title: 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).
abstract: 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 100nmol/cm2using 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±24pmol-eq/cm2/h for human and rat skin, respectively. In vivo, 27±5% was absorbed and 13% reached systemic circulation after 24h (maximum flux was 464±65pmol-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±0.3pmol-eq/cm2/h for human and rat skin; in vivo maximum flux for rat skin was 16±7pmol-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. <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.
  2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92g/mol logPest: 7.73-8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2,3,4,5-tetrabromobenzoate are TBB EHTeBB or EHTBB Abdallah and Harrad, 2011. bis(2-ethylhexyl) tetrabromophthalate (PubChem CID: 117291; CAS No. 26040-51-7 FW: 706.14g/mol logPest: 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP.
authors.affiliation: NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA. Electronic address: gabriel.knudsen@nih.gov.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Knudsen
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
authors.affiliation: NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sanders
authors.affiliation: NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: NCI Laboratory of Toxicology and Toxicokinetics, 111 T W Alexander Dr., Research Triangle Park, NC, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D000368:Aged; D000818:Animals; D001565:Benzoates / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D005411:Flame Retardants / Q000493:pharmacokinetics*; D006801:Humans; D010795:Phthalic Acids / Q000493:pharmacokinetics*; D051381:Rats; D012867:Skin / Q000378:metabolism*
chemical_list: C576261:2-ethylhexyl 2,3,4,5-tetrabromobenzoate; D001565:Benzoates; D005411:Flame Retardants; D010795:Phthalic Acids; C576262:bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate
keywords: 2-Ethylhexyl 2–3,4,5-tetrabromobenzoate; Bis(2-ethylhexyl) tetrabromophthalate; Brominated flame retardant; Dermal bioavailability; Parallelogram method; Persistent organic pollutant