title: Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.
abstract: The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10(6) LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Leona D
authors.initials: LD
authors.lastname: Scanlan
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Loguinov
authors.affiliation: ‡U.S. EPA, National Exposure Research Laboratory, Athens, Georgia 30605, United States.
authors.forename: Quincy
authors.initials: Q
authors.lastname: Teng
authors.affiliation: §University of Liverpool Institute for Integrative Biology, Liverpool, L69 7ZB, United Kingdom.
authors.forename: Philipp
authors.initials: P
authors.lastname: Antczak
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Dailey
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Nowinski
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Jonah
authors.initials: J
authors.lastname: Kornbluh
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Xin Xin
authors.initials: XX
authors.lastname: Lin
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Lachenauer
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Audrey
authors.initials: A
authors.lastname: Arai
authors.affiliation: ∥Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Nora K
authors.initials: NK
authors.lastname: Douglas
authors.affiliation: §University of Liverpool Institute for Integrative Biology, Liverpool, L69 7ZB, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Falciani
authors.affiliation: ∥Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, United States.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
authors.affiliation: †University of California Berkeley, Department of Nutritional Sciences and Toxicology, Berkeley, California 94720, United States.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Vulpe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016000:Cluster Analysis; D003621:Daphnia / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D004781:Environmental Exposure / Q000032:analysis; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D055442:Metabolome / Q000187:drug effects* / Q000235:genetics; D055432:Metabolomics; D066244:Proton Magnetic Resonance Spectroscopy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D005411:Flame Retardants; D012333:RNA, Messenger