Evaluation of in vitro and in vivo genotoxicity, acute oral toxicity, and subacute oral toxicity of Apocynum venetum leaf extract VENETRON®

Apocynum venetum is traditionally used as a Chinese herbal medicine and consumed as tea. VENETRON® is an A. venetum leaf extract used in health foods and supplements. Limited data are available on the genotoxicity and oral toxicity of VENETRON®. Therefore, we conducted in vitro chromosomal aberration tests, in vivo comet assays, micronucleus tests, and acute and 90-day repeated-dose oral toxicity tests in accordance with the Good Laboratory Practice and Organization for Economic Co-operation and Development guidelines. There was no increase in the number of aberrant cells up to 0.125 mg/mL in the chromosomal aberration test, no increase in the percentage of tail DNA up to 2000 mg/kg/day in the comet assay, and no increase in the percentage of micronucleated polychromatic erythrocytes up to 2000 mg/kg/day in the micronucleus test, indicating that VENETRON® was non-genotoxic. No mortalities and abnormal changes were observed in the acute toxicity test at 2000 mg/kg/day; therefore, the acute toxicity of VENETRON® was classified as Category 5. There were no abnormal changes in the subacute toxicity test at 1000 mg/kg/day; therefore, the no-observed-adverse-effect level was considered to be 1000 mg/kg/day. The results of this study complement the insufficient in vitro and in vivo safety data of VENETRON®. Considering its long history of use and previous studies, it is a highly safe functional ingredient for healthy foods and supplements and is suitable for daily use in humans.