Threshold of toxicological concern (TTC) is a concept that has been around for decades in human health sciences. Ecotoxicology recently adopted a variant of this concept as eco-TTC. Adoption of the concept of TTC considerably reduces the amount of animal testing required for regulatory purposes. We provide an application of a universal TTC for the entirety of acute fish toxicity data (i.e., establishment of an exposure level below which there would be minimal probability of acute fish toxicity for any chemical, without consideration of mechanism of action). We calculated TTC values for a number of subgroups using various approaches. These approaches were evaluated using data from a cohort of 69 999 acute fish toxicological assays. This database was normalized/curated for units, exposure duration, quality assurance/control, and duplicates, which reduced it to 47 694 assays. Data were not normally but log-normally distributed, making geometric means the most appropriate statistical parameter. Thus, we developed descriptive statistics using geometric means with 95, 99, and 99.9% confidence intervals. Various assessment factors (akin to predicted-no-effect concentration derivation) were applied to the geometric means to derive TTCs. Other approaches employed were the calculation of y = 0 intercepts as well as development of 95 and 99.75% cutoffs of cumulative data as well as modular uncertainty scoring tool (MUST) analysis. All of the methodologies derived highly congruent TTCs ranging from to 2 to 8 μg/L except for the 99.75th percentile cutoff of 0.3 μg/L. The data would be most useful in making a binary testing/no testing required decision. For acute fish toxicity, a TTC value of 2 μg/L was most appropriate, based on the 95th percentile of data distribution without any assessment factor. Environ Toxicol Chem 2021;40:1740–1749. © 2021 SETAC

中文翻译：

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迈向毒理学关注的普遍急性鱼类阈值

毒理学关注阈值 (TTC) 是一个在人类健康科学中已存在数十年的概念。生态毒理学最近采用了这个概念的一个变体，即生态 TTC。TTC 概念的采用大大减少了监管所需的动物试验数量。我们为所有急性鱼类毒性数据提供了一个通用 TTC 应用程序（即，建立一个暴露水平，低于该暴露水平，任何化学物质的急性鱼类毒性概率最小，而不考虑作用机制）。我们使用各种方法计算了许多子组的 TTC 值。使用来自 69 999 项急性鱼类毒理学试验的数据对这些方法进行了评估。该数据库针对单位、暴露持续时间、质量保证/控制和副本进行了标准化/管理，这将其减少到 47 694 次检测。数据不是正态分布而是对数正态分布，使几何平均值成为最合适的统计参数。因此，我们使用具有 95、99 和 99.9% 置信区间的几何平均值开发了描述性统计数据。将各种评估因素（类似于预测的无影响浓度推导）应用于几何平均值以得出 TTC。采用的其他方法是计算y  = 0 截距以及累积数据的 95% 和 99.75% 截止值以及模块化不确定性评分工具 (MUST) 分析的开发。除了 0.3 μg/L 的第 99.75 个百分位截止值外，所有方法都得出高度一致的 TTC，范围从 2 到 8 μg/L。这些数据在做出二进制测试/不需要测试的决定时最有用。对于鱼类的急性毒性，基于没有任何评估因素的数据分布的第 95 个百分位，TTC 值为 2 μg/L 是最合适的。环境毒物化学2021；40:1740–1749。© 2021 SETAC