title: Assessing in-vitro estrogenic effects of currently-used flame retardants.
abstract: Flame retardants are chemicals that are added to nearly all manufactured materials. Additionally, there has been a steady increase in diseases resulting from endocrine-disruption with an aligned increase in use of chemicals. Given the persistence, potential bioaccumulation, limited toxicological understanding, and vast use of flame retardants, there is a need to investigate potential endocrine-disruptive activity associated with these compounds in an effort for better risk assessment. We therefore used the MCF-7 flow-cytometric proliferation assay in an effort to establish potential estrogen-disrupting effects of twelve currently-used flame retardants. Triphenyl phosphate, tris(1,3-dichloro-2-propyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, and tetrabromobisphenol A showed statistically significant estrogenic activity, with hexabromocyclododecane being the most potent of the five (EC20 of 5.5 μM). Tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, tri(2-chloroethyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, tetrabromobisphenol A, and tris(2,3,-dibromopropyl) isocyanurate harboured anti-estrogenic activity when co-treating with 17β-estradiol, with hexabromocyclododecane showing the highest potency (IC20 of 17.6 μM). Interestingly, some compounds showed both estrogenic and anti-estrogenic effects, indicating both receptor-dependant and -independent mechanisms attributed to some of these compounds, in line with other studies. Multiple currently-used flame retardants may therefore act as xenoestrogens and anti-estrogens, or alter estrogen homeostasis, which could affect endocrine function.
authors.affiliation: Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium. Electronic address: boris.krivochiev@uantwerpen.be.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Krivoshiev
authors.affiliation: Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Dardenne
authors.affiliation: Department of Pharmaceutical Science, Toxicological Centre, University of Antwerp, Antwerp, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
authors.affiliation: Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Ronny
authors.initials: R
authors.lastname: Blust
authors.affiliation: Department of Biology, Systemic Physiological & Ecotoxicological Research, University of Antwerp, Antwerp, Belgium.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Husson
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004965:Estrogen Antagonists / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D061986:MCF-7 Cells; D010755:Organophosphates / Q000633:toxicity
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010755:Organophosphates
keywords: Endocrine disruption; Estrogenicity; Flame retardants; MCF-7