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Background: This study was conducted to investigate both the genotoxicity effects of M. officinalis aqueous extract on blood cells and the pathologic changes in the renal, cardiac and splenic tissues of Oncorhynchus mykiss. Methods: 300 fish (Oncorhynchus mykiss) were divided randomly into three groups (N=100 each), consisting of group, 1 (control), and groups 2 and 3 (experimental), which received 450 mg/kg and 1350 mg/kg of body weight the aqueous extract of M. officinalis, respectively. The fish were fed for 30 days, with the experimental groups given three treatments. Micronuclei test and comet assay were used to identify the histopathological damages, simultaneously. Results: We found significantly more micronuclei (33%) in erythrocytes of group 3 than those in group 2 (5%; p<0.05). Similarly, the results of comet assay were consistent with those obtained for the micronuclei test. The recorded DNA damages to erythrocytes was significantly higher in group 3 (35.75%) compared to that for group 2 (7.15%; p<0.05). The pathologic findings in the spleen, kidneys and heart tissues together with those obtained from the micronuclei test and comet assay confirmed the tissue and DNA damages after exposure to the extract. Abundant and severe cystic and atrophic glomeruli, renal tubular degeneration, hemorrhage and focal lymphocytic inflammation in heart, and increased melanomacrophage centers in the kidneys and spleen were observed at significantly higher frequency in group 3 than those in group 2 (p<0.05). Conclusion: The findings of this study demonstrated that the extract of M. officinalis at doses higher than 450 mg/kg per body weight caused toxic effects with severe tissue and DNA damages in O. mykiss fish. [ABSTRACT FROM AUTHOR]