Everds Nancy E
Amgen Inc, Seattle, Washington, USA
Toxicol Pathol. 2015 Jan;43(1):90-7. doi: 10.1177/0192623314555340. Epub 2014 Oct 31.
During the conduct of in vivo toxicology studies, in-life, clinical pathology, and anatomic pathology parameters are collected and interpreted. These sets of parameters are evaluated in an integrative manner to determine the overall toxicity of a test article. For clinical pathology parameters, the inherent variability and physiologic factors affecting each analyte must be understood prior to interpretation. Changes in clinical pathology parameters that are considered to be test article-related are then assessed with respect to changes in the concurrent data sets such as clinical signs and anatomic pathology to determine the underlying pathophysiology. In this article, examples of hemolysis and hepatotoxicity are used to demonstrate the relationships among the various parameters and data sets. Whereas there was tight correlation of all data sets in the example of hemolysis in rats, the examples of altered enzymes and other biomarkers indicating liver injury and dysfunction were more often discordant with other data sets.
在进行体内毒理学研究时,会收集并解读实验期间、临床病理学和解剖病理学参数。这些参数集以综合方式进行评估,以确定受试物的总体毒性。对于临床病理学参数,在解读之前必须了解影响每种分析物的固有变异性和生理因素。然后,将被认为与受试物相关的临床病理学参数变化与诸如临床体征和解剖病理学等同期数据集的变化进行评估,以确定潜在的病理生理学。在本文中,溶血和肝毒性的例子用于说明各种参数和数据集之间的关系。在大鼠溶血的例子中,所有数据集之间存在紧密的相关性,而表明肝损伤和功能障碍的酶及其他生物标志物变化的例子则更常与其他数据集不一致。