Development and Validation of Predictive Quantitative Structure–Activity Relationship Models for Estrogenic Activities of Hydroxylated Polychlorinated Biphenyls

Abstract

AbstractDisruption of the endocrine system by hydroxylated polychlorinated biphenyls (OH‐PCBs) is hypothesized, among other potential mechanisms, to be mediated via nuclear receptor binding. Due to the high cost and lengthy time required to produce high‐quality experimental data, empirical data to support the nuclear receptor binding hypothesis are in short supply. In the present study, two quantitative structure–activity relationship models were developed for predicting the estrogenic activities of OH‐PCBs. Findings revealed that model I (for the estrogen receptor α dataset) contained five two‐dimensional (2D) descriptors belonging to the classes autocorrelation, Burden modified eigenvalues, chi path, and atom type electrotopological state, whereas model II (for the estrogen receptor β dataset) contained three 2D and three 3D descriptors belonging to the classes autocorrelation, atom type electrotopological state, and Radial Distribution Function descriptors. The internal and external validation metrics reported for models I and II indicate that both models are robust, reliable, and suitable for predicting the estrogenic activities of untested OH‐PCB congeners. Environ Toxicol Chem 2023;42:823–834. © 2023 SETAC