Curbelo-Valiente A, Roa-Espitia AL, Moreno-Bustamante GM
… +4 more, de Jesús Solís-Heredia M, Tafoya-Domínguez D, Hernández-González EO, Quintanilla-Vega B
Temephos is a larvicide used in health campaigns against disease vectors, classified as slightly toxic. However, it has adverse effects on sperm function, the mechanisms of which are unknown. During fertilization, sperm...Temephos is a larvicide used in health campaigns against disease vectors, classified as slightly toxic. However, it has adverse effects on sperm function, the mechanisms of which are unknown. During fertilization, sperm are capacitated and proteins undergo tyrosine phosphorylation (p-Tyr), followed by actin cytoskeleton remodeling, which is important for the acrosome reaction (AR). Finally, IZUMO1 relocation during the AR is essential for gamete fusion. This study aimed to investigate the mechanism by which temephos decreases fertilization in male rats exposed to 10 or 100 mg/kg/day/5 days (WHO-NOAEL and LOAEL, respectively) and sacrificed 1-day after treatment. Sperm cells were collected from the cauda epididymis-vas deferens. No effects were observed with 10 mg/kg/day/5 days. However, at 100 mg/kg/day/5 days, the fertilization rate decreased (22%) and the chlortetracycline assay showed a decrease in Ca ionophore-induced AR (49%), suggesting that functional AR was impaired. This was confirmed by the decrease in p-Tyr and actin polymerization, which reduced IZUMO1 relocation. Furthermore, significant increases in protein serine and threonine phosphorylation (p-Ser and p-Thr) were observed, which may contribute to these effects. These results suggest that temephos exposure reduced the fertilization rate by decreasing sperm capacitation and actin polymerization, thereby affecting AR and IZUMO1 migration.
Acetaminophen (APAP) is a widely used antipyretic-analgesic drug. At high or cumulative doses, it can induce serious liver injury, though the full spectrum of its hepatotoxic mechanisms remains unclear. This study compre...Acetaminophen (APAP) is a widely used antipyretic-analgesic drug. At high or cumulative doses, it can induce serious liver injury, though the full spectrum of its hepatotoxic mechanisms remains unclear. This study comprehensively explored its pathogenic mechanisms by integrating network toxicology, molecular docking, in vivo and in vitro validations. Multi-source database screening identified 27 cross-targets associated with APAP hepatotoxicity. Protein-protein interaction (PPI) network and topological analyses revealed core targets central to APAP-induced liver injury. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that APAP-triggered hepatotoxicity involves critical biological processes, including cell cycle dysregulation, genetic damage, and disrupted signal transduction, with significant correlations to lipid and glucose metabolism, oxidative stress, and the PI3K/Akt/FOXO1 axis. Molecular docking confirmed strong binding affinity between APAP and core targets. Systematic in vivo and in vitro validation demonstrated that APAP inhibits PI3K/Akt signaling, thereby activating FOXO1, leading to disorders in glycolipid metabolism and intensified oxidative stress, ultimately aggravating hepatocyte damage. This mechanism plays an important regulatory role in the late-stage of APAP-induced hepatotoxicity, operating in parallel with the existing JNK mechanism. These findings provide new insights into the integrated mechanistic model of APAP-induced liver injury and suggest potential therapeutic targets.
PURPOSE: Mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a well-documented environmental endocrine disruptor with estrogen-like effects that promote the development...PURPOSE: Mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a well-documented environmental endocrine disruptor with estrogen-like effects that promote the development of hormone receptor-positive tumors. G protein-coupled receptor 30 (GPR30), also known as G protein-coupled estrogen receptor 1, has emerged as a key factor in the pathogenesis and progression of hormone-dependent tumors. This study elucidates the mechanism by which MEHP promotes breast cancer development via GPR30. METHODS: MCF-7 cells were exposed to different concentrations of MEHP, and GPR30 expression was inhibited using G15. Cell proliferation and cell cycle were assessed using the CCK-8 and flow cytometry, respectively. Cell migration and cell invasion were evaluated via scratch-wound assays and transwell migration assay. Western blotting and quantitative real-time reverse transcription PCR were performed to analyze the expression of GPR30 and epithelial-mesenchymal transition (EMT)-related mRNAs and proteins. RESULTS: Our findings demonstrate that MEHP exposure promotes the proliferation, migration, and invasion of MCF-7 cells, while concomitantly modulating the expression of GPR30, cell cycle-related and EMT-associated mRNAs and proteins. After inhibiting GPR30, the promoting effect of MEHP on MCF-7 cell proliferation and migration decreased. CONCLUSION: Notably, GPR30 inhibition attenuated MEHP-induced promotion of MCF-7 cell proliferation and migration through modulating the EMT process.
Efficient strategies for the human health risk assessment of micro- and nanoplastics (MNPs) are urgently needed to address the complexity and diversity of these materials. Here, we propose a risk assessment framework for...Efficient strategies for the human health risk assessment of micro- and nanoplastics (MNPs) are urgently needed to address the complexity and diversity of these materials. Here, we propose a risk assessment framework for MNPs following the oral route of exposure. The framework is based on a flexible and modular approach, drawing on modern concepts in risk assessment, such as Integrated Approaches to Testing and Assessment (IATAs) or Adverse Outcome Pathways (AOPs), and substantially relies on New Approach Methodologies (NAMs). The framework is structured into three different main steps: i) basic physicochemical characterization of testing materials, ii) intestinal crossing, iii) hazard assessment testing. Each step of the framework is supported by scientifically sound methods, enabling a mechanistic and hypothesis-driven risk assessment of MNPs.
Environmental pollution by micro- and nanoplastics (MNPs) raises concerns about their toxicity to humans, particularly through ingestion. While the impact of native MNPs is increasingly documented, environmentally degrad...Environmental pollution by micro- and nanoplastics (MNPs) raises concerns about their toxicity to humans, particularly through ingestion. While the impact of native MNPs is increasingly documented, environmentally degraded MNPs remain poorly studied. We assessed the intestinal impact of biodegradable and non-biodegradable nanoplastics (NPLs), polyethylene terephthalate (PET) and poly-lactic acid (PLA), both pristine and weathered in environmental conditions. The response of an in vitro intestinal model representative of healthy populations was compared with that of a model of genetic susceptibility to inflammatory bowel disease (IBD), using HT29-MTX cells cocultured with Caco-2 cells expressing either wild-type or mutated nucleotide-binding oligomerization domain 2 (NOD2). Non-differentiated and differentiated cells were exposed for 24 h to these NPLs. Cellular uptake, cytotoxicity, genotoxicity, oxidative stress, inflammation, and epithelial barrier integrity were evaluated. Although PET and PLA accumulated in cells, they showed no significant toxicity. Therefore, as demonstrated for polystyrene NPLs, PLA and PET particles do not cause major toxic impact to intestinal cells upon acute exposure in vitro and, in this exposure scenario, weathering in environmental conditions does not increase their toxicity.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) are challenging public health worldwide, with multifactorial pathogenic mechanisms. This study...Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) are challenging public health worldwide, with multifactorial pathogenic mechanisms. This study systematically employed network toxicology, molecular docking, molecular dynamics simulations and transcriptomics to investigate the metabolic toxicity mechanisms of the environmental pollutant dibutyl phthalate (DBP) its metabolite monobutyl phthalate (MBP). Protein-protein interaction network analysis identified 7 core proteins associated with MASLD and 5 with MASH, with ALBUMIN, PPARγ, HSP90AA1, and PTGS2 emerging as central hubs in DBP/MBP-induced hepatic metabolic disruption. Molecular docking experiments revealed strong DBP/MBP-key targets binding affinity, while molecular dynamics simulations demonstrated stable binding. RNA-seq profiling of DBP/MBP-exposed hepatocytes revealed significant transcriptomic alterations. KEGG pathway and GSEA analysis predictions with RNA-seq data pinpointed primary pathways potentially influenced by DBP/MBP, highlighting its multi-faceted impact on hepatic function. Furthermore, in vitro experiments validated the interaction of DBP/MBP with critical targets and demonstrated their ability to disrupt hepatocyte lipid homeostasis and promote lipid accumulation. This study provides mechanistic evidence linking DBP/MBP exposure to MASLD/MASH progression and lays a foundation for developing targeted therapeutic approaches.
Api AM, Bartlett A, Belsito D
… +31 more, Botelho D, Bruze M, Bryant-Friedrich A, Burton GA, Cancellieri MA, Chon H, Cronin M, Crotty S, Dagli ML, Dekant W, Deodhar C, Farrell K, Fryer AD, Jones L, Joshi K, Lapczynski A, Laskin DL, Lavelle M, Lee I, Moustakas H, Muldoon J, Penning TM, Piersma AH, Ritacco G, Sadekar N, Schember I, Schultz TW, Siddiqi F, Sipes IG, Sullivan G, Thakkar Y
The existing information supports the use of this material as described in this safety assessment. Pentadecane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, ph...The existing information supports the use of this material as described in this safety assessment. Pentadecane was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that pentadecane is not genotoxic and provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity endpoint. Data on read-across analog undecane (CAS # 1120-21-4) provide a calculated MOE >100 for the reproductive toxicity endpoint. Data from read-across analog hexadecane (CAS # 544-76-3) show that there are no safety concerns for pentadecane for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; pentadecane is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to pentadecane is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; pentadecane was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.
Diazepam is a widely used benzodiazepine, and its presence in animal-derived food products is strictly prohibited in China. However, the occasional detection of diazepam residues in freshwater fish has raised growing con...Diazepam is a widely used benzodiazepine, and its presence in animal-derived food products is strictly prohibited in China. However, the occasional detection of diazepam residues in freshwater fish has raised growing concerns regarding the safety of aquatic products and potential risks to human health. This study integrated network toxicology, cytotoxicity tests, transcriptomics and metabolomics to evaluate the neurotoxic effects and underlying mechanisms associated with diazepam and its principal metabolite, nordazepam. Both compounds exhibited notable neurotoxic effects, with microglial cells (HMC3) demonstrating greater sensitivity compared to oligodendrocytes (Mo 3.13) and neurons (SH-SY5Y). Network analysis and experimental data identified STAT3, CASP3, and TSPO as core targets mediating neurotoxicity associated with withdrawal symptoms, cognitive deficits, and motor impairments. Molecular docking and dynamics simulations further confirmed stable binding to these targets. These findings suggest that current risk assessments of diazepam residues necessitate reevaluation and underscore the critical role of microglial cells in diazepam and nordazepam-induced neurotoxicity, providing valuable insights for public health and dietary exposure safety.
To investigate the toxicological effects after individual or combined sub-chronical exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE formed during thermal processing of high-fat foods, this study implemented...To investigate the toxicological effects after individual or combined sub-chronical exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE formed during thermal processing of high-fat foods, this study implemented transcriptome-metabolome analysis of renal tissues in Kunming mice, supplemented with urine metabolomics study. Transcriptomic analysis highlighted perturbations in the PI3K-Akt signaling pathway, while metabolomic and integrated analyses both identified disruptions in glycerophospholipid metabolism. Urine metabolomic results further corroborated renal dysfunction, with altered tryptophan and purine metabolism. Results revealed that the exposure of three toxicants induced multi-organ metabolic network encompassing the kidney, liver, and even nervous system. Toxic effects were less pronounced when the three toxicants were exposed in combination while compared to their individual effects, suggesting the necessity for further investigation in the potential antagonistic mechanisms. Results provide critical insights into the co-exposure toxicity and interaction mechanisms of thermally induced toxicants in high-fat foods, offering toxicological foundations for establishing safety regulations.
Api AM, Bartlett A, Belsito D
… +31 more, Botelho D, Bruze M, Bryant-Friedrich A, Burton GA, Cancellieri MA, Chon H, Cronin M, Crotty S, Dagli ML, Dekant W, Deodhar C, Farrell K, Fryer AD, Jones L, Joshi K, Lapczynski A, Laskin DL, Lavelle M, Lee I, Moustakas H, Muldoon J, Penning TM, Piersma AH, Ritacco G, Sadekar N, Schember I, Schultz TW, Siddiqi F, Sipes IG, Sullivan G, Thakkar Y
BACKGROUND: Diethyl phthalate (DEP), a common plasticizer in cosmetics and personal care products, is known to induce oxidative stress and endocrine disruption. Its widespread use raises concerns about thyroid toxicity....BACKGROUND: Diethyl phthalate (DEP), a common plasticizer in cosmetics and personal care products, is known to induce oxidative stress and endocrine disruption. Its widespread use raises concerns about thyroid toxicity. OBJECTIVE: This study aimed to evaluate the genotoxic and endocrine effects of subacute DEP exposure on thyroid tissue in female Wistar albino rats using thyroid hormones, oxidative stress markers, DNA damage, and histopathology. METHODS: Twenty-eight female Wistar albino rats were divided into four groups (n = 7): control, 100 mg/kg, 300 mg/kg, and 600 mg/kg DEP. DEP was administered orally for 21 days. DNA damage was assessed by Comet Assay, oxidative stress markers (TAS, TOS, OSI) were measured, and serum TSH, T3, and T4 levels were determined by ELISA. Body weights were monitored, and thyroid tissues were examined histologically. RESULTS: Compared to the control group, T3 and T4 levels decreased (P < 0.05), TSH levels increased (p < 0.05), TAS levels decreased (p < 0.05), and TOS and OSI levels increased (p < 0.05). Comet Assay showed dose-dependent DNA damage (tail DNA%, p < 0.05). With higher DEP doses, thyroid tissue histopathology changed significantly. CONCLUSION: Subacute DEP exposure causes dose-dependent genotoxicity, oxidative stress, and endocrine disruption in thyroid tissue. These findings emphasize the need to limit environmental and human DEP exposure.
As an emerging contaminant, nanoplastics (NPs) are widespread in the food chain and environment, raising concerns about their potential toxicity. However, their effects on lipid metabolic homeostasis and the underlying m...As an emerging contaminant, nanoplastics (NPs) are widespread in the food chain and environment, raising concerns about their potential toxicity. However, their effects on lipid metabolic homeostasis and the underlying mechanisms remain unclear. This study used polystyrene nanoplastics (PS-NPs), common in food packaging, to examine their impact on adipogenic differentiation and lipid synthesis. Our research results indicated that after 10 days of oral exposure, PS-NPs significantly accumulated in the adipose tissue of mice. Within the exposure concentration range of 1-100 μg/mL, PS-NPs significantly increased the expression of genes related to adipogenesis, accelerated mitotic clonal expansion (MCE) during early differentiation, and enhanced triglyceride (TG) accumulation in mouse 3T3-L1 preadipocytes, leading to adipogenic differentiation and lipogenesis. These effects were positively correlated with the exposure concentration. Protein quantification and immunofluorescence revealed that PS-NPs promoted the nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ). Molecular dynamics simulations confirmed that PS-NPs bind to the nuclear localization signal (NLS) region of PPARγ. These findings suggested a new molecular mechanism in which PS-NPs influence PPARγ's subcellular localization through NPs-protein interactions, triggering adipogenic programs. This study provides valuable insights for the safety assessment and toxicology of nanoplastics.
The mucociliary system of the respiratory tract is a critical first-line defense that clears inhaled particles through coordinated ciliary motion. To investigate key events involved in respiratory disease pathogenesis an...The mucociliary system of the respiratory tract is a critical first-line defense that clears inhaled particles through coordinated ciliary motion. To investigate key events involved in respiratory disease pathogenesis and inhalation toxicity, physiologically relevant and functionally validated in vitro airway models are required. Although three-dimensional (3D) airway epithelial cultures differentiated under air-liquid interface (ALI) conditions recapitulate native airway architecture, robust quantitative evaluation of ciliary function beyond structural characterization remains limited. In this study, we developed and validated an automated Python-based analysis pipeline for objective quantification of ciliary activity, integrating temporal (ciliary beat frequency, CBF) and spatial (ciliary beat area, CBA) parameters in primary human small airway epithelial cells (hSAEC) and bronchial airway epithelial cells (hAECB) cultured under ALI conditions. The system enables whole-field, high-throughput, and user-independent analysis of high-speed video microscopy data, overcoming limitations of manual or ROI-based approaches. Biological relevance was demonstrated by strong concordance between automated ciliary metrics and established differentiation markers, including transepithelial electrical resistance, histological assessment, and immunocytochemical analysis. Time-resolved analysis revealed cell type-dependent ciliogenesis, with significant CBA expansion and CBF stabilization after 28 days of ALI differentiation. Overall, this study presents a scalable and quantitative framework for functional evaluation of airway epithelial differentiation, disease modeling.
OBJECTIVE: Nitrites and nitrates can undergo endogenous nitrosation to form nitrosamine in the human body. The association between nitrosation and cancer risk remains unclear. METHOD: Individuals from the UK Biobank coho...OBJECTIVE: Nitrites and nitrates can undergo endogenous nitrosation to form nitrosamine in the human body. The association between nitrosation and cancer risk remains unclear. METHOD: Individuals from the UK Biobank cohort who participated in the 24-h dietary assessment were included in this study. A physiologically based pharmacokinetic (PBPK) model was used to estimate the metabolic conversion of dietary nitrite and nitrate, with NDMA selected as the representative nitrosamine. The cancer risks were assessed using Cox proportional hazards regression. RESULTS: During the 12 years follow-up period, a total of 27,438 incident cancer cases were identified. Compared to participants in the lowest NDMA exposure range (<0.033 μg/day), those in the highest category (>0.044 μg/day) had a 4% higher risk of overall cancer (95% CI: 1.01-1.08) and a 12% higher risk of colorectal cancer (95% CI: 1.00-1.26). Additionally, the combination of being overweight and having high NDMA exposure was significantly associated with an increased cancer risk (Ptrend = 0.001). CONCLUSION: Elevated nitrosamines derived from dietary nitrite and nitrate increase the risk of overall cancer and colorectal cancer. Enhanced monitoring and attention of factors that promote nitrosation are essential, especially in high-risk populations.
Api AM, Bartlett A, Belsito D
… +31 more, Botelho D, Bruze M, Bryant-Friedrich A, Burton GA, Cancellieri MA, Chon H, Cronin M, Crotty S, Dagli ML, Dekant W, Deodhar C, Farrell K, Fryer AD, Jones L, Joshi K, Lapczynski A, Laskin DL, Lavelle M, Lee I, Moustakas H, Muldoon J, Penning TM, Piersma AH, Ritacco G, Sadekar N, Schember I, Schultz TW, Siddiqi F, Sipes IG, Sullivan G, Thakkar Y
This study collected free-range eggs from contaminated regions in China, with emphasis on legacy Hg mining areas. Total mercury (THg) and methylmercury (MeHg) were quantified in four egg compartments (white, yolk, shell...This study collected free-range eggs from contaminated regions in China, with emphasis on legacy Hg mining areas. Total mercury (THg) and methylmercury (MeHg) were quantified in four egg compartments (white, yolk, shell membrane, and shell). THg concentrations ranged from 1.39 to 90.76 μg/kg wet weight (ww), and MeHg from 0.74 to 40.56 μg/kg ww. While most samples met the Chinese food safety limit (50 μg/kg ww), eggs from mining areas consistently exceeded this threshold. THg distribution followed egg white > yolk > shell membrane > shell. Hg concentrations in egg white strongly correlated with those in whole eggs (ρ = 0.90), indicating that egg white serves as a reliable, non-invasive biomarker for Hg contamination. Health risk assessment suggests that Hg exposure from egg consumption generally remained within safe limits (HQ < 1). Nevertheless, exposure risks were significantly higher in Hg mining areas than in other areas. Further dietary exposure comparison revealed that Hg intake via eggs was lower than that via rice for adults but higher for children. These findings highlight that free-range eggs represent a significant Hg exposure pathway in Hg mining areas, emphasizing the necessity of targeted monitoring strategies to protect vulnerable populations, especially rural children.
Mercury (Hg) is a toxic environmental pollutant that can enter the human body through diet and environmental exposure and may be transferred to infants via breastfeeding. This study aimed to determine Hg concentrations i...Mercury (Hg) is a toxic environmental pollutant that can enter the human body through diet and environmental exposure and may be transferred to infants via breastfeeding. This study aimed to determine Hg concentrations in maternal fingernails and breast milk, identify factors influencing mercury levels in milk and assess potential health risks to breastfed infants. A total of 74 breastfeeding mothers were engaged from urban health centers. Hg concentrations were measured using atomic absorption spectrophotometry and dietary, maternal and infant characteristics were recorded through structured questionnaires. Hg concentrations in maternal fingernails ranged from 0.30 to 9.71 μg/g. In contrast, Hg levels in breast milk showed a narrower range 0.60-1.90 μg/L. Breast milk Hg levels did not differ significantly by maternal occupation, tablet use or fish consumption patterns (p > 0.05). Correlation analysis revealed a positive association between breast milk Hg and length of pregnancy (r = 0.323, p = 0.002) and a negative association with infant body weight (r = -0.327, p = 0.002). Multiple linear regression identified maternal age, infant age, fruit consumption, baby weight, number of children and dental filling history as significant predictors of mercury levels in breast milk (p < 0.05). Health risk assessment showed that the estimated daily intake of mercury exceeded the reference dose (0.16 μg/kg/day), with target hazard quotient values greater than one across all subgroups indicating a potential non-carcinogenic risk to breastfed infants. These findings highlight the need for continued monitoring of maternal mercury exposure while supporting safe breastfeeding practices.
While plant-based insect repellents are increasingly favored as eco-friendly and biocompatible alternatives to synthetic products like N,N-diethyl-meta-toluamide (DEET), they are not inherently free from dermatological r...While plant-based insect repellents are increasingly favored as eco-friendly and biocompatible alternatives to synthetic products like N,N-diethyl-meta-toluamide (DEET), they are not inherently free from dermatological risk. Many botanical ingredients, including citronella, lemongrass, and eucalyptus oils, contain bioactive compounds known to cause skin irritation or allergic reactions in sensitive individuals. Despite their widespread use, there remains limited research on their irritation potential using real-time, in vitro testing platforms. The objective of this study was to evaluate the skin irritation potential of commercial plant-based insect repellents and to investigate the mitigation effect of a micellar solution-based formulation using a novel electronically artificial stratum corneum (eASC). This study employed a capacitive biosensing system integrated into a lanolin-based lipid membrane to detect real-time changes in interfacial capacitance-an indicator of barrier disruption-upon exposure to various repellent products. Results demonstrated that certain plant-based repellents significantly altered membrane capacitance, indicating barrier disruption consistent with irritation. However, micellarization with PEG-40 hydrogenated castor oil markedly attenuated the dielectric response, suggesting reduced irritation potential. These findings underscore the importance of formulation strategy in reducing adverse skin reactions and validate the eASC platform as a cost-effective, indicator-free alternative to conventional irritation assays. This method provides a promising approach for rapid screening during product development and regulatory evaluation of topical botanical products.
BACKGROUND: Idesia polycarpa Maxim (Salicaceae), an East Asian deciduous tree, yields oil from its crimson berries that is rich in unsaturated fatty acids (>65% linoleic acid). While linoleic acid is an essential fatty a...BACKGROUND: Idesia polycarpa Maxim (Salicaceae), an East Asian deciduous tree, yields oil from its crimson berries that is rich in unsaturated fatty acids (>65% linoleic acid). While linoleic acid is an essential fatty acid with recognized health benefits, emerging evidence suggests that excessive intake may be associated with pro-inflammatory responses under certain conditions. This underscores the importance of conducting a systematic safety evaluation of refined IPMO. METHODS: Refined Idesia polycarpa Maxim oil (IPMO) underwent safety evaluation through GC-MS and GC-FID chemical characterization, combined with toxicological assessments in KM mice (acute oral toxicity, Ames assay, mammalian micronucleus, and spermatogonial chromosomal aberration tests). RESULTS: GC-MS identified 45 constituents dominated by hexanal (14.75%), (E)-Hept-2-enal (17.83%), and (E)-Oct-2-enall (9.60%). GC-FID revealed unsaturated fatty acids comprising 65.90 ± 0.87% linoleic acid (C18:2). Acute oral toxicity testing classified refined IPMO as non-toxic (LD > 10.0 g/kg). Ames tests (with/without S9 activation) showed no mutagenicity. Mammalian erythrocyte micronucleus frequencies exhibited no dose-dependent increases versus controls (p > 0.05). Spermatogonial chromosomal aberration rates in refined IPMO-treated groups showed no statistical differences from controls. CONCLUSIONS: Collectively, these findings support the safety of refined IPMO as a linoleic acid-rich edible oil, indicating its potential for use in food applications.