Toxicology letters最新文献_第3页

A core physiologically based toxicokinetic (PBTK) model for exposure assessment of multiple environmental phenols 多种环境酚暴露评估的核心生理毒性动力学（PBTK）模型。

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-08 DOI: 10.1016/j.toxlet.2025.111722

Jeong Weon Choi , Seungho Lee , Jangwoo Lee , Mi-Yeon Shin , Sungkyoon Kim

{"title":"A core physiologically based toxicokinetic (PBTK) model for exposure assessment of multiple environmental phenols","authors":"Jeong Weon Choi , Seungho Lee , Jangwoo Lee , Mi-Yeon Shin , Sungkyoon Kim","doi":"10.1016/j.toxlet.2025.111722","DOIUrl":"10.1016/j.toxlet.2025.111722","url":null,"abstract":"<div><div>Environmental phenols are widely used in consumer products and are of increasing concern due to their potential endocrine-disrupting effects. Physiologically based toxicokinetic (PBTK) models offer a powerful tool for estimating human exposure by translating biomonitoring data into external intake values. However, conventional PBTK models are typically chemical-specific and resource-intensive. In this study, we developed a core human PBTK model capable of describing the absorption, distribution, metabolism, and excretion (ADME) of four groups of environmental phenols—parabens (MeP, EtP, PrP), bisphenols (BPA, BPS), triclosan (TCS), and benzophenone-3 (BP-3)—based on shared toxicokinetic characteristics.</div><div>The model was calibrated and validated using human volunteer data and applied to urinary biomonitoring data from 3787 Korean adults in the Korean National Environmental Health Survey (KoNEHS 2015–2017). Estimated daily intakes (EDIs) for MeP, EtP, PrP, and BPA were estimated via reverse dosimetry and compared with values derived from the conventional fractional urinary excretion (<em>F</em><sub><em>ue</em></sub>) method. Median EDIs derived from the PBTK model were 3.7, 4.8, 0.4, and 0.02 μg/kg-bw/day for MeP, EtP, PrP, and BPA, respectively, and showed good agreement with <em>F</em><sub><em>ue</em></sub> based estimates.</div><div>The core model successfully captured blood and urinary concentration profiles across multiple phenols, demonstrating its potential as a practical and scalable framework for exposure assessment. Furthermore, the model was used in a reverse dosimetry framework to estimate human exposure levels from urinary biomonitoring data. This approach can be particularly valuable when chemical-specific models are unavailable, offering an efficient alternative for interpreting biomonitoring data in environmental health risk assessment.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"413 ","pages":"Article 111722"},"PeriodicalIF":2.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034286","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

Mouse model of prenatal valproic acid exposure: Effects on cortical morphogenesis and behavioral outcomes across environmental conditions 产前丙戊酸暴露小鼠模型：不同环境条件下对皮质形态发生和行为结果的影响。

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-05 DOI: 10.1016/j.toxlet.2025.09.004

Mizuki Tanizaki, Takuma Matsui, Rei Sugiyama, Niina Kiriyama, Munekazu Komada

{"title":"Mouse model of prenatal valproic acid exposure: Effects on cortical morphogenesis and behavioral outcomes across environmental conditions","authors":"Mizuki Tanizaki, Takuma Matsui, Rei Sugiyama, Niina Kiriyama, Munekazu Komada","doi":"10.1016/j.toxlet.2025.09.004","DOIUrl":"10.1016/j.toxlet.2025.09.004","url":null,"abstract":"<div><div>Autism spectrum disorder is a developmental disability characterized by impaired social communication and repetitive behaviors, and environmental and genetic factors are involved in its onset. The use of the antiepileptic drug valproic acid (VPA) during pregnancy is associated with neural tube defects and developmental disorders in the fetus. In this study, we aimed to identify abnormalities in cortical morphogenesis owing to prenatal VPA exposure and to elucidate the abnormalities in brain function associated with these abnormalities, particularly by comparing multiple and single environments. Pregnant mice were administered a single dose of 400 mg/kg/day of VPA on embryonic day 12, and the morphogenesis and behavioral characteristics of the fetal and newborn mouse brains were analyzed. Prenatal VPA exposure caused an increase in cell proliferation and morphological abnormalities in microglia. In the single-housing environment, a decrease in spontaneous locomotor activity and psychomotor activity, and an increase in anxiety-like behavior and abnormal social interactions, were observed. In the multiple-housing environment, no effect on spontaneous activity was detected, however, an effect on social interactions and social proximity was observed. These findings provide valuable insights into the effects of environmental factors during the fetal period on the risk of developmental disorders. Moreover, they indicate that developmental disorder-like behavior is also affected by the environment.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"413 ","pages":"Article 111719"},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016138","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

Bisphenol A exposure promotes proliferation and invasion capabilities of bladder cancer cells: Insights from gene expression and pathway analysis 双酚A暴露促进膀胱癌细胞的增殖和侵袭能力：来自基因表达和途径分析的见解

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-05 DOI: 10.1016/j.toxlet.2025.09.002

Bo Cong , He Liu , Minghui Sun , Dichao Hu , Tongjie Li , Wenbo Wu , Haitao Liu

{"title":"Bisphenol A exposure promotes proliferation and invasion capabilities of bladder cancer cells: Insights from gene expression and pathway analysis","authors":"Bo Cong , He Liu , Minghui Sun , Dichao Hu , Tongjie Li , Wenbo Wu , Haitao Liu","doi":"10.1016/j.toxlet.2025.09.002","DOIUrl":"10.1016/j.toxlet.2025.09.002","url":null,"abstract":"<div><div>Bisphenol A (BPA), a synthetic organic compound widely used in plastic products, toys, water pipes, and flame retardants, has been linked to the onset and progression of various cancers. This study explores the association between BPA and bladder cancer using bioinformatics approaches. We applied the ssGSEA algorithm to calculate BPA-related scores in TCGA-BLCA cohort and classify patients based on this. GO and KEGG pathway enrichment analyses identified key pathways associated with BPA-related genes. Prognostic genes were screened through differential expression, Cox regression, and Lasso regression, leading to the construction of a prognostic model. Pathway enrichment suggested that BPA exposure promotes bladder cancer progression by modulating the Epithelial-Mesenchymal Transition pathway. In vitro experiments demonstrated that exposure to 10⁻⁷ μM BPA significantly enhanced the proliferation and invasion of bladder cancer cells, with Western blot confirming that BPA induces the EMT phenotype in a dose-dependent manner. These findings suggest the involvement of the BPA-mediated regulatory network in bladder cancer progression, thereby providing novel insights into the molecular mechanisms underlying BPA-induced bladder cancer development upon environmental exposure.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"413 ","pages":"Article 111717"},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016152","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

Role of phthalates in breast cancer initiation, progression and drug rersistance: A scoping review and recommendations 邻苯二甲酸盐在乳腺癌发生、发展和耐药中的作用：范围回顾和建议。

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-05 DOI: 10.1016/j.toxlet.2025.111721

L. Benoit , C. Tomkiewicz , S. Bortoli , A.S. Bats , X. Coumoul , M. Koual

{"title":"Role of phthalates in breast cancer initiation, progression and drug rersistance: A scoping review and recommendations","authors":"L. Benoit , C. Tomkiewicz , S. Bortoli , A.S. Bats , X. Coumoul , M. Koual","doi":"10.1016/j.toxlet.2025.111721","DOIUrl":"10.1016/j.toxlet.2025.111721","url":null,"abstract":"<div><div>Phthalates are endocrine-disrupting chemicals (EDCs) with implications in breast cancer (BC). This review synthesizes epidemiological and experimental data to evaluate the role of phthalates in BC initiation, progression, and therapeutic resistance. We performed a scoping review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for breast cancer and phthalates were combined and not restricted to the English language. The search was performed from 2010 to July 2024. The primary outcome was to determine the role of phthalates in BC. Two hundred and forty-seven articles were screened from 2010 to 2024. Of the 90 studies included, 23 were reviews, 24 were epidemiologic and 43 were experimental. Epidemiological evidence is mixed, with certain studies identifying a correlation between high cumulative exposure to specific phthalates, such as dibutyl phthalate, and increased BC risk, particularly in estrogen receptor-positive subtypes. Conversely, other studies reported no significant associations. Experimental investigations have demonstrated that phthalates disrupt estrogenic signaling, induce BC cell proliferation, and potentiate metastasis. Additionally, phthalates contribute to chemoresistance by modulating drug metabolism and altering gene expression. Given the persistent exposure to phthalates this review calls for public health interventions and recommendations.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"413 ","pages":"Article 111721"},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016169","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

Clozapine-associated perturbation of arachidonic acid metabolism: A future direction for clozapine-induced cardiotoxicity 氯氮平相关的花生四烯酸代谢紊乱：氯氮平诱导的心脏毒性的未来方向。

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-04 DOI: 10.1016/j.toxlet.2025.09.005

Ellen Kingston, Kathryn Burns, Malcolm Tingle

{"title":"Clozapine-associated perturbation of arachidonic acid metabolism: A future direction for clozapine-induced cardiotoxicity","authors":"Ellen Kingston, Kathryn Burns, Malcolm Tingle","doi":"10.1016/j.toxlet.2025.09.005","DOIUrl":"10.1016/j.toxlet.2025.09.005","url":null,"abstract":"<div><div>Clozapine is an effective antipsychotic medication utilised for treatment-resistant schizophrenia. However, clinical use of clozapine is limited due to the risk of cardiotoxicities, including clozapine-induced myocarditis. Oxidation of clozapine and reduction of clozapine-<em>N</em>-oxide can be catalysed by the cardio-selective cytochrome P450 (CYP) isoforms CYP2J2, CYP1A1 and CYP1B1, which are also reported to metabolise arachidonic acid. Any interaction with CYP-catalysed arachidonic acid metabolism may perturb the balance of pro-inflammatory hydroxyeicosatetraenoic acids and anti-inflammatory epoxyeicosatrienoic acids, priming the heart to an inflammatory state. Thereby making it more susceptible to the damage that may induce clozapine-induced myocarditis. The purpose of this preliminary study was to investigate whether an interaction between arachidonic acid and clozapine or clozapine-<em>N-</em>oxide occurs at CYP2J2, CYP1A1 and CYP1B1, in comparison to the hepatic isoform CYP2C19. Our results demonstrated a clear perturbation of CYP1B1 catalysed arachidonic acid metabolism, with a concentration-dependent decrease in metabolite formation in the presence of clozapine and clozapine<em>-N</em>-oxide. Each isoform also had decreased <em>N-</em>desmethylclozapine formation relative to incubations with clozapine alone and impaired clozapine and clozapine-<em>N-</em>oxide REDOX cycling capacity. Although limited by analytical sensitivity, these data provide clear evidence of a metabolic interaction between arachidonic acid and clozapine. This offers a novel hypothesis to explain patient susceptibility and a feasible mechanism for the cardiac-selective inflammation observed in clozapine-induced myocarditis.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"412 ","pages":"Pages 234-245"},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008459","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

Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line 微生物和合成吲哚激活皮肤靶向AhR：来自AhaRaCaT报告细胞系的见解

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-02 DOI: 10.1016/j.toxlet.2025.09.001

Radim Vrzal, Aneta Grycová, Aneta Vrzalová

{"title":"Skin-targeted AhR activation by microbial and synthetic indoles: Insights from the AhaRaCaT reporter cell line","authors":"Radim Vrzal, Aneta Grycová, Aneta Vrzalová","doi":"10.1016/j.toxlet.2025.09.001","DOIUrl":"10.1016/j.toxlet.2025.09.001","url":null,"abstract":"<div><div>Disruption of the epidermal barrier contributes to skin disorders such as atopic dermatitis and psoriasis. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays a key role in skin homeostasis and immune regulation. While traditionally associated with toxicity, AhR has emerged as a promising therapeutic target, particularly via tryptophan-derived indoles. To support AhR research in a dermatological context, we developed AhaRaCaT, a stable luciferase-based reporter cell line derived from human keratinocytes (HaCaT), enabling the assessment of AhR transcriptional activity in a skin-relevant model. We characterized the inducibility of AhaRaCaT in response to model AhR ligands (TCDD, BaP, FICZ) in dose- and time-dependent assays. Antagonist profiling with MNF, CH223191, GNF, carvone, and jasmone yielded IC50 values over 4- and 24-hour exposures. A panel of indoles previously studied in other models was evaluated for AhR activation, revealing a robust luciferase response at 4 h that declined at 24 h, consistent with trends observed in other cell types. Selected indoles also induced <em>CYP1A1</em> mRNA expression and reversed cytokine-induced downregulation of <em>filaggrin</em> in HaCaT cells, highlighting their potential in mitigating inflammation-associated skin barrier defects. In summary, the AhaRaCaT cell line offers a sensitive and physiologically relevant tool for studying AhR signaling in skin, with broad applications in toxicology, dermatological research, and the development of AhR-targeted therapies for inflammatory skin diseases.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"412 ","pages":"Pages 191-201"},"PeriodicalIF":2.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932277","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

Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis 基于蛋白质代谢组学分析的甲醛诱导肝毒性表征

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-02 DOI: 10.1016/j.toxlet.2025.09.003

Sanjita Paudel , Hyunchae Sim , Eunjoo Kang , Minseo Kim , Chai Won Park , Ann-yae Na , Eun Ki Min , Ki-Tae Kim , Wonhwa Lee , Sangkyu Lee

{"title":"Characterization of formaldehyde-induced hepatotoxicity based on proteometabolomic analysis","authors":"Sanjita Paudel , Hyunchae Sim , Eunjoo Kang , Minseo Kim , Chai Won Park , Ann-yae Na , Eun Ki Min , Ki-Tae Kim , Wonhwa Lee , Sangkyu Lee","doi":"10.1016/j.toxlet.2025.09.003","DOIUrl":"10.1016/j.toxlet.2025.09.003","url":null,"abstract":"<div><div>Formaldehyde (FA) is a well-known environmental toxicant used in various industries, including biomedical, agriculture, and textiles, but poses significant health risks. Despite extensive research, the exact hepatotoxic mechanism of FA remains unclear. This study investigated FA-induced liver toxicity through an integrative analysis of proteomics and metabolomics in rat models, identifying 84 differentially expressed proteins and 66 metabolites. Using xMWAS and Reactome software, the study highlighted ferroptosis as a key pathway in FA-induced liver damage. STAT3/HO-1 were identified as crucial protein biomarkers, leading to ferroptosis via lipid peroxide accumulation through iron efflux. Validation through qPCR, western blot, and cell experiments confirmed the involvement of genes like <em>Stat3</em>, <em>Hmox-1</em>, and coagulation-related genes (<em>Fga</em>, <em>Fgb</em>, <em>Fgg</em>, <em>Serpina1</em>, and <em>A2M</em>). This research reveals a novel FA hepatotoxic mechanism involving ferroptosis and complement and coagulation pathways, offering potential for therapeutic interventions.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"412 ","pages":"Pages 212-222"},"PeriodicalIF":2.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988597","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

Aims and Scope 目标及范围

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-01 DOI: 10.1016/j.toxlet.2025.07.1356

引用次数: 0

CEC01-02 Chemical Respiratory Allergy: Identification of true chemical respiratory allergens 化学呼吸道过敏：鉴别真正的化学呼吸道过敏原

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-01 DOI: 10.1016/j.toxlet.2025.07.012

J. Arts

{"title":"CEC01-02 Chemical Respiratory Allergy: Identification of true chemical respiratory allergens","authors":"J. Arts","doi":"10.1016/j.toxlet.2025.07.012","DOIUrl":"10.1016/j.toxlet.2025.07.012","url":null,"abstract":"<div><div><em>See Pemberton et al. (2024)</em>: Asthma in the workplace (work-related asthma) is an important occupational health issue. It comprises two main subtypes: viz. pre-existing asthma which is exacerbated by work (work-exacerbated asthma or WEA) or asthma caused by work (occupational asthma or OA). The latter can be subdivided in non-allergic irritant-induced occupational asthma (IIOA) and in allergic occupational asthma (AOA). AOA may be fatal.</div><div>Current regulatory paradigms for the management of OA are not fit for purpose. For both effective human health protection and appropriate and proportionate regulation there is an important, yet unmet need, that sub-types of work-related asthma can be accurately identified and classified, and that chemical respiratory allergens that drive allergic asthma can be differentiated according to potency.</div><div>In my presentation I will address presently available strategies for the diagnosis and characterisation of asthma in the workplace, such as human health studies, clinical investigations and experimental approaches (structure-activity relationships, assessments of chemical reactivity, experimental animal studies and <em>in vitro</em> methods). Each of these approaches has limitations with respect to providing a clear discrimination between WEA and OA, and between AOA and IIOA. Against this background the need for improved characterisation of work-related asthma, in the context of more appropriate regulation is discussed.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S5"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010915","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

CEC04-02 How to rate essential information from analytics on test material 如何评价测试材料分析的重要信息

IF 2.9 3区医学

Toxicology letters Pub Date : 2025-09-01 DOI: 10.1016/j.toxlet.2025.07.026

T. Schupp

引用次数: 0