title: Comparing the effects of tetrabromobisphenol-A, bisphenol A, and their potential replacement alternatives, TBBPA-bis(2,3-dibromopropyl ether) and bisphenol S, on cell viability and messenger ribonucleic acid expression in chicken embryonic hepatocytes.
abstract: A market for alternative brominated flame retardants (BFRs) has emerged recently due to the phase out of persistent and inherently toxic BFRs. Several of these replacement compounds have been detected in environmental matrices, including wild birds. A chicken embryonic hepatocyte (CEH) assay was utilized to assess the effects of the BFR, tetrabromobisphenol-A (TBBPA), and its replacement alternative, tetrabromobisphenol A bis(2,3-dibromopropyl ether [TBBPA-DBPE]) on cell viability and messenger ribonucleic acid (mRNA) expression. Bisphenol A (BPA) and 1 of its replacement alternatives, bisphenol S (BPS), were also screened for effects. Both TBBPA and BPA decreased CEH viability with calculated median lethal concentration (LC50) values of 40.6 μM and 61.7 μM, respectively. However, the replacement alternatives, TBBPA-DBPE and BPS, did not affect cell viability (up to 300 μM). Effects on mRNA expression were determined using an Avian ToxChip polymerse chain reaction (PCR) array and a real-time (RT)-PCR assay for the estrogen-responsive genes, apolipoproteinII (ApoII) and vitellogenin (Vtg). A luciferase reporter gene assay was used to assess dioxin-like effects. Tetrabromobisphenol-A altered mRNA levels of 4 genes from multiple toxicity pathways and increased luciferase activity in the luciferase reporter gene assay, whereas its alternative, TBBPA-DBPE, only altered 1 gene on the array, Cyp1a4, and increased luciferase activity. At 300 μM, a concentration that decreased cell viability for TBBPA and BPA, the BPA replacement, BPS, altered the greatest number of transcripts, including both ApoII and Vtg. Bisphenol A exposure did not alter any genes on the array but did up-regulate Vtg at 10 μM. Characterization of the potential toxicological and molecular-level effects of these compounds will ideally be useful to chemical regulators tasked with assessing the risk of new and existing chemicals.
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, Ontario, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Ma
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.forename: Reza
authors.initials: R
authors.lastname: Farmahin
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000633:toxicity*; D001969:Bromobenzenes / Q000737:chemistry / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013450:Sulfones / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D000098831:Bisphenol S Compounds; D000098826:Bisphenol A Compounds
chemical_list: D016633:Apolipoprotein A-II; D001559:Benzhydryl Compounds; D001969:Bromobenzenes; D010636:Phenols; D011075:Polybrominated Biphenyls; D012333:RNA, Messenger; D013450:Sulfones; D014819:Vitellogenins; C555802:tetrabromobisphenol-S-bis(2,3-dibromopropyl ether); C543008:bisphenol S; D000098831:Bisphenol S Compounds; C020806:tetrabromobisphenol A; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Avian; Bisphenol A; Bisphenol S; PCR array; Tetrabromobisphenol A; Tetrabromobisphenol A bis(2,3-dibromopropyl ether)