title: Novel full logistic model for estimation of the estrogenic activity of chemical mixtures.
abstract: Estrogenic compounds as well as other biologically active substances are commonly present in the form of complex mixtures in the environment. There is still no satisfactory model that would be capable of predicting the toxic effects of mixtures containing partial receptor agonists and compounds with different parameters of their dose-response curves. Therefore, a novel Full Logistic Model (FLM) of prediction using all the parameters of dose-response curves has been suggested and compared with previously published approaches. We tested the receptor-binding activities of selected estrogens including full and partial agonists and their mixtures using yeast reporter gene assays and the human T47D cell line. Combination effects were modeled with FLM and predicted curves were compared with the data obtained experimentally. FLM yielded a good fit to the experimental data from both the receptor-binding assays and gave better predictions than the previously published approaches. FLM also provided satisfactory results regarding final partial agonistic dose-response curves with maximum influenced by the inhibitory effect of the partial agonist. FLM is not limited by any simplification like the toxic equivalency factor approach or generalized concentration addition and therefore it could be employed for mixtures containing chemicals with different parameters of their dose-response curves (maximum, minimum, inflex point or slope).
authors.affiliation: Laboratory of Environmental Biotechnology, Institute of Microbiology ASCR,v.v.i., Vídeňská 1083, 142 20 Prague, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Ezechiáš
authors.affiliation: Laboratory of Environmental Biotechnology, Institute of Microbiology ASCR,v.v.i., Vídeňská 1083, 142 20 Prague, Czech Republic; Institute for Environmental Studies, Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Prague, Czech Republic. Electronic address: cajthaml@biomed.cas.cz.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Cajthaml
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology; D001681:Biological Assay; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D016015:Logistic Models; D010636:Phenols / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D054377:Chemokine CXCL12; D004958:Estradiol; D004967:Estrogens; D010636:Phenols; C515255:CXCL12 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Additive effect; Concentration addition; Endocrine disrupting compounds; Estrogen receptor; Logistic curve; T47D