Dose Response of Tunicamycins in Sheep Following Intra-duodenal Administration

Annual ryegrass toxicity (ARGD is a neurological disease of livestock that is caused by corynetoxins (Cfs) and results in major economic losses to the Australian livestock industry annually. The commercially available tunicamycins (TMs) are structurally, biochemically and toxicologically very similar to the corynctoxins (Edgar et al. 1982; Vogel et al. 1982; lago et al. 1983; Frahn et al. 1984) and have been used to model ARGT due to the intrinsic difficulties in isolating large amounts of pure corynetoxins. MGT has been produced experimentally in sheep following oral dosing of infected ryegrass and by subcutaneous injection of tlmicamycins (Berry et al. 1982; Finnic and Jago 1985). In preparation for assessing the protective effect of mucosal vaccination for ARGT, it was necessary to delemline the dose-response relationship, especially that of the liver, of lunieamycins surgically administered into the duodenum of sheep as a model for the natural route of exposure to the toxins. The aim of this study was to determine the minimum single, intra-duodenal dose of tunicamycins that would significantly alter serum biochemistry (liver enzymes, albumin, total protein and total bilirubin) but would not induce overt clinical signs of the disease. This dose would subsequently be used as a challenge dose in the mucosal vaccination experiments.