention strategies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1815129"},"PeriodicalIF":4.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700933","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}
引用次数: 0
Acute toxicity and sex-dependent lethality of isotonitazene in fischer 344 rats. 异烟肼对fischer 344大鼠的急性毒性和性别依赖性致死。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-01 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1818684
Yesenia Lopez Hernandez, Horatiu Vinerean, Saurabh Aggarwal
{"title":"Acute toxicity and sex-dependent lethality of isotonitazene in fischer 344 rats.","authors":"Yesenia Lopez Hernandez, Horatiu Vinerean, Saurabh Aggarwal","doi":"10.3389/ftox.2026.1818684","DOIUrl":"10.3389/ftox.2026.1818684","url":null,"abstract":"<p><p>Isotonitazene is a highly potent benzimidazole-derived synthetic opioid increasingly implicated in fatal intoxications. Despite growing forensic detection, controlled <i>in vivo</i> toxicity data remain limited. We determined the median lethal dose (LD<sub>50</sub>) of isotonitazene in adult male and female Fischer 344 rats using the Dixon up-and-down procedure following single intraperitoneal administration. Mortality and clinical signs were monitored for 14 days. The estimated LD<sub>50</sub> was 0.08 mg/kg (95% CI 0.02996-0.182 mg/kg) in males and 0.25 mg/kg (95% CI 0.04841-0.768 mg/kg) in females, indicating greater male sensitivity. Rapid respiratory depression and neuromuscular rigidity occurred within minutes of dosing and preceded lethality. The narrow separation between survival and death demonstrates a steep dose-response relationship and limited safety margin. These findings provide quantitative data for toxicological risk assessment of nitazene opioids and underscore the importance of sex as a biological variable in opioid toxicity studies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1818684"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693945","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}
引用次数: 0
Leveraging developmental neurotoxicity data in zebrafish embryos through the use of artificial intelligence methods. 通过使用人工智能方法利用斑马鱼胚胎发育神经毒性数据。
IF 4.6
Frontiers in toxicology Pub Date : 2026-04-01 eCollection Date: 2026-01-01 DOI: 10.3389/ftox.2026.1789691
Harm J Heusinkveld, Ellen V S Hessel, Edwin P Zwart, Eric R Gremmer, Jeroen L A Pennings
{"title":"Leveraging developmental neurotoxicity data in zebrafish embryos through the use of artificial intelligence methods.","authors":"Harm J Heusinkveld, Ellen V S Hessel, Edwin P Zwart, Eric R Gremmer, Jeroen L A Pennings","doi":"10.3389/ftox.2026.1789691","DOIUrl":"https://doi.org/10.3389/ftox.2026.1789691","url":null,"abstract":"<p><strong>Introduction: </strong>The zebrafish is a well-known whole organism model to study developmental effects of chemical exposure, including developmental neurotoxicity (DNT). One method used to screen for DNT effects is the zebrafish light-dark transition test (LDT), which measures locomotory behavior under alternating light and dark conditions. Because the LDT is relatively new, experimental protocols and data analysis tools for this assay are still evolving. To advance our knowledge on potential applications of the LDT, we explored using artificial intelligence (AI) methods to distinguish between zebrafish exposed to vehicle controls or pharmaceuticals (fluoxetine, paroxetine, carbamazepine, phenytoin) on 5, 10 or 14 days post-fertilization (dpf).</p><p><strong>Methods: </strong>AI methods were trained to distinguish control versus exposed zebrafish behavior and then applied to assign fish to either group, using five-fold cross-validation. This was done with four different AI methods that differ in nature and complexity, namely Generalized Linear Model (GLM), Random Forest (RF), Gradient Boosting Machine (GBM), and Deep Learning (DL).</p><p><strong>Results: </strong>Average prediction accuracy increased from 67% at 5 dpf to 76% at 10 and 14 dpf upon continuous exposure. For fish analyzed at 14 dpf but exposed for shorter durations, we found DNT effects clearly persistent for the antidepressants fluoxetine and paroxetine, but less clearly for the anticonvulsants carbamazepine and phenytoin. The AI methods GLM, RF and DL showed comparable performance, whereas GBM accuracies were lower.</p><p><strong>Discussion: </strong>Compared to conventional univariate analysis, AI appears more sensitive in detecting DNT effects. Overall, this shows the potential of implementing AI methods in DNT screening of chemicals and further development of this approach.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"8 ","pages":"1789691"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693979","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书