[ $21{alpha}$ ]- and ${eta}$-Methylmelianodiol were isolated as the inhibitor of IL-5 bioactivity from Poncirus tripoliata. To develope as an anti-septic drug, the genotoxicity of $21{alpha};-and;{eta}-methylmelianodiol$ was subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of $21{alpha}-methylmelianodiol$ was determined the concentration of $25.51;{mu}g/mL;and;21.99;{mu}g/mL$ with and without S-9, respectively. Also $21{eta}-methylmelianodiol$ was determined the concentration of $24.15;{mu}g/mL;and;;22.46;{mu}g/mL$ with and without S-9, respectively. In the comet assay, DNA damage was not observed both $21{alpha}-methylmelianodiol;and;21{eta}-methylmelianodiol$ in mouse lymphoma cell line. Also, the mutant frequencies in the treated cultures were similar to the vehicle controls, and none of $21{alpha};-and;{eta}-methylmelianodiol$ with and without S-9 doses induced a mutant frequency over. twice the background. It is suggests that $21{alpha};-and;{eta}-methylmelianodiol$ are non-mutagenic in MOLY assay. The results of this battery of assays indicate that $21{alpha};-and;{eta}-methylmelianodiol$ have no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that $21{alpha};-and;{eta}-methylmelianodiol$, as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen.