© 1986 Oxford University Press
research-article |
Excretion Profiles of the Mycotoxin Deoxynivalenol, following Oral and Intravenous Administration to Sheep1
Animal Research Centre, Agriculture Canada, Central Experimental, Farm Ottawa Ontario K1A 0C6, Canada
Excretion Profiles of the Mycotoxin Deoxynivalenol, following Oral and Intravenous Administration to Sheep. PRELUSKY, D. B., VEIRA, D. M., TRENHOLM, H. L., AND HARTIN, K. E. (1986). Fundam. Appl. Toxicol. 6, 356–363. The excretion profiles of deoxynivalenol (DON) and metabolites (DON glucuronide conjugate, 3
,715-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
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.