Excretion profiles of the mycotoxin deoxynivalenol, following oral and intravenous administration to sheep

Abstract

The excretion profiles of deoxynivalenol (DON) and metabolites (DON glucuronide conjugate, 3α,7α,15-trihydroxytrichothec-9,12-diene-8-one (DOM-1), and DOM-1 glucuronide conjugate) were defined in male sheep following either intravenous (iv) or oral administration of the toxin at levels of 0.5 and 5.0 mg DON/kg body wt, respectively. After iv dosing, urinary DON levels declined in a biphasic fashion with an average elimination half-life (terminal phase) of 1.2 hr, diminishing to baseline concentrations by 8 hr. Maximum urinary excretion rates for the two major metabolites identified (conjugated DON, conjugated DOM-1) occurred 0.5–1.5 hr after dosing, exhibiting elimination half-lives of 2.2 and 3.1 hr, respectively. Total recovery accounted for only about 66.5% of the dose: 63.0% in the urine (24.1% DON, 21.2% conjugated DON, 0.5% DOM-1, 17.2% conjugated DOM-1) and 3.5% in bile (made up almost completely of conjugated DOM-1). The peak biliary excretion rate for conjugated DOM-1 was found to occur within 1 hr postdosing, which rapidly declined to baseline levels by 5 hr. Following oral administration, urinary excretion rates of the major metabolites (DON, conjugated DON, conjugated DOM-1) reached maximum 6–9 hr post-treatment, and declined exponentially with t 1 2 values of 3.2, 4.0, and 5.0 hr, respectively. Urinary and biliary recovery of administered DON averaged approximately 7.1%: 7.0% in urine (2.1% DON, 3.6% conjugated DON, 0.06% DOM-1, 1.2% conjugated DOM-1) and 0.11% in bile (predominately conjugated DOM-1). Between 54 and 75% of the oral dose was recovered in the feces. These findings indicate that DON and metabolites do not persist in the body following either a single oral or intravenous dose of DON and are rapidly excreted. However, following iv administration, a portion of the dose (33.5%) remained unaccounted, presumably converted to unidentified metabolites. Based on these results it appears that metabolism is the major process of elimination of DON in sheep.