Gene Transcription, Metabolite and Lipid Profiling in Eco-Indicator <i>Daphnia magna</i> Indicate Diverse Mechanisms of Toxicity by Legacy and Emerging Flame-Retardants

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 <i>Daphnia magna</i>. 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, ¹H 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 <i>Daphnia</i> after 48 h following 1/10 LC₅₀ exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10⁶ LC₅₀ to 1/2 LC₅₀. Analyses suggest FM550 impairs nutrient utilization or uptake in <i>Daphnia