Cedrela fissilis Vell. Inner Bark: LC-MS/MS-Based Chemical Profiling and Toxicological Effects.

Investigating the mechanistic toxicity of plant extracts is essential for safety assessment. The predictive toxicological effects of Cedrela fissilis were evaluated, and LC-MS/MS-based chemical profiling was performed. The hydroethanolic extract (HeECf) and ethyl acetate (EA) fraction were assessed in multimodel systems with different levels of biological organization. In Allium cepa, HeECf reduced root growth (29%-36%) and the mitotic index (50%-74%) at 500-1000 µg·mL- 1, whereas the EA fraction reduced only the mitotic index (30%-62%), with less pronounced effect. Chromosomal alterations were more frequent in HeECf than in EA. In Chinese hamster ovary cells, HeECf reduced cell viability (81%-68%) at 800-1000 µg·mL- 1 and compromised membrane integrity, whereas the EA fraction showed IC50 > 800 µg·mL- 1. In Drosophila melanogaster, HeECf completely inhibited pupal development at 1000 µg·mL- 1, whereas at 600, 700, and 800 µg·mL- 1 no toxic effects were observed, also partly related to xenobiotic metabolism. Thus, HeECf exhibited cytotoxic and genotoxic effects that impaired pupal development, likely driven by pentacyclic triterpenoids. In contrast, the EA fraction, enriched in flavonoids, displayed lower toxicity than HeECf. Overall, the toxicity of C. fissilis appears to be mechanistically linked to triterpenoid-mediated cytotoxic and genotoxic damage, contributing to developmental disruption.