School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK.
SAR QSAR Environ Res. 2011 Jul-Sep;22(5-6):621-37. doi: 10.1080/1062936X.2011.604100. Epub 2011 Aug 10.
Assessments necessary to ensure the safety of both humans and the environment are challenged by the sheer number of chemicals in use today. Chemical legislation, such as REACH, aims to use alternative methods to reduce the reliance on in vivo animal testing. Consequently, databases such as the TETRATOX database, containing data from the Tetrahymena pyriformis population growth impairment assay, have been used extensively to develop computational models which aid in priority setting and initial hazard assessments. To use any toxicological data, an assessment of quality is required. One important aspect of quality is the repeatability of the assay. This study considered TETRATOX assay data for 85 structurally and mechanistically diverse compounds. The repeatability of replicate determinations was assessed and factors relating to repeatability are discussed. Despite the majority of compounds demonstrating excellent repeatability, it was found that the mechanism of action is likely to be a modulating factor, with compounds acting via electrophilic mechanisms being more likely to exhibit reduced repeatability than those acting via narcotic mechanisms. It is evident from this study that the TETRATOX assay is a robust and highly repeatable assay, suitable for use in toxicological modelling studies and priority setting.
为确保人类和环境的安全,需要对当今使用的大量化学品进行评估。REACH 等化学法规旨在使用替代方法减少对体内动物测试的依赖。因此,广泛使用了包含来自梨形四膜虫种群生长抑制测定的数据的 TETRATOX 数据库等数据库,以开发有助于确定优先事项和初步危害评估的计算模型。要使用任何毒理学数据,都需要进行质量评估。质量的一个重要方面是测定的可重复性。本研究考虑了 85 种结构和作用机制不同的化合物的 TETRATOX 测定数据。评估了重复测定的重复性,并讨论了与重复性相关的因素。尽管大多数化合物表现出良好的重复性,但研究发现作用机制可能是一个调节因素,通过亲电子机制起作用的化合物比通过麻醉机制起作用的化合物更有可能表现出较低的重复性。从这项研究中可以明显看出,TETRATOX 测定是一种稳健且高度可重复的测定方法,适用于毒理学建模研究和确定优先事项。