{"title":"<i>Calendula officinalis</i> extract enhances wound healing by promoting fibroblast activity and reducing inflammation in mice.","authors":"Yalcin Alper Ozturan, Ibrahim Akin","doi":"10.1080/15569527.2025.2485129","DOIUrl":"10.1080/15569527.2025.2485129","url":null,"abstract":"<p><strong>Introduction: </strong>Despite evidence supporting the therapeutic potential of <i>Calendula officinalis</i>, well-designed and controlled studies are still needed to confirm its beneficial effects on various health conditions, including skin care. This study therefore evaluates the effectiveness of topically administered 5% aqueous <i>Calendula officinalis</i> extract on healing full-thickness skin wounds in male BALB/c mice.</p><p><strong>Methods: </strong>Seventy-two mice were divided into three groups: CAL (treated with calendula extract), PSS (treated with physiological saline), and NC (negative control/no treatment). Wound healing was assessed over 14 days using planimetric measurements, counting fibroblasts and macrophages, biochemical analyses of growth factors, inflammation markers, hydroxyproline levels, and genomic analyses.</p><p><strong>Results: </strong>The data obtained show that the application of CAL extract significantly reduces wound areas by day 7 compared to the NC and PSS groups. CAL extract also leads to an increase in fibroblasts, fibroblast growth factor, and hydroxyproline levels, while it reduces macrophages and inflammatory biomarkers levels in the healing wound. Genomic analyses indicate that topical application of CAL extract significantly reduces the expression of inflammatory biomarkers, including matrix metalloproteinases 2 and 9.</p><p><strong>Conclusions: </strong>These findings show that 5% aqueous CAL extract enhances wound healing promising new insights for the effective topical treatment of skin wounds.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"161-171"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771803","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}
Abdulrahman Bakather, Hind Amin, Waleed Nasif, Samir Shoughy
{"title":"Adverse effects of topical tacrolimus compounded ophthalmic preparations.","authors":"Abdulrahman Bakather, Hind Amin, Waleed Nasif, Samir Shoughy","doi":"10.1080/15569527.2025.2485139","DOIUrl":"10.1080/15569527.2025.2485139","url":null,"abstract":"<p><strong>Purpose: </strong>The main aim of this review is to provide an overview of the key ocular side effects associated with topical tacrolimus compounded ophthalmic preparations Materials and methods: Review of literature using Pubmed database.</p><p><strong>Results: </strong>The use of topical tacrolimus may be associated with side effects ranging from mild ocular discomfort to more server complications like loss of integrity of corneal surface, corneal ulcer and infectious keratitis. However, the use of topical tacrolimus is not associated with increased incidence of secondary glaucoma or cataract.</p><p><strong>Conclusion: </strong>It is imperative to understand the potential side effects associated with topical tacrolimus ophthalmic preparations to optimize the treatment outcomes and guarantee patient safety. Routine ophthalmic examinations should be conducted to detect these side effects early and address them appropriately.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"186-190"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751679","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}
Michael F Hughes, David G Ross, Jane Ellen Simmons
{"title":"Dermal irritancy assessment of microbial toxins and pesticidal contaminants found in recreational water using two- and three-dimensional human skin models.","authors":"Michael F Hughes, David G Ross, Jane Ellen Simmons","doi":"10.1080/15569527.2025.2485137","DOIUrl":"10.1080/15569527.2025.2485137","url":null,"abstract":"<p><strong>Purpose: </strong>Dermal exposure to freshwaters contaminated with pesticides and microbial toxins may result in toxicity. This study assessed the in vitro dermal irritancy of selected pesticides and microbial toxins using two- (2D) and three-dimensional (3D) human skin models.</p><p><strong>Materials and methods: </strong>The 2D model was normal human keratinocytes. The 3D model was EpiDerm, derived from normal human keratinocytes that forms a multi-layered differentiated human epidermal model. Pesticides included dimethipin, α-1,2,3,4,5,6-hexachlorocylohexane, oxyfluorfen, permethrin, profenofos, and tribufos. Toxins included cylindrospermopsin and microcystin-LA, -LR, and -RR. Exposure to contaminants was either 1 or 24 h. Viability was assessed by the MTT assay. Results were determined relative to negative control.</p><p><strong>Results: </strong>Significant effects in viability were observed in both models and time points. The greatest significant decrease in viability in the 2D model was tribufos at 1 h (23%) and cylindrospermopsin (37%) at 24 h. In the 3D model, the greatest significant decrease was microcystin-LA (16%) at 1 h and microcystin-RR (32%) at 24 h.</p><p><strong>Conclusion: </strong>Several microbial toxins and pesticides were cytotoxic in both models and time points. However, no contaminant tested in the 3D model for 1 h was > 50% cytotoxic, which would categorize a chemical as a dermal irritant (Organisation for Economic Cooperation and Development Test Guideline 439 for skin irritation). The 24 h exposure time point had a greater number of cytotoxic contaminants in both models, particularly the 2D model. Screening potential irritants in the 2D model for 24 h may prioritize chemicals for further assessment in the 3D model.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"172-185"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771823","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":"Which factor have more adverse effect on ocular surface of patients treated with antiglaucoma drops; drug type, number of drugs or drug intensity?","authors":"Yesim Altay","doi":"10.1080/15569527.2025.2479832","DOIUrl":"10.1080/15569527.2025.2479832","url":null,"abstract":"<p><strong>Purpose: </strong>To examine effects of topical antiglaucoma drops on ocular surface (OS)and meibomian glands(MG) in relation to drug type, number of drugs and drug intensity.</p><p><strong>Methods: </strong>This was a cross-sectional case study of 93 patients with glaucoma treated with topical anti-glaucoma drugs for more than 1 year. According to drug type we formed two groups; Group 1: Prostaglandin containing drops(monotherapy and combination therapy), Group 2:Non -PGA therapy.According to drug number, we formed three groups; Group 1:One active drug compound, Group 2: Two active drug compounds, Group 3:Three or more active drug compounds.We formed 2 groups accrding to drug intensity index (DII); Group 1: DII was < 50, Group 2: DII ≥ 50.Conjonctival hyperemia, ocular surface staining, tear break-up time (TBUT), and eyelid signs representing meibomian gland disease (eyelid vascularity, irregularity, nature of meibum and the Marx line score) have been compared between groups.</p><p><strong>Results: </strong>Prostaglandin containing drops group showed significantly worse results in comparison of TBUT, conjonctival hyperemia, ocular surface staining, lid margin vascularity, meibum quality, and Marx line score.Çonjonctival hyperemia, and lid margin vascularity were observed to be significantly higher in those using eye drops containing two or more active compounds.When the DII is increased only lid margin irregularity, and meibum quality are getting worse, significantly.</p><p><strong>Conclusion: </strong>Our results showed that the main factor contrubuting to OSD and MGD were prostaglandin analog therapy as a drug type. Management of ocular surface disease in glaucomatous patients is important when trying to reduce further ocular morbidity.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"141-146"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656450","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}
Goknur Demiran, Rukiye Yasak Guner, Mustafa Ozkara, Mustafa Tosun, Melih Akyol
{"title":"Therapeutic effect of systemic use of glatiramer acetate in imiquimod-induced mouse psoriasis model.","authors":"Goknur Demiran, Rukiye Yasak Guner, Mustafa Ozkara, Mustafa Tosun, Melih Akyol","doi":"10.1080/15569527.2025.2496638","DOIUrl":"10.1080/15569527.2025.2496638","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to evaluate the therapeutic potential of systemic glatiramer acetate (GA), a drug used in the treatment of multiple sclerosis (MS), in an imiquimod-induced psoriasis mouse model, given the common immunopathogenic mechanisms between the two diseases.</p><p><strong>Materials and methods: </strong>Fifty-four adult female BALB/c mice (16-18 weeks old) were divided into nine groups (6 mice each). A psoriasis-like model was induced in eight groups by application of 5% imiquimod cream for seven days. Systemic treatments included methotrexate (2 mg/kg/week), saline (1 mL/kg/day) and GA at doses ranging from 50 to 100 mcg, administered subcutaneously either during or after the induction phase. Clinical severity was assessed using the modified Psoriasis Area and Severity Index (mPASI), while histopathological and immunohistochemical analyses were performed to assess inflammation and cytokine expression, focusing on TNF-α, IL-1β and IL-17.</p><p><strong>Results: </strong>The highest mPASI scores were observed in the untreated psoriasis group, whereas the healthy control and mice treated with 50 mcg GA, especially after induction, showed the lowest scores. Statistically significant improvements in histopathological scores were observed (p < 0.05). GA treatment at 50 mcg resulted in the most favourable cytokine profile, with TNF-α and IL-17 levels comparable to the healthy group and a similar trend observed for IL-1β expression.</p><p><strong>Conclusions: </strong>Among the doses tested, 50 mcg GA administered after model induction was the most effective in reducing clinical severity and inflammatory cytokine expression. These findings suggest that GA is a promising systemic therapeutic agent for psoriasis.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"210-216"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976766","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 chitligsan nanosuspension gel and spray for enhancing full-thickness wound healing in a rat model.","authors":"Taner Arslan, Sıtkıcan Okur, Esra Modoğlu, Ayşe Gölgeli Bedir, Emrah Özakar, Serkan Yıldırım, İsmail Bolat, Yasemin Akçora","doi":"10.1080/15569527.2025.2496639","DOIUrl":"10.1080/15569527.2025.2496639","url":null,"abstract":"<p><strong>Introduction: </strong>This study explores the wound healing potential of Chitligsan (CHG), a novel formulation derived from the enzymatic and fossil-based components of Sahara soil, in nanosuspension-based gel and spray forms. Using a full-thickness wound model in Wistar rats, CHG's efficacy was compared with saline (control) and terramycin treatments.</p><p><strong>Methods: </strong>A total of 48 rats were divided into four groups: Control (saline), Spray (CHG spray), Gel (CHG gel), and Terramycin pomad. Wound areas were measured at days 3, 7, 14, and 21.</p><p><strong>Results: </strong>By day 21, CHG spray reduced wound size to 0.08 ± 0.01 cm<sup>2</sup>, while the gel achieved 0.09 ± 0.01 cm<sup>2</sup>, outperforming both control (0.34 ± 0.02 cm<sup>2</sup>) and terramycin (0.14 ± 0.05 cm<sup>2</sup>, <i>p</i> < 0.05). Histopathological analysis demonstrated superior epithelial regeneration, dense collagenization, and minimal inflammation in CHG-treated groups compared to others. The nanoscale size of CHG particles (89.6 ± 0.26 nm) and their stable zeta potential (-26.1 ± 1.5 mV) contributed to enhanced bioavailability and wound healing efficiency. Morphological and FTIR analyses confirmed the stability and compatibility of the nanosuspension.</p><p><strong>Conclusions: </strong>This study highlights CHG's potential as a biocompatible and effective wound care solution, offering significant advantages in granulation tissue formation and keratinization compared to conventional treatments.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"217-226"},"PeriodicalIF":1.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985965","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}
Qiong Ma, Tianchi Xu, Bo Ni, Changke Wang, Hongxiang Kang
{"title":"The retinal damage and dazzling effects of three-primary color lasers and their synthetic white laser on rabbit eyes.","authors":"Qiong Ma, Tianchi Xu, Bo Ni, Changke Wang, Hongxiang Kang","doi":"10.1080/15569527.2025.2455159","DOIUrl":"10.1080/15569527.2025.2455159","url":null,"abstract":"<p><strong>Purpose: </strong>With the increasing use of diode lasers emitting in the visible light spectrum, concerns about their potential to dazzle and cause eye damage have grown. This study aims to determine the maximum safe exposure levels and evaluate the retinal damage and dazzling effects caused by red, green, blue, and synthetic white lasers.</p><p><strong>Materials and methods: </strong>A chinchilla grey rabbit model was used for experimentation. Lasers with wavelengths of 635 nm (red), 520 nm (green), and 456 nm (blue), along with their combined output as synthetic white light, were directed at the rabbits' eyes for 0.2 s. Retinal damage was assessed using a fundus camera at 1 h and 24 h post-irradiation. Histological analysis was conducted to evaluate tissue changes. The dazzling effect was measured by recording the b-wave recovery time in the electroretinogram 0.1 s after laser exposure.</p><p><strong>Results: </strong>The maximum safe power density levels for red, green, blue, and synthetic white lasers were found to be 140, 60, 35, and 55 mJ/cm<sup>2</sup>, respectively. Exposures exceeding these thresholds resulted in visible retinal damage, including white-coagulated spots, hemorrhages, and corresponding histopathological changes. At an exposure level of 12.0 mJ/cm<sup>2</sup>, the b-wave recovery times for green, blue, and synthetic white light were 9.0, 8.0, and 7.8 s, respectively, while no dazzling effect was observed with the red laser.</p><p><strong>Conclusions: </strong>The synthetic white light laser exhibited slightly inferior safety compared to the green laser but was significantly safer than the blue laser, with fewer dazzling effects. These findings provide valuable insights for the safe use of visible light lasers.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"72-81"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381709","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}
Ozlem Bulbul, Renad Mammadov, Bahadır Suleyman, Ali Kulaber, Yunus Karaca, Huseyin Yaman, Engin Yenilmez, Aynur Sahin, Vildan Ozer
{"title":"Effect of elamipretide and methylprednisolone treatment on optic nerve, retina and brain damage in a methanol poisoning model: biochemical and histopathological evaluation.","authors":"Ozlem Bulbul, Renad Mammadov, Bahadır Suleyman, Ali Kulaber, Yunus Karaca, Huseyin Yaman, Engin Yenilmez, Aynur Sahin, Vildan Ozer","doi":"10.1080/15569527.2024.2430241","DOIUrl":"10.1080/15569527.2024.2430241","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity.</p><p><strong>Method: </strong>In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration.</p><p><strong>Results: </strong>In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (<i>p</i> = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (<i>p</i> = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (<i>p</i> = 0.009).</p><p><strong>Conclusion: </strong>Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"22-34"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726749","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":"Pharmacovigilance in intraocular antiangiogenic therapy.","authors":"Marianne Levon Shahsuvaryan","doi":"10.1080/15569527.2025.2475445","DOIUrl":"10.1080/15569527.2025.2475445","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Anti-VEGF (Vascular endothelial growth factor) agents have revolutionized ophthalmotherapy and are vital for various retinal disease treatment in ophthalmic practice. Ophthalmology has witnessed an explosion in the number of intravitreal injections delivered to patients over the past years. The rising popularity of anti-VEGF drugs came along with concerns about its safety in clinical use. The aim of this focused review is to critically analyze currently available findings on systemic safety.</p><p><strong>Materials and methods: </strong>A literature search was conducted using PubMed, Web of Science, and Google Scholar databases for studies published from January 2012 to February 2025. The reference lists of meta-analyses and selected studies were also reviewed. Eighty four articles of high or medium clinical relevance were selected for review. The exclusion criteria included non-English language publications, articles directly unrelated to the review topic, commentaries, conference abstracts.</p><p><strong>Results: </strong>Systemic safety concern in intraocular pharmacotherapy by antiangiogenic agents has a strong body of clinical evidence, resulting in plenty of peer reviewed clinical articles. It is certainly becoming recognized that anti-VEGF agents, despite given intraocularly, have the potential to cause systemic adverse events, such as cardiovascular, renal, neurological.</p><p><strong>Conclusions: </strong>Accumulating evidence obviate the need to raise medical professionals' awareness about systemic risk profile in patients with eye diseases treated by anti-VEGF, paying a special attention on patients with diabetes and older patients with multimorbidity. Early identification and prompt management of patients with undesirable systemic side effects secondary to intraocular pharmacotherapy by angiogenics can lessen disease severity, and help achieve earlier resolution.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"118-125"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623853","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":"Juvenile toxicity of atropine sulfate eye drops in young rats.","authors":"Wenqiang Zhang, Wei Yang, Lu Liu, Jinlong Dai, Linyi Wang, Yuankeng Huang, Xialing Lei, Junli Lin, Fafu Zhang, Jianmin Guo","doi":"10.1080/15569527.2024.2432507","DOIUrl":"10.1080/15569527.2024.2432507","url":null,"abstract":"<p><strong>Objectives: </strong>This study was to investigate the effects of atropine sulphate eye drops (ASED)on the development of partial systems in young rats and their toxic reactions following repeated eye-drop administration over a period of 40 days.</p><p><strong>Methods: </strong>SD rats of 20 days old were randomly assigned to control group, 0.01, 0.02, and 0.04% ASED groups, with 60 females and 25 males per group. ASED was given by eye drops from PND<sub>21</sub> onwards and normal saline was given in the control group at 10 μL/eye once a day for 40 days, in both right and left eyes. Rats of ASED groups were instilled with eye drops at the 10 μL/day per eye, from postnatal day 21 (PND<sub>21</sub>) to PND<sub>60</sub> for 40 consecutive days. The clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length of the rats were examined during the study period.</p><p><strong>Results: </strong>ASED at concentrations of 0.01, 0.02, 0.04%, dose levels of 0.002, 0.004, 0.008 mg/day per rat, had no toxicological effects on the clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length in rats.</p><p><strong>Conclusion: </strong>The no-observed-adverse-effect-level (NOAEL) of ASED in young SD rats equivalent to human over 2 years old was 0.008 mg/day at a concentration of 0.4 mg/mL.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"43-49"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767332","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}