Toxicology letters最新文献

Cyclohexane-1,2-dicarboxylic acid diisononyl ester (DINCH) and its metabolites in body fluids of rats and humans after single oral doses of DINCH. 单次口服环己烷-1,2-二羧酸二异壬基酯（DINCH）及其在大鼠和人体液中的代谢产物。

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-10-20 DOI: 10.1016/j.toxlet.2026.113224

Daniel Bury, Rainer Otter, Angelika Langsch, Alexandra Gotthardt, Benedikt Ringbeck, Patrick O Helmer, Heiko Hayen, Thomas Brüning, Holger M Koch

{"title":"Cyclohexane-1,2-dicarboxylic acid diisononyl ester (DINCH) and its metabolites in body fluids of rats and humans after single oral doses of DINCH.","authors":"Daniel Bury, Rainer Otter, Angelika Langsch, Alexandra Gotthardt, Benedikt Ringbeck, Patrick O Helmer, Heiko Hayen, Thomas Brüning, Holger M Koch","doi":"10.1016/j.toxlet.2026.113224","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.113224","url":null,"abstract":"The European Food Safety Authority (EFSA) has established a tolerable daily intake (TDI) of 1mg/kg bw/d for the plasticizer DINCH (Cyclohexane-1,2-dicarboxylic acid diisononyl ester). To characterize the maximum internal doses resulting from a single dosing and to assess species differences relevant for extrapolating rat toxicokinetics to humans, concentration-time profiles of DINCH and its metabolites (specific monoesters: MINCH, OH-MINCH, oxo-MINCH, cx-MINCH; non-specific metabolite: CHDA) were quantified in the blood of male Wistar rats and male human volunteers. Urinary excretion of metabolites was additionally evaluated for humans. Single oral doses of ring-deuterated DINCH were administered (rats: 1 or 40mg/kg bw; humans: 1mg/kg bw). In rats, gastrointestinal absorption exhibited saturation, as a 40-fold increase in administered dose resulted in only ~25-fold increases in Cmax and AUC. Across species, the hierarchy of Cmax in blood was consistent: DINCH > CHDA > cx-MINCH > MINCH > OH-MINCH > oxo-MINCH. Notably, Cmax values for DINCH and MINCH in blood after a 1mg/kg bw (1.74µM and 0.10µM) dose in humans were like those observed in rats following a 40-fold higher dose (4.4µM and 0.11µM). Corresponding AUC∞ values showed the same pattern, indicating greater systemic availability of DINCH in humans, although this is partly counter balanced by plasma protein binding. In humans, approximately 50% of MINCH and 70-80% of the other monoester metabolites were glucuronidated, whereas these metabolites remained unconjugated in rats. CHDA was unconjugated in both species. Overall, the data highlight both shared and species-specific features of DINCH metabolism in rats and humans.","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"113224"},"PeriodicalIF":3.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of bisphenol A exposure on hormone-associated benign and malignant disorders: a systematic review and meta-analysis. 双酚A暴露与激素相关的良性和恶性疾病的关系：系统回顾和荟萃分析。

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-10-19 DOI: 10.1016/j.toxlet.2026.113213

Sani Rachman Soleman, Sufi Desrini, Daivan Febri Juan Setiya, Ety Sari Handayani, Nur Aini Djunet, Kuswati, Muflihah Rizkawati, Muhammad Rafi Falah

{"title":"Association of bisphenol A exposure on hormone-associated benign and malignant disorders: a systematic review and meta-analysis.","authors":"Sani Rachman Soleman, Sufi Desrini, Daivan Febri Juan Setiya, Ety Sari Handayani, Nur Aini Djunet, Kuswati, Muflihah Rizkawati, Muhammad Rafi Falah","doi":"10.1016/j.toxlet.2026.113213","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.113213","url":null,"abstract":"Introduction: Bisphenol A (BPA) and its analogs have garnered considerable public and scientific attention due to their endocrine-disrupting properties in humans. This systematic review aims to address the question of whether exposure to Bisphenol A is associated with the risk of hormone-associated benign and malignant disorders.Methods: A comprehensive literature search was conducted from inception to February 2024 to identify eligible human case-control studies investigating exposure to BPA and its analogs. The study selection and data extraction processes were performed independently and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All analyses were conducted using Review Manager (RevMan) software, version 5.4.Results: Following the removal of duplicate records, 661 eligible articles were identified, with 44 studies ultimately included in the final analysis. Bisphenol A was the most frequently investigated contaminant, whereas its analogs were only reported in one study. Most studies reported PCOS, breast cancers, benign and malignant endometrial disorders and only one study reported prostate cancer. The result indicate that BPA exposure is associated with PCOS (SMD=1.19; CI95: 0.70-1.67), benign endometrial disorders (SMD=0.94; CI95: 0.15, 1.73), breast cancer (SMD=0.68; CI95: 0.44-0.92). Nevertheless, these associations demonstrate considerable heterogeneity.Conclusion: Bisphenol A exposure is associated with the risk endocrine-related benign and malignant disorders, such as PCOS, breast cancer, and benign endometrial disorders. Nevertheless, the interpretation of these findings is limited by substantial heterogeneity, largely attributable to small sample sizes in case and control groups.","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"113213"},"PeriodicalIF":3.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Snail-shRNA in AAV9 inhibited EMT and pulmonary fibrosis in silica-instilled mice. AAV9中的蜗牛shrna抑制二氧化硅灌注小鼠的EMT和肺纤维化。

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-10-17 DOI: 10.1016/j.toxlet.2026.113214

Yuhua Wang, Enna Hu, Siling Li, Jing Zhao, Zhonghui Zhu, Lin Tian, Yan Wang

{"title":"Snail-shRNA in AAV9 inhibited EMT and pulmonary fibrosis in silica-instilled mice.","authors":"Yuhua Wang, Enna Hu, Siling Li, Jing Zhao, Zhonghui Zhu, Lin Tian, Yan Wang","doi":"10.1016/j.toxlet.2026.113214","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.113214","url":null,"abstract":"Our previous study in vitro has shown that targeting transcription factor Snail might be a strategy for the treatment of silicosis. In this study, we evaluated the feasibility of the strategy in vivo. Here we used CBG transgenic mice which could be used to track and isolate alveolar epithelial type II cells (AT II cells) to confirm that 2.5mg silica could induce epithelial-mesenchymal transition (EMT) in AT II cells in vivo. Based on the results that 2.5mg silica induced a rapid elevation of Snail in the lungs of mice and the optimal injection dose and stable expression time of adeno-associated virus (AAV) 9 vectors, we finally decided to inject AAV9-mediated Snail knockdown at 1.0×1011 vg/mouse 1 week before silica instillation to inhibit the levels of Snail increased by silica. The results showed that Snail-shRNA in AAV9 prevented silica-induced EMT in AT II cells in CBG transgenic mice and inhibited EMT and pulmonary fibrosis induced by silica in wild-type mice. Quantitative proteomic analysis combined with dbEMT database mapping further indicated that Snail knockdown suppressed silica-induced EMT and fibrosis through a Fibronectin (FN1)-centered interaction network involving proMMP8 activation and JUN kinase signaling. These findings suggested that Snail could be used as a target for the treatment of pulmonary fibrosis in the future.","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"113214"},"PeriodicalIF":3.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of predisposing factors for hematotoxicity in occupational benzene-exposed workers using machine learning and SHAP interpretation. 使用机器学习和SHAP解释识别职业性苯暴露工人血液毒性的易感因素。

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-10-15 DOI: 10.1016/j.toxlet.2026.113212

Wanzhen Liao, Yuwei Zhang, Nannan Tu, Rongfang Yang, Lixian Wen, Yulu Cai, Qilong Liao, Yuan Jin, Wenxue Li, Xiumei Xing, Wen Chen, Yongmei Xiao, Liping Chen

{"title":"Identification of predisposing factors for hematotoxicity in occupational benzene-exposed workers using machine learning and SHAP interpretation.","authors":"Wanzhen Liao, Yuwei Zhang, Nannan Tu, Rongfang Yang, Lixian Wen, Yulu Cai, Qilong Liao, Yuan Jin, Wenxue Li, Xiumei Xing, Wen Chen, Yongmei Xiao, Liping Chen","doi":"10.1016/j.toxlet.2026.113212","DOIUrl":"10.1016/j.toxlet.2026.113212","url":null,"abstract":"Benzene is an important industrial material and environmental pollutant, and even low-level exposure has been associated with hematotoxicity. Therefore, the identification of predisposing factors for hematotoxicity induced by occupational benzene exposure is crucial for managing occupational benzene poisoning. Herein, we recruited 1513 petrochemical workers in southern China, including 847 control workers and 666 workers with hematotoxicity. After randomly dividing the dataset into a training set (75%) and a test set (25%), we employed six machine learning algorithms construct a prediction model. Through recursive feature elimination, 22 feature variables, including age, work years, department, benzene, toluene, xylene, noise, AST/ALT, ALP, GGT, TBIL, DBIL, TC, TG, LDL-C, HDL-C, GLU, SCr, Urea, UA, FEV1/FVC%, and DBP were initially identified. Styrene was included due to its occupational relevance, resulting in 23 input variables for model development. We found the XGBoost algorithm was the optimal model for identifying factors affecting hematotoxicity. SHAP analysis based on the XGBoost model further characterized the contributions of variables at both the overall and individual levels, identifying benzene, noise, work years, age, department, and liver function indicators as important factors while also showing the direction and magnitude of their associations with the predicted risk of hematotoxicity. In vitro experiments also shown that impaired liver function exacerbated 4-benzoquinone (1,4-BQ)-induced cytotoxicity in bone marrow cells and modulated the underlying molecular pathways. Together, liver function-related indicators emerged as important predictors of hematotoxicity risk among benzene-exposed workers. These findings may help inform occupational health surveillance and risk stratification in this population.","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"113212"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The penetration of the Novichok nerve agent A-234 in a human skin model and the assessment of several decontamination procedures. 诺维乔克神经毒剂a -234在人体皮肤模型中的渗透和几种去污程序的评估。

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-10-15 DOI: 10.1016/j.toxlet.2026.113209

Gabriele Horn, Timo Wille, Dirk Steinritz, Niko Amend

{"title":"The penetration of the Novichok nerve agent A-234 in a human skin model and the assessment of several decontamination procedures.","authors":"Gabriele Horn, Timo Wille, Dirk Steinritz, Niko Amend","doi":"10.1016/j.toxlet.2026.113209","DOIUrl":"https://doi.org/10.1016/j.toxlet.2026.113209","url":null,"abstract":"The recent use of a Novichok nerve agent for an assassination attempt on Alexei Navalny underlined the importance of identifying effective countermeasures. The immediate decontamination is essential to reduce the penetration of the chemical agent into the systemic circulation. Only limited data are available about the decontamination of Novichok nerve agents on the skin. In this study, we used an in vitro model of human skin to determine the efficacy of decontaminants to remove the agent A-234. The skin was exposed towards A-234 and after 5min or 30min the decontamination was initiated by applying different decontamination protocols (Reactive Skin Decontamination Lotion (RSDL), the potassium salt of the acetohydroxamic acid (AHAK), sodium hypochlorite (NaOCl) 2%, soapy water 2% and tap water). Then, the amount of penetrated A-234 was calculated using an acetylcholinesterase inhibition assay. The early decontamination with AHAK was most effective resulting in a complete decontamination, i.e. 0% residual A-234. In contrast, soapy water, tap water, RSDL and NaOCl showed a lower decontamination efficacy and the penetrated amount of A-234 was reduced by 89% (soapy water, tap water), 91% (RSDL) and 95% (NaOCl). The delayed decontamination after 30min also revealed a complete decontamination of A-234 by using AHAK and an inadequate decontamination using soapy water, tap water, RSDL and NaOCl. In conclusion, the results underline that the decontamination of the Novichok agent A-234 was similar to the V-series nerve agent VX. The relatively new AHAK was a promising decontaminant and deserves further investigation.","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":"113209"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

S14-02 When endocrine disruptors shape the mammary gland: In vitro models for studying development, differentiation, and involution 当内分泌干扰物塑造乳腺：研究发育、分化和退化的体外模型

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1016/j.toxlet.2026.112029

L. Kass

引用次数: 0

S16-02 Next-generation risk assessment (NGRA) into practice:assessment of non-genotoxic carcinogens as example forthe ASPA framework 下一代风险评估（NGRA）的实践：以ASPA框架为例的非遗传毒性致癌物评估

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1016/j.toxlet.2026.112037

M. Luijten

引用次数: 0

CEC02-02 Introduction to OPRA: A Probabilistic Risk Assessment Framework OPRA简介：概率风险评估框架

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1016/j.toxlet.2026.111958

A. Maertens

引用次数: 0

CEC03-01 Polymer identity challenges and how they matter for toxicology 聚合物特性挑战及其对毒理学的影响

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1016/j.toxlet.2026.111962

H.M. Hollnagel

引用次数: 0

CEC03-02 Water Solubility of polymers 聚合物的水溶性

IF 3.1 3区医学

Toxicology letters Pub Date : 2026-09-01 Epub Date: 2026-09-07 DOI: 10.1016/j.toxlet.2026.111963

B. Meisterjahn

引用次数: 0