A Comprehensive Toxicological Assessment of Fulvic Acid

Abstract

Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (all $p>0.05$ ) in all FA treatment groups in the bacterial reverse mutation test, in vitro mammalian chromosome aberration test, in vivo sperm shape abnormality assay, and in vivo mouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day subchronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (all $p>0.05$ ) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.