A Comprehensive Toxicological Assessment of Fulvic Acid.

Chongshan Dai,Shusheng Tang,Gaurav Sharma,Xilong Xiao,Yonglei Yuan,Guang Chen

doi:10.1155/2020/8899244

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.

Highlights

Materials and MethodsFemale- and male-specific pathogen-free (SPF) Sprague-Dawley (SD) rats and ICR mice were purchased from Vital River Animal Technology
Materials. e Fulvic acid (FA) used in the current experiment was extracted from weathered coal obtained. e effective content of FA was determined by Inner Mongolia Yongye Nongfeng Biotechnology Co
SD rats (8 weeks old, 180–220 g) and ICR mice (8 weeks old, 22-25 g) were used in acute toxicity tests and the protocol was carried out in accordance with guidelines No 423 and 425 of Organization for Economic Cooperation and Development (OECD) [30]. 10 male and 10 female ICR mice or SD rats were administrated with 5,000 mg/kg FA via oral gavage. e mice or rats in the control group were treated with an equal volume of 0.5% CMC-Na

Summary

Materials and Methods

Female- and male-specific pathogen-free (SPF) Sprague-Dawley (SD) rats and ICR mice were purchased from Vital River Animal Technology. SD rats (8 weeks old, 180–220 g) and ICR mice (8 weeks old, 22-25 g) were used in acute toxicity tests and the protocol was carried out in accordance with guidelines No 423 and 425 of OECD [30]. 10 male and 10 female ICR mice or SD rats were administrated with 5,000 mg/kg FA via oral gavage. E mice or rats in the control group were treated with an equal volume of 0.5% CMC-Na. After signal administration, surviving animals were observed for 14 days. All the surviving animals were euthanized intraperitoneally with overdose of sodium pentobarbital at 80 mg/kg and quickly sacrificed for anatomical observation and all protocols were conducted under FDA’s Good Laboratory Practice guidelines [27]

Subchronic Toxicity Study

Mutagenicity Studies

Results