title: 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.
authors.affiliation: Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry, Atlanta, USA. pruiz@cdc.gov
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: E
authors.initials: E
authors.lastname: Myshkin
authors.forename: P
authors.initials: P
authors.lastname: Quigley
authors.forename: O
authors.initials: O
authors.lastname: Faroon
authors.forename: J S
authors.initials: JS
authors.lastname: Wheeler
authors.forename: M M
authors.initials: MM
authors.lastname: Mumtaz
authors.forename: R J
authors.initials: RJ
authors.lastname: Brennan
mesh_terms: D047628:Estrogen Receptor alpha / Q000819:agonists*; D006801:Humans; D015233:Models, Statistical; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011078:Polychlorinated Biphenyls