title: Polyester monomers lack ability to bind and activate both androgenic and estrogenic receptors as determined by in vitro and in silico methods.
abstract: The paper presents results from the screening of seven monomers used by Eastman Chemical to make various polymers. Ethylene glycol, diethylene glycol, polytetramethylene glycol, isophthalic acid, monosodium-5-sulfoisophthalic acid, 1,4-cyclohexanedicarboxylic acid, and dimethylcyclohexanedicarboxylate were screened for potential androgenicity or estrogenicity. The following studies were conducted: QSAR for binding to the AR and ER, in vitro Androgen Receptor Binding Assay, in vitro Estrogen Receptor Binding Assays (alpha and beta isoforms), in vitro Androgen Receptor Transactivation Assay in human cells, and in vitro Estrogen Receptor Transactivation Assay in human cells. None of the QSAR models predicted that any of the monomers possessed appreciable binding affinity for either AR or ER. Binding assays showed no evidence of interaction with either the AR or the alpha or beta ER receptors. Similarly, the AR and ER transactivation assays were negative. Moreover, six of the seven monomers have been subjected to 13-week and developmental toxicity studies in rats with no androgen- or estrogen-related effects being noted. Given the negative results of the in vitro screening assays (except PMG which demonstrated cytotoxicity) as well as available repeated dose and developmental and reproductive studies, the data suggest that none of the monomers tested exhibit androgenic or estrogenic hazards.
authors.affiliation: Science Strategies, LLC, 1001 East Market Street, Suite 202, Charlottesville, VA 22902, USA. Electronic address: tom@sciencestrategies.com.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Osimitz
authors.affiliation: Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 661 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Welsh
authors.affiliation: Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 661 Hoes Lane, Piscataway, NJ 08854, USA.
authors.forename: Ni
authors.initials: N
authors.lastname: Ai
authors.affiliation: CeeTox, Inc., 4717 Campus Drive, Kalamazoo, MI 49008, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Toole
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000737:chemistry / Q000633:toxicity; D019855:Ethylene Glycol / Q000737:chemistry / Q000633:toxicity; D018857:Food Packaging; D006801:Humans; D062105:Molecular Docking Simulation; D010795:Phthalic Acids / Q000737:chemistry / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
chemical_list: D003510:Cyclohexanes; D010795:Phthalic Acids; D011091:Polyesters; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C011363:terephthalic acid; C023353:1,4-cyclohexanedimethanol; D019855:Ethylene Glycol
keywords: Androgenicity; Estrogenicity; In vitro; Polyester monomers; Polymer; QSAR