title: Bioavailability of the Fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig.
abstract: Experiments were carried out with 16 castrated male pigs (41.5 +/- 2.0 kg) to examine the toxicokinetics of deoxynivalenol (DON) from naturally contaminated wheat (16.6 mg DON/kg) after chronic exposure or one single oral dose (acute). The systemic absorption (bioavailability) of DON was estimated based on the area under the curves (AUC) after oral (chronic or acute) and intravenous application of pure DON (53 microg/kg live weight). Additionally, a balance study was conducted to quantitatively trace the DON metabolism. After intravenous (IV) DON application (n = 5), serum DON concentrations decreased biphasically with terminal elimination half-lives (t(1/2)beta) of between 4.2 and 33.6h. DON was rapidly absorbed following oral exposure and reached maximal plasma concentrations (C(max)) of 21.79 and 15.21 ng DON/ml serum after (t(max)) 88.4 and 99.1 min in the chronic (n = 5) and acute (n = 6) fed group, respectively. Thereafter serum DON levels declined slowly with an elimination half-life (t(1/2)beta) of 6.28 and 5.32 h for both oral groups. The mean bioavailability (F) of DON was 89% for the chronic group and 54% for the acute oral group. DON was highly distributed in all groups, with an apparent volume of distribution (V(d)) higher than the total body water. Glucuronide conjugation of deoxynivalenol was found in serum samples after oral exposure, but not after intravenous application. Dietary DON caused a significant increase in DON concentrations of urine and faeces, whereby the metabolite de-epoxy-DON was found only in the trials with a pre-period of longer than 4 weeks. The total recovery was 66.6 +/- 39.0% and 54.0 +/- 9.7% for the control and the chronic DON groups, respectively, with urine being the main excretory route. In conclusion, orally administered DON was quickly absorbed to an extent of over 50%, highly distributed and only poorly metabolized. Twenty-four hours following oral dosing, DON could not be detected in the serum, except in one chronically fed pig at the level of the detection limit.
authors.affiliation: Institute of Animal Nutrition, Federal Agricultural Research Centre, FAL, Bundesallee 50, 38116 Braunschweig, Germany. tanja.goyarts@fal.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Goyarts
authors.forename: Sven
authors.initials: S
authors.lastname: Dänicke
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D005243:Feces / Q000737:chemistry; D005506:Food Contamination; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D009183:Mycotoxins / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D018709:Statistics, Nonparametric; D013552:Swine / Q000378:metabolism*; D014255:Trichothecenes / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D014908:Triticum; D014556:Urine / Q000737:chemistry
chemical_list: D009183:Mycotoxins; D014255:Trichothecenes; C007262:deoxynivalenol