Use of Physiologically Based Kinetic Modeling to Predict Deoxynivalenol Metabolism and Its Role in Intestinal Inflammation and Bile Acid Kinetics in Humans.

ABSTRACT: Current points of departure used to derive health-based guidance values for deoxynivalenol (DON) are based on studies in laboratory animals. Here, an animal-free testing approach was adopted in which a reverse dosimetry physiologically based kinetic (PBK) modeling is used to predict in vivo dose response curves for DON's effects on intestinal pro-inflammatory cytokine secretion and intestinal bile acid reabsorption in humans from concentration-effect relationships for DON in vitro. The calculated doses for inducing a 5% added effect above the background level (ED₅) of DON for increasing IL-1β secretion in intestinal tissue and for increasing the amounts in the colon lumen of glycochenodeoxycholic acid (GCDCA) were 246 and 36 μg/kg bw/day, respectively. These in vitro-in silico-d

SUBMITTER: Wang J 

PROVIDER: S-EPMC10786035 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature