Disposition of the emerging brominated flame retardant, bis(2-ethylhexyl) tetrabromophthalate, in female Sprague Dawley rats: effects of dose, route and repeated administration.
1. Bis(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP; CAS No. 26040-51-7; PubChem CID: 117291; MW 706.15 g/mol, elsewhere: TeBrDEPH, TBPH, or BEHTBP) is used as an additive brominated flame retardant in consumer products. 2. Female Sprague Dawley rats eliminated 92-98% of [14C]-BEH-TEBP unchanged in feces after oral administration (0.1 or 10 μmol/kg). A minor amount of each dose (0.8-1%) was found in urine after 72 h. Disposition of orally administered BEH-TEBP in male B6C3F1/Tac mice was similar to female rats. 3. Bioaccumulation of [14C]-radioactivity was observed in liver and adrenals following 10 daily oral administrations (0.1 μmol/kg/day). These tissues contained 5- and 10-fold higher concentrations of [14C]-radioactivity, respectively, versus a single dose. 4. IV-administered [14C]-BEH-TEBP (0.1 μmol/kg) was slowly eliminated in feces, with >15% retained in tissues after 72 h. Bile and fecal extracts from these rats contained the metabolite mono-ethylhexyl tetrabromophthalate (TBMEHP). 5. BEH-TEBP was poorly absorbed, minimally metabolized and eliminated mostly by the fecal route after oral administration. Repeated exposure to BEH-TEBP led to accumulation in some tissues. The toxicological significance of this effect remains to be determined. This work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Project ZIA BC 011476).
a NCI Laboratory of Toxicology and Toxicokinetics , NC , USA.
Gabriel A
GA
Knudsen
a NCI Laboratory of Toxicology and Toxicokinetics , NC , USA.
J Michael
JM
Sanders
a NCI Laboratory of Toxicology and Toxicokinetics , NC , USA.
Linda S
LS
Birnbaum
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D010795:Phthalic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D036401:Toxicity Tests, Chronic
D005411:Flame Retardants; D010795:Phthalic Acids; C585475:bis(2-ethylhexyl)-2,3,4,5-tetrabromophtalate
ADME; bioaccumulation; brominated flame retardant; persistent organic pollutant; phthalate ester