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.

Migration studies and toxicity evaluation of cyclic polyesters oligomers from food packaging adhesives

“…To our knowledge, this is the first time AA-DEG-IPA-DEG and AA-DEG have been tested for ability to interfere with AR, AhR, and TTR. However, the monomers DEG and IPA have been tested for AR binding both in silico and in vitro, as well as in an AR transactivation assay, but exhibited no effect (Osimitz, Welsh, Ai, & Toole, 2015). These findings could suggest that the AA moiety of the compounds play a role in the observed antiandrogenic activities.…”

Determination of Endocrine Disruption Potential of Bisphenol A Alternatives in Food Contact Materials Using In Vitro Assays: State of the Art and Future Challenges

“…Other BPA replacements, such as CBDO, CHDM, and DMT monomer, had been demonstrated with no binding affinity to ER or AR by the ligand binding assay and reporter gene assay. , However, the cell proliferation assay showed that CHDM and DMT worked as the agonist on ER in MCF-7 cells . CHDM increased the secretion of E2 in H295R cells .…”

“…If the test compound disrupts the endocrine system via alternation of hormone production, the ligand binding assay and reporter gene assay will provide a false negative result. One example is that CHDM and TPA show no androgenic and estrogenic activity with ligand binding and reporter gene assays 76 but show endocrine disruption activity with the steroidogenesis assay and decreased reproduction with in vivo tests. 77 With regard to throughput, the reporter gene assay usually takes about 1 day to perform, while the cell proliferation and steroidogenesis assay takes several days of incubation.…”