| The effects of dose, route and time on the metabolic fate of T-2 toxin in rats and rabbits were examined. Male, Sprague-Dawley rats and male New Zealand White rabbits were administered tritium-labeled T-2 toxin at 0.15 mg/kg and 0.60 mg/kg of body weight by i.v., oral and dermal routes of administration. The excretion of total radioactivity was determined for six days and the metabolic profiles were determined using HPLC for days 1, 2 and 3.;The excretion of radioactivity in the excreta of both species was rapid and nearly complete after 6 days (>95%) in i.v. and orally dosed animals, but only 70 to 80 percent of the administered radioactivity was excreted in dermally dosed rats and rabbits.;The major metabolites in the excreta of rats and rabbits were 3'OH HT-2, HT-2, T-2 tetraol, deepoxy T-2 tetraol and several unknowns. In urine and fecal extracts from rats, these metabolites accounted for 59 and 25 percent of the extracted radioactivity, respectively. An unknown metabolite, tentatively identified as deepoxy 3'OH HT-2 accounted for another 47 percent of the extracted radioactivity in fecal extracts from rats. In urine and fecal extracts from rabbits, these major metabolites accounted for 71 and 60 percent of the extracted radioactivity, respectively. An unknown metabolite, tentatively identified as deepoxy 3'OH HT-2 accounted for an additional 26 percent of the extracted radioactivity in fecal extracts.;The major differences between rats and rabbits were the significant percentages of HT-2 and deepoxy T-2 tetraol in rabbits and the greater percentage of deepoxy 3'OH HT-2 in rats.;Within species, there were significant differences due to dose and route, but the effect of time was more significant. The significant percentages of deepoxy metabolites and their increase over time indicated that deepoxidation was an important pathway for the metabolism of T-2 toxin. Since the loss of the epoxide group has been reported to result in a significant decrease in toxicity, this pathway is also important in the detoxification of T-2 toxin. |
