{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:10:00Z","timestamp":1793495400921,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Imatinib mesylate (IM) is a widely used anticancer drug, mainly for treating chronic myeloid leukemia. However, pharmaceutical formulations may contain impurities, which in some cases can be more toxic than the parent compounds. This study aimed to compare the toxicity of IM and one of its impurities (IMP), N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine, using progressively complex models. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium, neutral red uptake and sulforhodamine B colorimetric assays. Mutagenic activity was assessed using the Ames test. In vivo assays were performed using both the invertebrate C. elegans and vertebrate zebrafish embryo models. In Vero cell cultures, the cytotoxicity of IM and IMP was found to be similar across the colorimetric assays tested. Neither IM nor IMP showed mutagenic effects in the Ames test. In the C. elegans lethality and development assay the toxicity profiles of the compounds were similar. However, in the Fish Embryo Acute Toxicity assay, the LC50 value for IMP (0.735\u00a0\u03bcg\/mL) was significantly lower than that for IM (60.86\u00a0\u03bcg\/mL), indicating greater toxicity for IMP. Furthermore, sublethal effects such as yolk-sac edema, pericardial edema, and tail deformities, were observed in embryos treated with IMP, even at low concentrations, indicating potential hazards associated with IMP. This study is the first to evaluate the toxicity of an IM subproduct, previously reported in pharmaceutical formulations, using different models. The Zebrafish model demonstrated higher sensitivity in predicting the toxic response of the TKI subproduct.<\/jats:p>","DOI":"10.1093\/toxres\/tfaf029","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:45:10Z","timestamp":1741121110000},"source":"Crossref","is-referenced-by-count":1,"title":["Toxicity assessment of imatinib mesylate and a related impurity: in vitro and in vivo approaches"],"prefix":"10.1093","volume":"14","author":[{"given":"C\u00e1ssia Franciele Rosa da Silva","family":"Rocha","sequence":"first","affiliation":[{"name":"Bioanalysis Laboratory, Health Sciences Institute, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 ,","place":["Brazil"]},{"name":"Postraduate Program in Toxicology, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna 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Toxicology, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 ,","place":["Brazil"]},{"name":"Molecular Microbiology Laboratory, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 ,","place":["Brazil"]},{"name":"Postgraduate Program in Environmental Quality Program in Cellular and Molecular Biology Applied to Health, Lutheran University of Brazil (ULBRA) , Farroupilha Avenue, 8001, Canoas, RS, 92425-020 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-7063","authenticated-orcid":false,"given":"Mariele Feiffer","family":"Char\u00e3o","sequence":"additional","affiliation":[{"name":"Bioanalysis Laboratory, Health Sciences Institute, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 ,","place":["Brazil"]},{"name":"Postraduate Program in Toxicology, Feevale University , ERS 239, 2755, Novo Hamburgo, RS, 93525-075 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