EVALUATION OF THE TOXICITY OF DRUG RESIDUES IN FOOD - THE CASE FOR RELAY TOXICITY STUDIES

The tissue residues of veterinary drugs given to food-producing animal s are an ill-defined mosaic of parent drug and metabolites. Consumers are only ever exposed to this mixture in the presence of a vast excess of the excipient, food. Given the modifying effects of food on the ab sorption and disposition of co-administered xenobiotics, it follows th at the toxicity of these residues can only be properly evaluated in th e presence of a large excess of food. Adoption of a relay toxicity str ategy addresses these two points. The proposed relay toxicity testing approach is as follows. The target species receives a recommended dosa ge regimen of the drug, but a dose level three- to five-fold higher th an normal and the animals ave then killed several days earlier than th e projected withdrawal period. The tissues from these animals, contain ing the residue mixture at artificially high concentrations, ave then administered to laboratory animals for conventional toxicological eval uation. In this approach the residues do not require individual identi fication and their potential toxicity is evaluated in the presence of the inescapable excipient, food Determination of an 'exposure' level w ithout observerable toxicity provides, in principle, the means of rela ting human safety to a No-Observed Effect Level in laboratory animals in the traditional manner.