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

Abstract

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. [ 14 C]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1-100 mmol/kg ($0.05-55 mg/kg) or repeated administration (0.1 mmol/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 mmol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [ 14 C]-radioactivity in urine and feces of a 100 mmol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 mmol/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 mmol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels.

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

“…Analyses of urine and extracts of skin and feces showed EH-TBB is metabolized in skin to TBBA and excreted as metabolite(s) in feces and urine after dermal absorption in the rat, putatively due to carboxylesterase activity. In the current study (as seen in Table 3), and consistent with previous studies conducted by the oral route in rats (46), there was minimal retention of either chemical in tissues after administration. Similar to previous observations for highly brominated polybrominated diphenyl ethers (PBDEs) (42), the skin appeared to act as a lipophilic “trap” for BEH-TEBP.…”

“…In order to link data characterizing the fate of orally-administered EH-TBB (46) and BEH-TEBP (63) in the female rat and the in vitro skin studies described above, 100 nmol/cm 2 was applied to the dorsal surface of female SD rats (N = 4 rats/chemical, 11 weeks old, approximately 200 g, Harlan Laboratories, Indianapolis, IA). One day prior to dosing, animals were lightly anesthetized by isoflurane inhalation and an electric clipper was used to remove hair from the dorsal scapular region.…”

A Review of Environmental Occurrence, Fate, and Toxicity of Novel Brominated Flame Retardants

“…Mean concentrations of DBDPE, HBB, PBT, and PBEB were 100, 0.8, 0.5, and 0.1 pg/g ww in three types of meat (chicken, beef, and mutton), respectively. 38 The concentrations of HBB, PBT, and BTBPE in chicken from four different places of China (Sichuan, Fujian, Jilin, Henan) were in the range of nd−4.3, nd−48.7, and 20.1−80.9 pg/g ww, respectively (Table 2). 120 In human milk from three European countries (Norway, The Netherlands, Slovakia), mean concentrations of HBB and PBT were 0.036−0.048 and 0.028−0.049 ng/g lw, respectively, and PBEB were rarely found (detection rate in human milk: Norway 2%, The Netherlands 0%, Slovakia 3%) (Table 2).…”

“…13 In air from Stockholm and the Great Lakes, the mean concentrations of DBDPE were 1.4 and 0.34−2.0 pg/m 3 , respectively, 14,29 which were a little lower than those found in airs from a typical residential region of Harbin, China (mean: 11 pg/m 3 ) 45 and from the northern shore of Taihu Lake, China (23 pg/m 3 ). 46 Much higher concentrations of DBDPE have been found in air from a BFRs production area in Weifang, northern China (240 pg/m 3 ), 38 an e-waste recycling site (209 pg/m 3 ) and a rural site (158 pg/ m 3 ) in southern China 47 and the Pearl River Delta, southern China (1916 pg/m 3 ) (Table 1). 48 The relatively high concentrations of DBDPE in air from China may be related to the high usage of DBDPE.…”

“…14,51,52 Comparable concentrations of HBB (range: 0.001−0.66 pg/m 3 ) and PBT (nd−0.02 pg/m 3 ) were detected in air from the East Greenland Sea. 23 Elevated levels of HBB, PBEB, and PBT were found in air from a BFRs production area in Weifang, China (mean: 2800, 9.2, and 3100 pg/m 3 , respectively) 38 and an e-waste recycling site in southern China (138, 41.0, 21.8 pg/m 3 , respectively) (Table 1). 47 Occurrence of TBB and TBPH in air from the Great Lakes was reported (Table 1).…”