啮齿类动物毒性实验死亡原因分析推荐方法简介

毒性病理学是药物非临床安全性评价的重要组成部分，组织病理学评价结果是毒性实验重要指标之一，对毒性实验的结果和结论非常关键。啮齿类动物尤其是大鼠和小鼠是非临床毒性实验常用的实验动物。死亡原因分析是啮齿类动物毒性实验组织病理学评价的一个重要内容，有助于毒性病理学家更好地理解病变的生物学意义，进一步提高对啮齿类动物毒性实验的评价和结果的解释。本文简要介绍了啮齿类动物濒死终点指标的判断标准，老年啮齿类动物大体和组织学病变的分类，不同种属啮齿类动物死亡原因，动物品系、性别和数量对死亡原因分析的影响，以及啮齿类动物毒性实验死亡原因分析推荐方法等内容。以期为我国药物非临床安全性评价领域毒性病理学家更好地分析死亡原因及进一步提高啮齿类动物毒性实验的组织病理学评价和结果解释提供一定参考。

Brief Introduction to a Proposed Method of Cause of Death Assignment in Rodent Toxicity Studies

Toxicologic pathology is an important part of the nonclinical safety evaluation of drugs. Histopathological assessment result is one of the key end-points of a toxicity study and contributes substantially to the outcome and conclusion of the toxicity study. Rodent animals, especially rats or mice, are commonly used in nonclinical toxicity studies. One of the key contents of the histopathological assessment of rodent toxicity studies is cause of death assignment, which may help toxicologic pathologists to better understand the biological significance of the lesions, to further improve the evaluation of the rodent toxicity studies and to have a much clearer of the results. The paper briefly introduced the end-point criteria for moribundity of rodents, categories of gross and histological lesions of aged rodents, cause of death of different species of rodents, effects of animal strain, sex, and number on the cause of death assignment, as well as a proposed method of the cause of death assignment in rodent toxicity studies. The purpose of the paper is to provide some references for toxicologic pathologists to better analyze the cause of death and to further improve the histopathological evaluation of the rodent toxicity studies as well as interpretation of the results during nonclinical safety evaluation of drugs in China.