Greener chemicals for the future: QSAR modelling of the PBT index using ETA descriptors

Abstract

Persistent, bioaccumulative and toxic (PBT) chemicals symbolize a group of substances that are not easily degraded; instead, they accumulate in different organisms and exhibit an acute or chronic toxicity. The limited empirical data on PBT chemicals, the high cost of testing together with the regulatory constraints and the international push for reduced animal testing motivate a greater reliance on predictive computational methods like quantitative structure–activity relationship (QSAR) models in PBT assessment. Papa and Gramatica have recently proposed a PBT index that could be computed directly from structural features. In the current study, we have modelled the experimentally derived PBT index data using an extended topological atom (ETA) along with constitutional descriptors to show the usefulness of the ETA indices in modelling the endpoint. The models developed through a double cross-validation (DCV) method gave the best results in terms of both internal and external validation metrics. The developed models were comparable in predictive quality to those previously reported. The current models were further used for consensus predictions of PBT behaviour for a set of pharmaceuticals and a set of synthetic drug-like compounds. The developed models can be used in PBT hazard screening for identification and prioritization of chemicals from the structural information alone.

Keywords:

• QSAR
• PBT
• chemometrics
• green chemicals and pharmaceuticals
• validation

Acknowledgments

PD is thankful to the All India Council for Technical Education, New Delhi for providing an MPharm scholarship. KR thanks the University Grants Commission, New Delhi providing financial assistance under the UPE-II scheme.