A Comprehensive Toxicological Safety Assessment of Superoxide Dismutase as a Novel Food Ingredient

This study systematically evaluated the toxicological safety of superoxide dismutase (SOD) as a novel food ingredient. Acute oral toxicity testing revealed no toxicity or mortality in mice of both sexes following a single gavage dose of 10 g/kg BW, classifying SOD as a practically nontoxic substance. In the 90‐day subchronic toxicity study, Wistar rats orally administered doses of 8.33, 25, or 75 mg/kg BW/day exhibited the following: Female rats in the high‐dose group showed significantly increased body weight during Weeks 11–13, transient fluctuations in food efficiency occurred in the low‐dose group, and high‐dose males displayed reduced neutrophil percentage (NEUT%) at termination, whereas all observed alterations in hematological, clinical chemistry, and urinalysis parameters lacked dose dependency and were largely disappeared during the recovery period. Histopathological examination revealed no substance‐specific lesions. Teratogenicity testing demonstrated a significant increase in fetal resorption rates in the 8.33 and 25 mg/kg BW groups ( p  < 0.01), whereas this effect showed no dose–response association and no structural malformations were observed. Three genotoxicity assays (mammalian erythrocyte micronucleus, chromosome aberration in vitro, and Ames tests) yielded negative results. Collectively, these findings demonstrate a favorable safety profile for SOD at the tested doses, with no evidence of genotoxicity either in vivo or in vitro.