International QSAR Foundation, Two Harbors, Minnesota 55616, USA.
SAR QSAR Environ Res. 2009 Jul;20(5-6):567-78. doi: 10.1080/10629360903278669.
This paper presents the results of an analysis of the rodent inhalation literature and the development of a quantitative structure-activity relationships (QSAR) model for 4-hour LC50 as baseline toxicity to complement the baseline toxicity model for aquatic animals. We used the same literature review criteria developed for the ECOTOX database which selects only primary references with explicit experimental methods to form a high-quality database. Our literature review focused on the primary references reporting a 4-hour exposure for a single species of rodent in which the chemical had been clearly tested as a vapour and for which the exposure concentrations were not ambiguous. An expert system was used to remove reactive chemicals, receptor-mediated toxicants, and any test that produced symptoms inconsistent with non-polar narcosis. The QSAR model derived for narcosis in rodents was log LC50 = 0.69 x log VP + 1.54 which had an r(2) of 0.91, which is significantly better than the baseline toxicity model for aquatic animals. This simple model suggests that there is no intrinsic barrier to estimating baseline toxicity for in vivo endpoints in mammalian or terrestrial toxicology.
本文介绍了对啮齿动物吸入文献的分析结果,并开发了一种定量构效关系 (QSAR) 模型,用于 4 小时 LC50 作为基线毒性,以补充水生动物的基线毒性模型。我们使用了与 ECOTOX 数据库相同的文献综述标准,该标准仅选择具有明确实验方法的主要参考文献,以形成高质量的数据库。我们的文献综述侧重于报告单一啮齿动物物种 4 小时暴露的主要参考文献,其中明确测试了化学物质作为蒸气,并且暴露浓度不模糊。专家系统用于去除反应性化学品、受体介导的毒物以及产生与非极性麻醉不一致的症状的任何测试。为啮齿动物麻醉推导的 QSAR 模型为 log LC50 = 0.69 x log VP + 1.54,其 r(2)为 0.91,明显优于水生动物的基线毒性模型。这个简单的模型表明,对于哺乳动物或陆地毒理学中的体内终点,估计基线毒性没有内在障碍。