THE TOXICOKINETICS AND TOXICODYNAMICS OF T-2 TOXIN IN SWINE AND CATTLE

T-2 toxin is a toxic mold metabolite, produced expecially by Fusarium sporotrichioides in grains with high moisture concentrations and undulating temperatures. Although T-2 toxicoses are not frequently reported in North America, a few serious outbreaks have occurred in farm animals. Sever epidemics affecting domestic animals and humans have been reported in the USSR. Moreover, there have been recent reports in the popular press of T-2 toxicoses in Asia as a result of alleged human exposure to a chemical warfare agent commonly called "Yellow Rain.";Gilts received T-2 toxin in sublethal and lethal intravascular doses, lethal oral doses, and sublethal dermal doses. Heifers received sublethal oral and both sublethal and lethal intravascular dosages. Lesions included lymphoid necrosis primarily affecting B-cells, but T-cells were also damaged. Necrosis of bone marrow cells occurred only at potentially lethal doses.;In swine the gastric fundus was severely congested and mucosal necrosis and hemorrhage sometimes occurrred in these areas. Intestinal lesions in swine were more severe after intragastric as opposed to intravascular doses. These included lymphoid necrosis, crypt necrosis, shortened microvilli, and vascular congestion.;One calf died after an intravascular dose of T-2 toxin at 1.2 mg/kg, having developed a "hemorrhagic bowel syndrome" with severe necrosis in the jejunum, ileum, and colon.;Clinical pathology studies in swine and calves revealed polycythemia and initial leukocytosis, largely attributable to neutrophilia, followed by lymphopenia. There were increases in aspartate aminotransferase, creatinine, blood urea nitrogen, inorganic phosphorus and decreases in serum calcium, which were sometimes profound.;After intravascular administration, the disappearance of parent T-2 toxin followed a 2-compartment open model with mean elimination phase half-lives of 13.8 and 17.4 minutes and mean apparent specific volumes of distribution of 0.366 and 0.376 l/kg in swine and calves, respectively. The fraction of T-2 toxin eliminated as parent compound in urine was negligible. In spite of administration of a lethal oral dose in swine and a toxic oral dose in calves, no parent T-2 toxin was detected in plasma or urine.;After intravascular administration, tissue concentrations of T-2 toxin were highest in lymphoid organs. Tissue residues of T-2 toxin were rapidly depleted and, after potentially lethal intravascular doses, no quantifiable T-2 toxin was present in any tissue at 4 hours after dosing. No T-2 toxin could be detected in liver, at 1 hour after dosing.