Background: Streptokinase and streptodornase are bacterial enzymes with established applications in thrombolysis and wound debridement; however, comprehensive data on their acute oral toxicity and genotoxic potential remain limited despite decades of clinical use.

Methods: Acute oral toxicity was assessed in 90 Wistar rats (five males and five females per group) administered single escalating doses of the lyophilized Streptokinase-Streptodornase preparation (1–8 g) suspended in PBS, with 14-day observation of clinical signs, body weight, organ weights, haematology, serum biochemistry, and histopathology. Genotoxicity was evaluated using the bacterial reverse mutation (Ames) test in five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, TA1537) at concentrations up to 5 mg/plate (±S9), the chromosomal aberration assay in CHO-K1 cells at 0,5–2,0 mg/mL (±S9), and the mammalian erythrocyte micronucleus assay in ICR mice at 500–2,000 mg/kg (48- and 72-hour sampling).

Results: No mortality, clinical signs of toxicity, or statistically significant differences in any measured parameter were observed in the acute oral toxicity study. The Ames test showed no increase in revertant colonies or cytotoxicity in any strain. Chromosomal aberration frequencies and micronucleated reticulocyte frequencies remained comparable to negative controls in all treated groups under both metabolic activation conditions, while positive controls produced the expected responses.

Conclusion: The Streptokinase-Streptodornase preparation demonstrated no acute oral toxicity and no genotoxic activity in the battery of standard assays performed, indicating a favourable safety profile.