Drug and Chemical Toxicology最新文献

{"title":"Absorption and toxicity of mineral oil after dermal and mucosal surface exposure: a review.","authors":"Niels Hadrup, Jorid B Sørli, Stephanie C Hammel, Anoop K Sharma","doi":"10.1080/01480545.2026.2743650","DOIUrl":"https://doi.org/10.1080/01480545.2026.2743650","url":null,"abstract":"<p><p>Dermal and mucosal surface exposure to mineral oils occurs in the occupational setting. To evaluate exposure levels at which toxicity occurs, we collected data on non-cancer toxicity of crude oil, refinery streams and refined mineral oils. This included extraction of no-observed-adverse-effect levels (NOAELs) and lowest-observed-adverse-effect levels (LOAELs). Concerning biokinetics, whole oils appear to have low skin penetration, while polycyclic aromatic hydrocarbon (PAH) fractions penetrate to a considerable extent. Concerning toxicity of crude oil, reported local effects in humans include skin rash and eczema. In animals, a LOAEL_{Skin irritation} was 0.4 mg/cm². Systemic effects of crude oils include a LOAEL_{Developmental effects} of 30 mg/kg body weight (bw). Concerning refinery streams, local effects of syntower bottoms showed a LOAEL_{Skin histopathology} of 0.1 mg/cm². Catalytically-cracked clarified oil had a LOAEL_Irritation of 3 mg/cm²; a systemic LOAEL on maternal body weight and developmental toxicity of clarified slurry oil was 1 mg/kg bw (NOAEL: 0.05 mg/kg bw). Systemic effects of refinery streams correlated with PAH content (mainly driven by one study). Concerning refined mineral oils, local effects reported in mechanics and metal workers include contact dermatitis, oil acne and nose and throat irritation (exposure involved used oils and other chemicals). A human LOAEL_{skin occlusion} of refined oil was 2 mg/cm²; in animals, skin irritation had LOAELs as low as 15 mg/cm² (NOAEL: 7.6 mg/cm²). Systemic effects of refined oils in rats included a LOAEL_{Depressed body weight} of 160 mg/kg bw. In conclusion, both local and systemic effects are observed after dermal exposure to mineral oils.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-18"},"PeriodicalIF":2.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126936","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":"Process-dependent chemical fingerprints and acute oral toxicity of four crude extracts of <i>Edgeworthia gardneri</i> (Wall.) Meisn in mice.","authors":"Zhenxing Zhou, Xinke Deng, Jun He, Bengui Ye, Lijuan Nie","doi":"10.1080/01480545.2026.2737968","DOIUrl":"https://doi.org/10.1080/01480545.2026.2737968","url":null,"abstract":"<p><p><i>Edgeworthia gardneri</i> (Wall.) Meisn is used as a Tibetan herbal tea and medicinal resource, but safety information is scarce. Four flower extracts from water decoction, water flash extraction (WFE), alcohol reflux, and alcohol flash extraction (AFE) (water decoction extract (WDE), WFE, alcohol reflux extract (ARE), and AFE, respectively) underwent preliminary acute oral toxicity assessment and high-performance liquid chromatography (HPLC) fingerprint-based chemical characterization. C57BL/6J mice were randomly assigned to a vehicle control or four extract groups (<i>n</i> = 10 per group; five males and five females); extract groups received a single oral dose of 1500 mg/kg. Animals were observed for 14 days; clinical signs, mortality, body weight, organ weights and coefficients, serum biochemical indices, and liver and kidney histopathology were assessed. HPLC fingerprinting identified 28 common peaks; peak responses and similarities differed among extracts, with WFE showing the greatest chromatographic deviation. No mortality or persistent signs of acute toxicity were observed. Body weight increased progressively without sustained suppression attributable to any extract. Organ coefficients and serum biochemical measurements showed sporadic changes without concordant toxicological significance. In male WDE-treated mice, serum aspartate aminotransferase (AST) increased, whereas alanine aminotransferase (ALT) and alkaline phosphatase (ALP) remained unchanged, and blinded liver scores did not indicate treatment-related injury. Under the tested single-dose conditions, the four <i>E. gardneri</i> flower extracts produced minimal evidence of acute oral toxicity in mice of either sex at 1500 mg/kg extract (crude-herb equivalents: 4.6-13.8 g/kg). These findings provide a reference for dose selection and methodology in future comparative safety assessments of different extraction processes. Compositional variations among extracts were noted, and their relevance to safety warrants further study.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105694","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":"Comparative evaluation of the effects of bisphenol A and/or bisphenol F on oxidative stress and cytokine responses in SH-SY5Y neuroblastoma cells: <i>in silico</i> and <i>in vitro</i>.","authors":"İbrahim Özçelik, Deniz Arca Çakir, Kübra Gizem Yildiztekin, Pınar Erkekoğlu","doi":"10.1080/01480545.2026.2737954","DOIUrl":"https://doi.org/10.1080/01480545.2026.2737954","url":null,"abstract":"<p><p>Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, whereas bisphenol F (BPF), a common BPA substitute, is less characterized, particularly regarding neuronal-derived cells and combined BPA + BPF exposure. Human SH-SY5Y neuroblastoma cells were exposed to BPA, BPF, or BPA + BPF for 24 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and oxidative stress and cytokine endpoints were evaluated at IC₂₀ concentrations. SwissTargetPrediction and molecular docking were used to examine potential interactions with estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR). BPA was more cytotoxic than BPF, with IC₅₀ values of 173.2 and 456.8 µM, respectively; the BPA + BPF combination IC₅₀ was 196.9 µM. BPA and BPA + BPF significantly increased reactive oxygen species by 15.74% and 18.32% and protein carbonyl levels by 227.69% and 172.67%, respectively. BPA markedly increased interleukin-6, whereas BPF strongly increased tumor necrosis factor-alpha. In contrast, TNF-α decreased in the BPA and BPA + BPF groups, while malondialdehyde showed a non-significant downward trend. Docking predicted interactions of both compounds with AR, ERα, and ERβ, with binding energies of -7.3 to -8.5 kcal/mol. BPA and BPF produced distinct cytotoxic, oxidative, and cytokine-response profiles after acute exposure. BPA-containing treatments were associated with greater oxidative stress-related changes, whereas BPF elicited a distinct inflammatory response. Predicted receptor interactions require functional validation, and further studies should assess chronic, low-dose, and mixed exposures.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.2,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069374","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":"Subacute oral glyphosate induces dose-dependent renal injury in male mice (<i>Mus musculus</i>).","authors":"Alaa Talal Qumsani, Mohamed E Elbeeh","doi":"10.1080/01480545.2026.2726183","DOIUrl":"https://doi.org/10.1080/01480545.2026.2726183","url":null,"abstract":"<p><p>Glyphosate is the most heavily applied herbicide worldwide and human exposure is now near-ubiquitous, yet its renal toxicity at near-threshold doses remains incompletely characterized. We tested whether subacute oral glyphosate produces integrated, dose-dependent renal injury in male mice (<i>Mus musculus</i>). Adult male mice (n = 10/group) received vehicle or technical-grade glyphosate at 10, 50 or 100 mg/kg/day by oral gavage for 28 days, with 50 mg/kg anchored near the chronic NOAEL. Serum renal-function markers, renal oxidative-stress markers (MDA, GSH, SOD, CAT) and hematoxylin-eosin histopathology were assessed in the same 40 animals. Glyphosate produced coherent, dose-dependent renal injury. At 100 mg/kg, serum urea, creatinine and uric acid rose by 63.5%, 46.9% and 84.7%, with hyponatraemia, hypochloraemia and hyperkalaemia; renal MDA increased 2.1-fold while GSH, SOD and CAT fell by 46-51%, and the composite lesion score rose from 0 to 9.5 (median). No endpoint differed from control at 10 mg/kg under the prespecified analysis (one heteroscedastic sensitivity test detected a low-dose MDA increase), whereas significant effects were present at 50 mg/kg. A monotone dose trend was confirmed for every endpoint tested (Jonckheere-Terpstra, FDR-adjusted p < 0.001), and exploratory benchmark doses lay below the 50 mg/kg anchor. These findings indicate dose-dependent renal injury under subacute conditions and warrant duration-matched, both-sex confirmation. The doses studied lie far above realistic human intakes and characterize hazard rather than risk.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069395","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":"Association between dexmedetomidine use and acute kidney injury in critically ill patients treated with amikacin.","authors":"Murat Kucuk, Ali Necati Gokmen, Bişar Ergün, Yasin Levent Ugur, Cihan Heybeli","doi":"10.1080/01480545.2026.2734920","DOIUrl":"https://doi.org/10.1080/01480545.2026.2734920","url":null,"abstract":"<p><p>Amikacin is frequently used in intensive care units (ICUs) for gram-negative infections; however, nephrotoxicity remains a concern. Recent data showed lower odds of acute kidney injury (AKI) in patients who received dexmedetomidine, a selective α2-adrenergic receptor agonist widely used in ICUs for sedation and analgesia. Possible benefits of dexmedetomidine in critical patients who are treated with nephrotoxic therapies have not been studied. We aimed to test this hypothesis in a retrospective cohort study of adult ICU patients treated with amikacin between January 2018 and July 2020. Multivariable logistic regression analysis was performed to assess whether dexmedetomidine exposure was associated with AKI. A total of 149 patients were included. AKI occurred in 52 patients (34.9%), with a median onset of 5 days after amikacin initiation. AKI severity was stage 1 in 25.0%, stage 2 in 28.8%, and stage 3 in 46.2% of cases. Renal replacement therapy was required in 17 patients (11.6%). Dexmedetomidine was administered to 50 patients (33.6%) during amikacin therapy. In multivariable analysis, higher baseline serum creatinine and heart failure were independently associated with higher odds of AKI, whereas dexmedetomidine use was independently associated with lower odds of AKI. In a propensity score-matched analysis, AKI occurred less frequently in the dexmedetomidine group (17.4% <i>vs.</i> 37.0%, <i>p</i> = 0.035). Overall, ICU mortality was 67.8%, and AKI remained an independent predictor of mortality. Dexmedetomidine use was associated with lower odds of AKI in critically ill patients receiving amikacin. Prospective studies are warranted to confirm these findings.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015904","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":"N-acetylcysteine modulates peripheral nerve excitability and conduction in a rat Model of chronic organophosphate exposure.","authors":"Seckin Tuncer, Tulay Tuncer Peker, Nizamettin Dalkılıc","doi":"10.1080/01480545.2026.2734923","DOIUrl":"https://doi.org/10.1080/01480545.2026.2734923","url":null,"abstract":"<p><p>Chronic low-dose exposure to organophosphate pesticides has been associated with persistent peripheral neurotoxicity, yet the functional mechanisms underlying axonal dysfunction remain insufficiently defined. We investigated the effects of chronic diazinon exposure on peripheral nerve excitability and conduction properties in rats and evaluated the potential protective role of N-acetylcysteine (NAC). Adult male Wistar rats were allocated to four groups (n = 9 each): control (CON), diazinon (COP), combined treatment (COP+NAC), and NAC alone (NAC) for four weeks. Axonal excitability of the caudal nerve was assessed in vivo using threshold tracking, and sciatic nerve compound action potentials were recorded ex vivo with estimation of conduction velocity distributions. Diazinon exposure reduced rheobase and refractoriness, shortened the relative refractory period, increased superexcitability, and decreased the resting I/V slope, consistent with membrane depolarization and altered sodium channel function. Compound action potential amplitude and area were significantly reduced, accompanied by a shift toward slower-conducting fibers, indicating preferential impairment of fast axons. Concurrent NAC treatment partially normalized excitability parameters and attenuated conduction velocity shifts, while NAC alone produced mild hyperpolarizing changes. These findings indicate that chronic diazinon exposure disrupts axonal membrane properties and selectively affects fast-conducting fibers, and that NAC may mitigate these functional alterations.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011988","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":"Phytotoxic and cytogenotoxic assessment of hydroquinone using plant and animal bioassays.","authors":"Andressa Bernardi, Letícia Simon Susin, Paola Reis Freimuth, Vitória Zucco Rizzon, Bárbara de Oliveira Folatre, Juliana Schmitt de Nonohay, Edna Sayuri Suyenaga, Luciano Basso da Silva","doi":"10.1080/01480545.2026.2731181","DOIUrl":"https://doi.org/10.1080/01480545.2026.2731181","url":null,"abstract":"<p><p>Hydroquinone (HQ) is a phenolic compound widely used in industrial processes and recognized as a priority pollutant. However, information on its ecotoxicological effects on plants and aquatic organisms remains limited. This study evaluated the toxicity of HQ using bioassays with the plant species <i>Allium cepa</i> and <i>Lactuca sativa</i> and the freshwater mussel <i>Limnoperna fortunei</i>. In <i>A. cepa</i>, nine HQ concentrations ranging from 0.125 mg/L to 200 mg/L were tested, and cytogenotoxicity was assessed through the mitotic index (MI), micronucleus (MN) frequency, and chromosomal abnormalities. In <i>L. sativa</i>, phytotoxicity was evaluated by seed germination and root growth at concentrations from 5 mg/L to 200 mg/L. Mussels were exposed to HQ concentrations from 0.0625 mg/L to 0.5 mg/L, and nuclear abnormalities in hemocytes were analyzed. HQ significantly reduced the MI and induced genotoxic effects in <i>A. cepa</i>, and inhibited seed germination and root growth in <i>L. sativa</i>. No significant increase in hemocyte nuclear abnormalities was observed in <i>L. fortunei</i>. These findings indicate that environmentally relevant HQ concentrations did not induce genotoxic effects in mussels, whereas higher concentrations ≥25 mg/L caused phytotoxic and cytogenotoxic effects in plants. This study provides novel <i>in vivo</i> data that address current gaps in the understanding of HQ ecotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-7"},"PeriodicalIF":2.2,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982393","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":"Study on the toxicokinetics and <i>in vivo</i> distribution of benzylpiperazine (BZP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) after single and combined administration in Wistar rats.","authors":"Shuo Yang, Jinting Liu, Liying Zhou, Wanting Xie, Yan Shi","doi":"10.1080/01480545.2026.2729765","DOIUrl":"https://doi.org/10.1080/01480545.2026.2729765","url":null,"abstract":"<p><p>Benzylpiperazine (BZP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) are early‑appearing piperazine‑type new psychoactive substances (NPSs) frequently detected in ecstasy. Their combined use produces cardiovascular stimulation (hypertension and tachycardia) comparable to dextroamphetamine, yet data on their toxicokinetics and tissue distribution are scarce. We investigated the pharmacokinetics and tissue distribution of BZP and TFMPP after intraperitoneal injection (2 mg kg^-1) in Wistar rats, both singly and in combination. Compared with single‑drug administration, combined dosing significantly altered <i>t</i>_1/2 of BZP, mean residence time (MRT), and apparent volume of distribution (<i>V</i>z/F), and reduced area under the curve (AUC) of TFMPP (<i>p</i> < 0.05). Apart from peak concentration (<i>C</i>max), the two compounds have similar toxicokinetic characteristics in some aspects. BZP and TFMPP were rapidly absorbed (<i>T</i>max 0.15-0.70 h). Elimination half‑lives were 0.36 h for BZP and 2.56 h for TFMPP. After a single dose, <i>C</i>max (173 ng/mL) of BZP was significantly lower than <i>C</i>max (284 ng/mL) of TFMPP. Twenty-four hours after administration, the tissue concentrations of BZP, whether given alone or in combination, ranked as follows: liver > kidney > lung > spleen > brain > heart. For TFMPP, the distribution pattern under combined administration was the same as that of BZP; however, when administered alone, its concentration in the brain was higher than that in the spleen. These findings indicate that co‑exposure to BZP and TFMPP can modify toxicokinetic behavior and tissue distribution, suggesting distinct poisoning dynamics from exposure to either compound alone.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967134","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":"Insights into the protective role of trigonelline in 5-fluorouracil-induced lung injury: targeting oxidative stress, inflammation, and apoptosis.","authors":"Hamit Uslu, Gözde Atila Uslu, Taha Abdulkadir Çoban, Mahmut Şahin, Ali Güngör, Serpil Aygörmez","doi":"10.1080/01480545.2026.2727996","DOIUrl":"https://doi.org/10.1080/01480545.2026.2727996","url":null,"abstract":"<p><p>5-Fluorouracil (5-FU) is an effective chemotherapeutic agent; however, its clinical use is frequently limited by toxicity in normal tissues, including the lungs. This study investigated the prophylactic protective effect of trigonelline (TRIG), a naturally occurring alkaloid, against 5-FU-induced pulmonary injury, with particular emphasis on oxidative stress, inflammation, and apoptosis. Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups (n = 7): Control, TRIG, 5-FU, and TRIG + 5-FU. TRIG (50 mg/kg) was administered orally for seven consecutive days before a single intraperitoneal injection of 5-FU (100 mg/kg). Pulmonary injury was evaluated using biochemical, histopathological, and immunohistochemical analyses. Administration of 5-FU reduced body weight gain, increased relative lung weight, disrupted oxidant-antioxidant homeostasis, and induced histopathological alterations in lung tissue. These changes were accompanied by increased TNF-α, NFκB-p65, MAPK, and Bax expression together with decreased Bcl-2 expression, indicating activation of inflammatory and apoptotic pathways. Prophylactic TRIG administration restored oxidant-antioxidant balance, suppressed TNF-α, NFκB-p65, MAPK, and Bax expression, increased Bcl-2 expression, and markedly improved histopathological findings, demonstrating attenuation of oxidative stress, inflammation, and apoptosis. TRIG protects against 5-FU-induced pulmonary injury through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. These findings provide experimental evidence supporting the prophylactic use of TRIG as a potential adjunctive strategy for reducing chemotherapy-associated pulmonary toxicity. Further experimental and preclinical studies are warranted to validate its efficacy, elucidate its molecular targets, and evaluate its translational potential.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911231","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":"Determination of a cytotoxicity threshold for α-Fe₂O₃ nanoparticles based on an in vitro-in vivo dosimetry model in alveolar epithelial cells.","authors":"Athena Rafieepour, Maryam Soleimani Alyar, Masoomeh Vahabi Shekarloo, Saber Moradi Hanifi, Mojtaba Yeganeh, Iraj Alimohammadi","doi":"10.1080/01480545.2026.2727999","DOIUrl":"https://doi.org/10.1080/01480545.2026.2727999","url":null,"abstract":"<p><p>This study aimed to extrapolate a cytotoxicity threshold in air using a combined in vitro-in vivo dosimetry model to assess the toxicity of α-Fe₂O₃ nanoparticles (NPs), innovatively applying this approach to NPs risk assessment. Cultured A549 cells treated with α-Fe₂O₃ NPs in various concentrations over 24-h and 72-h. Cell survival and mitochondrial membrane permeability were assessed using the MTT and MMP assay, respectively. The dose-response results served for estimating the Benchmark Dose (BMD) and BMDL using the EPA BMD software. BMDLs were extrapolated into equivalent air concentrations using the Combined Dosimetry model (CoDo). A significant loss in cell survival and a rise of mitochondrial membrane permeability, compared to the control group (P-value < 0.05), were observed after 24-h and 72-h, respectively. A time- and concentration-dependent pattern was observed in the toxicity of the A549 cell line. Extrapolated from a BMDL of 1.9 μg/mL, a 0.22 mg/m³ air concentration was found to correspond to the in vitro dose. The predicted cytotoxicity threshold falls below the current occupational exposure limits (OELs) for micro-scale particles. Although further in vivo and epidemiological studies are required to validate its relevance for occupational exposure settings, this modeling approach offers a valuable framework for preliminary risk assessment.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905400","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}