Absolute oral bioavailability, quantitative toxicokinetics and metabolite profiling of alternariol and alternariol monomethyl ether in pigs

• DOI: 10.1007/s00204-025-04050-y
• Publication Date: 2025-04-26T12:09:32Z
• Authors: Danica den Hollander; Siegrid De Baere; Celestien Holvoet; Mathias Devreese; Gunther Antonissen; Ann Martens; Kristel Demeyere; Kris Audenaert; Evelyne Meyer; Siska Croubels
• Keywords: Alternariol; ADME; Biotransformation

Abstract The mycotoxins alternariol (AOH) and monomethyl ether (AME), produced by Alternaria spp . , are common contaminants of food feed a potential threat to animal human health. To date, the most prominent data gaps for their comprehensive risk assessment concern information on in vivo absorption, distribution, metabolism excretion (ADME) toxicokinetic behavior. aim this study was determine absolute oral bioavailability, quantitative characteristics biotransformation AOH AME pigs, using crossover trials with intravenous administration single dose both at 2 mg/kg b.w. Plasma profiles phase I II metabolites were studied vena jugularis UPLC-MS/MS LC-HRMS methods. Furthermore, plasma from portae analyzed presystemic biotransformation. Urine collected urinary metabolite profiles. Results reveal low bioavailability (15%) (9%), caused absorption and/or extensive first-pass liver mainly II, lesser extent metabolites. Quantitative modeling IV showed high total body clearance (12.9 16.8 L/(h*kg b.w.), respectively), volume distribution (4.97 5.15 L/kg b.w., respectively) short elimination half-life 0.16 0.21 h, respectively. These findings may contribute development candidate biomarkers exposure biomonitoring studies since pigs considered suitable model extrapolate humans.