Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration

• Published in: Toxicological sciences Vol. 154; no. 2; pp. 392 - 402
• Main Authors: Knudsen, Gabriel A, Sanders, J Michael, Birnbaum, Linda S
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-12-2016
• Subjects: Administration, Oral; Animals; Benzoates - administration & dosage; Benzoates - pharmacokinetics; Benzoates - toxicity; Biotransformation; Drug Administration Schedule; Feces - chemistry; Female; Flame Retardants - administration & dosage; Flame Retardants - pharmacokinetics; Flame Retardants - toxicity; Gastrointestinal Absorption; Injections, Intravenous; Male; Mice; Models, Biological; Rats, Sprague-Dawley; Renal Elimination; Risk Assessment; Toxicokinetics; Toxicokinetics of Emerging Brominated Flame Retardant; disposition; 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate; metabolism
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfw176

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW 549.92 g/mol; CAS 183658-27-7) is a brominated component of flame retardant mixtures used as substitutes for some PBDEs. EH-TBB is added to various consumer products, including polyurethane foams, and has been detected in humans. The present study characterized the fate of EH-TBB in rodents. [
C]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1-100 µmol/kg (∼0.05-55 mg/kg) or repeated administration (0.1 µmol/kg/day × 5-10 days) by gavage to female Hsd:Sprague DawleySD (SD) rats. Cumulative excretion via feces increased (39-60%) with dose (0.1-10 µmol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [
C]-radioactivity in urine and feces of a 100 µmol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 µmol/kg dose in urine and less in feces than did gavaged rats, indicating partial biliary elimination of systemically available compound. No tissue bioaccumulation was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA-sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice indicated minimal sex- or species differences are likely for the disposition of EH-TBB. Approximately 85% of a 0.1 µmol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels.