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. [C-14]-EH-TBB or [C-14]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm(2) using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove "unabsorbed" [C-14]-radioactivity after continuous exposure (24 h). "Absorbed" was quantified using dermally retained [C-14]-radioactivity; "penetrated" was calculated based on [C-14]-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/cm(2)/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/cm(2)/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%; 12% 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 [C-14] -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.Chemical compounds studied in this article: 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92 g/mol logP(est): 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: 706.14 g/mol logP(est): 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP. Published by Elsevier Inc.