Toxicology letters最新文献

{"title":"The impact of diet and regular mixers on breath alcohol concentration: A comparative study","authors":"Asena Avci Akca ,&nbsp;Atholl Johnston","doi":"10.1016/j.toxlet.2025.05.009","DOIUrl":"10.1016/j.toxlet.2025.05.009","url":null,"abstract":"<div><h3>Objective</h3><div>The use of alcoholic beverages with 'diet' mixers is becoming more popular. The purpose of this study was to assess BrAC and the pace of stomach emptying in healthy volunteers after consuming either sucrose-containing or artificially sweetened alcoholic beverages.</div></div><div><h3>Method</h3><div>This was a two-way crossover trial with an open label. The subjects consumed alcohol on two consecutive occasions conducted in the morning (9:00am-12:00 pm), once with diet coke and once with standard coke. In a randomised order, twelve healthy participants (n = 12, 8 male and 4 female) aged 19–64 years were studied twice. They drank a standardised (0.5 g/kg body weight) volume of vodka (37.5 % ABV) over a time period of 1 minute in each session, prepared with either 'regular' coke with 35 g sugar in 330 mL or 'diet' coke with artificial sweetener which is aspartame. Their BrAC was measured every 15 minutes for 3 hours. Their breath samples for stomach emptying measurement were taken separately in breath bags right after the breath alcohol measurement. The gastric half-emptying time (t_1/2) and lag phase time (tl_ag) characteristics of these breath samples were determined.</div></div><div><h3>Results</h3><div>Diet coke increased both the peak BrAC (38.3 ± 9.45 vs. 34.8 ± 6.82 μg/100 mL) and the area under the breath ethanol curve between 0 and 180 minutes (45249.0 ± 95.7 vs. 40439.25 ± 72.5 μg·min/L). Using nonlinear regression analysis, the diet drink showed a shorter half-emptying time (t_1/2) than the regular drink (100.09 ± 35.42 vs. 110.74 ± 66.71 min), while the lag phase (t_lag) was slightly longer (49.35 ± 13.52 vs. 46.63 ± 13.90 min).\"</div></div><div><h3>Conclusions</h3><div>This study emphasises the need of considering factors other than the alcohol level of a drink when determining safe quantities of intake and the potential of intoxication. The lack of sucrose in diet mixers may cause faster stomach emptying of alcohol, increasing its absorption rate into the blood, resulting in higher peak BrAC and increased exposure to other alcohol-related dangers.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 145-151"},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133211","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":"Effect of cypermethrin on thyroid follicular epithelial cell injury via the ROS-NF-κB-NLRP3 pathway","authors":"Leina Jia ,&nbsp;Xiaoning Meng ,&nbsp;Yu Ma ,&nbsp;Jinyu Luo ,&nbsp;Xiaoqi Luo ,&nbsp;Huifang Yang ,&nbsp;Jian Zhou","doi":"10.1016/j.toxlet.2025.05.008","DOIUrl":"10.1016/j.toxlet.2025.05.008","url":null,"abstract":"<div><div>Cypermethrin (CYP, IUPAC name: [cyano-(3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate), a type II pyrethroid insecticide, is suggested to have potential adverse effects on human endocrine, immune, and neurotoxic systems. Objectives: In this study, we aimed to investigate whether CYP causes oxidative stress and pyroptosis in thyroid follicle epithelial cells through the activation of the ROS-NFκB-NLRP3 pathway, thereby causing inflammatory responses. Methods: Nthy-ori 3–1 cells were used as an in vitro model and exposed to CYP at different doses (0, 100, 200, 400, 800, and 1600 μmol/L) for 24 h. Results: CYP treatment enhanced oxidative damage in Nthy-ori 3–1 cells, characterized by cellular crumpling, indistinct borders, increased cellular gaps, appearance of intercellular grease droplets, and increased pyroptosis. Subsequent treatment with the caspase-1 inhibitor VX-765 enhanced cell viability in the VX-765 +CYP group, improving cell morphology, reducing pyroptotic vesicles, suppressing oxidative stress, and downregulating Interleukin-18(IL-18) (an inflammatory factor) level. Conclusion: The results demonstrate that CYP induces pyroptosis in Nthy-ori 3–1 cells through activation of the reactive oxygen species (ROS)-NF-κB-NLRP3 pathway.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 121-129"},"PeriodicalIF":2.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089403","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":"New insights into methylfuran metabolism","authors":"Daniel Bohlen ,&nbsp;Jonas Appel ,&nbsp;Lukas Eichel,&nbsp;Samuel Spengler,&nbsp;Carolin Kulosa,&nbsp;Fani Kougioumtzi,&nbsp;Simone Stegmüller,&nbsp;Nico Becker,&nbsp;Tobias Jochum,&nbsp;Elke Richling","doi":"10.1016/j.toxlet.2025.05.006","DOIUrl":"10.1016/j.toxlet.2025.05.006","url":null,"abstract":"<div><div>Methylfurans like 2,5-dimethylfuran (DMF), 2-methylfuran (2-MF), and 3-methylfuran (3‑MF) are heat-induced contaminants present in a variety of foods, such as coffee, roasted nuts and canned foods. Concerning their metabolism, toxicity, and safety information is scarce. Several studies indicate that cytochrome P450 mediated epoxidation resembles the main route of biotransformation for furan and different methylfurans, leading to the formation of highly reactive α, β-unsaturated dicarbonyls, suggested to be responsible for their reported hepatotoxic and potentially carcinogenic effects. It is assumed that side-chain oxidation by CYPs might represent an additional metabolic route for alkylfurans. The resulting alcohols may be rapidly oxidized to the corresponding carboxylic acid or serve as a substrate for sulfotransferases, which may also lead to the formation of reactive intermediates. To verify whether DMF is subject to unilateral side-chain hydroxylation, formation of 5-methyl-2-furfuryl alcohol and respective higher oxidized metabolites 5-methyl-2-furfural and 5-methyl-2-furancarboxylic acid were investigated in incubations of human liver microsomes using an established and validated GC-MS method. It was possible to monitor time- and concentration dependence of the formation of 5-methyl-2-furfuryl alcohol, while only minimal concentrations of higher oxidized metabolites were detected. In addition, side-chain oxidation of 2-MF and 3-MF were also investigated using an equivalent approach. However, formation of 2- and 3-furfuryl alcohol was not observed in human liver microsomal incubations, indicating structure dependence in metabolism of different alkyl furans.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 130-137"},"PeriodicalIF":2.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094977","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":"Study on the effect and mechanism of PM2.5 on the expression of Alzheimer’s disease-like pathological proteins in SH-SY5Y cells","authors":"Huiwen Kang ,&nbsp;Chenyang Si ,&nbsp;Xuan Shang ,&nbsp;Qian Song ,&nbsp;Wenli Zhang ,&nbsp;Jinlong Li ,&nbsp;Shoufang Jiang","doi":"10.1016/j.toxlet.2025.04.014","DOIUrl":"10.1016/j.toxlet.2025.04.014","url":null,"abstract":"<div><div>Fine particulate matter (PM_2.5) is recognized as one of the most harmful environmental pollutants to human health. Current research indicates that PM_2.5 exhibits neurotoxic effects, though the specific mechanisms remain unclear. In this study, SH-SY5Y cells were exposed to PM_2.5 (100 μg/mL for 24 h) to observe its effects on the expression of Alzheimer's disease (AD)-related proteins and explore the possible mechanisms of central nervous system injury caused by PM_2.5. Based on bioinformatics results, the study employed a PI3K inhibitor (LY294002, 10 μmol/L for 1 h) and a reactive oxygen species (ROS) inhibitor, N-acetyl-L-cysteine (NAC, 5 nmol/L for 1 h), as interventions. The results demonstrated that PM_2.5 exposure significantly intensified oxidative stress in SH-SY5Y cells, upregulated the expression of inflammatory factors, and increased apoptosis. Additionally, exposure to PM_2.5 led to elevated levels of AD-related pathological proteins, including amyloid-β (Aβ), and promoted Tau phosphorylation, further indicating its potential neurotoxic effects. Furthermore, the ROS/PI3K/Akt/GSK-3β pathway was found to play a key role in these processes. This research provides a basis for understanding the impact of PM_2.5 on Alzheimer’s disease patients and offers recommendations for the prevention of haze-related health risks, as well as for risk management by relevant governmental departments.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 109-120"},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942782","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":"Toxic effects of malachite green on plant and animal models: A study on root growth inhibition, hematological changes, histopathology, and molecular analysis","authors":"Rubait Hasan ,&nbsp;Md. Mahmudul Hasan ,&nbsp;Jamiatul Husna Shathi ,&nbsp;Esraa Tamam ,&nbsp;Amaal E. Ahmed ,&nbsp;Ariful Haque ,&nbsp;Zahidur Rahmann ,&nbsp;Md Tariqul Islam ,&nbsp;Md. Abu Reza ,&nbsp;Mohammad Shahangir Biswas ,&nbsp;Kazi Md. Faisal Hoque","doi":"10.1016/j.toxlet.2025.05.003","DOIUrl":"10.1016/j.toxlet.2025.05.003","url":null,"abstract":"<div><div>Malachite green (MG), a suggestive chemical for tumor development and carcinogenicity, is widely used as an illicit food coloring agent, posing risks to consumers and handlers. This study aimed to assess the toxic effects of MG in both plant and animal models. Different doses of MG (375, 750, and 1500 mg/L) were applied for 24 h to evaluate root growth inhibition, mitotic index (MI), and chromosomal aberrations in <em>Allium cepa</em> L. roots for genotoxicity analysis. In animal studies, forty Swiss albino mice were divided into four groups: control and three treatment groups, which were orally administered MG at 375 (low), 750 (medium), and 1500 (high) mg/kg body weight for 13 weeks. Hematological, biochemical, histopathological, and molecular analyses were performed on liver, kidney, and intestinal tissues post-treatment. MG significantly reduced root length and MI in <em>A. cepa</em> roots dose-dependently causing chromosomal abnormalities. MG treatment significantly lowered the body weights of mice and increased platelet, monocyte, and white blood cell counts, while reducing hemoglobin, hematocrit, and red blood cell counts. Serum analysis showed elevated ALT, ALP, AST, bilirubin, creatinine, and urea, indicating hepatotoxicity and nephrotoxicity. Histopathological examination revealed vacuolation, congestion, and inflammatory infiltration in the liver, glomerular shrinkage, tubular degeneration, and interstitial edema in the kidney, and epithelial sloughing, submucosal necrosis, and inflammatory infiltration in the colon. RT-qPCR analysis demonstrated increased Bcl-2, Beclin-1, and NF-κB mRNA expression with decreased Bax mRNA. These findings suggest MG is a potent genotoxic and carcinogenic agent even at lower doses threatening human health.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 61-73"},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936858","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":"NR1D1 mitigates IL-17a-induced small airway remodeling in biomass smoke-induced COPD","authors":"Lizhi Huang ,&nbsp;Juan Xu ,&nbsp;Hongbin Zhou ,&nbsp;Haiqing Li ,&nbsp;Weitao Cao ,&nbsp;Jinding Pu","doi":"10.1016/j.toxlet.2025.05.002","DOIUrl":"10.1016/j.toxlet.2025.05.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Biomass smoke (BS) exposure is a critical environmental risk factor for Chronic Obstructive Pulmonary Disease (COPD). In this study, mechanisms of biomass smoke (BS)-induced small airway disease are explored, with a focus on the roles of Interleukin-17a (IL-17a) and Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1).</div></div><div><h3>Methods</h3><div>This study included 20 BS exposure COPD (BS-COPD) patients and 13 controls, who underwent chest high-resolution computed tomography (HRCT) scans to assess emphysema and small airway disease. The control group was divided into a low- and high BS exposure control group. Serum IL-17a levels were measured. Wild-type and IL-17a-/- B6/C57 mice were exposed to wood smoke to establish a COPD model in mice. Airway pathology was evaluated by histological analysis. The effects of IL-17a and NR1D1 on cell proliferation of BEAS-2b cells exposed to wood smoke particulate matter 2.5 were assessed in vitro using flow cytometry and Western blotting.</div></div><div><h3>Results</h3><div>HRCT revealed significantly higher small airway disease and emphysema in BS-COPD patients compared to controls (p &lt; 0.01). Small airway disease exhibited the strongest negative correlation with FEV1%predicted (r = -0.61, p = 0.004). High-exposure control group showed significant BS Index correlations with small airway disease (r = 0.81, p = 0.049) and emphysema (r = 0.87, p = 0.025). Serum IL-17a levels correlated with small airway disease in BS-COPD (r = 0.48, p = 0.033). The mouse model demonstrated higher airway wall thickness and small airway disease in IL-17a-/- mice exposed to wood smoke. In vitro, IL-17a promoted BEAS-2b cell proliferation, an effect enhanced by NR1D1 downregulation.</div></div><div><h3>Conclusions</h3><div>BS exposure drives emphysema and small airway disease in non-COPD individuals. NR1D1 downregulation exacerbates IL-17a–mediated remodeling in vitro, suggesting therapeutic potential.</div></div><div><h3>Trial registration</h3><div>ChiCTR-OOC-16008692</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 74-86"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936859","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":"Impact of skin temperature and intradermal pH on transdermal fluoride absorption following hydrofluoric acid exposure: An ex vivo diffusion cell study in human skin","authors":"Suvarna Mini Vijayan ,&nbsp;Anna Wolfschmidt ,&nbsp;Thomas Göen ,&nbsp;Raymund E. Horch ,&nbsp;Ingo Ludolph ,&nbsp;Hans Drexler ,&nbsp;Sonja Kilo","doi":"10.1016/j.toxlet.2025.05.005","DOIUrl":"10.1016/j.toxlet.2025.05.005","url":null,"abstract":"<div><div>Accidents involving hydrofluoric acid (HF) can cause systemic poisoning due to the transdermal absorption of fluoride ions. The present study investigates the impact of skin temperature and intradermal pH on fluoride absorption and its kinetics. Human skin was exposed to 30 % HF for 3 minutes using a static diffusion cell model. The study compared cumulative fluoride absorption at two different skin temperatures (24°C and 32°C) and two intradermal pH values (6.5 and 7.2). Experiments were performed at least three times per treatment and per donor (n = 5), over a duration of 8 h and 12 h for pH and temperature experiments, respectively. Results showed that fluoride absorption increased with temperature, with a ∼17.8 % increase in cumulative penetration at 32°C compared to 24°C. The maximum flux rate through the skin was reached within the first hour and was ∼54 % lower at 24°C. Additionally, acidifying the skin to an intradermal pH of 6.5 led to a significant increase in cumulative fluoride absorption by ∼12.6 % and a ∼50.3 % increase in the maximum flux rate. The findings suggest that reducing fluoride absorption after accidental skin contact with HF may be achieved by lowering skin temperature and buffering intradermal pH to a physiological level. These results have important implications for first-aid measures in real-life scenarios involving HF exposure. Controlling skin temperature by cooling and intradermal pH with the addition of buffering agents may enhance decontamination strategies.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 87-96"},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942780","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":"Copper exposure at a daily dose twice the recommended in diabetic rats induces oxidative stress, vascular dysfunction and perivascular adipose tissue inflammation in diabetic rats","authors":"Julia Antonietta Dantas da Silva ,&nbsp;Filipe Martinuzo Filetti ,&nbsp;Natália Pimentel da Silva ,&nbsp;Karoline Neumann Gomes ,&nbsp;Jones Bernardes Graceli ,&nbsp;Andressa Bolsoni Lopes ,&nbsp;Dalton Valentim Vassallo ,&nbsp;Karolini Zuqui Nunes","doi":"10.1016/j.toxlet.2025.05.004","DOIUrl":"10.1016/j.toxlet.2025.05.004","url":null,"abstract":"<div><div>Individuals with diabetes often have a heightened risk of cardiovascular diseases and present copper (Cu) metabolism imbalances. We investigated the effect of chronic exposure to twice the recommended daily dose of CuCl₂ on vascular reactivity in isolated thoracic aorta segments of diabetic and non-diabetic rats. Eighty male Wistar rats, aged 12 weeks, were divided into four groups: Control (Ct), Copper (Cu), Diabetes Mellitus (DM), and Diabetes + Copper (DM+Cu). Type 1 diabetes was induced using a single dose of streptozotocin (65 mg/kg i.p), and the animals exposed to Cu received twice the recommended daily dose (25.7 µg/Kg/day CuCl₂) for 30 days. After treatment, we investigated vascular reactivity and performed histological evaluations on samples of aortas and perivascular adipose tissue (PVAT). Our findings revealed pronounced weight loss and higher hyperglycemia in the DM+Cu group compared to DM, along with increased pro-inflammatory factors in PVAT (IL-6). Vascular reactivity to phenylephrine decreased without PVAT, accompanied by elevated vasodilator factors: NO and H₂O₂, and involvement of K+ channels. Additionally, we observed an increase in the thickness of the aorta wall, collagen deposition. In the presence of PVAT, vascular reactivity increased in the DM+Cu and Cu groups. These findings demonstrate that exposure to double the recommended Cu dose in diabetic animals leads to endothelial and PVAT dysfunction, associated with elevation of vasodilator and pro-inflammatory factors.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 97-108"},"PeriodicalIF":2.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942781","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 Alarming Consequences of Workforce Reductions at the FDA, EPA, NIH and CDC in the United States","authors":"Martin van den Berg PhD (Editor-in-Chief, Regulatory Toxicology & Pharmacology and Current Opinion in Toxicology) ,&nbsp;Daniel R. Dietrich PhD (Editor-in-Chief, Chemico-Biological Interactions, Computational Toxicology, and Journal of Toxicology and Regulatory Policy) ,&nbsp;Sonja von Aulock PhD (Editor-in-Chief, ALTEX – Alternatives to Animal Experimentation) ,&nbsp;Anna Bal-Price PhD (Editor-in-Chief, Reproductive Toxicology) ,&nbsp;Michael D. Coleman PhD (Editor-in-Chief, Environmental Toxicology and Pharmacology) ,&nbsp;Mark T.D. Cronin PhD (Editor-in-Chief, Computational Toxicology) ,&nbsp;Paul Jennings PhD (Editor-in-Chief, Toxicology in Vitro) ,&nbsp;Angela Mally PhD (Editor-in-Chief, Toxicology Letters) ,&nbsp;Mathieu Vinken PhD (Editor-in-Chief, Toxicology and NAM Journal) ,&nbsp;Matthew C. Wright PhD (Editor-in-Chief, Food and Chemical Toxicology)","doi":"10.1016/j.toxlet.2025.05.001","DOIUrl":"10.1016/j.toxlet.2025.05.001","url":null,"abstract":"","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 30-31"},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908083","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":"Studies on acute dermal toxicity and dermal absorption of a nanoform zinc oxide (ZnO; NM-111) in rats","authors":"Tanja Hansen ,&nbsp;Thomas Tillmann ,&nbsp;Karin Wiench ,&nbsp;Otto Creutzenberg","doi":"10.1016/j.toxlet.2025.04.011","DOIUrl":"10.1016/j.toxlet.2025.04.011","url":null,"abstract":"<div><div>In two studies, the dermal toxicity (limit test following OECD TG 402) and toxicokinetics (with [⁶⁵Zn]-tagged ZnO following OECD TG 427) of a nanostructured ZnO particle were characterized. The overall aim was to assess the risk of its systemic availability. Wistar rats were dermally treated once with 2000 mg ZnO/kg b.w. (limit test). – Male rats were treated topically with 2 mg/cm^{2 65}ZnO for 6 h. Necropsy was done after the end of the exposure period (6 h) and after 24 and 72 h to investigate dermal absorption of ⁶⁵ZnO. ZnO showed no clinical signs of toxicity in the limit test. – ⁶⁵ZnO was not significantly absorbed following deposition: In the group means, 62–76 % of the dose applied were recovered in the not absorbed fraction. The amount of ⁶⁵ZnO in the <em>stratum corneum</em> was found to be approx. 15 %, 8 % and 4.6 % after 6, 24 and 72 h, respectively. The ⁶⁵ZnO content in the remaining skin at the application site (viable skin + remaining <em>stratum corneum</em>) accounted for approx. 10 %, 16 % and 16 % after 6, 24 and 72 h (total on/in the skin 25 %, 24 % and 20.6 % after 6, 24 and 72 h). No relevant radioactivity was found in faeces, urine, cage wash, organ or tissue samples.</div><div>The acute dermal limit test with ZnO resulted in ‘Unclassified’ (globally harmonized system). – Radioactivity, representative of ⁶⁵ZnO, was not detected systemically after dermal application. Overall, the results indicate that ⁶⁵ZnO was not absorbed with subsequent translocation beyond the skin into the blood compartment.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"409 ","pages":"Pages 42-49"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924041","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}