用于评估和管理化学风险的监管毒性值依赖于确定临界效应的出发点（POD），该临界效应是从现有毒性研究的全面和系统评估中得出的。然而，监管评估仅适用于一小部分化学物质。通过使用美国环境保护署毒性价值数据库的体内实验动物数据，我们开发了一种半自动化方法来确定替代的口服POD，在监管评估不可用的情况下生成相应的毒性值。我们开发了一个筛选数据集，限制了效应水平、暴露途径、研究设计和推导毒性值所需的物种。效应水平被调整为慢性人类等效基准剂量（BMDh）。我们假设BMDh分布的一个分位数可以作为替代POD，并通过对接到监管POD进行校准来确定适当的分位数。最后，我们通过标准化工作流程表征了替代POD的不确定性来源于内部和跨研究的变异，使用概率方法得出了毒性值。每种化学物质的BMDh分布都可以用对数正态分布充分拟合，其中25%分位数最能预测可用的监管POD（R2≥0.78，残差标准误差（RSE）≤0.53 log10单位）。我们从筛选数据集中推导了10,145种化学物质的替代POD，区分了一般非癌性和生殖/发育效应，其典型不确定性（95％置信度水平）分别为10倍和12倍。从这些POD中，我们推导出了概率参考剂量（在95％置信度下1％发病率），以及人口效应剂量（在10％发病率下）。通过提供校准至监管值的替代POD并推导相应的毒性值，我们已将化学物质的范围从744种扩展到了8,023种非癌性效应，以及从41种扩展到了6,697种生殖/发育效应。这些结果可在各种风险评估和风险管理背景下使用，从危险场所和生命周期影响评估到化学品优先和替代。 https://doi.org/10.1289/EHP11524。

Regulatory toxicity values used to assess and manage chemical risks rely on the determination of the point of departure (POD) for a critical effect, which results from a comprehensive and systematic assessment of available toxicity studies. However, regulatory assessments are only available for a small fraction of chemicals.Using in vivo experimental animal data from the U.S. Environmental Protection Agency's Toxicity Value Database, we developed a semiautomated approach to determine surrogate oral route PODs, and corresponding toxicity values where regulatory assessments are unavailable.We developed a curated data set restricted to effect levels, exposure routes, study designs, and species relevant for deriving toxicity values. Effect levels were adjusted to chronic human equivalent benchmark doses (BMDh). We hypothesized that a quantile of the BMDh distribution could serve as a surrogate POD and determined the appropriate quantile by calibration to regulatory PODs. Finally, we characterized uncertainties around the surrogate PODs from intra- and interstudy variability and derived probabilistic toxicity values using a standardized workflow.The BMDh distribution for each chemical was adequately fit by a lognormal distribution, and the 25th percentile best predicted the available regulatory PODs [R2≥0.78, residual standard error (RSE)≤0.53 log10 units]. We derived surrogate PODs for 10,145 chemicals from the curated data set, differentiating between general noncancer and reproductive/developmental effects, with typical uncertainties (at 95% confidence) of a factor of 10 and 12, respectively. From these PODs, probabilistic reference doses (1% incidence at 95% confidence), as well as human population effect doses (10% incidence), were derived.In providing surrogate PODs calibrated to regulatory values and deriving corresponding toxicity values, we have substantially expanded the coverage of chemicals from 744 to 8,023 for general noncancer effects, and from 41 to 6,697 for reproductive/developmental effects. These results can be used across various risk assessment and risk management contexts, from hazardous site and life cycle impact assessments to chemical prioritization and substitution. https://doi.org/10.1289/EHP11524.