Quantification of tetrabromo benzoic acid and tetrabromo phthalic acid in rats exposed to the flame retardant Uniplex FPR-45

Silva, Manori J.; Hilton, Donald; Furr, Johnathan; Gray, L. Earl; Preau, James L.; Calafat, Antònia M.; Ye, Xiaoyun

doi:10.1007/s00204-015-1489-6

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…Incidentally, TBBA has a log K ow of approximately 4.28 (predicted ACD/Labs) and a molecular weight of 437.7 Da and could potentially bind p-glycoprotein for active efflux. Although we did not evaluate TBMEHP in this study, it has been measured at much lower levels ($90Â lower) than TBBA in the urine of rats dosed with Uniplex FPR-45, a commercial flame retardant containing >95% BEH-TEBP and <5% EH-TBB (Silva et al, 2015). Because FM 550 is approximately 30% EH-TBB and 9% BEH-TEBP by formula, we predict that TBMEHP would be present at increasingly lower levels than TBBA in rat urine, potentially below method detection limits.…”

Section: Brominated Metabolitesmentioning

confidence: 99%

“…Furthermore, EH-TBB and BEH-TEBP have been measured in human hair and nails and the urinary metabolite of EH-TBB, 2,3,4,5-tetrabromobenzoic acid (TBBA), has been frequently detected in recent analyses of human urine, suggesting that human exposure to FM 550 is widespread (Butt et al, 2014;Hoffman et al, 2014;Liu et al, 2015). Other metabolites of FM 550 measured previously in urine include diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), and mono-(2-ethylhexyl) tetrabromophthalate (TBMEHP) (Van den Eede et al, 2013bEede et al, , 2014Silva et al, 2015) (Fig. 1).…”

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confidence: 99%

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Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Phillips¹,

Chen²,

Rock³

et al. 2016

Toxicol. Sci.

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FiremasterV R 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 mg of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200-to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip-PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.

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Section: Brominated Metabolitesmentioning

confidence: 99%

mentioning

confidence: 99%

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Phillips¹,

Chen²,

Rock³

et al. 2016

Toxicol. Sci.

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“…6, 9, 11, 13 We did not attempt to measure a biomarker for BEH-TEBP as a major metabolite has yet to be detected in urine or serum. 8 …”

Section: Introductionmentioning

confidence: 99%

Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts

Carignan

Fang

Stapleton

et al. 2016

Environment International

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Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n=53 urine samples total). We identified a 50% increase in the TPHP biomarker (p=0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p=0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S.

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“…Previous disposition studies investigating EH-TBB and/or BEH-TEBP alone or in commercial preparations (Firemaster 550, Firemaster BZ-54, Uniplex FRP-45), in mammals (45-47) or fish (48), found EH-TBB was more readily absorbed from the gut and excreted as metabolite(s) while BEH-TEBP was less likely to be absorbed but was more likely to bioaccumulate in liver and other organs after repeated administration. Disposition of newer formulations that contain EH-TBB and BEH-TEBP (e.g., Firemaster 600 (49)) have not been tested.…”

Section: Introductionmentioning

confidence: 99%

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)

Knudsen

Hughes

Sanders

et al. 2016

Toxicology and Applied Pharmacology

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2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [14C]-EH-TBB or [14C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm2 using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [14C]-radioactivity after continuous exposure (24h). “Absorbed” was quantified using dermally retained [14C]-radioactivity; “penetrated” was calculated based on [14C]-radioactivity in media (in vitro) or excreta+tissues (in vivo). Human skin absorbed EH-TBB (24±1%) while 0.2±0.1% penetrated skin. Rat skin absorbed more (51±10%) and was more permeable (2±0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11±7 and 102±24 pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464±65 pmol-eq/cm2/h). BEH-TEBP in vitro penetrance was minimal (<0.01%) for rat or human skin. BEH-TEBP absorption was 12±11% for human skin and 41±3% for rat skin. In vivo, total absorption was 27±9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3±0.2 and 1±0.3 pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7 pmol-eq/cm2/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [14C]-radioactivity in the perfusion media could not be characterized. Less than 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested.

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Quantification of tetrabromo benzoic acid and tetrabromo phthalic acid in rats exposed to the flame retardant Uniplex FPR-45

Cited by 9 publications

References 13 publications

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts

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)

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