Correction to Designing QSARs for Parameters of High Throughput Toxicokinetic Models Using Open-Source Descriptors.

The intrinsic metabolic clearance rate (Cl) and fraction of chemical unbound in plasma () serve as important parameters for high throughput toxicokinetic models, but experimental data are limited for many chemicals. Open-source quantitative structure-activity relationship (QSAR) models for both parameters were developed to offer reliable predictions for a diverse set of chemicals regulated under U.S. law, including pharmaceuticals, pesticides, and industrial chemicals. As a case study to demonstrate their utility, model predictions served as inputs to the TK component of a risk-based prioritization approach based on Bioactivity: Exposure Ratios (BER), in which a BER < 1 indicates exposures are predicted to exceed a biological activity threshold. When applied to a subset of the Tox21 screening library (6631 chemicals) we found that the proportion of chemicals with BER < 1 was similar using either (1337/6631; 20.16%) or (151/850; 17.76%) parameters. Further, when considering only the chemicals in the Tox21 set with data, there was a high concordance of chemicals classified with either BER < 1 or >1 using either or parameters (776/850, 91.30%). Thus, the presented QSARs may be suitable for prioritizing the risk posed by many chemicals for which measured TK data are lacking.