Conditional Toxicity Value (CTV) Predictor: An In Silico Approach for Generating Quantitative Risk Estimates for...

Human health assessments synthesize human, animal, and mechanistic data to produce toxicity values that are key inputs to risk-based decision making. Traditional assessments are data-, time-, and resource-intensive, and they cannot be developed for most environmental chemicals owing to a lack of appropriate data.

As recommended by the National Research Council, we propose a solution for predicting toxicity values for data-poor chemicals through development of quantitative structure-activity relationship (QSAR) models.

We used a comprehensive database of chemicals with existing regulatory toxicity values from U.S. federal and state agencies to develop quantitative QSAR models. We compared QSAR-based model predictions to those based on high-throughput screening (HTS) assays.

QSAR models for noncancer threshold-based values and cancer slope factors had cross-validation-based Q² of 0.25-0.45, mean model errors of 0.70-1.11 log₁₀ units, and applicability domains covering >80% of environmental chemicals. Toxicity values predicted from QSAR models developed in this study were more accurate and precise than those based on HTS assays or mean-based predictions. A publicly accessible web interface to make predictions for any chemical of interest is available at http://toxvalue.org.

An in silico tool that can predict toxicity values with an uncertainty of an order of magnitude or less can be used to quickly and quantitatively assess risks of environmental chemicals when traditional toxicity data or human health assessments are unavailable. This tool can fill a critical gap in the risk assessment and management of data-poor chemicals. https://doi.org/10.1289/EHP2998.