{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:17:45Z","timestamp":1787894265585,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNAM","award":["FM\/DI\/037\/2022"],"award-info":[{"award-number":["FM\/DI\/037\/2022"]}]},{"name":"UNAM","award":["014-CIC-2026"],"award-info":[{"award-number":["014-CIC-2026"]}]},{"award":["FM\/DI\/037\/2022"],"award-info":[{"award-number":["FM\/DI\/037\/2022"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]},{"award":["014-CIC-2026"],"award-info":[{"award-number":["014-CIC-2026"]}],"id":[{"id":"https:\/\/ror.org\/01tmp8f25","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Chiranthodendron pentadactylon Larreat (\u201cflor de manita\u201d) is traditionally used for gastrointestinal, cardiovascular, and neurological disorders. Objective: This study comprehensively integrated phytochemical characterization, in silico toxicological profiling, an exposure-informed Integrative Toxicity Prediction Model (ITPM), uncertainty analysis, and acute testing of a fresh flower aqueous extract (FFAE). Methods: Thirty-six phytochemicals were screened for hepatotoxicity, nephrotoxicity, Ames mutagenicity, carcinogenicity, hERG inhibition, reproductive-effects alerts, and acute oral toxicity. Five organ- or effect-specific endpoints were integrated into an exploratory Toxicological Alert Score (TAS), whereas reproductive alerts and predicted LD50 were reported separately. Seventeen compounds quantified in the FFAE were compared with a 20-compound literature-informed profile through 50,000 Monte Carlo iterations. Male CD-1 mice received a single FFAE dose of 300\u20135000 mg\/kg and were observed for 14 days. Results: Positive predictions occurred for hERG inhibition in 33 compounds (91.7%), hepatotoxicity in 29 (80.6%), nephrotoxicity and carcinogenicity in 28 each (77.8%), and mutagenicity in 21 (58.3%). Six compounds had predicted LD50 values \u2264 1000 mg\/kg. The proportional ITPM toxicity-evidence index was 6.91% for the experimental profile and 19.34% for the literature-informed profile. Monte Carlo means were 6.98% (95% uncertainty interval, 5.65\u20138.44%) and 19.32% (16.76\u201322.37%), respectively. No mortality, overt clinical signs, or treatment-related body weight differences occurred up to 5000 mg\/kg. Conclusions: Compound-level predictions identified priorities for confirmatory testing, while the extract-specific model yielded a lower comparative toxicity-evidence proportion, and the animal study showed low overall acute toxicity under the evaluated conditions. These findings do not establish general or long-term safety, calibrated risk probabilities, or biological neutralization of toxicological liabilities.<\/jats:p>","DOI":"10.3390\/ph19091354","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:54:42Z","timestamp":1787763282000},"page":"1354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting the Toxicity In Silico of the Aqueous Extract of Chiranthodendron\u00a0pentadactylon Flowers. Experimental Evaluation In Vivo"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1662-0872","authenticated-orcid":false,"given":"Oscar Salvador","family":"Barrera-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University National Autonomous of Mexico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil Alfonso","family":"Magos-Guerrero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University National Autonomous of Mexico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Luis","family":"Escobar-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University National Autonomous of Mexico (UNAM), Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"San Miguel-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Posgrado en Bot\u00e1nica, Campus Montecillo, Colegio de Posgraduados, M\u00e9xico-Texcoco Highway km 35.6, Texcoco 56230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-5044","authenticated-orcid":false,"given":"Maira","family":"Huerta-Reyes","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Nefrol\u00f3gicas, Hospital de Especialidades \u201cDr. Bernardo Sep\u00falveda Guti\u00e9rrez\u201d, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Cuauht\u00e9moc, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Silveira, D., and Boylan, F. 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