{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:19:09Z","timestamp":1790183949126,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marmara University ADEP","award":["ADT-2023-10806"],"award-info":[{"award-number":["ADT-2023-10806"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10\u2013200 \u00b5g\/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg\/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields.<\/jats:p>","DOI":"10.3390\/ijms26199461","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:54:48Z","timestamp":1759229688000},"page":"9461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Toxicological Assessment of Origanum majorana L.: Evaluation of Its Cytotoxicity, Genotoxicity, and Acute Oral Toxicity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-6089","authenticated-orcid":false,"given":"Ayfer","family":"Beceren","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0784-8779","authenticated-orcid":false,"given":"Ayse Nur","family":"Hazar-Yavuz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-5639","authenticated-orcid":false,"given":"Ozlem","family":"Bingol Ozakpinar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"},{"name":"Marmara Pharmacy Drug and Innovative Product Development Unit, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-0900","authenticated-orcid":false,"given":"Duygu","family":"Taskin","sequence":"additional","affiliation":[{"name":"Marmara Pharmacy Drug and Innovative Product Development Unit, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"},{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, University of Health Sciences, Istanbul 34668, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2656-0319","authenticated-orcid":false,"given":"\u0130smail","family":"Senkardes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Botany, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-6478","authenticated-orcid":false,"given":"Turgut","family":"Taskin","sequence":"additional","affiliation":[{"name":"Marmara Pharmacy Drug and Innovative Product Development Unit, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-9174","authenticated-orcid":false,"given":"Ozlem Tugce","family":"Cilingir-Kaya","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-8502","authenticated-orcid":false,"given":"Ahmad","family":"Kado","sequence":"additional","affiliation":[{"name":"ISLAB-2 Core Laboratory, Goztepe Prof. Dr. Suleyman Yalcin City Hospital, Istanbul 34722, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-1711","authenticated-orcid":false,"given":"Hatice Kubra","family":"Elcioglu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"},{"name":"Marmara Pharmacy Drug and Innovative Product Development Unit, Faculty of Pharmacy, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ekor, M. 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