Pharmacokinetic study and 28-day repeated oral toxicity study of Enniatin B in mice

Abstract

Enniatins are emerging fungal toxins that have attracted increasing concerns in recent years. In this study, a pharmacokinetic study of enniatin B (ENNB) was conducted in mice to examine absorption of ENNB after oral administration. Next, a 28-day repeated oral toxicity study of ENNB was conducted in mice to obtain a toxicological profile for risk assessment of enniatins. In the pharmacokinetic study, ENNB was administered orally (30 mg/kg) or intravenously (1 mg/kg) to 6-week-old male mice, and pharmacokinetic parameters were calculated. Concentrations of ENNB in feces and gene expression in the liver were also analyzed after oral administration. As a result, bioavailability was estimated to be 85.6%. In feces, an average of 5.26% of the oral dose of ENNB was detected. Liver RNA-Seq analysis revealed upregulation of many metabolism-related genes. In the 28-day toxicity study, ENNB was orally administered to 6-week-old mice at doses of 0, 7.5, 15, and 30 mg/kg, and hematology, blood biochemistry and histopathological examinations were performed. In males at 30 mg/kg, low erythrocyte counts, high BUN levels, and high absolute kidney weights were observed; however, histopathology and related parameters revealed no changes suggestive of ENNB effects. In conclusion, although ENNB is absorbed after oral administration, general toxicity is expected to occur at higher doses than those used in this study.