In vivo hydrolysis and toxicokinetics of T-2 toxin and T2-glucoside in broiler chickens

Of the trichothecene mycotoxin family, T-2 toxin (T-2) is regarded as the most toxic. As it is mainly detected in cereals, animals with a mainly cereal based diet, such as broiler chickens, are highly exposed to this toxin. Additionally to the free mycotoxin, modified forms of the mycotoxin may contribute to the degree of contamination as they might be hydrolyzed to the native mycotoxin upon ingestion. For T-2, the main modified form is T2-glucoside (T2-G). Although only limited occurrence data are available for T2-G, incidences of over 70% have been reported in cereals. The EFSA has recently estimated the relative contribution of T2-G to T-2 at 10%. In order to assess whether T2-G adds to the toxicity of T-2, a toxicokinetic study of T-2 and T2-G was performed in broiler chickens. For this a two-way cross-over animal trial was set up with orally (PO) and intravenously (IV) administered bolus of T-2, 0.74 mg/kg, in 6 broilers. Afterwards, three of those birds were administered an equimolar dose of T2-G, namely 1 mg/kg, PO or IV. Blood was collected up to two hours post administration and analysed by LC-MS/MS. After T-2 administration, the metabolite T-2 triol was not detected in any of the samples. Low levels of the metabolite HT-2 were detected. After IV or PO administration of T2-G, only trace amounts of T-2 (< 1 ng/mL) could be detected and no HT-2 or T-2 triol was found. These results demonstrate that the in vivo hydrolysis of T2-G to T-2 is negligible. The absolute oral bioavailability (F), a measure of systemic exposure to the toxin, of T-2 and T2-G was 2% and 9%, respectively. Plasma concentration-time profiles of T-2 and T2-G after IV administration were analysed by means of a two-compartmental model. Following toxicokinetic parameters were calculated and will be presented at the conference: volumes of distribution, total body clearance, distribution and elimination rate constants and half-lifes. The relatively high F and negligible in vivo hydrolysis of T2-G to T-2 highlights the need to investigate the (cyto)toxicity of this modified mycotoxin in order to perform an appropriate risk assessment.

Publication year:2015