Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis^∗

Abstract

Alternative methods, including quantitative structure–activity relationships (QSAR), are being used increasingly when appropriate data for toxicity evaluation of chemicals are not available. Approximately 40 mono-hydroxylated polychlorinated biphenyls (OH-PCBs) have been identified in humans. They represent a health and environmental concern because some of them have been shown to have agonist or antagonist interactions with human hormone receptors. This could lead to modulation of steroid hormone receptor pathways and endocrine system disruption. We performed QSAR analyses using available estrogenic activity (human estrogen receptor ER alpha) data for 71 OH-PCBs. The modelling was performed using multiple molecular descriptors including electronic, molecular, constitutional, topological, and geometrical endpoints. Multiple linear regressions and recursive partitioning were used to best fit descriptors. The results show that the position of the hydroxyl substitution, polarizability, and meta adjacent un-substituted carbon pairs at the phenolic ring contribute towards greater estrogenic activity for these chemicals. These comparative QSAR models may be used for predictive toxicity, and identification of health consequences of PCB metabolites that lack empirical data. Such information will help prioritize such molecules for additional testing, guide future basic laboratory research studies, and help the health/risk assessment community understand the complex nature of chemical mixtures.

Keywords:

• QSAR
• OH-PCB
• PCBs metabolites
• estrogenicity
• in silico metabolism

Acknowledgements

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Mention of trade names is not an endorsement of any commercial product.

Notes

Presented at the 15th International Workshop on Quantitative Structure–Activity Relationships in Environmental and Health Sciences (QSAR2012), 18–22 June 2012, Tallinn, Estonia.