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.
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. [14C]-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 [14C]-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.
NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina gabriel.knudsen@nih.gov.
Gabriel A
GA
Knudsen
NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina.
J Michael
JM
Sanders
NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, North Carolina.
Linda S
LS
Birnbaum
D000284:Administration, Oral; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D001711:Biotransformation; D004334:Drug Administration Schedule; D005243:Feces / Q000737:chemistry; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D065569:Gastrointestinal Absorption; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008954:Models, Biological; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination; D018570:Risk Assessment; D066007:Toxicokinetics
C576261:2-ethylhexyl 2,3,4,5-tetrabromobenzoate; D001565:Benzoates; D005411:Flame Retardants
2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate; disposition; metabolism.