Toxicology letters最新文献

{"title":"Fecal metabonomics combined with 16S rRNA gene sequencing to study the mechanisms of cantharidin-induced hepatotoxicity","authors":"Lijuan Xiong ,&nbsp;Jialu Zou ,&nbsp;Kexin Lin ,&nbsp;Xiaohong Zhang ,&nbsp;Caiying Yan ,&nbsp;Yanmei He ,&nbsp;Jianyong Zhang","doi":"10.1016/j.toxlet.2025.04.006","DOIUrl":"10.1016/j.toxlet.2025.04.006","url":null,"abstract":"<div><div>Cantharidin (CTD) serves as the principal bioactive compound in traditional Chinese medicine <em>Mylabris</em>, commonly employed in cancer treatment. Nevertheless, the clinical application of CTD is partly restricted by hepatotoxicity, and the toxicology mechanism is not fully elucidated. This study aims to explore the potential mechanism of CTD-induced hepatoxicity by targeted metabolomics-based UPLC-QTOF-MS/MS analysis and 16S rRNA sequencing. Studies have shown that the administration of CTD could lead to elevated serum biochemical indices including ALT and AST. Notably, dilatation of the liver central vein, hepatocellular necrosis, and slight vacuoles in rats were observed after CTD intervention. Fecal metabolomics found CTD could up-regulate 10 and down-regulate 33 metabolites, and metabolic pathway enrichment found that CTD could disrupt 2 metabolic pathways, including Arginine biosynthesis metabolism and β-Alanine metabolism. 16S rRNA gene sequencing analysis showed that CTD could increase the abundance of <em>Turicibacter and Clostridium sensu stricto 1</em>, but decrease the amounts of <em>Prevotella 1</em>. Our correlation analyses showed that alterations in the gut microbiota induced by CTD in rats may have impacted changes in the associated hepatic amino acid metabolism pathway. And the mechanism of action of CTD-induced hepatotoxicity may be related to inflammation, oxidative stress, impaired glucose metabolism and reduced hepatic glycogen storage. These findings will offer novel insights for the prevention and treatment of CTD-induced hepatotoxicity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 65-76"},"PeriodicalIF":2.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859741","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}

{"title":"Exposure to pesticides and cognitive function in school-age children of the Bolivar department (Colombia)","authors":"Maria Quintana-Mejia ,&nbsp;Flor Palacio-Herrera ,&nbsp;Jesus Olivero-Verbel ,&nbsp;Karina Caballero-Gallardo","doi":"10.1016/j.toxlet.2025.04.007","DOIUrl":"10.1016/j.toxlet.2025.04.007","url":null,"abstract":"<div><div>Joining efforts to address the interactions between social and environmental determinants of cognitive functioning allows the identification of structural barriers that guide government plans towards the fulfillment of the 2030 Agenda. This study examined the pesticide exposure and cognitive function in school-age children between the ages of 6–12 years old from Magangue, Achi, and Arjona (reference site) in the Bolivar Department (Colombia). A total of 323 school-age children participated in the study. A cross-sectional examination was conducted, including the measurement of blood serum pesticide concentrations using a gas chromatography–mass spectrometer (GC–MS) and cognitive function was assessed employing the Wechsler Intelligence Scale for Children, 4th edition. A comprehensive questionnaire was used to collect demographic information and exposure profiles. A total of fourteen organophosphate pesticides and 2 carbamates in human blood serum were detected. In Magangue, pesticides were quantified in 91 % of the participants, and in Achi in 34 %. At the comparison site, the results showed the presence of these pesticides in less than 2 % of the total samples analyzed. Interaction effects were observed between parental education, number of pesticides detected (&gt;LOD), IQ, and verbal comprehension index, which could generate alterations in reasoning, problem solving, memory and verbal comprehension. Interaction effects were observed between parental education, the number of pesticides detected, sum of pesticide concentrations detected in blood divided by the reported LD₅₀ of each chemical (ΣCPN/LD), and very low scores on the perceptual reasoning index, indicating compromised performance in abstract, logical, and analytical reasoning tasks. These findings underscore the magnitude of pesticide exposure as a public health concern, emphasizing the need for longitudinal studies to establish causal relationships between social determinants and neurotoxicant exposure as predictors of human development. The results contribute to governmental public health strategies aimed at protecting vulnerable populations and raising awareness of the risks associated with toxic exposures.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 105-118"},"PeriodicalIF":2.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887870","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}

{"title":"The role of the gut microbiome in the associations between lead exposure and child neurodevelopment","authors":"Amanda C. Wylie ,&nbsp;Nicolas Murgueitio ,&nbsp;Alexander L. Carlson ,&nbsp;Rebecca C. Fry ,&nbsp;Cathi B. Propper","doi":"10.1016/j.toxlet.2025.04.004","DOIUrl":"10.1016/j.toxlet.2025.04.004","url":null,"abstract":"<div><div>Lead is highly toxic to the developing brain. Given its persistence in the environment, new intervention strategies are needed to mitigate the impacts of lead on child neurodevelopment. The gut microbiome, referring to the bacteria and microorganisms residing in the gastrointestinal system, may be a viable target for intervention. This short review summarizes recent evidence linking the gut-brain axis to child developmental outcomes. We explore how lead-induced effects to the gut microbiome could indirectly affect child neurodevelopment, such that disrupting or offsetting this mediating process could buffer the effects of lead on child developmental outcomes. Unexpected findings with respect to child microbiota diversity and child cognitive and behavioral outcomes as well as lead exposure and adult microbiota diversity are discussed. When possible, we draw connections between observed changes to relative bacterial abundance, proposed bacterial functions, and downstream effects to brain development. We also explore how the gut microbiome might modify the toxicity of lead by impeding the uptake of lead across the gastrointestinal tract or through indirect mechanisms in such ways that the gut microbiome does not fit within a mediating pathway. In this case, promoting the buffering capacity of the gut microbiome may reduce the impacts of lead on child neurodevelopment. The goal of this short review is to bring attention to the potential role of the gut microbiome in the associations between lead exposure and child neurodevelopment with an eye towards intervention.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 95-104"},"PeriodicalIF":2.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867936","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}

{"title":"Synergistic cardiotoxic effects of captagon and azithromycin in rat via oxidative stress, apoptosis and upregulation of the PI3K/AKT/NF-kB pathway","authors":"Shaimaa A. Shehata ,&nbsp;Noha M. Abd El-Fadeal ,&nbsp;Islam Omar Abdel Fattah ,&nbsp;Abeer M. Hagras ,&nbsp;Enas M.A. Mostafa ,&nbsp;Mohamed M. Abdel-Daim ,&nbsp;Mohamed A. Abdelshakour ,&nbsp;Eman Kolieb ,&nbsp;Asmaa K.K. Abdelmaogood ,&nbsp;Youssef M. Rabee ,&nbsp;Khadiga M. Abdelrahman","doi":"10.1016/j.toxlet.2025.04.002","DOIUrl":"10.1016/j.toxlet.2025.04.002","url":null,"abstract":"<div><div>Fenethylline (Captagon) is a blend of amphetamine and theophylline that functions as a stimulant, while azithromycin (AZ) is a commonly prescribed macrolide antibiotic. The co-usage of illicit substances and therapeutic drugs can result in substantial health risk especially cardiotoxicity. This study aimed to assess cardiotoxicity effects of Captagon (Capta) and Azithromycin/Captagon interaction in adult male rats. Forty-two animals were assigned into 6 groups: Group I (Control) and group II (AZ (30 mg/kg/day) starting from the 14th day of the experiment and for 2 weeks. Group III (Capta10 mg/kg/day), group IV (Capta20 mg/kg/day), group V (AZ+Capta10) and group VI (AZ+Capta20) daily 28 days. Electrocardiogram (ECG), cardiac enzymes, oxidative stress markers, inflammatory genes expression, histopathological and immunohistochemical changes were assessed. Administration of AZ and Capta alone or in combination cause cardiotoxicity. This was indicated by elevated LDH and CTNI levels, ECG changes as increased HR, prolonged QT interval and elevated ST segment accompanied by cardiac histopathological changes. There was a significant reduction in antioxidants SOD, GSH, TAC, and catalase, alongside a significant rise in oxidative stress MDA and NO. Significant rise of ERK, TNF-α, NF-ҡB, PI3K/AKT, Il-1β and IL-6, in both the Capta20 and AZ+Capta groups in dose dependent manner. The Coadministration of AZ and Capta20 produced intense immunoexpression of caspase-3 and BAX and wide areas of negative reactivity for Bcl-2. Coadministration of AZ and Capta induced cardiotoxicity through oxidative stress, inflammation, and apoptosis pathways. It is important to educate healthcare providers and patients about the potential harmful interactions.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 77-94"},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859581","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}

{"title":"A battery of assays for chasing ricin and its activity","authors":"Shivani Dixit ,&nbsp;Ram Kumar Dhaked ,&nbsp;Greeshma TS ,&nbsp;Anjali Yadav ,&nbsp;Jagrati Parashar ,&nbsp;Nandita Saxena","doi":"10.1016/j.toxlet.2025.04.003","DOIUrl":"10.1016/j.toxlet.2025.04.003","url":null,"abstract":"<div><div>Ricin, a type-2 Ribosome-Inactivating Protein (RIP), is a dangerous biotoxin derived from castor plant seeds. It is classified as a Schedule 1 agent by the Chemical Weapon Convention (CWC) and a Category B agent by the Biological and Toxin Weapon Convention (BTWC). Despite their high toxicity, castor seed plants are widely used for the production of castor oil and in folk medicine systems for the treatment of various diseases. Due to the lack of a Food and Drug Administration (FDA) approved medication, early detection of biologically active ricin is critical for implementing suitable countermeasures in time to avert casualties. It is required to employ an integrated approach to distinguish between pure and crude ricin as well as active/inactive ricin. In the present study, a series of bioassays were performed to identify biologically active ricin and its different forms. This assessment included both field and lab-based assays to detect and differentiate different isoforms of ricin. The assays used are the lateral flow assay (LFA), hemagglutination assay (HA), In-vitro translational system (IVTS), cytotoxicity assay (CA), and mouse protection assay (MPA). Considering the ricin-contaminated scenario, the first step was to qualitatively determine the presence of ricin using LFA. Following that, a HA was optimized to differentiate between crude and pure ricin. In addition to this, the assay was also able to differentiate various cultivars and isoforms. IVTS assay was used to identify the enzymatic activity of the ricin A chain that inhibited translational machinery with IC₅₀ (50 % inhibitory concentration) of 11.2 ng/ml. Further neutralization with anti-ricin rabbit polyclonal antibodies (RPAb) confirmed the ricin-mediated translation inhibition and excluded the use of other RIPs (abrin, saproin, and viscumin). Cytotoxicity in HeLa cells was used as a cellular model with an estimated CC₅₀ value (50 % cytotoxic concentration) of 36 ng/ml. The neutralization experiment with RPAb specifically reversed the ricin-induced cytotoxicity. A mouse protection assay was done using 5X LD₅₀ of ricin, which caused mortality within 48 h. RPAb increased the survival, verdict the presence of ricin, and eliminated the presence of related RIPs. All the proposed assays suffice the requirement during ricin exposure scenario from the field to the laboratory. These assays are also capable of distinguishing crude/pure/cultivars, and isoforms of ricin. During an emergency, a combination of these assays will help us to make faster decisions and increase the therapeutic time window for treatment.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 43-53"},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835049","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}

{"title":"Multi-approach study on diethylhexyl phthalate and monoethylhexyl phthalate binding to lysozyme: In silico, bioactivity and surface plasmon resonance analyses","authors":"Müfide Aydoğan Ahbab ,&nbsp;Ilgaz Taşteki̇l ,&nbsp;Evren Gazel Pınar ,&nbsp;Pemra Özbek ,&nbsp;Emir Alper Türkoğlu","doi":"10.1016/j.toxlet.2025.04.005","DOIUrl":"10.1016/j.toxlet.2025.04.005","url":null,"abstract":"<div><div>Diethylhexyl phthalate (DEHP) and its metabolite monoethylhexyl phthalate (MEHP) are recognized as endocrine disruptors with significant toxicological effects on various human physiological systems. While previous research has explored phthalate-protein interactions, there is a notable gap in studies focusing on the interaction between these endocrine disruptors and lysozyme (L_ZM), a critical component of the immune system. This study aimed to investigate the interactions of DEHP and MEHP with chicken egg white lysozyme (CEWL_ZM) using molecular docking, molecular dynamics simulations, bioactivity and surface plasmon resonance (SPR) analyses to evaluate the molecular mechanisms, binding affinity, kinetic properties and bioactivity effects of these interactions. Complementary insights from molecular docking and molecular dynamics simulations indicate that DEHP has a stronger binding affinity for CEWL_ZM than MEHP. This affinity value was corroborated by an intense hydrophobic and van der Waals interaction network especially maintained by the active residue Leu75 and Asp101-Ala107. Although MEHP did not exhibit a significant effect on enzyme activity in lysozyme bioactivity assay, DEHP inhibited lysozyme with an IC₅₀ value of 453 µM. SPR analysis revealed that DEHP exhibits a significantly stronger binding affinity to CEWL_ZM compared to MEHP.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 54-64"},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855124","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}

{"title":"6PPD impairs immune responses and fin regeneration in zebrafish","authors":"Xiaoyu Mao ,&nbsp;Dashuang Mo ,&nbsp;Yuqin Cheng ,&nbsp;Mengzhu Lv","doi":"10.1016/j.toxlet.2025.04.001","DOIUrl":"10.1016/j.toxlet.2025.04.001","url":null,"abstract":"<div><div><em>N</em>-(1,3-Dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine (6PPD), a commonly used antioxidant in tire manufacturing, has been widely detected in the environment and shown to exhibit acute toxicity in several organs. However, the effects of 6PPD on immune responses, particularly following injury, remain poorly understood. In this study, we investigated the impact of 6PPD exposure on immune responses using zebrafish as a model. 6PPD exposure disrupted caudal fin regeneration at various stages of the regenerative process. Further analysis revealed that 6PPD impaired immune responses following fin amputation, as evidenced by the reduced number of lyz⁺/mpx⁺ neutrophils and the downregulation of key immune-related genes. Besides, the morphology of neutrophils was changed upon 6PPD exposure, indicating the defective migration of immune cells. The incubation of zebrafish larvae with lipopolysaccharide (LPS), which induces global immune responses, also exhibited impaired immune function when combined with 6PPD exposure. Additionally, the injection of LPS into the egg yolk or trunk exacerbated immune responses at the injury site, yet 6PPD exposure significantly reduced neutrophil accumulation and downregulated the expression of immune-related genes, confirming the toxicity of 6PPD in immune responses. These findings provide new insights into the toxic effects of 6PPD on immune responses during injury, highlighting its potential to impair immune function in animals and human.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 32-42"},"PeriodicalIF":2.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796331","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}

{"title":"Exploring gadolinium deposition in maternal and offspring mice: Impacts of gestational and lactational exposure","authors":"Ying Kong ,&nbsp;Kai Liu ,&nbsp;Shi Qiu ,&nbsp;Jiali Wang ,&nbsp;Shuai Zhang ,&nbsp;Kai Xu","doi":"10.1016/j.toxlet.2025.03.010","DOIUrl":"10.1016/j.toxlet.2025.03.010","url":null,"abstract":"<div><div>To investigate the gadolinium deposition induced by repeated administration of gadolinium-based contrast agents (GBCAs) in multi-organ/tissue of mother and pup mice during pregnancy and lactation, two hundred and seventy ICR mice were divided into three groups (non-pregnant, pregnant, and lactating; n = 90/group) and received gadodiamide, gadoterate meglumine, or saline intravenously (2.5 mmol Gd/kg once every two days for a total of 10 doses) throughout the entire gestation or lactation period. Gadolinium concentration detection, histological analyses, and transmission electron microscopy were performed on mother and pup mice at the completion of the injection, one month later, and three months later. Our results showed that (i)exposure to GBCAs during pregnancy resulted in gadolinium deposition in fetal organs more significantly with gadodiamide, with the greatest deposition observed in the kidneys and the least in the brain, interestingly, the fetal body was found with no detectable gadolinium deposits one month after birth, that (ii) exposure to GBCAs during lactation did not result in detectable gadolinium deposition in the organs/tissues of the unweaned pups, and that (iii)gadolinium deposition decreased more rapidly in the first month in all tissues examined from all maternal and non-pregnant mice, and gadolinium deposition was found to be lower in the kidneys of both pregnant and lactating mice than in non-pregnant mice. Collectively, exposure to GBCAs during pregnancy resulted in gadolinium deposition in their fetuses with no significant organ toxicity found, and breastfeeding continued after exposure to GBCAs during lactation may not pose a risk of gadolinium deposition to the pups.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 13-22"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789029","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}

{"title":"Do urinary metabolites reflect occupational exposure to organophosphate flame retardants? A case study in electronic waste recycling workers.","authors":"Sabrina Gravel ,&nbsp;Inna Tata Traore ,&nbsp;Miriam L. Diamond ,&nbsp;Liisa Jantunen ,&nbsp;Joseph Zayed ,&nbsp;France Labrèche ,&nbsp;Marc-André Verner","doi":"10.1016/j.toxlet.2025.03.012","DOIUrl":"10.1016/j.toxlet.2025.03.012","url":null,"abstract":"<div><div>Organophosphate esters (OPEs) are commonly used in electronic devices to meet safety standards, but electronic-waste recycling (e-recycling) workers may face significant exposure to those potentially hazardous compounds in their workplace. We examined the relationship between urinary OPE metabolites and their parent compounds in the air, in Canadian e-recycling facilities. We collected personal air samples and end-of-shift urine samples from workers at six e-recycling facilities. We employed linear and Tobit regression models to assess associations between air concentrations of triphenyl phosphate (TPhP) and three metabolites, of tris (2-chloroethyl) phosphate (TCEP) and two metabolites, of tris (2-chloroisopropyl) phosphate (TCPP) and two metabolites, of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), and of tris (2-butoxyethyl) phosphate (TBOEP) and one metabolite each. The 85 participants, mostly male (78 %) and aged between 25 and 54, had concentrations of OPEs detected in 90–100 % of air samples, with geometric means of TPhP, TCEP, TBOEP and TDCPP, of 351, 404, 261 and 250 picomoles per cubic metre respectively. The proportion of detection of their corresponding metabolites varied between 32 % and 98 %. Regression models including the urinary flow rate as a covariate showed that a doubling of the air concentration of TCEP was associated with a 42–107 % increase in its metabolites, and a doubling of air concentration of TBOEP, with a 77 % increase. The paucity of data on the toxicokinetics of OPEs limits the determination of appropriate urinary metabolites to monitor OPE occupational exposure. Such additional data, in combination with workplace contextual information, may help clarify the major routes of exposure and the corresponding contributing sources.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 23-31"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788961","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}

{"title":"Using explainable machine learning to predict the irritation and corrosivity of chemicals on eyes and skin","authors":"Yingxu Liu ,&nbsp;Yang Liu ,&nbsp;Simeng Zhang ,&nbsp;Chen Zeng ,&nbsp;Qing Zhang ,&nbsp;Yunya Jiang ,&nbsp;Xi Yang ,&nbsp;Lidan Zheng ,&nbsp;Qian Ge ,&nbsp;Yanmin Zhang ,&nbsp;Yadong Chen ,&nbsp;Mengyi Lu ,&nbsp;Haichun Liu","doi":"10.1016/j.toxlet.2025.03.008","DOIUrl":"10.1016/j.toxlet.2025.03.008","url":null,"abstract":"<div><div>Contact with specific chemicals often results in corrosive and irritative responses in the eyes and skin, playing a pivotal role in assessing the potential hazards of personal care products, cosmetics, and industrial chemicals to human health. While traditional animal testing can provide valuable information, its high costs, ethical controversies, and significant demand for animals limit its extensive use, particularly during preliminary screening stages. To address these issues, we adopted a computational modeling approach, integrating 3316 experimental data points on eye irritation and 3080 data points on skin irritation, to develop various machine learning and deep learning models. Under the evaluation of the external validation set, the best-performing models for the two tasks achieved balanced accuracies (BAC) of 73.0 % and 75.1 %, respectively. Furthermore, interpretability analyses were conducted at the dataset level, molecular level, and atomic level to provide insights into the prediction outcomes. Analysis of substructure frequencies identified structural alert fragments within the datasets. This information serves as a reference for identifying potentially irritating chemicals. Additionally, a user-friendly visualization interface was developed, enabling non-specialists to easily predict eye and skin irritation potential. In summary, our study provides a new avenue for the assessment of irritancy potential in chemicals used in pesticides, cosmetics, and ophthalmic drugs.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"408 ","pages":"Pages 1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767481","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}