Journal of Applied Toxicology最新文献

{"title":"Comparative Toxicity and Residual Activity of Botanical and Synthetic Insecticides Against Multiple Life Stages of Aleurodicus dispersus (Hemiptera: Aleyrodidae).","authors":"T Boopathi, N Anusha, J G Prasuna","doi":"10.1002/jat.4873","DOIUrl":"https://doi.org/10.1002/jat.4873","url":null,"abstract":"<p><p>The spiraling whitefly, Aleurodicus dispersus Russell (Hemiptera: Aleyrodidae) is a highly polyphagous and invasive pest that poses serious challenges to crop protection, particularly in tropical and subtropical agroecosystems. Given the rising concern over pesticide resistance and environmental risks associated with conventional insecticides, this study was conducted under controlled laboratory conditions to compare the efficacy of selected botanicals, fish oil rosin soap (FORS), organic salt, and synthetic insecticides against multiple life stages of A. dispersus. Standardized bioassays-including direct spray, dry film (simulating residual contact toxicity), and ovicidal assays-were employed to evaluate stage-specific responses in nymphs, adults, and eggs. Azadirachtin 5.0% and Azadirachtin 0.15% achieved over 96% adult mortality in the dry film method, suggesting notable residual efficacy. Among synthetic insecticides, Acetamiprid 20% SP showed the highest ovicidal activity (70.2% by day 10) and the lowest LC₅₀ (184.80 ppm). Neem-based treatments like Azadirachtin 0.03% and NSKE 5% demonstrated slower but significant toxic effects (LC₅₀ range: 2834.21-9359.42 ppm). Probit analysis supported consistent dose-response relationships. Rather than suggesting immediate field adoption, the findings highlight promising candidates for further evaluation under semi-field and field conditions. This is one of the first comprehensive studies to simultaneously assess direct, residual, and ovicidal effects of both botanical and synthetic insecticides against A. dispersus, offering valuable insights for integrating fast-acting and environmentally safer options in whitefly management programs.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure Risks of Trans-Perfluoro (4-Methyl-2-Pentene) Byproduct in C₆F₁₂O Fire Suppressants: Toxicological Mechanisms and Implications.","authors":"Biao Zhou, Muying Ge, Kai Wang, Peiyao Chen, Jin He, Haiting Wu, Wanyu Yang, Hongru Zhou","doi":"10.1002/jat.4868","DOIUrl":"https://doi.org/10.1002/jat.4868","url":null,"abstract":"<p><p>C₆F₁₂O fire agent is widely used in various fire extinguishing scenarios due to its excellent properties. The most abundant byproduct in C₆F₁₂O fire extinguishing agent is perfluoro (4-methyl-2-pentene) (C₆F₁₂). Currently, there is a lack of reports on the toxic mechanisms of trans-C₆F₁₂. This study investigated the acute oral toxicity of trans-C₆F₁₂ in rats, the damage mechanisms to major organs, and evaluated the inflammatory status of various organs. The experimental design comprised four treatment groups: a control group, a low-dose group (250 mg/kg), a medium-dose group (500 mg/kg), and a high-dose group (750 mg/kg), encompassing the range from sublethal to lethal concentrations. The median lethal dose (LD50) for trans-C₆F₁₂ revealed its mild acute toxicity, with male rats exhibiting significantly higher sensitivity. Clinical observations showed that trans-C₆F₁₂ oral exposure caused symptoms such as lethargy and reduced appetite. Pathological analysis revealed that trans-C₆F₁₂ primarily caused significant damage to the respiratory and urinary systems, particularly in lung and kidney tissues. Additionally, moderate damage was observed in the liver, heart, and spleen, whereas only mild pathological changes were detected in the classical hippocampus, and no effects were observed in ocular tissues. Further analysis of the inflammatory cytokine IL-1β levels showed that lung and kidney tissues were more sensitive to the toxicity of trans-C₆F₁₂, exhibiting significant inflammatory responses. In contrast, the inflammatory responses in other organs were relatively weak. This study revealed the toxicity of trans-C₆F₁₂ and its toxicological mechanisms, providing important references for the safe use of C₆F₁₂O fire extinguishing agent.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of di (2-Ethylhexyl) Phthalate-Induced Lipid Metabolism Disorders: A Review.","authors":"Xiaoqi Fang, Tianrun Wang, Shihao Lou, Ying Qiao, Bo Zhang, Liting Zhou","doi":"10.1002/jat.4867","DOIUrl":"https://doi.org/10.1002/jat.4867","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that can be absorbed by the human body through various pathways. Numerous studies have indicated the adverse effects of DEHP on lipid metabolism. Experimental and population studies have provided evidence for DEHP-induced lipid metabolism disorder. This review discusses the cellular pathophysiological changes leading to lipid metabolism disorders, including inflammation, apoptosis, autophagy, and oxidative stress. We also summarize the key molecules and signaling pathways involved in the lipid metabolism disorder induced by DEHP. Additionally, multiple omics such as metabolomics, transcriptomics, and epigenetics are discussed in this review. Furthermore, this article provides some directions for future research about the mechanisms of lipid metabolism disorders caused by DEHP, aiming to offer more detailed and reliable theoretical evidence for the prevention and treatment of lipid metabolism disorders.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic Effects of \"25.2% Boscalid + 12.8% Pyraclostrobin\" Fungicide.","authors":"Yasin Eren","doi":"10.1002/jat.4864","DOIUrl":"https://doi.org/10.1002/jat.4864","url":null,"abstract":"<p><p>It is known that different pesticides used against domestic or agricultural pests have toxic effects. In this study, 25.2% boscalid and 12.8% pyraclostrobin were used in the test material. Kate A1 Russian wheat variety was used for Triticum growth inhibition tests. According to the Triticum root and stem growth test, the concentration value that halves the root and stem length is known as the \"EC50 value\" According to the test, the root length of the control group was 6.98 ± 0.65 cm and the length of the stem was 9.36 ± 0.71 cm. According to the Triticum test, the EC50 value of the fungicide was determined as 2500 ppm. The value that halves the stem length of the control group was determined as 1250 ppm. Some doses of this fungicide (625, 1250, 2500, 5000, and 10,000 ppm) were observed to inhibit root and stem growth, and these concentrations' results were statistically significant according to Dunnett's t-test. In the root mitotic index analysis, 5000 cells were counted for each concentration, and it was determined that all concentrations tested had negative effects on mitotic activity. It was observed that the concentration of 10,000 ppm was the most decreasing (0.53 ± 0.18 cm) mitotic index %. The recommended dose of the tested fungicide in the fight against agricultural pests is around 500 ppm, and this indicates that the fungicide will have limited cytogenetic effects. The mitotic index test indicated that 2500 and upper concentrations had toxic effects on the mitotic index. The most toxic effect was in the 10,000 ppm treatment. The MTT test showed that all concentrations had a cytotoxic effect on MDBK cells. But 625 ppm concentration in all treatment periods and 1250 ppm 24-h results were statistically no significant according to Dunnett's t-test.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening Hub Genes of Ferroptosis in Pb-Induced Acute Kidney Injury Based on GEO Database Bioinformatics and Experimental Validation.","authors":"Xin Fang, Shidi Gao, Le Zhang, Jingyu Gao, Ting Li, Chaofan Wang, Jiayunzhu Xu, Chenxu Li, Rifeng Lu, Li Guo","doi":"10.1002/jat.4866","DOIUrl":"https://doi.org/10.1002/jat.4866","url":null,"abstract":"<p><p>This study aimed to explore the role of ferroptosis-related genes in Pb-induced acute kidney injury (AKI) using bioinformatics and animal experiments, potentially providing a new direction for future research. Differentially expressed genes related to Pb-induced AKI mediated by ferroptosis were identified using databases. Subsequently, hub genes were identified through enrichment and protein-protein interaction analyses. Western blot and immunohistochemistry were used to verify the expression of hub genes and ferroptosis marker protein GPX4, and the levels of Fe²⁺, GSH, and MDA in tissues were determined. Drug prediction was performed using the DSigDB database and molecular docking. The hub genes were screened: heme oxygenase 1 (HMOX1), CD44 molecule (CD44), arachidonate 15-lipoxygenase (ALOX15), and NADPH quinone dehydrogenase 1 (NQO1). In 600 mg/kg lead acetate-induced AKI rat models, kidney tissues exhibited significantly lower levels of HMOX1, CD44, NQO1, and glutathione peroxidase 4 (GPX4) proteins, while showing higher levels of ALOX15 protein. Furthermore, significantly elevated levels of Fe²⁺ and malondialdehyde were observed, accompanied by decreased levels of reduced glutathione; potential therapeutic drugs may include resveratrol, retinoic acid, valproic acid, and tert-butylhydroquinone. Our study reveals an association between Pb exposure and the dysregulation of ferroptosis-related genes (HMOX1, CD44, ALOX15, and NQO1). We hypothesize that these genetic alterations may contribute to ferroptosis and subsequent AKI. Further research with larger sample sizes and additional experimental validation is needed.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomphalaria alexandrina and Artemia salina as Bioindicators of Glyphosate-Isopropyl Ammonium Herbicide Pollution: Biological, Physiological, and Molecular Docking Studies.","authors":"Amina Mohamed Ibrahim, Hassnaa Ahmed Saleh, Mostafa Y Morad","doi":"10.1002/jat.4870","DOIUrl":"https://doi.org/10.1002/jat.4870","url":null,"abstract":"<p><p>Glyphosate is a widely used herbicide in agriculture that raises biological, environmental, and health problems. It might affect aquatic life and change the quality of water because it is extremely soluble and can enter water bodies through runoff and soil absorption. The present study aims to explore the implications of glyphosate-isopropyl ammonium herbicide on Biomphalaria alexandrina and Artemia salina as bioindicators. Probit analysis was used to detect its sublethal concentrations on these models; then the present investigation studies its deleterious effects on biological and physiological parameters of B. alexandrina with emphasis on its mechanism to inhibit both sexual hormones by molecular docking. Results show that glyphosate herbicide has a molluscicidal activity against B. alexandrina snails with a half lethal concentration (LC₅₀) of 14.4 mg/L and was toxic against A. salina with LC₅₀ (19.02 mg/L). It had miracicidal and cercaricidal properties. Snails exposed to LC₁₀ or LC₂₅ of glyphosate herbicide exhibited decreases in survival, fecundity, reproductive rates, testosterone, 17β-estradiol, catalase, superoxide dismutase activities, glycogen phosphorylase, and triglycerides, although levels of malonaldehyde, total antioxidant capacity, glucose, and succinate dehydrogenase levels were elevated compared to the control group. The molecular docking simulation has revealed a potential interaction between the ligand molecule, glyphosate-isopropyl ammonium, with estrogen protein and testosterone at their active receptors. In conclusion, B. alexandrina and A. salina proved to be important ecotoxicological bioindicators for glyphosate-isopropyl ammonium, suggesting that in order to minimize any negative effects on aquatic life, this pesticide needs to be closely monitored and controlled.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene Microplastics Induce Inflammatory Responses and Promote M2-Associated Cytokine Expression in Mouse Lung Tissues.","authors":"Yujeong Lee, Dongseon Kim, Minkyoung Sung, Soo-Eun Sung, Joo-Hee Choi, Kyung-Ku Kang, Sijoon Lee","doi":"10.1002/jat.4871","DOIUrl":"https://doi.org/10.1002/jat.4871","url":null,"abstract":"<p><p>Microplastic pollution, particularly polystyrene microplastics (PS-MPs), poses significant environmental and health risks; however, its biological effects remain poorly understood. PS-MPs are persistent in the environment and can accumulate in biological tissues, raising concerns regarding their potential health effects. Although previous studies highlight oxidative stress and inflammation from microplastics, the specific immune responses in lung tissues remain underexplored. Therefore, the present study was conducted to investigate the biodistribution of PS-MPs and the inflammatory response induced by them in lung tissues. Fragmented PS-MPs (10-50 μm, 2000 mg/kg oral exposure) were manufactured and subjected to physical and chemical characterization using particle size analyzers, Raman spectroscopy, and scanning electron microscopy. Fluorescence imaging was performed using cyanine 5.5 carboxylic acid-labeled PS-MPs (Cy-PS-MPs) for tracking particle distribution. Ex vivo imaging confirmed the accumulation of Cy-PS-MPs in lung tissues, which was further validated by Raman spectroscopy. Histopathological analyses revealed granulomatous inflammation with macrophage infiltration in treated groups, along with significant upregulation of TGF-β and IL-10, cytokines commonly associated with M2 macrophage responses. These results emphasize the immunomodulatory and inflammatory responses induced by PS-MPs, providing insights into their mechanisms of action and potential health effects. Therefore, this study suggests the importance of understanding chronic immune responses and tissue remodeling following exposure to microplastics, which could contribute to long-term respiratory pathologies and fibrosis.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of Total Daily Fluoride Intake in Europe and Correlation to Equivalent Doses in Epidemiological Studies.","authors":"Stefanie Scheffler, Falko Partosch, Ariane Zwintscher, Annette Bitsch","doi":"10.1002/jat.4865","DOIUrl":"https://doi.org/10.1002/jat.4865","url":null,"abstract":"<p><p>European populations are chronically exposed to fluoride, as fluoride is supplemented for caries prophylaxis and is furthermore present in some food sources. As there is evidence that fluoride exposure at drinking water concentrations above 1.5 mg/L is associated with lower IQ in children, total daily intake in Europe might be close to or above this exposure level. Concerning health effects in Europe, epidemiological data are limited. Therefore, it would be beneficial to consider existing studies from non-EU countries to transfer observed effects to the exposure situation in Europe. Additionally, animal data could also deliver supporting information, if equivalent doses could be calculated. In this work, a methodology was developed to determine daily fluoride intake and excretion in Europe and align it to concentrations reported in animal and epidemiological studies. With this, a total daily intake of 2.05-mg fluoride for 3-year-old children and 3.8-mg fluoride for adults was estimated. For 3-year-olds, this value exceeds the current recommendations of fluoride intake by EFSA and even the tolerable upper intake level. The daily urinary fluoride excretion was calculated to be 0.72 mg/day, and for adults, it was 2.05 mg/day. For in vivo studies, rat exposure to fluoride drinking water concentrations of 12.5 ppm was considered to be equivalent to the daily fluoride intake in Europe. With the presented approach, equivalent doses can be applied to select international epidemiological as well as in vivo studies reflecting the fluoride exposure situation in European countries to extrapolate potential health effects.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Assessment of Drug-Induced Liver Injury Using Three-Dimensional Cultured HepaSH Cells Derived From Chimeric Mouse Model With Humanized Liver.","authors":"Xingming Liu, Yuichiro Higuchi, Yuta Sakamoto, Shota Yanagida, Shotaro Uehara, Hiroshi Suemizu, Yasunari Kanda, Hiroyuki Kawagishi","doi":"10.1002/jat.4863","DOIUrl":"https://doi.org/10.1002/jat.4863","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is a serious adverse event and a common cause of postmarketing drug withdrawal. Despite nonclinical assessments of DILI risk, which are predominantly conducted in experimental animals, DILI remains a frequent adverse event, highlighting the need to improve nonclinical assessments. Extensive studies have demonstrated that primary human hepatocytes (PHHs) and their three-dimensional (3D) cultures, such as spheroids, exhibit high predictability of drug-induced hepatotoxicity in vitro. However, lot-to-lot variations and inconsistent availability of PHHs remain major limitations. In contrast, HepaSH cells, which are hepatocytes derived from humanized liver chimeric mice, are more consistently available than PHHs and display gene expression levels of drug-metabolizing factors similar to those of PHHs with minimal variation. In this study, we investigated whether HepaSH cell-derived spheroids can be used to assess DILI risk. HepaSH cells were cultured in two-dimensional (2D) and three-dimensional (3D) conditions for up to 21 days. Gene expression and phenotypic analyses revealed that 3D-cultured HepaSH cells exhibited greater functional development of hepatic characteristics than 2D-cultured cells. Cytotoxic assessment using DILI-associated drugs listed in the DILIrank public dataset demonstrated that spheroids cultured in chemically defined William's media exhibited the highest sensitivity to drugs classified as having a high risk of DILI. Thus, our data suggest that human hepatic spheroids generated from HepaSH cells can be used to assess DILI risk in vitro. Further studies involving large-scale compound screening using HepaSH cells would be necessary to investigate the predictability of human DILI in nonclinical assessments.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intralitter Variability Influences the Developmental Impact of Valproic Acid Exposure in CD-1 Mice.","authors":"Lauren T L Brown, Megan E Cull, Lihua Xue, Louise M Winn","doi":"10.1002/jat.4860","DOIUrl":"https://doi.org/10.1002/jat.4860","url":null,"abstract":"<p><p>Valproic acid (VPA) is an antiepileptic and mood-stabilizing drug that causes teratogenic effects, including neural tube defects (NTDs), when taken during pregnancy. Although animal models are widely used to study VPA teratogenicity, most rely on litter means, which overlook variability within the litter. In litter-bearing species like mice, fetal development can vary by sex, uterine horn location, and intrauterine position. This study examined whether these intralitter variables affect fetal and placental outcomes following VPA exposure. Pregnant CD-1 mice received a subcutaneous injection of saline (vehicle control), 400 mg/kg, or 600 mg/kg VPA on gestational day (GD) 9 and were euthanized on GD 18. Fetuses and placentas were collected, weighed, and stratified by exposure, NTD status, sex, uterine horn location, and intrauterine position. Fetal and placental weights were normalized to maternal weight gain and live litter size or the number of live fetuses in each uterine horn. VPA exposure produced a clear dose-dependent effect, with 600 mg/kg significantly increasing postimplantation losses and NTD frequency. These effects were further influenced by intralitter variables, particularly sex and uterine horn location. Fetal weight increased at 400 mg/kg VPA but was unchanged at 600 mg/kg, while placental weight decreased and placental efficiency increased at both doses, suggesting possible compensatory adaptations. At 600 mg/kg VPA, sex differences in placental weight and efficiency were lost, and fetuses in the left uterine horn were significantly lighter than those in the right, indicating location-dependent susceptibility. Intrauterine position did not significantly affect outcomes. These findings demonstrate that intralitter variables influence fetal and placental responses to VPA and underscore the need to account for these factors to improve the translational relevance of developmental toxicology studies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}