Kacew S, Ruben Z, McConnell R F
Department of Pharmacology, University of Ottawa, Canada.
Toxicol Pathol. 1995 Nov-Dec;23(6):701-14; discussion 714-5. doi: 10.1177/019262339502300608.
The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.
在农业、能源生产、交通运输、制药以及其他提高生活质量的产品中使用化学品所产生的有益效果已得到明确证实。然而，持续接触这些化学品仅在益处远大于毒性表现的情况下才具有优势。根据法律规定，确定毒性风险需要使用实验动物来确定化学物质暴露对人类是否安全。为了模拟人类状况，研究人员有责任选择一种已确立药代动力学和毒代动力学原理且与人类相似的物种。在化学毒性测试中使用大鼠的一些优势包括：（a）在代谢、解剖结构和生理参数方面与人类相似；（b）寿命短，尤其适用于致癌研究；（c）易于获得、繁殖容易且饲养成本相对较低；（d）存在大量数据库，便于将当前结果与已报道的文献结果进行比较。然而，大鼠的选择可能会因几个因素而变得复杂，如性别、年龄和营养，但特别是品系，目前已知存在超过200种不同品系的大鼠。本综述的目的是证明大鼠品系对化学品的反应存在差异，且观察到的易感性取决于所检查的组织。显然，不同品系的基因型不同，这可能是对化学品敏感性差异的原因。在解释毒性风险与人类的相关性时，需要考虑品系作为影响对毒物作用易感性的一个因素。
