Galer D M, Monro A M
Pfizer Central Research, Groton, CT 06340, USA.
Food Addit Contam. 1998 May-Jun;15(4):494-500. doi: 10.1080/02652039809374671.
The tissue residues of veterinary drugs given to food-producing animals 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 absorption and disposition of co-administered xenobiotics, it follows that the toxicity of these residues can only be properly evaluated in the presence of a large excess of food. Adoption of a relay toxicity strategy addresses these two points. The proposed relay toxicity testing approach is as follows. The target species receives a recommended dosage regimen of the drug, but a dose level three- to five-fold higher than normal and the animals are then killed several days earlier than the projected withdrawal period. The tissues from these animals, containing the residue mixture at artificially high concentrations, are then administered to laboratory animals for conventional toxicological evaluation. In this approach the residues do not require individual identification and their potential toxicity is evaluated in the presence of the inescapable excipient, food. Determination of an 'exposure' level without observerable toxicity provides, in principle, the means of relating human safety to a No-Observed Effect Level in laboratory animals in the traditional manner.
给予食用动物的兽药在组织中的残留是由母体药物和代谢物构成的难以明确界定的混合物。消费者接触到的只是在大量赋形剂（即食物）存在情况下的这种混合物。鉴于食物对同时施用的外来化合物吸收和代谢的影响，这些残留物的毒性只能在大量食物存在的情况下才能得到恰当评估。采用接力毒性策略可以解决这两个问题。提议的接力毒性测试方法如下。目标物种接受推荐的药物给药方案，但剂量水平比正常情况高3至5倍，然后在预计停药期提前几天处死动物。接着将这些动物体内含有高浓度残留混合物的组织给予实验动物进行常规毒理学评估。在这种方法中，残留物无需逐一鉴定，其潜在毒性在不可避免的赋形剂（即食物）存在的情况下进行评估。原则上，确定无明显毒性的“接触”水平提供了一种将人类安全性与实验动物的无观察到效应水平以传统方式联系起来的方法。
