IF 4.8 3区医学

Toxicology Pub Date : 2025-07-09 DOI: 10.1016/j.tox.2025.154230

Donghyeon Kim , Jinhee Choi

{"title":"AI-based toxicity prediction models using ToxCast data: Current status and future directions for explainable models","authors":"Donghyeon Kim , Jinhee Choi","doi":"10.1016/j.tox.2025.154230","DOIUrl":"10.1016/j.tox.2025.154230","url":null,"abstract":"<div><div>Artificial intelligence (AI) offers new opportunities for developing toxicity prediction models to screen environmental chemicals. U.S. EPA’s ToxCast program provides one of the largest toxicological databases and has consequently become the most widely used data source for developing AI-driven models. ToxCast In this review, we analyzed 93 peer-reviewed papers published since 2015 to provide an overview of ToxCast data-based AI models. We overviewed the current landscape in terms of database structure, target endpoints, molecular representations, and learning algorithms. Most models focus on data-rich endpoints and organ-specific toxicity mechanisms, particularly endocrine disruption and hepatotoxicity. While conventional molecular fingerprints and descriptors are still common, recent studies employ alternative representations—graphs, images, and text—leveraging advances in deep learning. Likewise, traditional supervised machine-learning algorithms remain prevalent, but newer work increasingly adopts semi- and unsupervised approaches to tackle data-sparsity challenges. Beyond classical structure-based QSAR, ToxCast data are also being used as biological features to predict in vivo toxicity. We conclude by discussing current limitations and future directions for applying ToxCast-based AI models to accelerate next-generation risk assessment (NGRA).</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154230"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620698","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

Screening Industrial Chemicals for Human Developmental Toxicity in the DevTox Germ Layer Reporter Platform. 在DevTox胚层报告平台上筛选工业化学品对人类发育的毒性。

IF 4.8 3区医学

Toxicology Pub Date : 2025-07-09 DOI: 10.1016/j.tox.2025.154232

John T Gamble, Jesse Rogers, Kristen Breaux, Madison Feshuk, Carter Thunes, Katie Paul Friedman, Chad Deisenroth

{"title":"Screening Industrial Chemicals for Human Developmental Toxicity in the DevTox Germ Layer Reporter Platform.","authors":"John T Gamble, Jesse Rogers, Kristen Breaux, Madison Feshuk, Carter Thunes, Katie Paul Friedman, Chad Deisenroth","doi":"10.1016/j.tox.2025.154232","DOIUrl":"https://doi.org/10.1016/j.tox.2025.154232","url":null,"abstract":"<p><p>The EPA New Chemicals Collaborative Research Program (NCCRP) seeks to maximize the efficiency and robustness of the new chemical review process under the Toxic Substances Control Act (TSCA) using new approach methods (NAMs) that represent the best available science. Consideration of the possible health hazards to pregnant women, and their developing offspring, for new chemical submissions is challenged by an insufficient number of acceptable screening modalities to quickly identify potential hazards to humans. The DevTox Germ Layer Reporter (GLR) assay platform evaluates chemical effects on early germ layer development and has been demonstrated to be a viable option for rapid chemical screening. The objective of this study was to screen a structurally diverse set of 171 representative chemicals selected from the TSCA non-confidential active inventory, and 54 in vitro assay reference chemicals, for potential developmental toxicity in the DevTox GLR-Endo assay. Assay performance metrics, as well as predictivity across a set of 16 reference developmental toxicants, were consistent with prior reporting and within acceptable parameters. Of the 38 reference chemicals not previously evaluated in the assay, 25 were identified as active, with 13 demonstrating selectivity for the SOX17 assay endpoint. For the test chemical set, 60 of the 165 chemicals analyzed were active, with 29 exhibiting a degree of selective activity. The results provide coverage of a critical toxicological domain for a set of chemicals relevant to the development of NAM-based methods for the NCCRP and may inform the development of tools in a NAMs-based hazard assessment strategy.</p>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"154232"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620699","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

Two roads to fibrosis: Contrasting initiating mechanisms of Bleomycin and TGFβ-1 in lung fibroblasts 两种纤维化途径：博莱霉素和TGFβ-1在肺成纤维细胞中的启动机制对比

IF 4.8 3区医学

Toxicology Pub Date : 2025-07-09 DOI: 10.1016/j.tox.2025.154233

Nicoletta D’Alessandro , Lena Möbus , Giusy del Giudice , Noora Perho , Angela Serra , Dario Greco

{"title":"Two roads to fibrosis: Contrasting initiating mechanisms of Bleomycin and TGFβ-1 in lung fibroblasts","authors":"Nicoletta D’Alessandro , Lena Möbus , Giusy del Giudice , Noora Perho , Angela Serra , Dario Greco","doi":"10.1016/j.tox.2025.154233","DOIUrl":"10.1016/j.tox.2025.154233","url":null,"abstract":"<div><div>Pulmonary fibrosis, a progressive and debilitating disease, presents a significant global health challenge. Even though often idiopathic, drug-induced fibrosis is increasing its incidence. Traditional chemical safety assessments, relying on apical endpoints from <em>in-vivo</em> models, are limited in capturing the early molecular events initiating fibrosis, consequently limiting the potential for early diagnosis and mechanism-driven treatment. This study employed a toxicogenomic approach on <em>in-vitro</em> MRC-5 fibroblasts, a crucial cell type involved in fibrosis, to dissect the initiating profibrotic mechanisms of Bleomycin (1, 1.5, 2 μg/mL), a profibrotic triggering stimulus, comparing it with TGFβ-1(5, 10, 15 ng/mL), a known sustaining mediator of fibrosis over 24, 48, and 72 h. Our analysis reveals that while both agents alter matrix-related processes, their initiation mechanisms diverge. Specifically, TGFβ-1 directly induces myofibroblast transition, whereas Bleomycin potentially induces an indirect transition through the establishment of a senescence-associated secretory phenotype (SASP). By capturing the early SASP signature, we identified a critical driver of Bleomycin-induced fibroblast fibrosis, relevant to drug-induced fibrosis where antineoplastic agents are a major concern. This study underscores the critical importance of integrating mechanistic understanding into chemical safety assessment, thereby facilitating the development and implementation of safer, more sustainable chemical development.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154233"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614328","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

Ferroptosis contributing to spermatocyte injury induced by silica nanoparticles via BRCA1/GPX4 signaling 二氧化硅纳米颗粒通过BRCA1/GPX4信号通路诱导精母细胞损伤

IF 4.8 3区医学

Toxicology Pub Date : 2025-07-07 DOI: 10.1016/j.tox.2025.154231

Jianhui Liu , Enjie Zhang , Shaofei Su , Shuanghua Xie , Ruixia Liu , Lihua Ren , Chenghong Yin

{"title":"Ferroptosis contributing to spermatocyte injury induced by silica nanoparticles via BRCA1/GPX4 signaling","authors":"Jianhui Liu , Enjie Zhang , Shaofei Su , Shuanghua Xie , Ruixia Liu , Lihua Ren , Chenghong Yin","doi":"10.1016/j.tox.2025.154231","DOIUrl":"10.1016/j.tox.2025.154231","url":null,"abstract":"<div><div>Amorphous silica nanoparticles (SiNPs) have gradually been established to pose a threat to male reproductive health, but the underlying mechanisms are not yet fully elucidated. Ferroptosis is an emerging programmed cell death mechanism associated with spermatogenic disorders. Here, we examined how ferroptosis contributes to SiNP-induced male reproductive damage and assessed the regulatory role of the BRCA1/GPX4 axis in this context. GC-2spd cells were exposure to SiNPs with concentrations of 0, 10, and 20 μg/mL and RNA sequencing of GC-2spd cells was performed. Follow-up experiments were performed to validate the enrichment analysis findings. According to the bioinformatic analysis, after exposure to SiNPs, oxidative stress, ferroptosis and cell cycle pathway were markedly enriched. SiNPs triggered iron overload and significantly decreased the expression levels of glutathione peroxidase 4 (GPX4) and glutathione (GSH) in GC-2spd cells, while upregulating malondialdehyde (MDA) and heme oxygenase-1 (HO-1). Of particular note, the ferroptosis inhibitor Ferrostatin-1 (Fer-1) and a potent iron chelator deferoxamine (DFO) attenuated SiNPs-induced lipid peroxidation, iron overload and cytotoxicity. Of mechanistic importance, we found that BRCA1 targeted GPX4 as a pivotal factor in mediating ferroptosis triggered by SiNPs. Curcumin, the specifical activator of BRCA1, treatment significantly alleviate SiNPs-stimulated down-regulation on expressions of BRCA1 and GPX4. Our findings first emphasize that BRCA1/GPX4 signal-mediated ferroptosis was a factor in SiNPs-caused spermatocyte injury, which offers novel insights for clarifying the toxicity of SiNPs and for the safe application of SiNPs-related nanoproducts in the future.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154231"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581281","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

Formyl peptide receptor 2 (FPR2) mediates cisplatin-induced cochlear inflammation and hair cell apoptosis 甲酰基肽受体2 （FPR2）介导顺铂诱导耳蜗炎症和毛细胞凋亡。

IF 4.8 3区医学

Toxicology Pub Date : 2025-07-05 DOI: 10.1016/j.tox.2025.154229

Jiaojiao Hou , Rui Liang , Yuhan Lin , Daiyao Liu , Jiamei Li , Yifan Liu , Tao Xu , Shuangyue Liu , Aimei Wang

{"title":"Formyl peptide receptor 2 (FPR2) mediates cisplatin-induced cochlear inflammation and hair cell apoptosis","authors":"Jiaojiao Hou , Rui Liang , Yuhan Lin , Daiyao Liu , Jiamei Li , Yifan Liu , Tao Xu , Shuangyue Liu , Aimei Wang","doi":"10.1016/j.tox.2025.154229","DOIUrl":"10.1016/j.tox.2025.154229","url":null,"abstract":"<div><div>Despite its efficacy in cancer treatment, cisplatin is significantly limited by its debilitating ototoxicity and the poorly understood mechanisms underlying this adverse effect. This study investigates the role of formyl peptide receptor 2 (FPR2), a G protein-coupled receptor, in cisplatin-induced hearing loss. We demonstrate a significant upregulation of FPR2 in the cochlea of mice after cisplatin exposure, accompanied by profound hearing loss. Blocking FPR2 with either genetic (knockdown) or pharmacological (antagonist Boc-2, 50 µg/kg) strategies mitigates cisplatin-induced hearing impairment. Our in vivo experiments indicate that intraperitoneal injection of Boc-2 substantially alleviated the increase in auditory brainstem response (ABR) thresholds induced by cisplatin in mice. Mechanistically, FPR2 directly activates ERK1/2 and NF-κB signaling pathways, triggering a pro-inflammatory cytokine storm and subsequent hair cell apoptosis in the cochlea. Furthermore, FPR2 inhibition substantially attenuates cisplatin-induced inflammatory factor release and hair cell death. These findings identify FPR2 as a novel mediator of cisplatin-induced ototoxicity, suggesting its potential as a therapeutic target for preventing hearing loss in cancer patients.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154229"},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576332","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

Retraction notice to "Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals" [Toxicology 246 (2008) 101-111]. 对“砷诱导的线粒体不稳定导致暴露个体的程序性细胞死亡”的撤回通知[毒理学246(2008)101-111]。

IF 4.8 3区医学

Toxicology Pub Date : 2025-07-01 DOI: 10.1016/j.tox.2025.154228

Nilanjana Banerjee, Mayukh Banerjee, Sudipto Ganguly, Santu Bandyopadhyay, Jayanta K Das, Apurba Bandyopadhay, Mitali Chatterjee, Ashok K Giri

引用次数: 0

miR-144-3p suppression mediates Nrf2 activation induced by developmental arsenic exposure in mice miR-144-3p抑制介导发育性砷暴露小鼠诱导的Nrf2激活。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-30 DOI: 10.1016/j.tox.2025.154227

Ruirui Wu , Xin Chen , Yongqin Xia , Mengqi Cui , Sihang Hou , Yuxin Hu , Huihui Wang , Jingbo Pi , Yuanyuan Xu

{"title":"miR-144-3p suppression mediates Nrf2 activation induced by developmental arsenic exposure in mice","authors":"Ruirui Wu , Xin Chen , Yongqin Xia , Mengqi Cui , Sihang Hou , Yuxin Hu , Huihui Wang , Jingbo Pi , Yuanyuan Xu","doi":"10.1016/j.tox.2025.154227","DOIUrl":"10.1016/j.tox.2025.154227","url":null,"abstract":"<div><div>Developmental arsenic exposure enhances the risk for hepatic diseases in later life, which has been found to be related to Nrf2 activation. Epigenetic alterations are suggested to contribute to Nrf2 activation but the potential mechanism is to be elucidated. This study reveals that developmental exposure to 0.5 ppm arsenic induced a 1.5-fold increase in hepatic Nrf2 activity in weaned pups, as indicated by over-expression of Nrf2 and its downstream genes. Blood GSH/GSSG ratio showed a 4.4-fold increase in pups after 0.5 ppm arsenic exposure. <em>Nrf2</em> deficiency attenuated arsenic-induced GSH/GSSG ratio elevation. DNA methylation at the global level and Nrf2 promoter region was not significantly altered in the liver of pups exposed to arsenic during the developmental stage. The levels of miR-144-3p and miR-27a-3p in the liver of pups were significantly decreased to 40 % and 70 % of control by 0.5 ppm arsenic exposure, respectively. The levels of miR-101a-3p and miR-155-5p in the liver of pups were significantly increased to 2.2 and 1.8-fold of control by 0.5 ppm arsenic exposure, respectively. Notably, transfection with a miR-144-3p inhibitor significantly increased mRNA levels of <em>Nrf2</em> (2.2-fold) and its target genes <em>Gsr</em> (1.8-fold), <em>Gclc</em> (1.5-fold), and <em>Gclm</em> (2.0-fold) in primary mouse hepatocytes. Taken together, our data suggest that developmental arsenic exposure induced activation of Nrf2 via miR-144-3p suppression.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154227"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555028","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

Deficiency of aldehyde dehydrogenase 2 sensitizes cells to glutamate-induced cytotoxicity via elevation of GluN1 expression 醛脱氢酶2缺乏通过升高GluN1表达使细胞对谷氨酸诱导的细胞毒性敏感。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-29 DOI: 10.1016/j.tox.2025.154226

Jing Zhang, Yan Zhao

{"title":"Deficiency of aldehyde dehydrogenase 2 sensitizes cells to glutamate-induced cytotoxicity via elevation of GluN1 expression","authors":"Jing Zhang, Yan Zhao","doi":"10.1016/j.tox.2025.154226","DOIUrl":"10.1016/j.tox.2025.154226","url":null,"abstract":"<div><div>Glutamate is the principal excitatory neurotransmitter in the central nervous system. It is essential for neurotransmission and synaptic plasticity; however, excessive glutamate leads to neuronal toxicity, which is considered as a key mechanism contributing to neurodegeneration. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in ethanol metabolism, which converts the toxic alcohol metabolite acetaldehyde to acetate; meanwhile, ALDH2 is also important for the detoxification of other reactive aldehydes such as lipid peroxidation product 4-hydroxy-2-nonenal. ALDH2 deficiency has been associated with the acceleration of neurodegeneration and cognitive impairment accompanied by increased brain oxidative damages. However, there is a lack of reports on how ALDH2 deficiency affects glutamate-induced cytotoxicity. In the present study, it was found that ALDH2-deficient N2a cells exhibited heightened susceptibility to glutamate, displaying aggravated oxidative stress, mitochondrial dysfunction, and calcium imbalance in response to glutamate. ALDH2 deficiency led to reduced antioxidant capacity and elevated intracellular calcium concentration at basal state, thus predisposing the cells to a higher sensitivity to glutamate. Further analyses showed that ALDH2 deficiency elevated the expression of GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs), which are major ionic glutamate receptors allowing the passage of calcium. Consistently, treatment with the NMDAR channel blocker MK-801 (100 μM) or knockdown of GluN1 reduced the susceptibility of <em>Aldh2</em><sup>-/-</sup> cells to glutamate, suggesting that the elevation of GluN1 was a key determinant for the increased sensitivity of ALDH2-deficient cells to glutamate-induced cytotoxicity. The results demonstrated that ALDH2 plays a critical protective role in glutamate-induced neuronal cytotoxicity, while blocking the overactivation of NMDARs might be beneficial for preventing glutamate-induced neuronal toxicity in individuals with defective ALDH2.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154226"},"PeriodicalIF":4.8,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544977","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

Cadmium-mediated autophagy increases ferroptosis of ovarian granulosa cells 镉介导的自噬增加卵巢颗粒细胞的铁下垂

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-24 DOI: 10.1016/j.tox.2025.154224

Lu Yang , Yanling Xu , Yixiao Gao , Xiaoyan Wan , Na Chen

{"title":"Cadmium-mediated autophagy increases ferroptosis of ovarian granulosa cells","authors":"Lu Yang , Yanling Xu , Yixiao Gao , Xiaoyan Wan , Na Chen","doi":"10.1016/j.tox.2025.154224","DOIUrl":"10.1016/j.tox.2025.154224","url":null,"abstract":"<div><div>Cadmium (Cd) is a pervasive environmental toxicant that poses significant threats to female reproductive health. Accumulating evidence has linked Cd exposure to ovarian dysfunction and infertility. As critical somatic components of ovarian follicles, granulosa cells (GCs) regulate folliculogenesis and oocyte maturation, and their dysfunction is implicated in various reproductive disorders including premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). However, the precise mechanisms underlying Cd-induced GC injury are not yet fully understood. Here, we demonstrate that Cd exposure triggers GC death via ferroptosis, an iron-dependent form of regulated cell death characterized by uncontrolled lipid peroxidation. Mechanistically, Cd induces mitochondrial dysfunction and glutathione peroxidase 4 (GPX4) downregulation, leading to reactive oxygen species (ROS) accumulation and subsequent oxidative damage. Intriguingly, we identified autophagy activation as a key regulator of Cd-triggered ferroptosis, evidenced by increased LC3-II conversion and autophagic flux. Importantly, the protective effect of chloroquine (Cq) against Cd-induced cell death provides compelling evidence for the essential role of autophagic activation in mediating Cd-triggered ferroptosis. Our findings not only elucidate a novel molecular pathway connecting Cd exposure to female infertility but also provide preclinical evidence for targeting the autophagy-ferroptosis axis in reproductive toxicology.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154224"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501691","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 Cost Outcome Pathway framework: Integrating socio-economic impacts to Adverse Outcome Pathways for supporting policy makers 成本结果路径框架：将社会经济影响与不利结果路径相结合，以支持政策制定者

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-24 DOI: 10.1016/j.tox.2025.154225

Thibaut Coustillet , Angela Bearth , Xavier Coumoul , Anne-Sophie Villégier , Michèle Bisson , Ellen Fritsche , Jean-Marc Brignon , Florence Zeman , Karine Audouze

{"title":"The Cost Outcome Pathway framework: Integrating socio-economic impacts to Adverse Outcome Pathways for supporting policy makers","authors":"Thibaut Coustillet , Angela Bearth , Xavier Coumoul , Anne-Sophie Villégier , Michèle Bisson , Ellen Fritsche , Jean-Marc Brignon , Florence Zeman , Karine Audouze","doi":"10.1016/j.tox.2025.154225","DOIUrl":"10.1016/j.tox.2025.154225","url":null,"abstract":"<div><div>The Adverse Outcome Pathway (AOP) concept leverages existing data to formalize and disseminate knowledge and is a well-accepted concept in chemical risk assessment. However, it does not handle the socio-economic impact that environmentally-induced diseases may generate, which might be highly relevant for risk management and prioritization. Here, we propose to connect the AOP framework by bridging an Adverse Outcome (AO) to Cost Outcomes (CO) creating so-called Cost Outcome Pathways (COPs) for including the socio-economic costs of exposure to chemicals into the AOP framework. Exposures to certain classes of chemicals have been linked to loss of intellectual quotient (IQ) points in children. This may lead to healthcare costs and reduced working productivity and contribute to increasing the substantial socio-economic burden worldwide. As an <em>in silico</em> case study, a new COP related to neurodevelopmental toxicity was designed, with a connection between the AO ‘decreased, IQ’ and an umbrella CO ‘increased, socio-economic burden’. This framework can support policymaking in the public health sector and might also hold great potential for other environmental exposure-related diseases such as cancer, obesity or neurodegeneration, which are diseases known to have detrimental socio-economic impacts.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154225"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490107","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

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