title: QSAR classification models for the screening of the endocrine-disrupting activity of perfluorinated compounds.
abstract: Perfluorinated compounds (PFCs) are a class of emerging pollutants still widely used in different materials as non-adhesives, waterproof fabrics, fire-fighting foams, etc. Their toxic effects include potential for endocrine-disrupting activity, but the amount of experimental data available for these pollutants is limited. The use of predictive strategies such as quantitative structure-activity relationships (QSARs) is recommended under the REACH regulation, to fill data gaps and to screen and prioritize chemicals for further experimentation, with a consequent reduction of costs and number of tested animals. In this study, local classification models for PFCs were developed to predict their T4-TTR (thyroxin-transthyretin) competing potency. The best models were selected by maximizing the sensitivity and external predictive ability. These models, characterized by robustness, good predictive power and a defined applicability domain, were applied to predict the activity of 33 other PFCs of environmental concern. Finally, classification models recently published by our research group for T4-TTR binding of brominated flame retardants and for estrogenic and anti-androgenic activity were applied to the studied perfluorinated chemicals to compare results and to further evaluate the potential for these PFCs to cause endocrine disruption.
authors.affiliation: QSAR Research Unit in Environmental Chemistry and Ecotoxicology, DSTA, University of Insubria, Varese, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Kovarich
authors.forename: E
authors.initials: E
authors.lastname: Papa
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Gramatica
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005411:Flame Retardants / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D008956:Models, Chemical; D011228:Prealbumin / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D052244:Endocrine Disruptors; D005411:Flame Retardants; D006845:Hydrocarbons, Fluorinated; D011228:Prealbumin; D011960:Receptors, Estrogen; D013963:Thyroid Hormones